bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance Monitoring of Mycobacterium tuberculosis Dried Culture Spots for Use with the GeneXpert System within a National Program in South Africa
Authors: Gous N. , Cunningham B. , Kana B. , Stevens W. , Scott L. E.
Published: September 2013

The use of dried culture spots (DCSs) has been reported in the verification of GeneXpert instruments as being “fit for purpose” for the South African National implementation program. We investigated and compared the performance of the DCSs for verification across different bulk batches, testing the settings and cadre of staff, and the Xpert MTB/RIF assay version. Four bulk batches (V005 to V008) were used to prepare (i) 619 DCS panels for laboratory testing on G3 or G4 cartridges by a technologist, (ii) 13 DCS panels (batch V005) used for clinic verification on G3 cartridges by a nurse or lay counselor, and (iii) 20 DCS panels (batch V005) used for the verification of 10 GeneXpert 16 module instruments in mobile vehicles on the G3 cartridge performed by a scientist. The stabilities of the DCSs over 6 months at 4°C, room temperature, and 37°C were investigated. The mean cycle threshold (

C
T

) and standard deviation (SD) for probe A were calculated. The proportions of variability in the

C
T

values across bulk batches, assay versions, and settings and cadre of staff were determined using regression analysis. Overall, the DCSs demonstrated SDs of 3.3 (
n
= 660) for the G3 cartridges and 3.8 (
n
= 1,888) for the G4 cartridges, with an overall error rate of 1.5% and false rifampin resistance rate of 0.1%. The proportions of variability (
R
2
) in the

C
T

values explained by batch were 14%, by setting and cadre of staff, 5.6%, and by assay version, 4.2%. The most stable temperature in a period of up to 6 months was 37°C (SD, 2.7). The DCS is a robust product suitable for storage, transport, and use at room temperature for the verification of the GeneXpert instrument, and the testing can be performed by non-laboratory-trained personnel in nonlaboratory settings.
Evaluation and Implementation of FilmArray Version 1.7 for Improved Detection of Adenovirus Respiratory Tract Infection
Authors: Doern Christopher D. , Lacey Damon , Huang Rong , Haag Crissie
Published: September 2013

The BioFire FilmArray respiratory panel is a multiplex PCR technology capable of detecting a number of bacteria and viruses that cause respiratory tract infection. The assay is technically simple to perform and provides rapid results, making it an appealing option for physicians and laboratorians. The initial product released by BioFire (version 1.6) was reported to have poor sensitivity for adenovirus detection and was therefore of concern when testing immunocompromised patients. This study evaluates the redesigned FilmArray assay (version 1.7) for detection of adenovirus. In this evaluation, we performed both retrospective and prospective verification studies, as well as a detailed serotype analysis. We found that version 1.7 demonstrated improved adenovirus sensitivity. In retrospective studies, sensitivity improved from 66.6% to 90.5%, and in prospective studies, it improved from 42.7% to 83.3%. In addition, when 39 clinically relevant serotypes were tested, 8 were not detected by version 1.6 and only 1 was not detected by version 1.7. The limit of detection remained the same when tested against serotype 4 but improved by 2 log units for serotype 7. Lastly, turnaround time analyses showed that the FilmArray assay was completed 3 h and 9 min after collection, which was more than a 37-h improvement over the previous multiplex PCR assay performed in our laboratory.
Adenovirus E4orf4 Protein-Induced Death of p53
−/−
H1299 Human Cancer Cells Follows a G
1
Arrest of both Tetraploid and Diploid Cells due to a Failure To Initiate DNA Synthesis
Authors: Cabon Lauriane , Sriskandarajah Neera , Mui Melissa Z. , Teodoro Jose G. , Blanchette Paola , Branton Philip E.
Published: September 2013

The adenovirus E4orf4 protein selectively kills human cancer cells independently of p53 and thus represents a potentially promising tool for the development of novel antitumor therapies. Previous studies suggested that E4orf4 induces an arrest or a delay in mitosis and that both this effect and subsequent cell death rely largely on an interaction with the B55 regulatory subunit of protein phosphatase 2A. In the present report, we show that the death of human H1299 lung carcinoma cells induced by expression of E4orf4 is typified not by an accumulation of cells arrested in mitosis but rather by the presence of both tetraploid and diploid cells that are arrested in G
1
because they are unable to initiate DNA synthesis. We believe that these E4orf4-expressing cells eventually die by various processes, including those resulting from mitotic catastrophe.
Efficient Replication of Epstein-Barr Virus-Derived Plasmids Requires Tethering by EBNA1 to Host Chromosomes
Authors: Hodin Theresa L. , Najrana Tanbir , Yates John L.
Published: September 2013

The EBNA1 protein of Epstein-Barr virus enables plasmids carrying
oriP
both to duplicate and to segregate efficiently in proliferating cells. EBNA1 recruits the origin recognition complex (ORC) to establish a replication origin at one element of
oriP
, DS (
d
yad
s
ymmetry); at another element, FR (
f
amily of
r
epeats), EBNA1 binds to an array of sites from which it tethers plasmids to host chromosomes for mitotic stability. We report experiments leading to the conclusion that tethering by EBNA1 to host chromosomes is also needed within interphase nuclei in order for plasmids to be replicated efficiently from
oriP
. The DNA-binding domain of EBNA1, which lacks chromosome-binding ability, was found to support weak, DS-specific replication in HEK293 cells after transient transfection, being 17% as active as wild-type EBNA1. The low efficiency of replication was not due to the failure of the DNA-binding domain to retain plasmids within nuclei, because plasmids were recovered in similar amounts and entirely from the nuclear fraction of these transiently transfected cells. A derivative of EBNA1 with its chromosome-tethering domains replaced by a 22-amino-acid nucleosome-binding domain was fully active in supporting
oriP
functions. The implication is that EBNA1's DNA-binding domain is able to recruit ORC to DS, but either this step or subsequent replication is only efficient if the plasmid is tethered to a host chromosome. Finally, with some cell lines, DS can hardly support even transient plasmid replication without FR. A loss of plasmids lacking FR from nuclei cannot account for this requirement, suggesting that the stronger tethering to chromosomes by FR is needed for plasmid replication within the nuclei of such cells.
The T Antigen Locus of Merkel Cell Polyomavirus Downregulates Human Toll-Like Receptor 9 Expression
Authors: Shahzad Naveed , Shuda Masahiro , Gheit Tarik , Kwun Hyun Jin , Cornet Iris , Saidj Djamel , Zannetti Claudia , Hasan Uzma , Chang Yuan , Moore Patrick S. , Accardi Rosita , Tommasino Massimo
Published: September 2013

Establishment of a chronic infection is a key event in virus-mediated carcinogenesis. Several cancer-associated, double-stranded DNA (dsDNA) viruses act via their oncoproteins to downregulate Toll-like receptor 9 (TLR9), a key receptor in the host innate immune response that senses viral or bacterial dsDNA. A novel oncogenic virus, Merkel cell polyomavirus (MCPyV), has been recently identified that causes up to 80% of Merkel cell carcinomas (MCCs). However, it is not yet known whether this oncogenic virus also disrupts immune-related pathways. We find that MCPyV large T antigen (LT) expression downregulates TLR9 expression in epithelial and MCC-derived cells. Accordingly, silencing of LT expression results in upregulation of mRNA TLR9 levels. In addition, small T antigen (sT) also appears to inhibit TLR9 expression, since inhibition of its expression also resulted in an increase of TLR9 mRNA levels. LT inhibits TLR9 expression by decreasing the mRNA levels of the C/EBPβ transactivator, a positive regulator of the TLR9 promoter. Chromatin immunoprecipitation reveals that C/EBPβ binding at a C/EBPβ response element (RE) in the TLR9 promoter is strongly inhibited by expression of MCPyV early genes and that mutation of the C/EBP RE prevents MCPyV downregulation of TLR9. A survey of BK polyomavirus (BKPyV), JC polyomavirus (JCPyV), KI polyomavirus (KIPyV), MCPyV, simian virus 40 (SV40), and WU polyomavirus (WUPyV) early genes revealed that only BKPyV and MCPyV are potent inhibitors of TLR9 gene expression. MCPyV LT targeting of C/EBP transactivators is likely to play an important role in viral persistence and potentially inhibit host cell immune responses during MCPyV tumorigenesis.
The L Gene of J Paramyxovirus Plays a Critical Role in Viral Pathogenesis
Authors: Li Zhuo , Xu Jie , Chen Zhenhai , Gao Xiudan , Wang Lin-Fa , Basler Christopher , Sakamoto Kaori , He Biao
Published: September 2013

J paramyxovirus (JPV) was first isolated from moribund mice with hemorrhagic lung lesions in Australia in the 1970s. Recent sequencing of JPV (JPV-LW) confirms that JPV is a paramyxovirus with several unique features. However, neither JPV-LW nor a recombinant JPV based on its sequence (rJPV-LW) caused obvious illness in mice. In this work, we analyzed a different JPV isolate (JPV-BH), which behaved differently from JPV-LW; JPV-BH grew more slowly in Vero cells and had less of a cytopathic effect on tissue culture cells but caused severe disease in mice. We have determined the whole genome sequence of JPV-BH. There were several nucleotide sequence differences between JPV-BH and JPV-LW, one in the leader sequence, one in the GX gene, and three in the L gene. The high sequence identity between JPV-BH and JPV-LW suggests that JPV-BH and JPV-LW are the same virus strain but were obtained at different passages from different laboratories. To understand the roles of these nucleotide sequence differences in pathogenicity in mice, we generated a recombinant JPV-BH strain (rJPV-BH) and hybrid rJPV-BH strains with sequences from the leader sequence (rJPV-BH-Le-LW), the GX gene (rJPV-BH-GX-LW), and the L gene (rJPV-BH-L-LW) of JPV-LW and compared their pathogenicities in mice. We have found that rJPV-BH-L-LW was attenuated in mice, indicating that nucleotide sequence differences in the L gene play a critical role in pathogenesis.
Novel Apoptosis Suppressor Apsup from the Baculovirus Lymantria dispar Multiple Nucleopolyhedrovirus Precludes Apoptosis by Preventing Proteolytic Processing of Initiator Caspase Dronc
Authors: Yamada Hayato , Kitaguchi Koji , Hamajima Rina , Kobayashi Michihiro , Ikeda Motoko
Published: September 2013

We previously identified a novel baculovirus-encoded apoptosis suppressor, Apsup, from the baculovirus
Lymantria dispar
multiple nucleopolyhedrovirus (LdMNPV). Apsup inhibits the apoptosis of
L. dispar
Ld652Y cells triggered by infection with
p35
-defective
Autographa californica
MNPV (vAcΔp35) and exposure to actinomycin D or UV light. Here, we examined the functional role of Apsup in apoptosis regulation in insect cells. Apsup prevented apoptosis and the proteolytic processing of
L. dispar
initiator caspase Dronc (Ld-Dronc) in Ld652Y cells triggered by overexpression of Ld-Dronc, LdMNPV inhibitor-of-apoptosis 3 (IAP3), or
Hyphantria cunea
MNPV IAP1. In vAcΔp35-infected apoptotic Ld652Y cells, Apsup restricted apoptosis induction and prevented processing of endogenous Ld-Dronc. Conversely, upon RNA interference (RNAi)-mediated silencing of
apsup
, LdMNPV-infected Ld652Y cells, which typically support high-titer virus replication, underwent apoptosis, accompanied by the processing of endogenous Ld-Dronc. Furthermore, endogenous Ld-Dronc coimmunoprecipitated with transiently expressed Apsup, indicating that Apsup physically interacts with Ld-Dronc. Apsup prevented the apoptosis of Sf9 cells triggered by vAcΔp35 infection but did not inhibit apoptosis or activation of caspase-3-like protease in vAcΔp35-infected
Drosophila melanogaster
S2 cells. Apsup also inhibited the proteolytic processing of
L. dispar
effector caspase Ld-caspase-1 in the transient expression assay but did not physically interact with Ld-caspase-1. These results demonstrate that Apsup inhibits apoptosis in Ld652Y cells by preventing the proteolytic processing of Ld-Dronc. Together with our previous findings showing that Apsup prevents the processing of both overexpressed Ld-Dronc and
Bombyx mori
Dronc, these results also demonstrate that Apsup functions as an effective apoptotic suppressor in various lepidopteran, but not dipteran, insect cells.
Configuration of Viral Ribonucleoprotein Complexes within the Influenza A Virion
Authors: Sugita Yukihiko , Sagara Hiroshi , Noda Takeshi , Kawaoka Yoshihiro
Published: September 2013

The influenza A virus possesses an eight-segmented, negative-sense, single-stranded RNA genome (vRNA). Each vRNA segment binds to multiple copies of viral nucleoproteins and a small number of heterotrimeric polymerase complexes to form a rod-like ribonucleoprotein complex (RNP), which is essential for the transcription and replication of the vRNAs. However, how the RNPs are organized within the progeny virion is not fully understood. Here, by focusing on polymerase complexes, we analyzed the fine structure of purified RNPs and their configuration within virions by using various electron microscopies (EM). We confirmed that the individual RNPs possess a single polymerase complex at one end of the rod-like structure and that, as determined using immune EM, some RNPs are incorporated into budding virions with their polymerase-binding ends at the budding tip, whereas others align with their polymerase-binding ends at the bottom of the virion. These data further our understanding of influenza virus virion morphogenesis.
Characterization of Mus musculus Papillomavirus 1 Infection
In Situ
Reveals an Unusual Pattern of Late Gene Expression and Capsid Protein Localization
Authors: Handisurya Alessandra , Day Patricia M. , Thompson Cynthia D. , Buck Christopher B. , Pang Yuk-Ying S. , Lowy Douglas R. , Schiller John T.
Published: September 2013

Full-length genomic DNA of the recently identified laboratory mouse papillomavirus 1 (MusPV1) was synthesized
in vitro
and was used to establish and characterize a mouse model of papillomavirus pathobiology. MusPV1 DNA, whether naked or encapsidated by MusPV1 or human papillomavirus 16 (HPV 16) capsids, efficiently induced the outgrowth of papillomas as early as 3 weeks after application to abraded skin on the muzzles and tails of athymic NCr nude mice. High concentrations of virions were extracted from homogenized papillomatous tissues and were serially passaged for >10 generations. Neutralization by L1 antisera confirmed that infectious transmission was capsid mediated. Unexpectedly, the skin of the murine back was much less susceptible to virion-induced papillomas than the muzzle or tail. Although reporter pseudovirions readily transduced the skin of the back, infection with native MusPV1 resulted in less viral genome amplification and gene expression on the back, including reduced expression of the L1 protein and very low expression of the L2 protein, results that imply skin region-specific control of postentry aspects of the viral life cycle. Unexpectedly, L1 protein on the back was predominantly cytoplasmic, while on the tail the abundant L1 was cytoplasmic in the lower epithelial layers and nuclear in the upper layers. Nuclear localization of L1 occurred only in cells that coexpressed the minor capsid protein, L2. The pattern of L1 protein staining in the infected epithelium suggests that L1 expression occurs earlier in the MusPV1 life cycle than in the life cycle of high-risk HPV and that virion assembly is regulated by a previously undescribed mechanism.
Herpes Simplex Virus 1 Counteracts Tetherin Restriction via Its Virion Host Shutoff Activity
Authors: Zenner Helen L. , Mauricio Rui , Banting George , Crump Colin M.
Published: September 2013

The interferon-inducible membrane protein tetherin (Bst-2, or CD317) is an antiviral factor that inhibits enveloped virus release by cross-linking newly formed virus particles to the producing cell. The majority of viruses that are sensitive to tetherin restriction appear to be those that acquire their envelopes at the plasma membrane, although many viruses, including herpesviruses, envelope at intracellular membranes, and the effect of tetherin on such viruses has been less well studied. We investigated the tetherin sensitivity and possible countermeasures of herpes simplex virus 1 (HSV-1). We found that overexpression of tetherin inhibits HSV-1 release and that HSV-1 efficiently depletes tetherin from infected cells. We further show that the virion host shutoff protein (Vhs) is important for depletion of tetherin mRNA and protein and that removal of tetherin compensates for defects in replication and release of a Vhs-null virus. Vhs is known to be important for HSV-1 to evade the innate immune responsein vivo. Taken together, our data suggest that tetherin has antiviral activity toward HSV-1 and that the removal of tetherin by Vhs is important for the efficient replication and dissemination of HSV-1.
Replication Stress and Mitotic Dysfunction in Cells Expressing Simian Virus 40 Large T Antigen
Authors: Hu Liang , Filippakis Harilaos , Huang Haomin , Yen Timothy J. , Gjoerup Ole V.
Published: September 2013

We previously demonstrated that simian virus 40 (SV40) large T antigen (LT) binds to the Bub1 kinase, a key regulator of the spindle checkpoint and chromosome segregation. Bub1 mutations or altered expression patterns are linked to chromosome missegregation and are considered to be a driving force in some human cancers. Here we report that LT, dependent on Bub1 binding, causes micronuclei, lagging chromatin, and anaphase bridges, which are hallmarks of chromosomal instability (CIN) and Bub1 insufficiency. Using time-lapse microscopy, we demonstrate that LT imposes a Bub1 binding-dependent delay in the metaphase-to-anaphase transition. Kinetochore fibers reveal that LT, via Bub1 binding, causes aberrant kinetochore (KT)-microtubule (MT) attachments and a shortened interkinetochore distance, consistent with a lack of tension. Previously, we showed that LT also induces the DNA damage response (DDR) via Bub1 binding. Using inducible LT cell lines, we show that an activated DDR was observed before the appearance of anaphase bridges and micronuclei. Furthermore, LT induction in serum-starved cells demonstrated γ-H2AX accumulation in cells that had not yet entered mitosis. Thus, DDR activation can occur independently of chromosome segregation defects. Replication stress pathways may be responsible, because signatures of replication stress were observed, which were attenuated by exogenous supplementation with nucleosides. Our observations allow us to propose a model that explains and integrates the diverse manifestations of genomic instability induced by LT.
Polycomb Repressive Complex 2 Silences Human Cytomegalovirus Transcription in Quiescent Infection Models
Authors: Abraham Christopher G. , Kulesza Caroline A.
Published: September 2013

Chromatin-based regulation of herpesviral transcriptional programs is increasingly appreciated as a mechanism for modulating infection outcomes. Transcriptionally permissive euchromatin predominates during lytic infection, whereas heterochromatin domains refractory to transcription are enriched at lytic genes during latency. Reversibly silenced facultative heterochromatin domains are often enriched for histone H3 trimethylated on lysine 27 (H3K27me3), a modification catalyzed by Polycomb repressive complex 2 (PRC2). The requirement for PRC2 in suppressing the human cytomegalovirus (HCMV) lytic transcriptional program during latency has not been thoroughly evaluated. Therefore, we disrupted PRC2 activity in the highly tractable THP1 and NT2D1 quiescent-infection models by treating cells with small-molecule inhibitors of PRC2 activity. Compared to control cells, disruption of PRC2 in HCMV-infected THP1 or NT2D1 cells resulted in significant increases in viral transcript levels and the detection of viral protein. Using chromatin immunoprecipitation, we demonstrated that enrichment of H3K27me3, deposited by PRC2, correlates inversely with lytic transcriptional output, suggesting that PRC2 catalytic activity at viral chromatin directly represses lytic transcription. Together, our data suggest that PRC2-mediated repression of viral transcription is a key step in the establishment and maintenance of HCMV latency.
Structure of the Fusion Core and Inhibition of Fusion by a Heptad Repeat Peptide Derived from the S Protein of Middle East Respiratory Syndrome Coronavirus
Authors: Gao Jing , Lu Guangwen , Qi Jianxun , Li Yan , Wu Ying , Deng Yao , Geng Heyuan , Li Hongbin , Wang Qihui , Xiao Haixia , Tan Wenjie , Yan Jinghua , Gao George F.
Published: September 2013

Middle East respiratory syndrome coronavirus (MERS-CoV) recently emerged as a severe worldwide public health concern. The virus is highly pathogenic, manifesting in infected patients with an approximately 50% fatality rate. It is known that the surface spike (S) proteins of coronaviruses mediate receptor recognition and membrane fusion, thereby playing an indispensable role in initiating infection. In this process, heptad repeats 1 and 2 (HR1 and HR2) of the S protein assemble into a complex called the fusion core, which represents a key membrane fusion architecture. To date, however, the MERS-CoV fusion core remains uncharacterized. In this study, we performed a series of biochemical and biophysical analyses characterizing the HR1/HR2 complexes of this novel virus. The HR sequences were variably truncated and then connected with a flexible amino acid linker. In each case, the recombinant protein automatically assembled into a trimer in solution, displaying a typical α-helical structure. One of these trimers was successfully crystallized, and its structure was solved at a resolution of 1.9 Å. A canonical 6-helix bundle, like those reported for other coronaviruses, was revealed, with three HR1 helices forming the central coiled-coil core and three HR2 chains surrounding the core in the HR1 side grooves. This demonstrates that MERS-CoV utilizes a mechanism similar to those of other class I enveloped viruses for membrane fusion. With this notion, we further identified an HR2-based peptide that could potently inhibit MERS-CoV fusion and entry by using a pseudotyped-virus system. These results lay the groundwork for future inhibitory peptidic drug design.
Parvovirus B19 Uptake Is a Highly Selective Process Controlled by VP1u, a Novel Determinant of Viral Tropism
Authors: Leisi Remo , Ruprecht Nico , Kempf Christoph , Ros Carlos
Published: September 2013

The VP1 unique region (VP1u) of human parvovirus B19 (B19V) is the immunodominant part of the viral capsid. Originally inaccessible, the VP1u becomes exposed upon primary attachment to the globoside receptor. To study the function of the exposed VP1u in B19V uptake, we expressed this region as a recombinant protein. Here, we report that purified recombinant VP1u binds and is internalized in UT7/Epo cells. By means of truncations and specific antibodies, we identified the most N-terminal amino acid residues of VP1u as the essential region for binding and internalization. Furthermore, the recombinant VP1u was able to block B19V uptake, suggesting that the protein and the virus undertake the same internalization pathway. Assays with different erythroid and nonerythroid cell lines showed that the N-terminal VP1u binding was restricted to a few cell lines of the erythroid lineage, which were also the only cells that allowed B19V internalization and infection. These results together indicate that the N-terminal region of VP1u is responsible for the internalization of the virus and that the interacting receptor is restricted to B19V-susceptible cells. The highly selective uptake mechanism represents a novel determinant of the tropism and pathogenesis of B19V.
Phylogenomic Network and Comparative Genomics Reveal a Diverged Member of the ϕKZ-Related Group, Marine Vibrio Phage ϕJM-2012
Authors: Jang Ho Bin , Fagutao Fernand F. , Nho Seong Won , Park Seong Bin , Cha In Seok , Yu Jong Earn , Lee Jung Seok , Im Se Pyeong , Aoki Takashi , Jung Tae Sung
Published: September 2013

Bacteriophages are the largest reservoir of genetic diversity. Here we describe the novel phage ϕJM-2012. This natural isolate from marine
Vibrio cyclitrophicus
possesses very few gene contents relevant to other well-studied marine
Vibrio
phages. To better understand its evolutionary history, we built a mathematical model of pairwise relationships among 1,221 phage genomes, in which the genomes (nodes) are linked by edges representing the normalized number of shared orthologous protein families. This weighted network revealed that ϕJM-2012 was connected to only five members of the
Pseudomonas
ϕKZ-like phage family in an isolated network, strongly indicating that it belongs to this phage group. However, comparative genomic analyses highlighted an almost complete loss of colinearity with the ϕKZ-related genomes and little conservation of gene order, probably reflecting the action of distinct evolutionary forces on the genome of ϕJM-2012. In this phage, typical conserved core genes, including six RNA polymerase genes, were frequently displaced and the hyperplastic regions were rich in both unique genes and predicted unidirectional promoters with highly correlated orientations. Further, analysis of the ϕJM-2012 genome showed that segments of the conserved N-terminal parts of ϕKZ tail fiber paralogs exhibited evidence of combinatorial assortment, having switched transcriptional orientation, and there was recruitment and/or structural changes among phage endolysins and tail spike protein. Thus, this naturally occurring phage appears to have branched from a common ancestor of the ϕKZ-related groups, showing a distinct genomic architecture and unique genes that most likely reflect adaptation to its chosen host and environment.
Pain and fracture after anterior cruciate ligament reconstruction caused by giant cell tumour of the distal femur
Authors: Dowen Daniel , Kakkar Rahul , Dildey Petra , Gerrand Craig
Published: September 2013

The causes of pain after an anterior cruciate ligament (ACL) reconstruction are numerous and may have complex origins. We present an unusual case in which pain after an ACL reconstruction developed secondary to a giant cell tumour of the bone occurring around a fixation screw in the distal femur, with an associated fracture through the femoral tunnel of a previously well-functioning reconstruction. We discuss the aetiology and the treatment of a complex clinical scenario.
Oral health and impact on performance of athletes participating in the London 2012 Olympic Games: a cross-sectional study
Authors: Needleman I , Ashley P , Petrie A , Fortune F , Turner W , Jones J , Niggli J , Engebretsen L , Budgett R , Donos N , Clough T , Porter S
Published: September 2013

Background

Oral health is important both for well-being and successful elite sporting performance. Reports from Olympic Games have found significant treatment needs; however, few studies have examined oral health directly. The aim of this study was to evaluate oral health, the determinants of oral health and the effect of oral health on well-being, training and performance of athletes participating in the London 2012 Games.

Methods

Cross-sectional study at the dental clinic within the Polyclinic in the athletes’ village. Following informed consent, a standardised history, clinical examination and brief questionnaire were conducted.

Results

302 athletes from 25 sports were recruited with data available for 278. The majority of athletes were from Africa, the Americas and Europe. Overall, the results demonstrated high levels of poor oral health including dental caries (55% athletes), dental erosion (45% athletes) and periodontal disease (gingivitis 76% athletes, periodontitis 15% athletes). More than 40% of athletes were ‘bothered’ by their oral health with 28% reporting an impact on quality of life and 18% on training and performance. Nearly half of the participants had not undergone a dental examination or hygiene care in the previous year.

Conclusions

The oral health of athletes attending the dental clinic of the London 2012 Games was poor with a resulting substantial negative impact on well-being, training and performance. As oral health is an important element of overall health and well-being, health promotion and disease prevention interventions are urgently required to optimise athletic performance.
Strengths and weaknesses of working with the Global Trigger Tool method for retrospective record review: focus group interviews with team members
Authors: Schildmeijer Kristina , Nilsson Lena , Perk Joep , Årestedt Kristofer , Nilsson Gunilla
Published: September 2013

Objectives

The aim was to describe the strengths and weaknesses, from team member perspectives, of working with the Global Trigger Tool (GTT) method of retrospective record review to identify adverse events causing patient harm.

Design

A qualitative, descriptive approach with focus group interviews using content analysis.

Setting

5 Swedish hospitals in 2011.

Participants

5 GTT teams, with 5 physicians and 11 registered nurses.

Intervention

5 focus group interviews were carried out with the five teams. Interviews were taped and transcribed verbatim.

Results

8 categories emerged relating to the strengths and weaknesses of the GTT method. The categories found were:Usefulness of the GTT, Application of the GTT, Triggers, Preventability of harm, Team composition, Team tasks, Team members’ knowledge development and Documentation. Gradually, changes in the methodology were made by the teams, for example, the teams reported how the registered nurses divided up the charts into two sets, each being read respectively. The teams described the method as important and well functioning. Not only the most important, but also the most difficult, was the task of bringing the results back to the clinic. The teams found it easier to discuss findings at their own clinics.

Conclusions

The GTT method functions well for identifying adverse events and is strengthened by its adaptability to different specialties. However, small, gradual methodological changes together with continuingly developed expertise and adaption to looking at harm from a patient's perspective may contribute to large differences in assessment over time.
Pharmacist intervention for glycaemic control in the community (the RxING study)
Authors: Al Hamarneh Yazid N , Charrois Theresa , Lewanczuk Richard , Tsuyuki Ross T
Published: September 2013

Objective

To determine the effect of a community pharmacist prescribing intervention on glycaemic control in patients with poorly controlled type 2 diabetes.

Design

Pragmatic, before–after design.

Setting

12 community pharmacies in Alberta, Canada.

Participants

Type 2 diabetes receiving oral hypoglycaemic medications and with glycated haemoglobin (HbA1c) of 7.5–11%.

Intervention

Pharmacists systematically identified potential candidates by inviting patients with type 2 diabetes to test their HbA1c using validated point-of-care technology. Pharmacists prescribed 10 units of insulin glargine at bedtime, adjusted by increments of 1 unit daily to achieve a morning fasting glucose of ≤5.5 mmol/L. The patients were followed up at 2, 4, 8, 14, 20 and 26 weeks.

Primary outcome

Change in HbA1c from baseline to week 26.

Secondary outcomes

Proportion of patients achieving target HbA1c, changes in oral hypoglycaemic agents, quality of life and patient satisfaction, persistence on insulin glargine, number of insulin dosage adjustments per patient and number of hypoglycaemic episodes.

Results

We screened 365 patients of whom 111 were eligible. Of those, 100 (90%) were enrolled in the study; all 11 patients who did not consent refused to use insulin. Average age was 64 years (SD 10.4), while average diabetes duration was 10.2 years (SD 7). HbA1c was reduced from 9.1% (SD 1) at baseline to 7.3% (SD 0.9); a change of 1.8% (95% CI 1.4 to 2, p<0.001). Fasting plasma glucose was reduced from 11 (SD 3.3) to 6.9 mmol/L (SD 1.8); a change of 4.1 mmol/L (95% CI of 3.3 to 5, p=0.007). Fifty-one per cent of the patients achieved the target HbA1c of ≤7% at the end of the study.

Conclusions

This is the first completed study of independent prescribing by pharmacists. Our results showed similar improvements in glycaemic control as previous physician-led studies. RxING provides further evidence for the benefit of pharmacist care in diabetes.

Trial registration

clinicaltrials.gov; Identifier:NCT01335763.
The effects of UV light on calcium metabolism in ball pythons (Python regius)
Authors: Hedley J. , Eatwell K.
Published: September 2013

Despite the popularity of keeping snakes in captivity, there has been limited investigation into the effects of UV radiation on vitamin D levels in snakes. The aim of this study was to investigate the effects of UV‐b radiation on plasma 25‐hydroxyvitamin D3 levels and ionised calcium concentrations in ball pythons (Python regius). Blood samples were taken from 14 ball pythons, which had never been exposed to UV‐b light, to obtain baseline 25‐hydroxyvitamin D3 levels and ionised calcium concentrations. Blood samples were then taken again from the same snakes 70 days later after one group (Group 1, n=6 females) were exposed to UV‐b radiation daily, and the other group (Group 2, n=5 males and 3 females) were exposed to no UV‐b radiation. Mean±sd 25‐hydroxyvitamin D3 levels on day 0 in Group 1 were 197±35 nmol/l, and on day 70 were 203.5±13.8 nmol/l. Mean±sd 25‐hydroxyvitamin D3 levels in Group 2 on day 0 were 77.7±41.5 nmol/l, and on day 70 were 83.0±41.9 nmol/l. Mean±sd ionised calcium levels at day 0 were 1.84±0.05 mmol/l for Group 1, and on day 70 were 1.78±0.07 mmol/l. Mean±sd ionised calcium levels at day 0 were 1.79±0.07 mmol/l for Group 2, and on day 70 were 1.81±0.05 mmol/l. No association was demonstrated between exposure to UV‐b radiation and plasma 25‐hydroxyvitamin D3 and ionised calcium concentrations. These results may provide baseline parameters for future studies in this and other snake species to determine ability to utilise UV‐b light for vitamin D production.
ON THE PERIODICITY AND GLOBAL STABILITY FOR A DISCRETE DELAYED PREDATOR–PREY MODEL
Authors: XU CHANGJIN , LI PEILUAN
Published: September 2013

In this paper, a discrete version of continuous non-autonomous predator–prey model with delays is investigated. By using Gaines and Mawhin's continuation theorem of coincidence degree theory and the method of Lyapunov function, some sufficient conditions for the existence and globally asymptotically stability of positive periodic solution of difference equations in consideration are established. Finally, some numerical examples are given to verify the theoretical analysis.
ON THE STRUCTURE OF THE UNITARY SUBGROUP OF THE GROUP ALGEBRA 𝔽2qD2n
Authors: RAZA ZAHID , AHMAD MAQSOOD
Published: September 2013

We discuss the structure of the unitary subgroup V*(𝔽2qD2n) of the group algebra 𝔽2qD2n, where D2n= 〈x, y | x2n-1= y2= 1, xy = yx2n-1-1〉 is the dihedral group of order 2nand 𝔽2qis any finite field of characteristic 2, with 2qelements. We will prove that [Formula: see text], see Theorem 3.1.
A RECENT EULERIAN–LAGRANGIAN CFD METHODOLOGY FOR MODELING DIRECT INJECTION DIESEL SPRAYS
Authors: DESANTES JOSÉ M. , HOYAS SERGIO , GIL ANTONIO , DUNG KHUONG ANH , RAVET FRÉDÉRIC
Published: September 2013

The global objective of this work is to show the capabilities of the Eulerian–Lagrangian spray atomization (ELSA) model for the simulation of Diesel sprays in cold starting conditions. Our main topic is to focus in the analysis of spray formation and its evolution at low temperature 255 K (-18°C) and nonevaporative conditions. Spray behavior and several macroscopic properties, included the liquid spray penetration, and cone angle are also characterized. This study has been carried out using different ambient temperature and chamber pressure conditions. Additionally, the variations of several technical quantities, as the area coefficient and effective diameter are also studied. The results are compared with the latest experimental results in this field obtained in our institute. In the meantime, we also compare with the normal ambient temperature at 298 K (25°C) where the numerical validation of the model has shown a good agreement.
INNOVATION APPROACHES FOR OLD PRODUCTS REVITALISATION AFTER TECHNOLOGICAL CHANGE: THE RISE OF TECHNOLOGY REVERSE
Authors: SCHIAVONE FRANCESCO
Published: September 2013

Incumbent companies sometimes innovate and attempt to revitalise old technology-based products, in decline after technological change, by improvements of their technical performance and/or extensions of their lifetime into the market. The name of this innovation approach is "sailing ship effect," the acceleration of innovation in the old technology in response to the threat from the new. However, in theory firms could achieve revitalisation even by an alternative innovation approach based on the development of completely new products. The article reports an illustrative case study: the innovation approach of some of the main incumbent organisations in photography industry after the emergence of digital cameras. In this case, incumbent companies developed and launched film scanners, new technology-based products aimed at supporting users of old analog cameras after the rise of digital imaging. The article contributes to the extant literature about innovation approaches for old products' revitalisation by analysing how established firms can achieve this goal with completely new technological products. The approach of technology reverse is proposed.
THE LÜROTH SEMIGROUP OF A PLANE CURVE C OVER 𝔽qAND THE PRIMITIVE SET OF P ∈ C(𝔽q)
Authors: Ballico Edoardo
Published: September 2013

Let C ⊂ ℙ2be a smooth and geometrically connected curve defined over 𝔽q. We study the Lüroth semigroup of C over 𝔽q, i.e. the set L(C, q) of all degrees > 0 of some spanned line bundle on C defined over 𝔽q. Fix P ∈ C(𝔽q). We also study the set of all t ∈ ℕ such that both [Formula: see text] and ωC(–tP) are spanned (the primitive set of P), when q is a square, C is the Hermitian curve and P ∈ C(𝔽q).
Palaeoclimatic imprint, distribution and genesis of Zechstein Main Dolomite (Upper Permian) petroleum source rocks in Poland: Sedimentological and geochemical rationales
Authors: Słowakiewicz Mirosław , Gąsiewicz Andrzej
Published: September 2013

Arid palaeoclimatic conditions and marine current circulation influenced organic matter productivity and its distribution and preservation in the Upper Permian (Zechstein) Main Dolomite (Ca2) source rocks in Poland. The gaseous and liquid hydrocarbons occurring within the Main Dolomite show distinctive geochemical characteristics which distinguish them from those derived from Carboniferous or other Permian strata and indicate that the main type of organic matter from which they were derived was of microbial origin. It is suggested here that the majority of the Ca2 hydrocarbons come from
in situ
organic matter (intraformational deposits). The lagoonal and slope zones are enriched in total organic carbon (TOC) compared to both the oolite shoal and basinal facies. These sedimentary settings were dominated by various biolaminated microbialite facies. The basinal areas, previously believed to be the location of the main source rocks for hydrocarbons found in the Main Dolomite, appear to have little source rock potential. Geochemical and geological features such as high organic productivity in lagoonal and slope zones of the Main Dolomite indicate that at least some of the hydrocarbons may have been generated from
in situ
deposited and degraded organic matter. This conclusion may improve prediction of the occurrence of hydrocarbon deposits in the Ca2.
Implementing the argument web
Authors: Bex Floris , Lawrence John , Snaith Mark , Reed Chris
Published: September 2013

Improve online public discourse by connecting opinions across blogs, editorials, and social media.
Evaluating a startup venture
Authors: Cusumano Michael A.
Published: September 2013

Considering the key elements of successful startups.
Beyond efficiency
Authors: Ackley David H.
Published: September 2013

Esteem for efficiency should be tempered with respect for robustness.
Controlling for cybersecurity risks of medical device software
Authors: Fu Kevin , Blum James
Published: September 2013

Medical device hacking is a red herring. But the flaws are real.
Something Bad Might Happen: Lawyers, anonymization and risk
Authors: Oswald Marion
Published: September 2013

The line between personal and anonymous information is often unclear. Increasingly it falls to lawyers to understand and manage the risks associated with the sharing of "anonymized" data sets.
Habits: Our cognitive shortcut
Authors: Nave Gidi
Published: September 2013

Accepting the habitual system as an inseparable part of our minds, understanding its limitation and the way it works, may help us to achieve our long-term goals.
The Tor Project: An inside view
Authors: Misata Kelley
Published: September 2013

A decade since the first version was released, Tor continues to be at the center of the debate around online privacy.
Profile: Jessica StaddonManaging Google's privacy research
Authors: Scoică Adrian
Published: September 2013

In this profile, Jessica Staddon discusses managing privacy research for one the world's best-known technology corporations.
Coordination When Information is Scarce: How privacy can help
Authors: Roth Aaron
Published: September 2013

There is something to be gained by borrowing the tools of differential privacy and applying them to solve problems in seemingly unrelated fields.
Aquaporins in avian kidneys: function and perspectives
Authors: Nishimura Hiroko , Yang Yimu
Published: September 2013

For terrestrial vertebrates, water economy is a prerequisite for survival, and the kidney is their major osmoregulatory organ. Birds are the only vertebrates other than mammals that can concentrate urine in adaptation to terrestrial environments. Aquaporin (AQP) and glyceroporin (GLP) are phylogenetically old molecules and have been found in plants, microbial organisms, invertebrates, and vertebrates. Currently, 13 AQPs/aquaGLPs and isoforms are known to be present in mammals. AQPs 1, 2, 3, 4, 6, 7, 8, and 11 are expressed in the kidney; of these, AQPs 1, 2, 3, 4, and 7 are shown to be involved in fluid homeostasis. In avian kidneys, AQPs 1, 2, 3, and 4 have been identified and characterized. Also, gene and/or amino acid sequences of AQP5, AQP7, AQP8, AQP9, AQP11, and AQP12 have been reported in birds. AQPs 2 and 3 are expressed along cortical and medullary collecting ducts (CDs) and are responsible, respectively, for the water inflow and outflow of CD epithelial cells. While AQP4 plays an important role in water exit in the CD of mammalian kidneys, it is unlikely to participate in water outflow in avian CDs. This review summarizes current knowledge on structure and function of avian AQPs and compares them to those in mammalian and nonmammalian vertebrates. Also, we aim to provide input into, and perspectives on, the role of renal AQPs in body water homeostasis during ontogenic and phylogenetic advancement.
Loss of neurotrophin-3 from smooth muscle disrupts vagal gastrointestinal afferent signaling and satiation
Authors: Fox Edward A. , Biddinger Jessica E. , Baquet Zachary C. , Jones Kevin R. , McAdams Jennifer
Published: September 2013

A large proportion of vagal afferents are dependent on neurotrophin-3 (NT-3) for survival. NT-3 is expressed in developing gastrointestinal (GI) smooth muscle, a tissue densely innervated by vagal mechanoreceptors, and thus could regulate their survival. We genetically ablated NT-3 from developing GI smooth muscle and examined the pattern of loss of NT-3 expression in the GI tract and whether this loss altered vagal afferent signaling or feeding behavior. Meal-induced c-Fos activation was reduced in the solitary tract nucleus and area postrema in mice with a smooth muscle-specific NT-3 knockout ( SM-NT-3KO) compared with controls, suggesting a decrease in vagal afferent signaling. Daily food intake and body weight of SM-NT-3KOmice and controls were similar. Meal pattern analysis revealed that mutants, however, had increases in average and total daily meal duration compared with controls. Mutants maintained normal meal size by decreasing eating rate compared with controls. Although microstructural analysis did not reveal a decrease in the rate of decay of eating in SM-NT-3KOmice, they ate continuously during the 30-min meal, whereas controls terminated feeding after 22 min. This led to a 74% increase in first daily meal size of SM-NT-3KOmice compared with controls. The increases in meal duration and first meal size of SM-NT-3KOmice are consistent with reduced satiation signaling by vagal afferents. This is the first demonstration of a role for GI NT-3 in short-term controls of feeding, most likely involving effects on development of vagal GI afferents that regulate satiation.
Separate evaluation of target facilitation and distractor suppression in the activity of macaque lateral intraparietal neurons during visual search
Authors: Nishida Satoshi , Tanaka Tomohiro , Ogawa Tadashi
Published: September 2013

During visual search, neurons in the lateral intraparietal area (LIP) discriminate the target from distractors by exhibiting stronger activation when the target appears within the receptive field than when it appears outside the receptive field. It is generally thought that such target-discriminative activity is produced by the combination of target-related facilitation and distractor-related suppression. However, little is known about how the target-discriminative activity is constituted by these two types of neural modulation. To address this issue, we recorded activity from LIP of monkeys performing a visual search task that consisted of target-present and target-absent trials. Monkeys had to make a saccade to a target in the target-present trials, whereas they had to maintain fixation in the target-absent trials, in which only distractors were presented. By introducing the activity from the latter trials as neutral activity, we were able to separate the target-discriminative activity into target-related elevation and distractor-related reduction components. We found that the target-discriminative activity of most LIP neurons consisted of the combination of target-related elevation and distractor-related reduction or only target-related elevation. In contrast, target-discriminative activity composed of only distractor-related reduction was observed for very few neurons. We also found that, on average, target-related elevation was stronger and occurred earlier compared with distractor-related reduction. Finally, we consider possible underlying mechanisms, including lateral inhibitory interactions, responsible for target-discriminative activity in visual search. The present findings provide insight into how neuronal modulations shape target-discriminative activity during visual search.