bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Haemophilus influenzae Clones Associated with Invasive Disease a Decade after Introduction of H. influenzae Serotype b Vaccination in Italy
Authors: Giufrè Maria , Cardines Rita , Accogli Marisa , Pardini Manuela , Cerquetti Marina
Published: June 2013

The introduction of
Haemophilus influenzae
serotype b (Hib) conjugate vaccines has changed the epidemiology of invasive
H. influenzae
disease, with a shift in the predominant serotype from Hib to nonencapsulated
H. influenzae
(ncHi). The objective of this study was to identify the genotypes/clones associated with invasive
H. influenzae
disease in Italy. Eighty-seven
H. influenzae
strains isolated in the years 2009 to 2011 within the National Surveillance of Invasive Bacterial Disease program were analyzed. Strains were characterized by serotyping, antimicrobial susceptibility testing, and multilocus sequence typing (MLST). Genetic polymorphisms in the
bla
TEM
gene promoter region as well as the occurrence of both adhesin genes (
hmwA
and
hia
) and the IgA1 protease-encoding gene (
igaB
) were also investigated. Of 87 strains, 67 were ncHi and 20 were encapsulated. Eleven strains were β-lactamase positive, harboring the
bla
TEM
gene. Most
bla
TEM
genes (10/11) were associated with a Pdel promoter region exhibiting a 135-bp deletion; the remaining strain possessed the Pa/Pb overlapping promoter. MLST analysis showed that encapsulated isolates were clonal, with each serotype sharing a few related sequence types (STs). Forty-six different STs were identified among the 67 ncHi strains. Despite this heterogeneity, a group of closely related STs (ST103, ST139, and ST145) encompassed almost 25% of all ncHi strains and 45.5% of the β-lactamase producers carrying the Pdel promoter. These major ST clones were found to be associated with the
hmwA
gene but not with the
igaB
gene. To conclude, although the heterogeneity of the ncHi population was confirmed, diffusion of major successful ST clones was documented.
Development and Comparative Evaluation of a Plate Enzyme-Linked Immunosorbent Assay Based on Recombinant Outer Membrane Antigens Omp28 and Omp31 for Diagnosis of Human Brucellosis
Authors: Tiwari Sapana , Kumar Ashu , Thavaselvam Duraipandian , Mangalgi Smita , Rathod Vedika , Prakash Archana , Barua Anita , Arora Sonia , Sathyaseelan Kannusamy
Published: June 2013

Brucellosis is an important zoonotic infectious disease of humans and livestock with worldwide distribution and is caused by bacteria of the genus
Brucella
. The diagnosis of brucellosis always requires laboratory confirmation by either isolation of pathogens or detection of specific antibodies. The conventional serological tests available for the diagnosis of brucellosis are less specific and show cross-reactivity with other closely related organisms. These tests also necessitate the handling of
Brucella
species for antigen preparation. Therefore, there is a need to develop reliable, rapid, and user-friendly systems for disease diagnosis and alternatives to vaccine approaches. Keeping in mind the importance of brucellosis as an emerging infection and the prevalence in India, we carried out the present study to compare the recombinant antigens with the native antigens (cell envelope and sonicated antigen) of
Brucella
for diagnosis of human brucellosis by an indirect plate enzyme-linked immunosorbent assay (ELISA). Recombinant outer membrane protein 28 (rOmp28) and rOmp31 antigens were cloned, expressed, and purified in the bacterial expression system, and the purified proteins were used as antigens. Indirect plate ELISAs were then performed and standardized for comparison of the reactivities of recombinant and native antigens against the 433 clinical samples submitted for brucellosis testing, 15 culture-positive samples, and 20 healthy donor samples. The samples were separated into four groups based on their positivity to rose bengal plate agglutination tests (RBPTs), standard tube agglutination tests (STATs), and 2-mercaptoethanol (2ME) tests. The sensitivities and specificities of all the antigens were calculated, and the rOmp28 antigen was found to be more suitable for the clinical diagnosis of brucellosis than the rOmp31 antigen and native antigens. The rOmp28-based ELISA showed a very high degree of agreement with the conventional agglutination tests and promising results for further use in clinical screening and serodiagnosis of human brucellosis.
Inhibitory Humoral Responses to the Plasmodium falciparum Vaccine Candidate EBA-175 Are Independent of the Erythrocyte Invasion Pathway
Authors: Badiane Aida S. , Bei Amy K. , Ahouidi Ambroise D. , Patel Saurabh D. , Salinas Nichole , Ndiaye Daouda , Sarr Ousmane , Ndir Omar , Tolia Niraj H. , Mboup Souleymane , Duraisingh Manoj T.
Published: June 2013

Plasmodium falciparum
utilizes multiple ligand-receptor interactions for invasion. The invasion ligand EBA-175 is being developed as a major blood-stage vaccine candidate. EBA-175 mediates parasite invasion of host erythrocytes in a sialic acid-dependent manner through its binding to the erythrocyte receptor glycophorin A. In this study, we addressed the ability of naturally acquired human antibodies against the EBA-175 RII erythrocyte-binding domain to inhibit parasite invasion of
ex vivo
isolates, in relationship to the sialic acid dependence of these parasites. We have determined the presence of antibodies to the EBA-175 RII domain by enzyme-linked immunosorbent assay (ELISA) in individuals from areas of Senegal where malaria is endemic with high and low transmission. Using affinity-purified human antibodies to the EBA-175 RII domain from pooled patient plasma, we have measured the invasion pathway as well as the invasion inhibition of clinical isolates from Senegalese patients in
ex vivo
assays. Our results suggest that naturally acquired anti-EBA-175 RII antibodies significantly inhibit invasion of Senegalese parasites and that these responses can be significantly enhanced through limiting other ligand-receptor interactions. However, the extent of this functional inhibition by EBA-175 antibodies is not associated with the sialic acid dependence of the parasite strain, suggesting that erythrocyte invasion pathway usage by parasite strains is not driven by antibodies targeting the EBA-175/glycophorin A interaction. This work has implications for vaccine design based on the RII domain of EBA-175 in the context of alternative invasion pathways.
The Receptor Binding Domain of Botulinum Neurotoxin Serotype A (BoNT/A) Inhibits BoNT/A and BoNT/E Intoxications
In Vivo
Authors: Ben David Alon , Diamant Eran , Barnea Ada , Rosen Osnat , Torgeman Amram , Zichel Ran
Published: June 2013

The receptor binding domain of botulinum neurotoxin (BoNT), also designated the C terminus of the heavy chain (H
C
), is a promising vaccine candidate against botulism. In this study, a highly efficient expression system for the protein was developed in
Escherichia coli
, which provided yields that were 1 order of magnitude higher than those reported to date (350 mg H
C
per liter). The product was highly immunogenic, protecting mice from a challenge with 10
5
50% lethal dose (LD
50
) after a single vaccination and generating a neutralizing titer of 49.98 IU/ml after three immunizations. In addition, a single boost with H
C
increased neutralizing titers by up to 1 order of magnitude in rabbits hyperimmunized against toxoid. Moreover, we demonstrate here for the first time
in vivo
inhibition of BoNT/A intoxication by H
C
/A, presumably due to a blockade of the neurotoxin protein receptor SV2. Administration of H
C
/A delayed the time to death from 10.4 to 27.3 h in mice exposed to a lethal dose of BoNT/A (
P
= 0.0005). Since BoNT/A and BoNT/E partially share SV2 isoforms as their protein receptors, the ability of H
C
/A to cross-inhibit BoNT/E intoxication was evaluated. The administration of H
C
/A together with BoNT/E led to 50% survival and significantly delayed the time to death for the nonsurviving mice (
P
= 0.003). Furthermore, a combination of H
C
/A and a subprotective dose of antitoxin E fully protected mice against 850 mouse LD
50
of BoNT/E, suggesting complementary mechanisms of protection consisting of toxin neutralization by antibodies and receptor blocking by H
C
/A.
Improved Detection of Bacterial Pathogens in Patients Presenting with Gastroenteritis by Use of the EntericBio Real-Time Gastro Panel I Assay
Authors: Koziel Monika , Kiely Rachel , Blake Liam , O'Callaghan Isabelle , Corcoran Gerard D. , Lucey Brigid , Sleator Roy D.
Published: June 2013

In this study, we evaluated the use of EntericBio real-time Gastro Panel I (Serosep, Limerick, Ireland) for routine use in a clinical microbiology laboratory for simultaneous detection of
Campylobacter jejuni
,
coli
, and
lari
, Shiga toxin-producing
Escherichia coli
(STEC),
Salmonella
spp., and
Shigella
spp. in feces. This system differs from its predecessor (the EntericBio Panel II system, Serosep) in that it allows real-time detection of pathogens directly from feces, without pre-enrichment. It also specifically detects
Campylobacter jejuni
,
coli
, and
lari
rather than all
Campylobacter
species, as is the case with the previous system. A total of 528 samples from patients presenting with acute gastroenteritis were screened prospectively with this assay, and results were compared with those of the current method, which combines screening the samples with a molecular assay (the EntericBio Panel II assay) and retrospective culture of the specimens in which the target was detected. Discrepancy analysis was conducted using culture and molecular methods. The real-time assay produced 84 positive results, specifically,
Campylobacter
spp. (
n
= 44); Stx1 and/or Stx2 (
n
= 35);
Shigella
spp. (
n
= 3); and
Salmonella
spp. (
n
= 6). Of these, 4 samples represented coinfections with
Campylobacter
spp. and STEC. The real-time assay showed an increased detection rate for pathogens, apart from
Salmonella
spp. Four
Campylobacter
-positive and 6 Stx-positive results remained unconfirmed by any other method used. The isolation rates for PCR-positive samples were as follows:
Campylobacter
spp., 80%; STEC, 45.7%;
Salmonella
spp., 100%; and
Shigella
spp., 66.7%. The sensitivity, specificity, positive predictive value, negative predictive value, and efficiency were 100%, 97.8%, 88.1%, 100%, and 98.1%, respectively.
How Positive-Strand RNA Viruses Benefit from Autophagosome Maturation
Authors: Richards Alexsia L. , Jackson William T.
Published: June 2013

The autophagic degradation pathway is a powerful tool in the host cell arsenal against cytosolic pathogens. Contents trapped inside cytosolic vesicles, termed autophagosomes, are delivered to the lysosome for degradation. In spite of the degradative nature of the pathway, some pathogens are able to subvert autophagy for their benefit. In many cases, these pathogens have developed strategies to induce the autophagic signaling pathway while inhibiting the associated degradation activity. One surprising finding from recent literature is that some viruses do not impede degradation but instead promote the generation of degradative autolysosomes, which are the endpoint compartments of autophagy. Dengue virus, poliovirus, and hepatitis C virus, all positive-strand RNA viruses, utilize the maturation of autophagosomes into acidic and ultimately degradative compartments to promote their replication. While the benefits that each virus reaps from autophagosome maturation are unique, the parallels between the viruses indicate a complex relationship between cytosolic viruses and host cell degradation vesicles.
Template RNA Length Determines the Size of Replication Complex Spherules for Semliki Forest Virus
Authors: Kallio Katri , Hellström Kirsi , Balistreri Giuseppe , Spuul Pirjo , Jokitalo Eija , Ahola Tero
Published: June 2013

The replication complexes of positive-strand RNA viruses are always associated with cellular membranes. The morphology of the replication-associated membranes is altered in different ways in different viral systems, but many viruses induce small membrane invaginations known as spherules as their replication sites. We show here that for Semliki Forest virus (SFV), an alphavirus, the size of the spherules is tightly connected with the length of the replicating RNA template. Cells with different model templates, expressed in
trans
and copied by the viral replicase, were analyzed with correlative light and electron microscopy. It was demonstrated that the viral-genome-sized template of 11.5 kb induced spherules that were ∼58 nm in diameter, whereas a template of 6 kb yielded ∼39-nm spherules. Different sizes of viral templates were replicated efficiently in
trans
, as assessed by radioactive labeling and Northern blotting. The replication of two different templates, in
cis
and
trans
, yielded two size classes of spherules in the same cell. These results indicate that RNA plays a crucial determining role in spherule assembly for SFV, in direct contrast with results from other positive-strand RNA viruses, in which either the presence of viral RNA or the RNA size do not contribute to spherule formation.
Characterization of the 2012 Highly Pathogenic Avian Influenza H7N3 Virus Isolated from Poultry in an Outbreak in Mexico: Pathobiology and Vaccine Protection
Authors: Kapczynski Darrell R. , Pantin-Jackwood Mary , Guzman Sofia G. , Ricardez Yadira , Spackman Erica , Bertran Kateri , Suarez David L. , Swayne David E.
Published: June 2013

In June of 2012, an H7N3 highly pathogenic avian influenza (HPAI) virus was identified as the cause of a severe disease outbreak in commercial laying chicken farms in Mexico. The purpose of this study was to characterize the Mexican 2012 H7N3 HPAI virus (A/chicken/Jalisco/CPA1/2012) and determine the protection against the virus conferred by different H7 inactivated vaccines in chickens. Both adult and young chickens intranasally inoculated with the virus became infected and died at between 2 and 4 days postinoculation (p.i.). High virus titers and viral replication in many tissues were demonstrated at 2 days p.i. in infected birds. The virus from Jalisco, Mexico, had high sequence similarity of greater than 97% to the sequences of wild bird viruses from North America in all eight gene segments. The hemagglutinin gene of the virus contained a 24-nucleotide insert at the hemagglutinin cleavage site which had 100% sequence identity to chicken 28S rRNA, suggesting that the insert was the result of nonhomologous recombination with the host genome. For vaccine protection studies, both U.S. H7 low-pathogenic avian influenza (LPAI) viruses and a 2006 Mexican H7 LPAI virus were tested as antigens in experimental oil emulsion vaccines and injected into chickens 3 weeks prior to challenge. All H7 vaccines tested provided ≥90% protection against clinical disease after challenge and decreased the number of birds shedding virus and the titers of virus shed. This study demonstrates the pathological consequences of the infection of chickens with the 2012 Mexican lineage H7N3 HPAI virus and provides support for effective programs of vaccination against this virus in poultry.
Murine Cytomegalovirus Protein pM79 Is a Key Regulator for Viral Late Transcription
Authors: Chapa Travis J. , Johnson L. Steven , Affolter Christopher , Valentine Mark C. , Fehr Anthony R. , Yokoyama Wayne M. , Yu Dong
Published: June 2013

Herpesvirus genes are temporally expressed during permissive infections, but how their expression is regulated at late times is poorly understood. Previous studies indicate that the human cytomegalovirus (CMV) gene, UL79, is required for late gene expression. However, the mechanism remains to be fully elucidated, and UL79 homologues in other CMVs have not been studied. Here, we characterized the role of the conserved murine CMV (MCMV) gene M79. We showed that M79 encoded a protein (pM79) which was expressed with early-late kinetics and localized to nuclear viral replication compartments. M79 transcription was significantly decreased in the absence of viral DNA synthesis but markedly stimulated by pM79. To investigate its role, we created the recombinant virus SM
in
79, in which pM79 expression was disrupted. While marker-rescued virus grew efficiently in fibroblasts, SM
in
79 failed to produce infectious progeny but was rescued by pM79 expression
in trans
. During SM
in
79 infection, representative viral immediate-early and early gene products as well as viral DNA accumulated sufficiently. Formation of viral replication compartments also appeared normal. Pulsed-field gel electrophoresis analysis indicated that the overall structure of replicating viral DNA was indistinguishable between wild-type and SM
in
79 infection. Viral tiled array and quantitative PCR analysis revealed that many late transcripts sensitive to a viral DNA synthesis inhibitor (phosphonoacetic acid) were markedly reduced by pM79 mutation. This study indicates that cytomegaloviruses use a conserved mechanism to promote transcription at late stages of infection and that pM79 is a critical regulator for at least a subset of viral DNA synthesis-dependent transcripts.
Infection with Feline Immunodeficiency Virus Directly Activates CD4
+
CD25
+
T Regulatory Cells
Authors: Miller Michelle M. , Fogle Jonathan E. , Tompkins Mary B.
Published: June 2013

Lentivirus infection activates CD4
+
CD25
+
T regulatory (Treg) cells. Activation of Treg cells may be due to direct virus infection or chronic antigenic stimulation. Herein we demonstrate that
in vitro
feline immunodeficiency virus (FIV) infection, but not UV-inactivated virus, activates Treg cells as measured by immunosuppressive function and upregulation of GARP, FoxP3, and membrane-bound transforming growth factor β (TGF-β). These data demonstrate for the first time that AIDS lentiviruses infect and activate Treg cells, potentially contributing to immune dysfunction.
High Levels of CD2 Expression Identify HIV-1 Latently Infected Resting Memory CD4+T Cells in Virally Suppressed Subjects
Authors: Iglesias-Ussel Maria , Vandergeeten Claire , Marchionni Luigi , Chomont Nicolas , Romerio Fabio
Published: June 2013

Resting memory CD4+T cells are the largest reservoir of persistent infection in HIV-1-positive subjects. They harbor dormant, stably integrated virus despite suppressive antiretroviral therapy, posing an obstacle to a cure. Surface markers that identify latently infected cells remain unknown. Microarray analyses comparing resting latently infected and uninfected CD4+T cells generatedin vitroshowed profound differences in the expression of gene programs related to transcriptional and posttranscriptional regulation, cell proliferation, survival, cycle progression, and basic metabolism, suggesting that multiple biochemical and metabolic blocks contribute to preventing viral production in latently infected cells. We identified 33 transcripts encoding cell surface markers that are differentially expressed between latently infected and uninfected cells. Quantitative reverse transcriptase PCR (RT-QPCR) and flow cytometry analyses confirmed that the surface marker CD2 was expressed at higher levels on latently infected cells. To validate this resultin vivo, we sorted resting memory CD4+T cells expressing high and low surface levels of CD2 from six HIV-1-infected subjects successfully treated with antiretroviral drugs for at least 3 years. Resting memory CD4+CD2highT cells from all subjects harbored higher HIV-1 DNA copy numbers than all other CD4+T cell subsets. Moreover, afterex vivoviral reactivation, robust viral RNA production was detected only from resting memory CD4+CD2highT cells but not from other cell subsets. Altogether, these results show that a high CD2 expression level is a hallmark of latently infected resting memory CD4+T cellsin vivo.
Hospital workers’ perceptions of waste: a qualitative study involving photo-elicitation
Authors: Goff Sarah L , Kleppel Reva , Lindenauer Peter K , Rothberg Michael B
Published: June 2013

Objectives

To elicit sources of waste as viewed by hospital workers.

Design

Qualitative study using photo-elicitation, an ethnographic technique for prompting in-depth discussion.

Setting

U.S. academic tertiary care hospital.

Participants

Physicians, nurses, pharmacists, administrative support personnel, administrators and respiratory therapists.

Methods

A purposive sample of personnel at an academic tertiary care hospital was invited to take up to 10 photos of waste. Participants discussed their selections using photos as prompts during in-depth interviews. Transcripts were analysed in an iterative process using grounded theory; open and axial coding was performed, followed by selective and thematic coding to develop major themes and subthemes.

Results

Twenty-one participants (nine women, average number of years in field=19.3) took 159 photos. Major themes included types of waste and recommendations to reduce waste. Types of waste comprised four major categories: Time, Materials, Energy and Talent. Participants emphasised time wastage (50% of photos) over other types of waste such as excess utilisation (2.5%). Energy and Talent were novel categories of waste. Recommendations to reduce waste included interventions at the micro-level (eg, individual/ward), meso-level (eg, institution) and macro-level (eg, payor/public policy).

Conclusions

The waste hospital workers identified differed from previously described waste both in the types of waste described and the emphasis placed on wasted time. The findings of this study represent a possible need for education of hospital workers about known types of waste, an opportunity to assess the impact of novel types of waste described and an opportunity to intervene to reduce the waste identified.
Household-based socioeconomic position and diabetes-related mortality among married and cohabiting persons: findings from a census-based cohort study (Flanders, 2001–2010)
Authors: Vandenheede Hadewijch , Vanroelen Christophe , Gadeyne Sylvie , De Grande Hannelore , Deboosere Patrick
Published: June 2013

Background

Diabetes prevalence is high worldwide, affecting entire populations. Yet some population groups are more susceptible than others. In contemporary western societies, socioeconomically disadvantaged groups are disproportionally affected. The pattern is less clear for diabetes mortality. Researchers argue increasingly in favour of looking beyond individual socioeconomic position (SEP). In light of the above, this paper looks at the relationship between individual-based and household-based SEP measures and diabetes mortality.

Methods

Data consisted of the Belgian 2001 census for the Flanders region linked to register data on cause-specific mortality during the period 2001–2010. The study population included all 35-year-old to 74-year-old official inhabitants of Flanders married or cohabiting at the 2001 census. Age-standardised death rates (direct standardisation) and mortality rate ratios (MRRs; Poisson regression) were computed for the different SEP groups.

Results

Inverse gradients were observed by own education, partner's education and housing status (combination of housing tenure and quality). For example, among 55-year-olds to 74-year-olds, MRRs according to partner's education were 3.0 (95% CI 2.4 to 3.8) for women with a lower-educated partner and 1.6 (95% CI 1.2 to 2.0) for women with a higher secondary-educated partner, relative to women with a higher-educated partner. As for housing status, diabetes-related mortality was particularly high among tenants and low-quality owners. The association between each of the SEP measures and diabetes-related mortality remained after adjusting for the other measures.

Conclusions

There were large differences in diabetes-related mortality according to both individual-based and household-based SEP measures, indicating the importance of the individual and household levels for understanding socioeconomic inequalities in diabetes mortality.
One year of burns at a Role 3 Medical Treatment Facility in Afghanistan
Authors: Jeevaratnam Johann A , Pandya A N
Published: June 2013

Objectives

Historically, burns have formed a significant proportion of the casualties of war. The management of burns in recent conflict has been found to be a resource-heavy undertaking, though its impact on both personnel and resources in current conflicts is unclear. A case analysis has been carried out in order to quantify the logistical impact of the management of burns on Role 3 Medical Treatment Facility (MTF) infrastructure and to examine if and how the cause and management of burns have evolved in early 21st century conflict.

Methods

All casualties treated for burns at a Role 3 MTF over one calendar year were identified and scanned copies of their notes obtained from the UK Joint Theatre Trauma Registry and retrospectively analysed.

Results

88 of the 1461 (6.0%) trauma patients presenting to the Role 3 MTF over the year were treated for burns of whom 52.3% were combat troops and 45.4% civilians. Half of the burns were caused by non-conflict related mechanisms; the two commonest mechanisms were flame burns in 38/88 mostly non-conflict related cases and blast in 30/88 cases most of which were conflict related.

Conclusions

The management of burns at war is a complex process. It is further confounded by the management of civilians with non-conflict related burns, which places a predictable strain on Role 3 MTF resources: theatre time, nursing time, dressing resources and bed space. This must be planned for in current and future deployed operations.
Madness, childhood adversity and narrative psychiatry: caring and the moral imagination
Authors: Thomas Philip , Longden Eleanor
Published: June 2013

The dominance of technological paradigms within psychiatry creates moral and ethical tensions over how to engage with the interpersonal narratives of those experiencing mental distress. This paper argues that such paradigms are poorly suited for fostering principled responses to human suffering, and proposes an alternative approach that considers a view of relationships based in feminist theories about the nature of caring. Four primary characteristics are presented which distinguish caring from technological paradigms: (1) a concern with the particular nature of contexts, (2) embodied practice, (3) the dialogical basis of caring and (4) the existential basis of caring. From this we explore the role of the moral imagination and our ability, through narrative, to acknowledge, engage with and bear witness to the injustices that shape the lives of those who suffer. This, we argue, is at the heart of caring. Clinical implications are discussed, including an exposition of the importance of narrative in recovery from trauma and distress. Narrative Psychiatry, The Sanctuary Model of care, and Soteria, are outlined as examples of this type of practice.
Endovascular repair of a double-lumen dissecting aneurysm
Authors: Johnson Andrew Kelly , Gerard Carter S , Lopes Demetrius Klee
Published: June 2013

Treating dissections and dissecting aneurysms requires maintenance of flow through the true lumen and exclusion of the false lumen from the circulation. A dissecting aneurysm of the vertebral artery presented with both a true and false lumen within the aneurysmal sac. Stenting of the true lumen followed by coil embolization of both lumens was performed. Management options and decision-making are discussed for this unique situation.
Cerebral aneurysm treatment is beginning to shift to low volume centers
Authors: Brinjikji Waleed , Lanzino Giuseppe , Kallmes David F , Cloft Harry J
Published: June 2013

Background and purpose

A recent expansion of the neurointerventional workforce in the USA could lead to a trend toward cerebral aneurysms being increasingly treated at low volume centers. Such a trend could have a negative impact on patient care as higher volume centers are known to have better outcomes.

Methods

Using the Nationwide Inpatient Sample, we evaluated trends in aneurysm treatment in the USA from 2001 to 2010. Annual volumes of both ruptured and unruptured aneurysms were counted, as well as annual percentages of cases treated at high volume centers (≥50 aneurysms/year clipped or coiled).

Results

The number of ruptured aneurysms treated per year has fluctuated between 9000 and 12 000 from 2003 to 2010. In 2001–2002, 27.4% of intracranial aneurysm patients were treated with clipping or coiling at high volume centers, with a peak of 70.1% in 2007–2008. This proportion dropped to 61.8% in 2009–2010. The proportion of patients clipped at high volume centers was 23.3% in 2001–2002 and peaked at 65.0% in 2007–2008. In 2009–2010, the proportion dropped to 58.6%. For coiling patients, 46.4% were treated at high volume centers in 2001–2002, with a peak of 70.1% in 2007–2008, and a drop to 61.8% in 2009–2010.

Conclusion

A trend toward less cerebral aneurysms being treated in high volume centers in 2009 and 2010 is worrisome because high volume centers are known to tend to have better outcomes. This trend is likely due to recent expansion of the neurointerventional workforce.
Characterisation of dog sensitisation to grass pollen in western France from 1999 to 2010
Authors: Roussel A. J. J. , Bruet V. , Bourdeau P. J.
Published: June 2013

Very few studies have investigated the seasonal aspect of grass pollen sensitisation or its evolution in the allergic canine population. The aim of this study was to evaluate both these aspects. A study of canine grass pollen sensitisation was performed throughout the statistical analysis of 261 intradermal skin testings (IDT=25 allergens tested on average) performed from January 1999 to December 2010. IDTs were performed on dogs with pruritic allergic skin disease. χ2 Tests were used for statistical analysis. Two hundred and thirteen dogs (81.6 per cent) were sensitised to at least one allergen, and 56 (21.5 per cent) to at least one grass pollen. No increase in the rate of positive IDT was recorded over three periods: 1999–2002, 2003–2006 and 2007–2010. No statistical correlation was detected between sex, age or birth month and grass sensitisation. Moreover, no link was found between the season in which the IDT was performed and sensitisation, indicating that there is no seasonality to the sensitisation. However, considering the grasses tested over these three periods (grass mix and rye grass), a clear and significant increase in the percentage of dogs sensitised to grass pollen was observed between 1999–2002 and 2007–2010 (14.4 per cent and 27.7 per cent, respectively). The possible reasons for this sensitisation increase of dogs to grass pollen are discussed.
Mutual effects between aromatic amino acids and guanosine upon vitamin B2 photosensitization in the presence of visible light
Authors: Montaña M. Paulina , Ferrari Gabriela , Gatica Eduardo , Natera José , Massad Walter , García Norman A.
Published: June 2013

Considering the importance of the visible-light-induced photodynamic effect in complex bioenvironments, mutual effects between the individual aromatic amino acids (AAs) tyrosine (Tyr), tryptophan (Trp), and histidine (His) and the nucleoside guanosine (GUO) were investigated in pH 7 aqueous solution with vitamin B2 (riboflavin (Rf)) as a dye sensitizer. The quantum yields of oxygen uptake (Φ–O2) for most of the AA−GUO mixtures studied, taken as a measure of overall photooxidation susceptibility, are not straightforwardly predictable from the individual behaviour of the components of the mixture. The final result depends on several connected factors, such as the respective abilities of the substrates as quenchers of the long-lived Rf triplet excited state and the generated reactive oxygen species singlet molecular oxygen (O2(1Δg)) and superoxide radical anion ([Formula: see text]). A mechanistic interpretation of the Rf-sensitized results can be roughly resumed as follows: Tyr at pH 7 exerts a protective effect on the photooxidation of the mixture Tyr−GUO due to the O2(1Δg) physical quenching by the AA. The same effect was observed for Trp−GUO and His−GUO at pH 7. In these cases, it is attributed to the quenching of3Rf* by GUO in detriment of the Type II route. For the system Tyr−GUO at pH 9, a marked decrease in the Φ–O2occurred for the mixture as compared with the respective Φ–O2for the individual components. It was ascribed to the participation of a radical-mediated mechanism without oxygen consumption in a competitive pathway with the [Formula: see text]-mediated route.
Environmental and geospatial factors drive juvenile Chinook salmon distribution during early ocean migration
Authors: Burke Brian J. , Liermann Martin C. , Teel David J. , Anderson James J.
Published: June 2013

Migrating animals rely on a variety of cues to guide them, but the relative importance of those signals may vary with size, life stage, or location. During their initial ocean migration, yearling Chinook salmon (Oncorhynchus tshawytcha) from the Columbia River have stock-specific spatial distributions that shift through time. We used a two-process mixture model to examine how the distribution of yearling migrants from three Chinook salmon stocks varies as a function of geospatial (e.g., latitude and distance from shore) and environmental (e.g., chlorophyll a and temperature) covariates. In this framework, one process described the probability of being inside the spatial, temporal, and environmental boundaries of the migration route, and one process described the patchy distribution of salmon abundance within that route. We found that both environmental and geospatial covariates explained substantial portions of observed spatial patterns in abundance, suggesting that these stocks responded to multiple cues during migration. However, model selection criteria indicated that fish distributions were more affected by geospatial than by environmental covariates. We conclude that during migration, behavioral responses to environmental variation are secondary to responses to geospatial variation, sometimes resulting in suboptimal environmental conditions. This may have sublethal effects on growth and could ultimately influence stock-specific responses to broad-scale climate changes.
Snails keep the pace: shift in upper elevation limit on mountain slopes as a response to climate warming
Authors: Baur Bruno , Baur Anette
Published: June 2013

Predicted biological responses to climate warming are changes in phenology and poleward shifts or upslope displacements of the distribution of species. We investigated changes in the upper elevational limit of the land snail Arianta arbustorum (L., 1758) by repeating historical records from 1916 to 1917 on nine mountain slopes in the Swiss National Park in 2011–2012. We found that the upper elevational limit for snail populations has risen, on average, by 164 m in 95 years, accompanying a 1.6 °C rise in mean annual temperature in the investigation area. The higher temperature results in an upslope shift of the vegetation and in a prolonged activity period of the snails. Upslope extension of snail distribution was not influenced by the inclination of the slope, but it was larger on south-exposed slopes (mean: 233 m) than on north to northeast exposed slopes (122 m). On some slopes we found that the snails have already reached natural barriers (vertical rock walls with no soil), preventing any farther upward dispersal. To our knowledge, this is the first evidence for an invertebrate species with low dispersal capacity ascending to higher elevations in a mountain area in response to climate warming.
SPINFLATION WITH BACKREACTION
Authors: KAVIANI DARIUSH
Published: June 2013

We study brane inflation in flux compactifications at the nonlinear level, solving the D3-brane DBI-equations of motion including backreaction from the D3–D7 brane potential and from perturbations of the warp factor. We first numerically compute the exact functional form of the Kähler modulus valid on the entire supergravity background and obtain a two-field potential along radial and harmonic directions. We find that a valid perturbative expansion on the entire supergravity background with the Kähler modulus integrated out adiabatically in DBI inflation requires hierarchies of scales that determine compactification parameters different from those typical in slow-roll models. Our numerical results then show that the DBI inflationary solutions are quite robust against these nonlinear corrections.
NUMERICAL SOLUTIONS OF IDEAL TWO-FLUID TRANSVERSE EQUATIONS VERY CLOSED TO THE EVENT HORIZON OF REISSNER–NORDSTRÖM–ANTI-DE SITTER BLACK HOLE
Authors: ATIQUR RAHMAN M.
Published: June 2013

The Alfvén and high frequency electromagnetic waves propagating in a relativistic two-fluid plasma influenced by the gravitational field of the Reissner–Nordström–anti-de Sitter (RNAdS) black hole have been investigated applying 3+1 split of spacetime. The extremal cases also discussed here based on the simple observation that the near-horizon geometry of a static extremal black hole contains two-dimensional anti-de Sitter factor even in the presence of positive cosmological constant. We reformulate the relativistic two-fluid equations with the set of simultaneous linear equations for the perturbations. We derive the dispersion relation for these waves and solve numerically for the wave number k.
Non-abelian cohomology jump loci from an analytic viewpoint
Authors: Dimca Alexandru , Papadima Ştefan
Published: June 2013

For a space, we investigate its CJL (cohomology jump loci), sitting inside varieties of representations of the fundamental group. To do this, for a CDG (commutative differential graded) algebra, we define its CJL, sitting inside varieties of flat connections. The analytic germs at the origin 1 of representation varieties are shown to be determined by the Sullivan 1-minimal model of the space. Up to a degree q, the two types of CJL have the same analytic germs at the origins, when the space and the algebra have the same q-minimal model. We apply this general approach to formal spaces (obtaining the degeneration of the Farber–Novikov spectral sequence), quasi-projective manifolds, and finitely generated nilpotent groups. When the CDG algebra has positive weights, we elucidate some of the structure of (rank one complex) topological and algebraic CJL: all their irreducible components passing through the origin are connected affine subtori, respectively rational linear subspaces. Furthermore, the global exponential map sends all algebraic CJL into their topological counterpart.
Singularly perturbed problems with a turning point: The non-compatible case
Authors: Jung Chang-Yeol , Temam Roger
Published: June 2013

The singularly perturbed problems with a turning point were discussed in [21]. The case where the limit problem is compatible with the given data was fully resolved. However, with limited compatibility conditions on the data, the asymptotic expansions were constructed only up to the order of the level of compatibilities. In this paper, using a smooth cut-off function compactly supported around the turning point we resolve the difficulties incurred from the non-compatible data and finally provide the full asymptotic expansions up to any order.
SECONDARY SCIENCE TEACHERS' DEVELOPMENT OF PEDAGOGICAL CONTENT KNOWLEDGE AS RESULT OF INTEGRATING NANOSCIENCE CONTENT IN THEIR CURRICULUM
Authors: WISCHOW EMILY D. , BRYAN LYNN , BODNER GEORGE M.
Published: June 2013

Nanoscale science is a rapidly-developing, multidisciplinary field of science and research that combines engineering, chemistry, physics, biology, and information technology pushes and the boundary between the science and the technology required to conduct it. Nanoscale science involves investigating and working with matter on the scale of 1–100 microns and has broad societal implications for new technologies. It is estimated that the worldwide workforce necessary to support the field of nanoscale science and nanotechnology will be close to 2 million by 2015 (National Nanotechnology Initiative, 2005). With such rapid developments in nanoscale science and technology, it is becoming more incumbent upon K-12 science teachers to provide the learning experiences necessary for students to understand the principles that govern behavior at the nanoscale and develop the skills needed to apply these concepts to improve everyday life. While onlya limited amount of nanoscale curricular materials are available for K-12 and undergraduate education many important unanswered questions exist, including: How do science teachers learn to teach nanoscale science?
GROUP OUTLIER FACTOR: A NEW SCORE USING SELF-ORGANISING MAP FOR GROUP-OUTLIER AND NOVELTY DETECTION
Authors: CHAIBI AMINE , LEBBAH MUSTAPHA , AZZAG HANANE
Published: June 2013

This paper describe a new concept of "cluster outlier-ness". In order to quantify it, we propose a relative isolation score named group outlier factor (GOF). GOF is a score, which is computed during a clustering process using self-organizing maps. The main difference between GOF and existing methods is that, being an outlier is not associated to a single pattern but to a cluster. Thus, an outlier factor (OF) with respect to each cluster is computed for each new sample and compared to the GOF score associated for each cluster. OF is used as a novelty detection classifier. This approach allows to identify meaningful outlier-clusters and detects novel patterns that previous approaches could not find. Experimental results and comparison studies show that the use of GOF sensibly improves the results in term of cluster-outlier and novelty detection.
Chenodeoxycholic acid stimulates Cl− secretion via cAMP signaling and increases cystic fibrosis transmembrane conductance regulator phosphorylation in T84 cells
Authors: Ao Mei , Sarathy Jayashree , Domingue Jada , Alrefai Waddah A. , Rao Mrinalini C.
Published: June 2013

High levels of chenodeoxycholic acid (CDCA) and deoxycholic acid stimulate Cl− secretion in mammalian colonic epithelia. While different second messengers have been implicated in this action, the specific signaling pathway has not been fully delineated. Using human colon carcinoma T84 cells, we elucidated this cascade assessing Cl− transport by measuring I− efflux and short-circuit current ( Isc). CDCA (500 μM) rapidly increases I− efflux, and we confirmed by Isc that it elicits a larger response when added to the basolateral vs. apical surface. However, preincubation with cytokines increases the monolayer responsiveness to apical addition by 55%. Nystatin permeabilization studies demonstrate that CDCA stimulates an eletrogenic apical Cl− but not a basolateral K+ current. Furthermore, CDCA-induced Isc was inhibited (≥67%) by bumetanide, BaCl2, and the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh-172. CDCA-stimulated Isc was decreased 43% by the adenylate cyclase inhibitor MDL12330A and CDCA increases intracellular cAMP concentration. The protein kinase A inhibitor H89 and the microtubule disrupting agent nocodazole, respectively, cause 94 and 47% reductions in CDCA-stimulated Isc. Immunoprecipitation with CFTR antibodies, followed by sequential immunoblotting with Pan-phospho and CFTR antibodies, shows that CDCA increases CFTR phosphorylation by approximately twofold. The rapidity and side specificity of the response to CDCA imply a membrane-mediated process. While CDCA effects are not blocked by the muscarinic receptor antagonist atropine, T84 cells possess transcript and protein for the bile acid G protein-coupled receptor TGR5. These results demonstrate for the first time that CDCA activates CFTR via a cAMP-PKA pathway involving microtubules and imply that this occurs via a basolateral membrane receptor.
Proximal tubular NHEs: sodium, protons and calcium?
Authors: Alexander R. Todd , Dimke Henrik , Cordat Emmanuelle
Published: June 2013

Na+/H+exchange activity in the apical membrane of the proximal tubule is fundamental to the reabsorption of Na+and water from the filtrate. The role of this exchange process in bicarbonate reclamation and, consequently, the maintenance of acid-base homeostasis has been appreciated for at least half a century and remains a pillar of renal tubular physiology. More recently, apical Na+/H+exchange, mediated by Na+/H+exchanger isoform 3 (NHE3), has been implicated in proximal tubular reabsorption of Ca2+and Ca2+homeostasis in general. Overexpression of NHE3 increased paracellular Ca2+flux in a proximal tubular cell model. Consistent with this observation, mice with genetic deletion of Nhe3 have a noticable renal Ca2+leak. These mice also display decreased intestinal Ca2+uptake and osteopenia. This review highlights the traditional roles of proximal tubular Na+/H+exchange and summarizes recent novel findings implicating the predominant isoform, NHE3, in Ca2+homeostasis.
TGF-β/Smad3 activates mammalian target of rapamycin complex-1 to promote collagen production by increasing HIF-1α expression
Authors: Rozen-Zvi Benaya , Hayashida Tomoko , Hubchak Susan C. , Hanna Christian , Platanias Leonidas C. , William Schnaper H.
Published: June 2013

Transforming growth factor (TGF)-β is a major mediator of kidney fibrosis. In the past decade it was recognized that, besides canonical Smad signaling, many other signaling pathways participate in the process of TGF-β-induced fibrogenesis. One such pathway involves mammalian target of rapamycin complex (mTORC)1. We recently reported that the hypoxia-inducible factor (HIF)-1 is essential for TGF-β-induced collagen expression regardless of ambient oxygen tension. A modulator of HIF expression other than oxygen tension is mTORC1. We therefore sought to evaluate a possible role for mTORC1 activity in TGF-β-induced fibrogenesis. mTORC1 activity was increased in human mesangial cells treated with TGF-β in a TGF-β receptor-dependent manner. Short hairpin (sh)RNA to Smad3 decreased, while overexpression of Smad3 increased, the mTORC1 activity, suggesting that TGF-β stimulation of mTORC1 also requires Smad3. Pretreatment with rapamycin or shRNA for a regulatory molecule of mTORC1, Raptor, reduced TGF-β-induced COL1A2-luc activity and collagen I protein expression. mTORC1 inhibition also prevented the TGF-β-stimulated increase in both hypoxia-responsive element (HRE) activity and HIF-1α protein expression, while activation of mTORC1 by active Rheb increased basal but not TGF-β-induced HRE activity. shRNA to Smad3 reduced HRE activity, while overexpression of Smad3 increased HIF-1α protein expression and activity in an mTORC1-dependent manner. Lastly, overexpression of HIF-1α bypassed the inhibitory effect of mTORC1 blockade on collagen expression. These results suggest that Smad3/mTORC1 interaction to promote HIF-1 expression is a key step in normoxic kidney fibrogenesis.