bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of key messages for adolescents on providing basic mental health first aid to peers: a Delphi consensus study
Authors: Ross Anna M. , Hart Laura M. , Jorm Anthony F. , Kelly Claire M. , Kitchener Betty A.
Published: January 2012

Aim: Most young people fail to receive professional treatment for mental disorders; however, they do indicate a preference for sharing problems with peers. This article describes key messages about knowledge and actions to form the basis of a basic Mental Health First Aid (MHFA) course for adolescents to increase recognition of and help seeking for mental health problems by teaching the best knowledge and helping actions a young person can undertake to support a peer with a mental health problem.

Methods: The Delphi method was used to achieve consensus among Australian and Canadian youth mental health experts regarding the importance of statements that describe helping actions a young person can take, and information they should have, to support a friend with a mental health problem. There were two expert panels, one consisting of 36 youth mental health consumer advocates and the other of 97 Youth MHFA instructors. Panellists rated each statement according to how appropriate it would be as a basic mental health first aid message for both a junior adolescent (12–15 years) and a senior adolescent (16–18 years).

Results: Out of 98 statements, 78 were endorsed as key basic MHFA messages for junior adolescents and 81 were endorsed for senior adolescents.

Conclusion: The study has identified key messages for adolescents on how they can help a peer. These messages will form the basis of the curriculum for an MHFA course for adolescents, which will aim to facilitate early recognition of and help seeking for mental health problems in adolescents.
Social functioning in early psychosis: are all the domains predicted by the same variables?
Authors: Bourdeau Geneviève , Masse Marjolaine , Lecomte Tania
Published: January 2012

Aim: The study aims to determine the predictive value of negative symptoms, depression, short‐term verbal learning and gender on three areas of social functioning – social life, vocational functioning and independent living skills – in a sample of 88 individuals with early psychosis.

Methods: Participants were recruited from Early Psychosis Intervention programmes and community mental health clinics in British Columbia, Canada, and completed the following measures: Client's Assessment of Strengths, Interests, and Goals, Brief Psychiatric Rating Scale, Beck Depression Inventory and California Verbal Learning Task.

Results: Multiple linear regressions revealed that: more negative symptoms and higher depression predicted a less active social life; more negative symptoms and poorer short‐term verbal learning ability predicted lower vocational functioning; and more negative symptoms and male gender predicted lower independent living skills.

Conclusion: Results suggest that negative symptoms are predictive of all three areas of functioning but that specific variables add significant unique variance to individual areas of social functioning. Although a global social functioning score can be considered useful, greater precision can be gained by the use of domain‐specific measures.
Risk factors for mother‐to‐child transmission of hepatitis C virus: Maternal high viral load and fetal exposure in the birth canal
Authors: Murakami Jun , Nagata Ikuo , Iitsuka Toshiyuki , Okamoto Manabu , Kaji Shunsaku , Hoshika Tadataka , Matsuda Ryu , Kanzaki Susumu , Shiraki Kazuo , Suyama Akihiko , Hino Shigeo
Published: January 2012

Aim:  Mother‐to‐child transmission (MTCT) is the major transmission pathway of hepatitis C virus (HCV) in children. However, its risk factors remain unsettled for introduction of putative intervention.

Methods:  Pregnant women screened for HCV and MTCT in children born to antibody‐positive mothers were prospectively studied in Tottori, Japan.

Results:  Among 41 856 screened women, 188 (0.45%) were HCV antibody‐positive, of whom 61% had detectable HCV RNA. While 10 of the 34 children (29%) born to high viral load (HVL: ≥6.0 × 105 IU/mL) mothers were infected, none born to RNA‐detectable but non‐HVL mothers were infected (P < 0.001). MTCT among vaginally delivered children born to HVL mothers was analyzed. Children delivered after 4 h or more of labor were more frequently infected than were those born within 4 h of labor (P = 0.019). Premature rupture of fetal membranes was significantly more common in infected children than in uninfected children (P < 0.001). Durations of membrane rupture and labor were longer in infected children than in uninfected children (P = 0.008 and P = 0.040, respectively). Elective cesarean section that eliminates these risk factors, other than HVL, significantly reduced MTCT from nine of 22 (41%) to none of nine children (0%) (P = 0.032).

Conclusion:  Our data suggest that contamination of the fetus in the birth canal with infected maternal blood is a major risk factor for HCV MTCT, in addition to maternal HVL. To rationalize intervention by elective cesarean section, the natural history of infected children should be carefully evaluated.
Neoliberalization and Its Geographic Limits: Comparative Reflections from Forest Peripheries in the Global North
Authors: Hayter Roger , Barnes Trevor J.
Published: January 2012

abstract

Recently, a number of economic geography studies have emphasized that when neoliberalism is grounded in particular places, it takes on hybrid forms, a result of local contingencies that are found at those sites. This article contributes to this literature by explicating the processes by which hybridization occurs by drawing on a comparative study of neoliberalism in three contemporary forest‐based regions in the Global North: British Columbia, Canada; Tasmania, Australia; and the North Island, New Zealand. A key term for us is geographic limits, by which we mean regionally specific constellations (assemblages) of institutional and material forms that resist; hybridize; or, at junctures, even offset neoliberalism with alternative agendas. In turn, our idea of geographic limits is derived from our larger conceptual framework that integrates Anna Tsing's (2005) concept of friction with the notion of remapping and a four‐leg stakeholder model that consists of different, albeit overlapping, institutional agencies that represent the political, the industrial, the environmental, and the cultural. These institutions provide the animus for a remapping that variously implements, modifies, and occasionally counters neoliberalism.
Optimal Sensor Location in Laminated Die System
Authors: Seo Jaho , Khajepour Amir , Huissoon Jan P.
Published: January 2012

The objective of this research is to identify optimal temperature sensor locations in a laminated die system for the purpose of predicting the temperature distribution throughout the die to control heating and cooling rates. Potential locations (referred to as target nodes) are grouped based on the similarity of their thermal response using both K-means and a proposed temperature ratio clustering method. A sensitivity analysis of the temperature distribution for these groups of target nodes identifies the sensor location for each cluster that exhibits the highest sensitivity to variable inputs. A comparison of sensor locations identified by each clustering method with the sensitivity analysis is presented and is used to evaluate the optimal sensor location in terms of consistency in generating these sensor locations, the degree of sensitivity, the mutual interaction through principal component analysis, limiting the number of sensors, and the accuracy in estimating the temperature distribution.
Data-Weighting Based Discrete-Time Adaptive Iterative Learning Control for Nonsector Nonlinear Systems With Iteration-Varying Trajectory and Random Initial Condition
Authors: Chi Ronghu , Hou Zhongsheng , Jin Shangtai
Published: January 2012

In this paper, a new discrete-time adaptive iterative learning control (AILC) approach is presented to deal with nonsector nonlinearities by incorporating a recursive least-squares algorithm with a nonlinear data weighted coefficient. This scheme is also extended as a d-iteration-ahead adaptive iterative learning predictive control to address for multiple inputs multiple outputs (MIMO) nonlinear systems with unknown input gains. A major distinct feature of the presented methods is that the global stability result is obtained through Lyapunov analysis without assuming any linear growth condition on the nonlinearities. Another distinct feature is that the pointwise convergence of the presented methods is achieved over a finite interval without requiring any identical conditions on the initial states and reference trajectory.
Effects of proton irradiation energies on degradation of AlGaN/GaN high electron mobility transistors
Authors: Kim Hong-Yeol , Kim Jihyun , Liu Lu , Lo Chien-Fong , Ren Fan , Pearton Stephen J.
Published: January 2012

The authors report the proton energy dependence of the degradation of AlGaN/GaN high electron mobility transistors (HEMTs) with GaN cap layers from 5 to 15 MeV at a fixed dose of 5 × 1015 cm−2. All the samples degraded after proton irradiation. However, higher damage in dc electrical properties was observed at lower proton energies. Saturation currents at VDS = 6 V and VGS = 0 V reduced by 47% after proton irradiation at 5 MeV energy, but the reduction was less by 25% and 9% at 10 and 15 MeV, respectively. Similar trends were observed in other electrical properties [transconductance (gm) and gate leakage currents]. This energy dependence from 5 to 15 MeV can be explained by the energy-dependent penetration depth of the proton. Protons with higher kinetic energy can penetrate deeper while creating less numbers of defects at shallow depths where the active layers of the HEMTs are located. These results are in good agreement with stopping and range of ions in matter results. The optimization of the AlGaN/GaN HEMT structure will be critical for space-borne applications where high fluxes of protons are encountered.
Changes in Wind Pattern Alter Albatross Distribution and Life-History Traits
Authors: Weimerskirch Henri , Louzao Maite , de Grissac Sophie , Delord Karine
Published: January 2012

Riding the Wind

Pelagic seabirds rely on wind to move between breeding and foraging areas, and albatrosses—which travel thousands of kilometers over sea—are well-known wind riders.

Weimerskirch
et al.

(p.
211
; see the cover) monitored foraging and reproduction in wandering albatrosses over 40 years and found that a change in wind patterns, probably induced by climate change, had a notable impact on important life history traits. Greater wind strength increased the rate of travel for the birds and shortened their foraging trips. These shorter trips improved breeding success and resulted in an increase in adult mass. Thus, over the past half-century, environmental changes have improved conditions for the albatross.
Bistability in Atomic-Scale Antiferromagnets
Authors: Loth Sebastian , Baumann Susanne , Lutz Christopher P. , Eigler D. M. , Heinrich Andreas J.
Published: January 2012

Structured Memories

High-density magnetic memory is generally produced by using ferromagnetic materials. As the density increases and the memory elements become closer together, stray fields can result in cross-talk and a corruption of the stored information. Antiferromagetic structures, however, are expected to be relatively insensitive to magnetic fields and so should, in principle, allow the elements to be packed in even closer.

Loth
et al.

(p.
196
) carried out low-temperature experiments to construct antiferromagnetic structures atom by atom. Electrical switching of the magnetic states was observed, and data could be robustly stored on the structure for several hours, albeit at low temperature.
Maxing Out Our Take
All the Fish in the Sea
Maximum Sustainable Yield and the Failure of Fisheries Management

by Carmel Finley

University of Chicago Press, Chicago, 2011. 222 pp. $35. ISBN 9780226249667.
Authors: Safina Carl
Published: January 2012

Locating the origins of maximum sustainable yield in efforts to protect U.S. commercial fisheries against their competitors, Finley argues that the collapse of world fisheries does not illustrate the tragedy of the commons but stems from deliberate governmental and international policy.
Top Indian Chemist Helps Make the Case for Science Windfall
Authors: Bagla Pallava
Published: January 2012

In an interview with
Science
, chemist C.N.R. Rao, science adviser to Indian Prime Minister Manmohan Singh, talked about the need to create a critical mass of capable scientists in India.
Identification of Anti-Alpha Toxin Monoclonal Antibodies That Reduce the Severity of Staphylococcus aureus Dermonecrosis and Exhibit a Correlation between Affinity and Potency
Authors: Tkaczyk C. , Hua L. , Varkey R. , Shi Y. , Dettinger L. , Woods R. , Barnes A. , MacGill R. S. , Wilson S. , Chowdhury P. , Stover C. K. , Sellman B. R.
Published: January 2012

Staphylococcus aureusalpha toxin (AT) is an important virulence determinant and may be a valid target for immunoprophylaxis against staphylococcal disease. Here we report the identification of potent inhibitory anti-AT monoclonal antibodies (MAbs) derived using B-cell hybridoma technology from VelocImmune mice engineered to produce IgG with a human variable domain. A small panel of inhibitory MAbs blocked AT-mediated lysis of rabbit red blood cells, A549 human lung epithelial cells, and THP-1 human monocytic cells, in a dose-dependent manner. Binding studies indicated that these MAbs recognize a similar epitope on AT and exhibit dissociation constants (KD) ranging from 0.50 to 15 nM. In anS. aureusdermonecrosis model, mice passively immunized with anti-AT inhibitory MAbs exhibited significant reductions of lesion size relative to mice treated with an irrelevant IgG control. Interestingly, there was a correlation between MAb affinity for a single epitope, the 50% inhibitory concentration (IC50) in the AT hemolytic assay, and lesion size reduction in the dermonecrosis model. A representative high-affinity MAb, 2A3.1, was demonstrated to significantly reduce lesion size following infection with three different clinical isolates (USA300, CC30, and CC5). Taken together, these results indicate thatin vitropotency of anti-AT MAbs predictsin vivopotency in this model, supporting their continued preclinical evaluation as molecules for immunoprophylaxis against staphylococcal skin and soft tissue infections caused by diverse clinical isolates.
Draft Genome Sequence of the Virulent Strain 01-B526 of the Fish Pathogen Aeromonas salmonicida
Authors: Charette Steve J. , Brochu Francis , Boyle Brian , Filion Geneviève , Tanaka Katherine H. , Derome Nicolas
Published: January 2012

Aeromonas salmonicida
is an important fish pathogen, mainly of salmonids. This bacterium causes a disease named furunculosis, which is particularly detrimental for the aquaculture industry. Here, we present the draft genome sequence of
A. salmonicida
01-B526, a strain isolated from a brook trout that is more virulent than
A. salmonicida
reference strain A449, for which a genome sequence is available.
Genome Sequence of Edwardsiella ictaluri 93-146, a Strain Associated with a Natural Channel Catfish Outbreak of Enteric Septicemia of Catfish
Authors: Williams M. L. , Gillaspy A. F. , Dyer D. W. , Thune R. L. , Waldbieser G. C. , Schuster S. C. , Gipson J. , Zaitshik J. , Landry C. , Banes M. M. , Lawrence M. L.
Published: January 2012

Edwardsiella ictaluri
is the cause of extensive mortalities and economic losses to the channel catfish industry of the southeast United States. Here we report the complete genome of
Edwardsiella ictaluri
93-146. Whole-genome sequence analysis of
E. ictaluri
provides a tool for understanding the genomic regions specific to the species and the
Edwardsiella
genus.
Rapid Typing of Extended-Spectrum β-Lactamase- and Carbapenemase-Producing Escherichia coli and Klebsiella pneumoniae Isolates by Use of SpectraCell RA
Authors: Willemse-Erix Diana , Bakker-Schut Tom , Slagboom-Bax Femke , Jachtenberg Jan-willem , Lemmens-den Toom Nicole , Papagiannitsis Costas C. , Kuntaman Kuntaman , Puppels Gerwin , van Belkum Alex , Severin Juliëtte A. , Goessens Wil , Maquelin Kees
Published: January 2012

Enterobacteriaceae
are important pathogens of both nosocomial and community-acquired infections. In particular, strains with broad-spectrum beta-lactamases increasingly cause problems in health care settings. Rapid and reliable typing systems are key tools to identify transmission, so that targeted infection control measures can be taken. In this study, we evaluated the performance of Raman spectroscopic analysis (RA) for the typing of multiresistant
Escherichia coli
and
Klebsiella pneumoniae
isolates using the SpectraCell RA bacterial strain analyzer (River Diagnostics). Analysis of 96 unrelated isolates revealed that RA generated highly reproducible spectra and exhibited a discriminatory power that is comparable to pulsed-field gel electrophoresis. Furthermore, adequate results were obtained for three collections of clinical isolates. RA was able to discriminate outbreak-related isolates from isolates that were not involved in an outbreak or transmission. Furthermore, it was found that the RA approach recognized clones, irrespective of the extended-spectrum β-lactamase type. It can be concluded that RA is a suitable typing technique for
E. coli
and
K. pneumoniae
isolates. Combining high reproducibility, speed, and ease-of-use, this technique may play an important role in monitoring the epidemiology of these important nosocomial species.
Clinical and Laboratory Characteristics of Clostridium difficile Infection in Patients with Discordant Diagnostic Test Results
Authors: Kaltsas Anna , Simon Matt , Unruh Larissa H. , Son Crystal , Wroblewski Danielle , Musser Kimberlee A. , Sepkowitz Kent , Babady N. Esther , Kamboj Mini
Published: January 2012

The aim of this study was to compare the clinical and laboratory characteristics of
Clostridium difficile
infection (CDI) in patients with discordant test results for the cytotoxin assay (CYT) and PCR assays. A retrospective study from May to August 2008 and March to May 2010 was performed. CDI was diagnosed in 128 patients. PCR increased the yield of
C. difficile
cases by 2-fold compared to that of the CYT assay. Fifty-six cases (44%) were detected by PCR only (CYT negative). Forty-nine percent of patients with non-NAP1 strains were detected by PCR only, compared to 28% of those infected with NAP1 strains (
P
< 0.05). No significant differences were found in the clinical severity of illness and outcome among patients that tested positive for CDI by both tests (CYT and PCR) compared to those that tested positive by PCR only.
Vesicular Stomatitis Virus as an Oncolytic Agent against Pancreatic Ductal Adenocarcinoma
Authors: Murphy Andrea M. , Besmer Dahlia M. , Moerdyk-Schauwecker Megan , Moestl Natascha , Ornelles David A. , Mukherjee Pinku , Grdzelishvili Valery Z.
Published: January 2012

Vesicular stomatitis virus (VSV) is a promising oncolytic agent against a variety of cancers. However, it has never been tested in any pancreatic cancer model. Pancreatic ductal adenocarcinoma (PDA) is the most common and aggressive form of pancreatic cancer. In this study, the oncolytic potentials of several VSV variants were analyzed in a panel of 13 clinically relevant human PDA cell lines and compared to conditionally replicative adenoviruses (CRAds), Sendai virus and respiratory syncytial virus. VSV variants showed oncolytic abilities superior to those of other viruses, and some cell lines that exhibited resistance to other viruses were successfully killed by VSV. However, PDA cells were highly heterogeneous in their susceptibility to virus-induced oncolysis, and several cell lines were resistant to all tested viruses. Resistant cells showed low levels of very early VSV RNA synthesis, indicating possible defects at initial stages of infection. In addition, unlike permissive PDA cell lines, most of the resistant cell lines were able to both produce and respond to interferon, suggesting that intact type I interferon responses contributed to their resistance phenotype. Four cell lines that varied in their permissiveness to VSV-ΔM51 and CRAd dl1520 were tested in mice, and the
in vivo
results closely mimicked those
in vitro
. While our results demonstrate that VSV is a promising oncolytic agent against PDA, further studies are needed to better understand the molecular mechanisms of resistance of some PDAs to oncolytic virotherapy.
Functional Interferon System Is Required for Clearance of Lassa Virus
Authors: Yun Nadezhda E. , Poussard Allison L. , Seregin Alexey V. , Walker Aida G. , Smith Jennifer K. , Aronson Judith F. , Smith Jeanon N. , Soong Lynn , Paessler Slobodan
Published: January 2012

Lassa virus (LASV) is the causative agent of Lassa hemorrhagic fever (LF) in humans, a deadly disease endemic to West Africa that results in 5,000 to 10,000 deaths annually. Here we present results demonstrating that functional type I and type II interferon (IFN) signaling is required for efficient control of LASV dissemination and clearance.
The Viral Protein Tat Can Inhibit the Establishment of HIV-1 Latency
Authors: Donahue Daniel A. , Kuhl Björn D. , Sloan Richard D. , Wainberg Mark A.
Published: January 2012

The establishment of HIV-1 latency can result from limiting levels of transcription initiation or elongation factors, restrictive chromatin modifications, transcriptional interference, and insufficient Tat activity. Since the viral protein Tat can counteract many of these factors, we hypothesized that the presence of exogenous Tat during infection might inhibit the establishment of latency. This was explored using a Jurkat model of latency establishment and reactivation. PCR and reverse transcriptase PCR (RT-PCR) confirmed the latent state in this model and showed evidence of transcriptional interference. To address our hypothesis, cells undergoing infection were first exposed to either purified recombinant Tat or a transactivation-negative mutant. Only the former resulted in a modest inhibition of the establishment of latency. Next, Jurkat cells stably expressing intracellular Tat were used in our latency model to avoid limitations of Tat delivery. Experiments confirmed that intracellular Tat expression did not affect the susceptibility of these cells to viral infection. Eight weeks after infection, Jurkat cells expressing Tat harbored up to 1,700-fold fewer (
P
< 0.01) latent viruses than Jurkat cells that did not express Tat. Additionally, Tat delivered by a second virus was sufficient to reactivate most of the latent population. Our results suggest that inhibition of the establishment of latent infection is theoretically possible. In a hypothetical scenario of therapy that induces viral gene expression during acute infection, activation of viruses which would otherwise have entered latency could occur while concurrent highly active antiretroviral therapy (HAART) would prevent further viral spread, potentially decreasing the size of the established latent reservoir.
Human Metapneumovirus (HMPV) Binding and Infection Are Mediated by Interactions between the HMPV Fusion Protein and Heparan Sulfate
Authors: Chang Andres , Masante Cyril , Buchholz Ursula J. , Dutch Rebecca Ellis
Published: January 2012

Human metapneumovirus (HMPV) is a major worldwide respiratory pathogen that causes acute upper and lower respiratory tract disease. The mechanism by which this virus recognizes and gains access to its target cell is still largely unknown. In this study, we addressed the initial steps in virus binding and infection and found that the first binding partner for HMPV is heparan sulfate (HS). While wild-type CHO-K1 cells are permissive to HMPV infection, mutant cell lines lacking the ability to synthesize glycosaminoglycans (GAGs), specifically, heparan sulfate proteoglycans (HSPGs), were resistant to binding and infection by HMPV. The permissiveness to HMPV infection was also abolished when CHO-K1 cells were treated with heparinases. Importantly, using recombinant HMPV lacking both the G and small hydrophobic (SH) proteins, we report that this first virus-cell binding interaction is driven primarily by the fusion protein (HMPV F) and that this interaction is needed to establish a productive infection. Finally, HMPV binding to cells did not require β1 integrin expression, and RGD-mediated interactions were not essential in promoting HMPV F-mediated cell-to-cell membrane fusion. Cells lacking β1 integrin, however, were less permissive to HMPV infection, indicating that while β1 integrins play an important role in promoting HMPV infection, the interaction between integrins and HMPV occurs after the initial binding of HMPV F to heparan sulfate proteoglycans.
Restricted Replication of Xenotropic Murine Leukemia Virus-Related Virus in Pigtailed Macaques
Authors: Del Prete Gregory Q. , Kearney Mary F. , Spindler Jon , Wiegand Ann , Chertova Elena , Roser James D. , Estes Jacob D. , Hao Xing Pei , Trubey Charles M. , Lara Abigail , Lee KyeongEun , Chaipan Chawaree , Bess Julian W. , Nagashima Kunio , Keele Brandon F. , Macallister Rhonda , Smedley Jeremy , Pathak Vinay K. , KewalRamani Vineet N. , Coffin John M. , Lifson Jeffrey D.
Published: January 2012

Although xenotropic murine leukemia virus-related virus (XMRV) has been previously linked to prostate cancer and myalgic encephalomyelitis/chronic fatigue syndrome, recent data indicate that results interpreted as evidence of human XMRV infection reflect laboratory contamination rather than authentic
in vivo
infection. Nevertheless, XMRV is a retrovirus of undefined pathogenic potential that is able to replicate in human cells. Here we describe a comprehensive analysis of two male pigtailed macaques (
Macaca nemestrina
) experimentally infected with XMRV. Following intravenous inoculation with >10
10
RNA copy equivalents of XMRV, viral replication was limited and transient, peaking at ≤2,200 viral RNA (vRNA) copies/ml plasma and becoming undetectable by 4 weeks postinfection, though viral DNA (vDNA) in peripheral blood mononuclear cells remained detectable through 119 days of follow-up. Similarly, vRNA was not detectable in lymph nodes by
in situ
hybridization despite detectable vDNA. Sequencing of cell-associated vDNA revealed extensive G-to-A hypermutation, suggestive of APOBEC-mediated viral restriction. Consistent with limited viral replication, we found transient upregulation of type I interferon responses that returned to baseline by 2 weeks postinfection, no detectable cellular immune responses, and limited or no spread to prostate tissue. Antibody responses, including neutralizing antibodies, however, were detectable by 2 weeks postinfection and maintained throughout the study. Both animals were healthy for the duration of follow-up. These findings indicate that XMRV replication and spread were limited in pigtailed macaques, predominantly by APOBEC-mediated hypermutation. Given that human APOBEC proteins restrict XMRV infection
in vitro
, human XMRV infection, if it occurred, would be expected to be characterized by similarly limited viral replication and spread.
Luria-Delbrück Estimation of Turnip Mosaic Virus Mutation Rate
In Vivo
Authors: de la Iglesia Francisca , Martínez Fernando , Hillung Julia , Cuevas José M. , Gerrish Philip J. , Daròs José-Antonio , Elena Santiago F.
Published: January 2012

A potential drawback of recent antiviral therapies based on the transgenic expression of artificial microRNAs is the ease with which viruses may generate escape mutations. Using a variation of the classic Luria-Delbrück fluctuation assay, we estimated that the spontaneous mutation rate in the artificial microRNA (amiR) target of a plant virus was ca. 6 × 10
−5
per replication event.
The Simian Virus 40 Late Viral Protein VP4 Disrupts the Nuclear Envelope for Viral Release
Authors: Giorda Kristina M. , Raghava Smita , Hebert Daniel N.
Published: January 2012

Simian virus 40 (SV40) appears to initiate cell lysis by expressing the late viral protein VP4 at the end of infection to aid in virus dissemination. To investigate the contribution of VP4 to cell lysis, VP4 was expressed in mammalian cells where it was predominantly observed along the nuclear periphery. The integrity of the nuclear envelope was compromised in these cells, resulting in the mislocalization of a soluble nuclear marker. Using assays that involved the cellular expression of VP4 or the treatment of cells with purified VP4, we found that the central hydrophobic domain and a proximal C-terminal nuclear localization signal of VP4 were required for (i) cytolysis associated with prolonged expression; (ii) nuclear envelope accumulation; and (iii) disruption of the nuclear, red blood cell, or host cell membranes. Furthermore, a conserved proline within the hydrophobic domain was required for membrane perforation, suggesting that this residue was crucial for VP4 cytolytic activity. These results indicate that VP4 forms pores in the nuclear membrane leading to lysis and virus release.
The longitudinal prevalence of MRSA in care home residents and the effectiveness of improving infection prevention knowledge and practice on colonisation using a stepped wedge study design
Authors: Horner C , Wilcox M , Barr B , Hall D , Hodgson G , Parnell P , Tompkins D
Published: January 2012

Objectives

To determine the prevalence and health outcomes of meticillin-resistantStaphylococcus aureus(MRSA) colonisation in elderly care home residents. To measure the effectiveness of improving infection prevention knowledge and practice on MRSA prevalence.

Setting

Care homes for elderly residents in Leeds, UK.

Participants

Residents able to give informed consent.

Design

A controlled intervention study, using a stepped wedge design, comprising 65 homes divided into three groups. Baseline MRSA prevalence was determined by screening the nares of residents (n=2492). An intervention based upon staff education and training on hand hygiene was delivered at three different times according to group number. Scores for three assessment methods, an audit of hand hygiene facilities, staff hand hygiene observations and an educational questionnaire, were collected before and after the intervention. After each group of homes received the intervention, all participants were screened for MRSA nasal colonisation. In total, four surveys took place between November 2006 and February 2009.

Results

MRSA prevalence was 20%, 19%, 22% and 21% in each survey, respectively. There was a significant improvement in scores for all three assessment methods post-intervention (p≤0.001). The intervention was associated with a small but significant increase in MRSA prevalence (p=0.023). MRSA colonisation was associated with previous and subsequent MRSA infection but was not significantly associated with subsequent hospitalisation or mortality.

Conclusions

The intervention did not result in a decrease in the prevalence of MRSA colonisation in care home residents. Additional measures will be required to reduce endemic MRSA colonisation in care homes.
Does the effect of vitamin A supplements depend on vaccination status? An observational study from Guinea-Bissau
Authors: Fisker Ane B , Aaby Peter , Bale Carlito , Balde Ibraima , Biering-Sørensen Sofie , Agergaard Jane , Martins Cesario , Bibby Bo M , Benn Christine S
Published: January 2012

Objective

Vitamin A supplementation (VAS) is estimated to reduce all-cause mortality by 24%. Previous studies indicate that the effect of VAS may vary with vaccination status. The authors evaluated the effect of VAS provided in campaigns on child survival overall and by sex and vaccination status at the time of supplementation.

Design

Observational cohort study.

Setting and participants

The study was conducted in the urban study area of the Bandim Health Project in Guinea-Bissau. The authors documented participation or non-participation in two national vitamin A campaigns in December 2007 and July 2008 for children between 6 and 35 months of age. Vaccination status was ascertained by inspection of vaccination cards. All children were followed prospectively.

Outcome measures

Mortality rates for supplemented and non-supplemented children were compared in Cox models providing mortality rate ratios (MRRs).

Results

The authors obtained information from 93% of 5567 children in 2007 and 90% of 5799 children in 2008. The VAS coverage was 58% in 2007 and 68% in 2008. Mortality in the supplemented group was 1.5% (44 deaths/2873 person-years) and 1.6% (20 deaths/1260 person-years) in the non-supplemented group (adjusted MRR=0.78 (0.46; 1.34)). The effect was similar in boys and girls. Vaccination cards were seen for 86% in 2007 and 84% in 2008. The effect of VAS in children who had measles vaccine as their last vaccine (2814 children, adjusted MRR=0.34 (0.14; 0.85)) differed from the effect in children who had diphtheria–tetanus–pertussis vaccine as their last vaccine (3680 children, adjusted MRR=1.29 (0.52; 3.22), p=0.04 for interaction).

Conclusion

The effect of VAS differed by most recent vaccination, being beneficial after measles vaccine but not after diphtheria–tetanus–pertussis vaccine.
Exposure to bisphosphonates and risk of cancer: a protocol for nested case–control studies using the QResearch primary care database
Authors: Vinogradova Yana , Coupland Carol , Hippisley-Cox Julia
Published: January 2012

Introduction

Bisphosphonates are becoming a common treatment for osteoporosis particularly after discovery of the association between hormone replacement therapy and increased risk of breast cancer. As osteoporosis develops with age, treatment is a long-term intervention. Randomised control trials typically have limited follow-up times, which restricts investigation of the effects of the drugs on risk of primary cancers. A few observational studies have demonstrated a reduced risk of breast cancer and possibly of endometrial cancer in bisphosphonate users. Two epidemiological studies have studied the effect of the drugs on oesophageal cancer but did not reach any definite conclusions. So far, no effects on colorectal and stomach cancer have been shown. This study will investigate the association of bisphosphonates with risks of the 10 most common primary cancers.

Methods and analysis

A series of nested case–control studies will be based on the general population using records from 660 UK general practices within the QResearch Database. Cases will be patients with primary cancers diagnosed between 1996 and 2011. Each case will be matched by age, sex, practice and calendar year to five controls, who are alive and registered with the practice at the time of diagnosis of the case. Exposure to bisphosphonates will be defined as at least one prescription during the study period. For the most common cancers with substantial numbers of observations, the effect of the duration of the treatment and different types of bisphosphonates will be studied. Conditional logistic regression will be applied to produce ORs adjusted for smoking status, socioeconomic status, ethnicity, cancer-specific co-morbidities and use of other medications.
Addressing geographical variation in the progression of non-communicable diseases in Peru: the CRONICAS cohort study protocol
Authors: Miranda J Jaime , Bernabe-Ortiz Antonio , Smeeth Liam , Gilman Robert H , Checkley William ,   CRONICAS Cohort Study Group
Published: January 2012

Background

The rise in non-communicable diseases in developing countries has gained increased attention. Given that around 80% of deaths related to non-communicable diseases occur in low- and middle-income countries, there is a need for local knowledge to address such problems. Longitudinal studies can provide valuable information about disease burden of non-communicable diseases in Latin America to inform both public health and clinical settings.

Methods

The CRONICAS cohort is a longitudinal study performed in three Peruvian settings that differ by degree of urbanisation, level of outdoor and indoor pollution and altitude. The author sought to enrol an age- and sex-stratified random sample of 1000 participants at each site. Study procedures include questionnaires on socio-demographics and well-known risk factors for cardiopulmonary disease, blood draw, anthropometry and body composition, blood pressure and spirometry before and after bronchodilators. All participants will be visited at baseline, at 20 and 40 months. A random sample of 100 households at each site will be assessed for 24 h particulate matter concentration. Primary outcomes include prevalence of risk factors for cardiopulmonary diseases, changes in blood pressure and blood glucose over time and decline in lung function.

Discussion

There is an urgent need to characterise the prevalence and burden of non-communicable diseases in low- and middle-income countries. Peru is a middle-income country currently undergoing a rapid epidemiological transition. This longitudinal study will provide valuable information on cardiopulmonary outcomes in three different settings and will provide a platform to address potential interventions that are locally relevant or applicable to other similar settings in Latin America.
The effect of MELatOnin on Depression, anxietY, cognitive function and sleep disturbances in patients with breast cancer. The MELODY trial: protocol for a randomised, placebo-controlled, double-blinded trial
Authors: Hansen Melissa Voigt , Madsen Michael Tvilling , Hageman Ida , Rasmussen Lars Simon , Bokmand Susanne , Rosenberg Jacob , Gögenur Ismail
Published: January 2012

Introduction

Breast cancer represents about one-third of all cancer diagnoses and accounts for about 15% of cancer deaths in women. Many of these patients experience depression, anxiety, sleep disturbances and cognitive dysfunction. This may adversely affect quality of life and also contribute to morbidity and mortality. Melatonin is a regulatory circadian hormone having, among others, a hypnotic and an antidepressive effect. It has very low toxicity and very few adverse effects compared with the more commonly used antidepressants and hypnotics.

Methods and analysis

The objective of this double-blind, randomised, placebo-controlled trial is to investigate whether treatment with oral melatonin has a prophylactic or ameliorating effect on depressive symptoms, anxiety, sleep disturbances and cognitive dysfunction in women with breast cancer. Furthermore, the authors will examine whether a specific clock-gene, PER3, is correlated with an increased risk of depressive symptoms, sleep disturbances or cognitive dysfunction. The MELODY trial is a prospective double-blinded, randomised, placebo-controlled trial in which the authors intend to include 260 patients. The primary outcome is depressive symptoms measured by the Major Depression Inventory. The secondary outcomes are anxiety measured by a Visual Analogue Scale, total sleep time, sleep efficiency, sleep latency and periods awake measured by actigraphy and changes in cognitive function measured by a neuropsychological test battery. Tertiary outcomes are fatigue, pain, well-being and sleep quality/quantity measured by Visual Analogue Scale and sleep diary and sleepiness measured by the Karolinska Sleepiness Scale. The PER3 genotype is also to be determined in blood samples.
Effects of an intravenous bolus of alfaxalone versus propofol on intraocular pressure in sheep
Authors: Torres M‐D. , Andaluz A. , García F. , Fresno L. , Moll X.
Published: January 2012

The objective of this prospective study was to determine the effects of a single intravenous bolus of alfaxalone in 2‐hydroxypropyl‐β‐cyclodextrin and propofol on the intraocular pressure (IOP) in sheep. Ten Ripollesa sheep with a bodyweight of 48.5 (6.8) kg (mean [sd]) were used in the study. Twenty‐four hours before the experimental procedure, a complete ophthalmic examination was performed in all animals. The day of the study, intravenous alfaxalone (2 mg/kg) or propofol (6 mg/kg) was randomly administered in a cross‐over design, with a washout period of two weeks. Measurements of IOP, globe position and pupil size were obtained at basal time, before induction (time 0) and at two, five, 10, 15, 20, 30, 45, 60, 90 and 120 minutes after drug administration. Occasional side effects and time to standing were also noted. Intravenous administration of alfaxalone and propofol in sheep resulted in no alteration of IOP. Nevertheless, a decrease in the pupil size was observed in both groups. This present study shows that alfaxalone and propofol, administrated as a single intravenous bolus, are good options for maintaining IOP during anaesthesia in sheep, although marked miosis was observed after administration.
ON A CLASS OF RICCI-FLAT DOUGLAS METRICS
Authors: SEVIM ESRA SENGELEN , SHEN ZHONGMIN , ZHAO LILI
Published: January 2012

In this paper, we study a special class of Finsler metrics which are defined by a Riemannian metric and a 1-form on a manifold. We find equations that characterize Ricci-flat Douglas metrics among this class.
Synthesis of long-wavelength chlorins by chemical modification for methyl pyropheophorbide-a and their in vitro cell viabilities
Authors: Wang Jin Jun , Li Jia Zhu , Jakus Judit , Shim Young Key
Published: January 2012

A series of novel chlorophyll-a homologs with long wavelength absorption were synthesized via modification of methyl pyropheophorbide-a used as starting material. For introducing electron-withdrawing group methylenemalononitrile moiety was established on the periphery of modified chlorin by Knoevenagel reaction of malononitrile with formyl group at 3-, 15-position and 131-carbonyl group on the exocyclic ring. All of chlorins containing the methylenemalononitrile structure show Qy-absorption at more than 700 nm. Moreover, we have examined a preliminary in vitro photodynamic anticancer effect of these new derivatives on mouse sarcoma S-180 cell line.
Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes
Authors: Storey Stephen M. , McIntosh Avery L. , Huang Huan , Landrock Kerstin K. , Martin Gregory G. , Landrock Danilo , Payne H. Ross , Atshaves Barbara P. , Kier Ann B. , Schroeder Friedhelm
Published: January 2012

A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in <1 min and initial rate and maximal uptake of HDL free cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/ Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null mice and hepatocytes. Taken together, these results suggest that L-FABP, particularly in the absence of SCP-2, plays a significant role in HDL-mediated cholesterol uptake in cultured primary hepatocytes.
Mechanisms of p53 activation and physiological relevance in the developing kidney
Authors: Aboudehen Karam , Hilliard Sylvia , Saifudeen Zubaida , El-Dahr Samir S.
Published: January 2012

The tumor suppressor protein p53 is a short-lived transcription factor due to Mdm2-mediated proteosomal degradation. In response to genotoxic stress, p53 is stabilized via posttranslational modifications which prevent Mdm2 binding. p53 activation results in cell cycle arrest and apoptosis. We previously reported that tight regulation of p53 activity is an absolute requirement for normal nephron differentiation (Hilliard S, Aboudehen K, Yao X, El-Dahr SS Dev Biol 353: 354–366, 2011). However, the mechanisms of p53 activation in the developing kidney are unknown. We show here that metanephric p53 is phosphorylated and acetylated on key serine and lysine residues, respectively, in a temporal profile which correlates with the maturational changes in total p53 levels and DNA-binding activity. Site-directed mutagenesis revealed a differential role for these posttranslational modifications in mediating p53 stability and transcriptional regulation of renal function genes (RFGs). Section immunofluorescence also revealed that p53 modifications confer the protein with specific spatiotemporal expression patterns. For example, phos-p53S392is enriched in maturing proximal tubular epithelial cells, whereas acetyl-p53K373/K382/K386are expressed in nephron progenitors. Functionally, p53 occupancy of RFG promoters is enhanced at the onset of tubular differentiation, and p53 loss or gain of function indicates that p53 is necessary but not sufficient for RFG expression. We conclude that posttranslational modifications are important determinants of p53 stability and physiological functions in the developing kidney. We speculate that the stress/hypoxia of the embryonic microenvironment may provide the stimulus for p53 activation in the developing kidney.
Running perturbations reveal general strategies for step frequency selection
Authors: Snyder Kristine L. , Snaterse Mark , Donelan J. Maxwell
Published: January 2012

Recent research has suggested that energy minimization in human walking involves both a fast preprogrammed process and a slow optimization process. Here, we studied human running to test whether these two processes represent control mechanisms specific to walking or a more general strategy for minimizing energetic cost in human locomotion. To accomplish this, we used free response experiments to enforce step frequency with a metronome at values above and below preferred step frequency and then determined the response times for the return to preferred steady-state step frequency when the auditory constraint was suddenly removed. In forced response experiments, we applied rapid changes in treadmill speed and examined response times for the processes involved in the consequent adjustments to step frequency. We then compared the dynamics of step frequency adjustments resulting from the two different perturbations to each other and to previous results found in walking. Despite the distinct perturbations applied in the two experiments, both responses were dominated by a fast process with a response time of 1.47 ± 0.05 s with fine-tuning provided by a slow process with a response time of 34.33 ± 0.50 s. The dynamics of the processes underlying step frequency adjustments in running match those found previously in walking, both in magnitude and relative importance. Our results suggest that the underlying mechanisms are fundamental strategies for minimizing energetic cost in human locomotion.