bluuebunny/crossref_metadata_2025 huggingface dataset:
Serology-Enabled Discovery of Genetically Diverse Hepaciviruses in a New Host
Authors: Burbelo Peter D. , Dubovi Edward J. , Simmonds Peter , Medina Jan L. , Henriquez Jose A. , Mishra Nischay , Wagner Jason , Tokarz Rafal , Cullen John M. , Iadarola Michael J. , Rice Charles M. , Lipkin W. Ian , Kapoor Amit
Published: April 2012

Genetic and biological characterization of new hepaciviruses infecting animals contributes to our understanding of the ultimate origins of hepatitis C virus (HCV) infection in humans and dramatically enhances our ability to study its pathogenesis using tractable animal models. Animal homologs of HCV include a recently discovered canine hepacivirus (CHV) and GB virus B (GBV-B), both viruses with largely undetermined natural host ranges. Here we used a versatile serology-based approach to determine the natural host of the only known nonprimate hepacivirus (NPHV), CHV, which is also the closest phylogenetic relative of HCV. Recombinant protein expressed from the helicase domain of CHV NS3 was used as antigen in the luciferase immunoprecipitation system (LIPS) assay to screen several nonprimate animal species. Thirty-six samples from 103 horses were immunoreactive, and viral genomic RNA was present in 8 of the 36 seropositive animals and none of the seronegative animals. Complete genome sequences of these 8 genetically diverse NPHVs showed 14% (range, 6.4% to 17.2%) nucleotide sequence divergence, with most changes occurring at synonymous sites. RNA secondary structure prediction of the 383-base 5′ untranslated region of NPHV was refined and extended through mapping of polymorphic sites to unpaired regions or (semi)covariant pairings. Similar approaches were adopted to delineate extensive RNA secondary structures in the coding region of the genome, predicted to form 27 regularly spaced, thermodynamically stable stem-loops. Together, these findings suggest a promising new nonprimate animal model and provide a database that will aid creation of functional NPHV cDNA clones and other novel tools for hepacivirus studies.
Identification of a Divalent Metal Cation Binding Site in Herpes Simplex Virus 1 (HSV-1) ICP8 Required for HSV Replication
Authors: Bryant Kevin F. , Yan Zhipeng , Dreyfus David H. , Knipe David M.
Published: April 2012

Herpes simplex virus 1 (HSV-1) ICP8 is a single-stranded DNA-binding protein that is necessary for viral DNA replication and exhibits recombinase activity
in vitro
. Alignment of the HSV-1 ICP8 amino acid sequence with ICP8 homologs from other herpesviruses revealed conserved aspartic acid (D) and glutamic acid (E) residues. Amino acid residue D1087 was conserved in every ICP8 homolog analyzed, indicating that it is likely critical for ICP8 function. We took a genetic approach to investigate the functions of the conserved ICP8 D and E residues in HSV-1 replication. The E1086A D1087A mutant form of ICP8 failed to support the replication of an ICP8 mutant virus in a complementation assay. E1086A D1087A mutant ICP8 bound DNA, albeit with reduced affinity, demonstrating that the protein is not globally misfolded. This mutant form of ICP8 was also recognized by a conformation-specific antibody, further indicating that its overall structure was intact. A recombinant virus expressing E1086A D1087A mutant ICP8 was defective in viral replication, viral DNA synthesis, and late gene expression in Vero cells. A class of enzymes called DDE recombinases utilize conserved D and E residues to coordinate divalent metal cations in their active sites. We investigated whether the conserved D and E residues in ICP8 were also required for binding metal cations and found that the E1086A D1087A mutant form of ICP8 exhibited altered divalent metal binding in an
in vitro
iron-induced cleavage assay. These results identify a novel divalent metal cation-binding site in ICP8 that is required for ICP8 functions during viral replication.
Multifunctional CD4 Cells Expressing Gamma Interferon and Perforin Mediate Protection against Lethal Influenza Virus Infection
Authors: Brown Deborah M. , Lee Sarah , Garcia-Hernandez Maria de la Luz , Swain Susan L.
Published: April 2012

CD4 effectors generatedin vitrocan promote survival against a highly pathogenic influenza virus via an antibody-independent mechanism involving class II-restricted, perforin-mediated cytotoxicity. However, it is not known whether CD4 cells activated during influenza virus infection can acquire cytolytic activity that contributes to protection against lethal challenge. CD4 cells isolated from the lungs of infected mice were able to confer protection against a lethal dose of H1N1 influenza virus A/Puerto Rico 8/34 (PR8). Infection of BALB/c mice with PR8 induced a multifunctional CD4 population with proliferative capacity and ability to secrete interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-α) in the draining lymph node (DLN) and gamma interferon (IFN-γ) and IL-10 in the lung. IFN-γ-deficient CD4 cells produced larger amounts of IL-17 and similar levels of TNF-α, IL-10, and IL-2 compared to wild-type (WT) CD4 cells. Both WT and IFN-γ−/−CD4 cells exhibit influenza virus-specific cytotoxicity; however, IFN-γ-deficient CD4 cells did not promote recovery after lethal infection as effectively as WT CD4 cells. PR8 infection induced a population of cytolytic CD4 effectors that resided in the lung but not the DLN. These cells expressed granzyme B (GrB) and required perforin to lyse peptide-pulsed targets. Lethally infected mice given influenza virus-specific CD4 cells deficient in perforin showed greater weight loss and a slower time to recovery than mice given WT influenza virus-specific CD4 cells. Taken together, these data strengthen the concept that CD4 T cell effectors are broadly multifunctional with direct roles in promoting protection against lethal influenza virus infection.
The association between jockey experience and race-day falls in flat racing in Australia
Authors: Hitchens Peta L , Blizzard C Leigh , Jones Graeme , Day Lesley M , Fell James
Published: April 2012

Objectives

Apprentice thoroughbred racing jockeys have a higher fall rate than their more experienced counterparts. The authors describe rates of occurrence and investigate risk factors for falls among less-experienced thoroughbred flat racing jockeys in Australia who commenced their race riding career between August 2002 and July 2009.

Methods

Data on race-day falls were extracted from stewards' reports. Denominator data were provided by Racing Information Services Australia on races conducted in Australia. HRs were estimated using time-to-event (survival analysis) methods.

Results

Factors found to be associated with falls by less-experienced jockeys (as indicated by number of career rides or career stage) were older jockey age at commencement of career (p=0.001), fewer previous rides this meeting (p<0.001), fewer previous starts by the horse (p<0.001), younger horse age (p<0.001), lower race grade (p<0.001), lower prize money (p<0.001), shorter race distance (p<0.001) and drier track rating (p<0.001). Apprentice experience was inversely and strongly associated with increased rates of falls (p<0.001). Three indicators of less accomplished horses (lower race grade, fewer previous starts by the horse and less prize money at stake) and two race conditions (drier tracks and shorter race distance) were found to be associated with a progressively higher hazard of falls for less-experienced jockeys.

Conclusions

This study identified factors that preferentially contribute to falls by inexperienced jockeys. The authors suggest that consideration be given to restricting apprentice jockeys with little race-riding experience from riding horses that have not yet won a race (maiden) or that have had few previous race starts.
Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon
Authors: Suply Etienne , de Vries Philine , Soret Rodolphe , Cossais François , Neunlist Michel
Published: April 2012

Postnatal changes in the enteric nervous system (ENS) are involved in the establishment of colonic motility. In adult rats, butyrate induced neuroplastic changes in the ENS, leading to enhanced colonic motility. Whether butyrate can induce similar changes during the postnatal period remains unknown. Enemas (Na-butyrate) were performed daily in rat pups between postnatal day (PND) 7 and PND 17. Effects of butyrate were evaluated on morphological and histological parameters in the distal colon at PND 21. The neurochemical phenotype of colonic submucosal and myenteric neurons was analyzed using antibodies against Hu, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS). Colonic motility and neuromuscular transmission was assessed in vivo and ex vivo. Butyrate (2.5 mM) enemas had no impact on pup growth and histological parameters compared with control. Butyrate did not modify the number of Hu-immunoreactive (IR) neurons per ganglia. A significant increase in the proportion (per Hu-IR neurons) of nNOS-IR myenteric and submucosal neurons and ChAT-IR myenteric neurons was observed in the distal colon after butyrate enemas compared with control. In addition, butyrate induced a significant increase in both nitrergic and cholinergic components of the neuromuscular transmission compared with control. Finally, butyrate increased distal colonic transit time compared with control. We concluded that butyrate enemas induced neuroplastic changes in myenteric and submucosal neurons, leading to changes in gastrointestinal functions. Our results support exploration of butyrate as potential therapy for motility disorders in preterm infants with delayed maturation of the ENS.
Early apoptosis in different models of cardiac hypertrophy induced by high renin-angiotensin system activity involves CaMKII
Authors: Velez Rueda J. Omar , Palomeque Julieta , Mattiazzi Alicia
Published: April 2012

The objective of this study was to establish whether 1) hyperactivity of renin-angiotensin-aldosterone system (RAAS) produces apoptosis in early stages of cardiac disease; and 2) Ca2+-calmodulin-dependent protein kinase II (CaMKII) is involved in these apoptotic events. Two models of hypertrophy were used at an early stage of cardiac disease: spontaneously hypertensive rats (SHR) and isoproterenol-treated rats (Iso-rats). At 4 mo, SHR showed blood pressure, aldosterone serum levels, used as RAAS activity index, and left ventricular mass index, used as hypertrophy index, above control values by 84.2 ± 2.6 mmHg, 211.2 ± 25.8%, and 8.6 ± 1.1 mg/mm, respectively. There was also an increase in apoptotis (Bax-to-Bcl-2 ratio and terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling positive cells) associated with an enhancement of CaMKII activity with respect to age-matched controls (phosphorylated-CaMKII, 98.7 ± 14.1 above control). Similar results were observed in 4-mo-old Iso-rats. Cardiac function studied by echocardiography remained unaltered in all groups. Enalapril treatment significantly prevented hypertrophy, apoptosis, and CaMKII activity. Moreover, intracellular Ca2+ handling in isolated myocytes was similar between SHR, Iso-rats, and their aged-matched controls. However, SHR and Iso-rats showed a significant increase in superoxide anion generation (lucigenin) and lipid peroxidation (thiobarbituric acid reactive substance). In transgenic mice with targeted cardiomyocyte expression of a CaMKII inhibitory peptide (AC3-I) or a scrambled control peptide (AC3-C), Iso treatment increased thiobarbituric acid reactive substance in both strains, whereas it increased CaMKII activity and apoptosis only in AC3-C mice. Endogenous increases in RAAS activity induce ROS and CaMKII-dependent apoptosis in vivo. CaMKII activation could not be associated with intracellular Ca2+ increments and was directly related to the increase in oxidative stress.
Antitumor Mechanisms of Targeting the PDK1 Pathway in Head and Neck Cancer
Authors: Bhola Neil E. , Freilino Maria L. , Joyce Sonali C. , Sen Malabika , Thomas Sufi M. , Sahu Anirban , Cassell Andre , Chen Ching-Shih , Grandis Jennifer R.
Published: April 2012

G-protein–coupled receptors (GPCR) activate the epidermal growth factor receptor (EGFR) and mediate EGFR-independent signaling pathways to promote the growth of a variety of cancers, including head and neck squamous cell carcinoma (HNSCC). Identification of the common signaling mechanisms involved in GPCR-induced EGFR-dependent and EGFR-independent processes will facilitate the development of more therapeutic strategies. In this study, we hypothesized that phosphoinositide-dependent kinase 1 (PDK1) contributes to GPCR–EGFR cross-talk and signaling in the absence of EGFR and suggests that inhibition of the PDK1 pathway may be effective in the treatment of HNSCC. The contribution of PDK1 to the EGFR-dependent and EGFR-independent signaling in HNSCC was determined using RNA interference, a kinase-dead mutant, and pharmacologic inhibition. In vivo xenografts studies were also carried out to determine the efficacy of targeting PDK1 alone or in combination with the U.S. Food and Drug Administration–approved EGFR inhibitor cetuximab. PDK1 contributed to both GPCR-induced EGFR activation and cell growth. PDK1 also mediated activation of p70S6K in the absence of EGFR. Blockade of PDK1 with a small molecule inhibitor (AR-12) abrogated HNSCC growth, induced apoptosis, and enhanced the antiproliferative effects of EGFR tyrosine kinase inhibitors in vitro. HNSCC xenografts expressing kinase-dead PDK1 showed increased sensitivity to cetuximab compared with vector-transfected controls. Administration of AR-12 substantially decreased HNSCC tumor growth in vivo. These cumulative results show that PDK1 is a common signaling intermediate in GPCR–EGFR cross-talk and EGFR-independent signaling, and in which targeting the PDK1 pathway may represent a rational therapeutic strategy to enhance clinical responses to EGFR inhibitors in HNSCC. Mol Cancer Ther; 11(6); 1236–46. ©2012 AACR.
Combination of Rad001 (Everolimus) and Propachlor Synergistically Induces Apoptosis through Enhanced Autophagy in Prostate Cancer Cells
Authors: Tai Sheng , Sun Yin , Liu Nan , Ding Boxiao , Hsia Elaine , Bhuta Sunita , Thor Ryan K. , Damoiseaux Robert , Liang Chaozhao , Huang Jiaoti
Published: April 2012

PI3K/AKT/mTOR pathway plays a key role in the tumorigenesis of many human cancers including prostate cancer. However, inhibitors of this pathway, such as Rad001, have not shown therapeutic efficacy as a single agent. Through a high-throughput screen of 5,000 widely used small molecules, we identified compounds that can synergize with Rad001 to inhibit prostate cancer cells. One of the compounds, propachlor, synergizes with Rad001 to induce apoptosis of castration-resistant prostate cancer cells via enhanced autophagy. This enhanced autophagic cell death is accompanied by increased Beclin1 expression as well as upregulation of Atg5–Atg12 conjugate and LC3-2. Rad001 and propachlor can also synergistically inhibit tumors in a xenograft animal model of prostate cancer. These findings provide a novel direction to develop combination therapies for advanced and metastatic prostate cancer that has failed the currently available therapies. Mol Cancer Ther; 11(6); 1320–31. ©2012 AACR.
Elimination of Local Abnormal Ventricular Activities
Authors: Jaïs Pierre , Maury Philippe , Khairy Paul , Sacher Frédéric , Nault Isabelle , Komatsu Yuki , Hocini Mélèze , Forclaz Andrei , Jadidi Amir S. , Weerasooryia Rukshen , Shah Ashok , Derval Nicolas , Cochet Hubert , Knecht Sebastien , Miyazaki Shinsuke , Linton Nick , Rivard Lena , Wright Matthew , Wilton Stephen B. , Scherr Daniel , Pascale Patrizio , Roten Laurent , Pederson Michala , Bordachar Pierre , Laurent François , Kim Steven J. , Ritter Philippe , Clementy Jacques , Haïssaguerre Michel
Published: April 2012

Background—

Catheter ablation of ventricular tachycardia (VT) is effective and particularly useful in patients with frequent defibrillator interventions. Various substrate modification techniques have been described for unmappable or hemodynamically intolerable VT. Noninducibility is the most frequently used end point but is associated with significant limitations, so the optimal end point remains unclear. We hypothesized that elimination of local abnormal ventricular activities (LAVAs) during sinus rhythm or ventricular pacing would be a useful and effective end point for substrate-based VT ablation. As an adjunct to this strategy, we used a new high-density mapping catheter and frequently used epicardial mapping.

Methods and Results—

Seventy patients (age, 67±11 years; 7 female) with VT and structurally abnormal ventricle(s) were prospectively enrolled. Conventional mapping was performed in sinus rhythm in all, and a high-density Pentaray mapping catheter was used in the endocardium (n=35) and epicardially. LAVAs were recorded in 67 patients (95.7%; 95% confidence interval, 89.2–98.9). Catheter ablation was performed targeting LAVA with an irrigated-tip catheter placed endocardially via a transseptal or retrograde aortic approach or epicardially via the subxiphoid approach. LAVAs were successfully abolished or dissociated in 47 of 67 patients (70.1%; 95% confidence interval, 58.7–80.1). In multivariate analysis, LAVA elimination was independently associated with a reduction in recurrent VT or death (hazard ratio, 0.49; 95% confidence interval, 0.26–0.95;
P
=0.035) during long-term follow-up (median, 22 months).

Conclusions—

LAVAs can be identified in most patients with scar-related VT. Elimination of LAVAs is feasible and safe and is associated with superior survival free from recurrent VT.
The Age Associations of Blood Pressure, Cholesterol, and Glucose
Authors: Singh Gitanjali M. , Danaei Goodarz , Pelizzari Pamela M. , Lin John K. , Cowan Melanie J. , Stevens Gretchen A. , Farzadfar Farshad , Khang Young-Ho , Lu Yuan , Riley Leanne M. , Lim Stephen S. , Ezzati Majid
Published: April 2012

Background—

The age association of cardiovascular disease may be in part because its metabolic risk factors tend to rise with age. Few studies have analyzed age associations of multiple metabolic risks in the same population, especially in nationally representative samples. We examined worldwide variations in the age associations of systolic blood pressure (SBP), total cholesterol (TC), and fasting plasma glucose (FPG).

Methods and Results—

We used individual records from 83 nationally or subnationally representative health examination surveys in 52 countries to fit a linear model to risk factor data between ages 30 and 64 years for SBP and FPG, and between 30 and 54 years for TC. We report the cross-country variation of the slope and intercept of this relationship. We also assessed nonlinear associations in older ages. Between 30 and 64 years of age, SBP increased by 1.7 to 11.6 mm Hg per 10 years of age, and FPG increased by 0.8 to 20.4 mg/dL per 10 years of age in different countries and in the 2 sexes. Between 30 and 54 years of age, TC increased by 0.2 to 22.4 mg/dL per 10 years of age in different surveys and in the 2 sexes. For all risk factors and in most countries, risk factor levels rose more steeply among women than among men, especially for TC. On average, there was a flattening of age-SBP relationship in older ages; TC and FPG age associations reversed in older ages, leading to lower levels in older ages than in middle ages.

Conclusions—

The rise with age of major metabolic cardiovascular disease risk factors varied substantially across populations, especially for FPG and TC. TC rose more steeply in high-income countries and FPG in the Oceania countries, the Middle East, and the United States. The SBP age association had no specific income or geographical pattern.
Subacute Ischemic Stroke Is Associated With Focal
11
C PiB Positron Emission Tomography Retention But Not With Global Neocortical Aβ Deposition
Authors: Ly John V. , Rowe Christopher C. , Villemagne Victor L. , Zavala Jorge A. , Ma Henry , Sahathevan Ramesh , O'Keefe Graeme , Gong Sylvia J. , Gunawan Rico , Churilov Leonid , Saunder Tim , Ackerman Uwe , Tochon-Danguy Henri , Donnan Geoffrey A.
Published: April 2012

Background and Purpose—

Conflicting evidence exists as to whether focal cerebral ischemia contributes to cerebral amyloid deposition. We aimed to look at Aβ deposits, detected by N-methyl-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (PiB) positron emission tomography, in patients with recent ischemic stroke. Specifically, we hypothesized that patients with recent ischemic stroke have higher local and neocortical PiB positron emission tomography retention and that this may be associated with major vascular risk factors.

Methods—

Ischemic stroke patients were studied using PiB positron emission tomography within 30 days and compared to age-matched controls. Distribution volume ratio maps were created using Logan graphical analysis with the cerebellar cortex as a reference.

Results—

Among the 21 ischemic stroke patients (median age, 76 years; interquartile range, 68–77), the ipsilateral peri-infarct region PiB retention was higher compared to the contralateral mirror region, with a PiB distribution volume ratio difference of 0.29 (95% CI, 0.2–0.44;
P
=0.001) at median 10 (interquartile range, 7–14) days after stroke. Two patients also had higher PiB retention within the infarct compared to the contralateral side. There was no difference in the neocortical PiB retention elsewhere in the brain among ischemic stroke patients compared with 22 age-matched normal controls (
P
=0.22). Among the risk factors in the ischemic stroke patients, diabetes was associated with a higher neocortical PiB retention (Spearman Rho=0.48; 95% CI, 0.28–0.72).

Conclusions—

PiB retention was higher in the peri-infarct region among patients with recent ischemic stroke. This did not translate into a higher global neocortical PiB retention except possibly in patients with diabetes. The cause of the focal PiB retention is uncertain and requires further investigation.
Baseline Cardiovascular Risk Predicts Subsequent Changes in Resting Brain Function
Authors: Beason-Held Lori L. , Thambisetty Madhav , Deib Gerard , Sojkova Jitka , Landman Bennett A. , Zonderman Alan B. , Ferrucci Luigi , Kraut Michael A. , Resnick Susan M.
Published: April 2012

Background and Purpose—

The Framingham Heart Study group cardiovascular disease risk profile (FCRP) score was used to assess the relationship between baseline cardiovascular risk and subsequent changes in resting state cerebral blood flow (CBF) in cognitively normal older participants from the Baltimore Longitudinal Study of Aging.

Methods—

Ninty-seven cognitively normal participants underwent annual resting-state positron emission tomography scans at baseline and over a period of up to 8 years (mean interval, 7.4 years). Images quantifying voxel-wise longitudinal rates of CBF change were calculated and used to examine the relationship between baseline FCRP score and changes over time in regional CBF. Individual components of the FCRP score (age, cholesterol, blood pressure, smoking status, and type 2 diabetes) were also correlated with changes in regional CBF to examine the independent contributions of each component to the overall pattern of change.

Results—

Higher baseline FCRP scores were associated with accelerated longitudinal decline in CBF in orbitofrontal, medial frontal/anterior cingulate, insular, precuneus, and brain stem regions. Of the components that comprise the FCRP score, higher diastolic blood pressure and diabetes were associated independently with greater decline in the medial frontal/anterior cingulate and insular regions, respectively.

Conclusions—

Baseline cardiovascular risk factors are associated with greater rates of decline in resting state regional brain function. The regions showing accelerated decline participate in higher-order cognitive processes and are also vulnerable to age-related neuropathology. These results, in conjunction with other studies, encourage early treatment of cardiovascular risk factors in older individuals.
Force and Contact Location Shading Methods for Use Within Two- and Three-Dimensional Polygonal Environments
Authors: Doxon Andrew J. , Johnson David E. , Tan Hong Z. , Provancher William R.
Published: April 2012

Current state-of-the-art haptic interfaces only provide kinesthetic (force) feedback, yet studies have shown that providing tactile feedback in concert with kinesthetic information can dramatically improve a person's ability to dexterously interact with and explore virtual environments. In this research, tactile feedback was provided by a device, called a contact location display (CLD), which is capable of rendering the center of contact to a user. The chief goal of the present work was to develop algorithms that allow the CLD to be used with polygonal geometric models, and to do this without the resulting contact location feedback being overwhelmed by the perception of polygonal edges and vertices. Two haptic shading algorithms were developed to address this issue and successfully extend the use of the CLD to 2D and 3D polygonal environments. Two experiments were run to evaluate these haptic shading algorithms. The first measured perception thresholds for rendering faceted objects as smooth objects. It was found that the addition of contact location feedback significantly increased user sensitivity to edges and that the use of shading algorithms was able to significantly reduce the number of polygons needed for objects to feel smooth. The second experiment explored the CLD device's ability to facilitate exploration and shape recognition within a 3D environment. While this study provided a validation of our 3D algorithm, as people were able to identify the rendered objects with reasonable accuracy, this study underscored the need for improvements in the CLD device design in order to be effectively used in general 3D environments.
Navigating in Virtual Worlds Using a Self-Paced SSVEP-Based Brain–Computer Interface with Integrated Stimulation and Real-Time Feedback
Authors: Legény Jozef , Abad Raquel Viciana , Lécuyer Anatole
Published: April 2012

An open question in research nowadays is the usability of brain–computer interfaces (BCI) conceived to extend human capabilities of interaction within a virtual environment. Several paradigms are used for BCI, but the steady-state visual-evoked potential (SSVEP) stands out as it provides a higher information transfer rate while requiring less training. It is an electroencephalographic response detectable when the user looks at a flickering visual stimulus. This research proposes a novel approach for SSVEP-based BCI controller used here for navigation within a 3D virtual environment. For the first time, the flickering stimuli were integrated into virtual objects as a part of the virtual scene in a more transparent and ecological way. As an example, when navigating inside a virtual natural outdoor scene, we could embed the SSVEP flashes in the wings of virtual butterflies surrounding the user. We could also introduce the use of animated and moving stimulations when using SSVEP-based BCI, as the virtual butterflies were left with the possibility of moving and flying in front of the user. Moreover, users received real-time feedback of their mental activity and were thus aware of their detected SSVEP directly and continuously. An experiment has been conducted to assess the influence of both the feedback and the integrated controller on navigation performance and subjective preference. We found that the usage of a controller integrated within the virtual scene along with the feedback seems to improve subjective preference and feeling of presence, despite reduced performance in terms of speed. This suggests that SSVEP-based BCI interfaces for virtual environments could move on from static targets and use integrated and animated stimuli presented in an ecological way for controls in systems where performance demands could be relaxed to benefit an improvement in interaction naturalness.
Highly Automated Driving, Secondary Task Performance, and Driver State
Authors: Merat Natasha , Jamson A. Hamish , Lai Frank C. H. , Carsten Oliver
Published: April 2012

Objective:

A driving simulator study compared the effect of changes in workload on performance in manual and highly automated driving. Changes in driver state were also observed by examining variations in blink patterns.

Background:

With the addition of a greater number of advanced driver assistance systems in vehicles, the driver’s role is likely to alter in the future from an operator in manual driving to a supervisor of highly automated cars. Understanding the implications of such advancements on drivers and road safety is important.

Method:

A total of 50 participants were recruited for this study and drove the simulator in both manual and highly automated mode. As well as comparing the effect of adjustments in driving-related workload on performance, the effect of a secondary Twenty Questions Task was also investigated.

Results:

In the absence of the secondary task, drivers’ response to critical incidents was similar in manual and highly automated driving conditions. The worst performance was observed when drivers were required to regain control of driving in the automated mode while distracted by the secondary task. Blink frequency patterns were more consistent for manual than automated driving but were generally suppressed during conditions of high workload.

Conclusion:

Highly automated driving did not have a deleterious effect on driver performance, when attention was not diverted to the distracting secondary task.

Application:

As the number of systems implemented in cars increases, an understanding of the implications of such automation on drivers’ situation awareness, workload, and ability to remain engaged with the driving task is important.
The Concept of Time in Rehabilitation and Psychosocial Adaptation to Chronic Illness and Disability
Authors: Livneh Hanoch
Published: April 2012

Human fascination with the concept of time can be traced to antiquity. Time has been viewed as fundamental to all human experience, and efforts to understand its nature, structure, and relationship to the human experience have generated a burgeoning body of literature, over the past two millennia, among philosophers, astronomers, physicists, and more recently psychologists. Yet, the field of rehabilitation counseling has been rather silent on the role of time and especially its place in understanding psychosocial adaptation to chronic illnesses and disabilities. In the first part of this article, the author seeks to (a) provide a brief review of the current understanding of the nature and structure of time and (b) explore the role that time plays in the context of personality theories and the therapeutic approaches spawned by them. Implications to the study of chronic illnesses and disabilities are discussed throughout the narrative.
Out-of-sample stock return predictability in Australia
Authors: Dou Yiwen (Paul) , Gallagher David R. , Schneider David , Walter Terry S.
Published: April 2012

We provide one of the first comprehensive studies on out-of-sample stock returns predictability in Australia. While most of the empirically well-known predictive variables fail to generate out-of-sample predictability, we document a significant out-of-sample prediction in forecasting ahead one-year and, to a lesser extent, one-quarter future excess returns, using a combination forecast of variables. We also find improved asset allocation using the combination forecast of these predictors. The combining methods are useful in predicting sector premia. Specifically, a sector rotation strategy relying on the combining methods outperforms the market by 3.27% per annum on a risk-adjusted basis.
Insolvency administration as a strategic response to financial distress
Authors: Routledge James , Morrison David
Published: April 2012

This study considers whether the strategic decision to enter voluntary administration (VA) rather than to trade the company’s business for a protracted period of declining performance is systematically related to the effective monitoring of management decision-making. Analysis that tests the association between strategic entry into VA and the likelihood that a company will reorganize in VA is also presented. We find about half of the companies in our sample entered VA as a strategic choice. The likelihood of strategic entry to VA increased with the proportion of independent board directors, the existence of an audit committee and a dual CEO/chair board structure. Subsequent analysis of reorganization outcomes suggests that strategic entry into VA improves prospects for a successful reorganization.
Aortic root pathology in Marfan syndrome increases the risk of migraine with aura
Authors: Koppen H , Vis JC , Gooiker DJ , Knudsen S , Bouma BJ , Tijssen JGP , de Mol BAJM , Mulder BJM , Russell MB , Ferrari MD
Published: April 2012

Aim: To assess the lifetime prevalence of migraine in patients with Marfan syndrome (MFS) and to investigate a history of aortic root replacement (AR) as a possible risk factor.

Methods: In a multicentre study 123 MFS patients ( n = 52 with AR, n = 71 without AR), 82 age- and sex-matched controls and 51 patients with AR but without MFS, were interviewed using a semi-structured headache questionnaire. A multinomial logistic regression model was used to investigate risk factors for migraine with and without aura, adjusting for age and gender.

Results: Lifetime migraine prevalence was increased in female MFS patients (51%) compared to healthy female controls (29%), p = 0.017. In males lifetime migraine prevalence among MFS patients was only numerically increased. Lifetime prevalence of migraine with aura was increased among MFS patients compared to healthy controls both in males (19% vs. 3%, p = 0.048) and females (30% vs. 14%, p = 0.049). A history of AR, independently from MFS, gender and age, increased the lifetime prevalence of migraine with aura (OR 3.1 [1.2–8.0]). In all but one patient migraine started before the AR.

Conclusions: The lifetime prevalence of migraine with aura, but not migraine without aura, is increased in patients with MFS. This association is driven by a history of AR. The replacement procedure itself is unlikely to be causally associated with migraine as in nearly all subjects, migraine started before the procedure. However this study adds to the evidence that underlying vessel wall pathology may be involved in migraine with aura.
Delayed development of visual motion processing in childhood migraine
Authors: Braunitzer Gábor , Rokszin Alice , Kóbor Jenő , Benedek György , Nagy Attila , Kincses Zsigmond Tamás
Published: April 2012

Introduction: Altered visual processing has been observed in adult migraineurs. But because visual processing has not been studied in paediatric cases, it is not known whether such visual system alterations are already present in early development. We therefore used a dynamic visual task to investigate motion detection threshold in paediatric migraine.

Methods: Fourteen migraineurs and 21 controls participated in the study (age range: 8–17 years). The minimal percentage of coherently moving dot stimuli at which subjects were still able to detect coherent movement (absolute threshold) was determined using a random dot kinematogram paradigm.

Results: Motion coherence detection threshold was higher in migraineurs ( p < 0.05). This difference between groups was more pronounced at younger ages, but migraineurs seem to catch up with healthy controls over the years.

Conclusions: Children with migraine exhibit a delayed development of visual motion processing. This might be a useful supplementary biomarker in paediatric migraine.
Cost-Effectiveness Analysis of Autologous Chondrocyte Implantation
Authors: Samuelson Eric M. , Brown David E.
Published: April 2012

Background: Autologous chondrocyte implantation (ACI) involves the use of a periosteal patch (ACI-P) as a cover for transplanted chondrocytes. Theoretically, this periosteal patch provides mesenchymal stem cells and growth factors that encourage chondrocyte development/differentiation. However, there is a significant rate of graft hypertrophy with the use of periosteum compared with using a type I/III collagen patch (ACI-C). This type I/III collagen patch, although not approved by the United States Food and Drug Administration for ACI, has been used extensively in Europe and in an “off-label” nature in the United States as a cover during ACI.

Purpose: To examine the cost effectiveness of ACI and determine whether ACI-C is more cost effective than ACI-P.

Study Design: Economic and decision analysis; Level of evidence, 2.

Methods: Outcome data and complication rates from patients undergoing ACI (ACI-P and ACI-C) were derived from the best evidence in the literature. Costs were determined by examining the typical patient charges undergoing ACI at a local orthopaedic hospital. The costs, results, and complication rates were used to develop a decision analysis model comparing ACI-P to ACI-C.

Results: The cost of ACI-P was $66,752 and for ACI-C was $66,939.50 ($187.50 difference). The cost per quality-adjusted life year (QALY) for ACI-P was $9466 compared with $9243 for ACI-C. Sensitivity analysis was performed regarding the additional cost of the type I/III collagen patch ($780) in ACI-C as well as the rate of graft hypertrophy after ACI-P (25%). This analysis revealed that the cost of the type I/III collagen patch would have to reach $1721, or the rate of graft hypertrophy after ACI-P reduced to almost 11%, before ACI-P became more cost effective than ACI-C.

Conclusion: This cost-effectiveness analysis reveals that, while both ACI-P and ACI-C are cost effective, ACI-C is slightly more cost effective than ACI-P. This is likely secondary to the significant rate of patch-related complications associated with ACI-P, which is significantly reduced with ACI-C. Although the model is very sensitive to differences in outcomes between ACI-P and ACI-C, there is no high-quality evidence to suggest that there is a significant difference between the two. Thus, ACI-P becomes more cost effective if the cost of the type I/III collagen membrane is significantly increased or if the rate of graft hypertrophy after ACI-P were to be markedly reduced.
Validation of the Spanish Version of the Woodcock-Johnson Mathematics Achievement Tests for Children Aged 6 to 13
Authors: Diamantopoulou Sofia , Pina Violeta , Valero-Garcia Ana V. , González-Salinas Carmen , Fuentes Luis J.
Published: April 2012

This study validated the four mathematics tests of the Spanish version of the Woodcock-Johnson III (WJ-III) Achievement (ACH) battery for use in the first six grades of school in Spain. Developmental effects and gender differences were also examined. Participants were a normal population sample of 424 (216 boys) children aged 6 to 13 years. Results showed that the tests have good test-retest and internal reliability and good construct and criterion-related validity. Significant main effects of schooling were obtained with scores increasing across the six school grades, but scores between fourth and fifth graders did not differ significantly. Overall, boys scored higher than girls on all tests but the effect sizes of these gender differences were small ( d ≤ .12).
Effectiveness of antibacterial copper additives in silicone implants
Authors: Gosau Martin , Bürgers Ralf , Vollkommer Tobias , Holzmann Thomas , Prantl Lukas
Published: April 2012

Staphylococcus epidermidis plays a major role in capsular contractures of silicone breast implants. This in vitro study evaluates the antibacterial effect of copper on S. epidermidis in silicone implants. Specimens of a silicone material used for breast augmentation (Cu0) and specimens coated with different copper concentrations (Cu1, Cu2) were artificially aged. Surface roughness and surface free energy were assessed. The specimens were incubated in an S. epidermidis suspension. We assessed the quantification and the viability of adhering bacteria by live/dead cell labeling with fluorescence microscopy. Additionally, inhibition of bacterial growth was evaluated by agar diffusion, broth culture, and quantitative culture of surface bacteria. No significant differences in surface roughness and surface free energy were found between Cu0, Cu1 and Cu2. Aging did not change surface characteristics and the extent of bacterial adhesion. Fluorescence microscopy showed that the quantity of bacteria on Cu0 was significantly higher than that on Cu1 and Cu2. The ratio of dead to total adhering bacteria was significantly lower on Cu0 than on Cu1 and Cu2, and tended to be higher for Cu2 than for Cu1. Quantitative culture showed equal trends. Copper additives seem to have anti-adherence and bactericidal effects on S. epidermidis in vitro.
Clinical assessment of calcium phosphate cement to treat tibial plateau fractures
Authors: Yin Xiaofan , Li Jianyong , Xu Jun , Huang Zhongyue , Rong Ke , Fan Cunyi
Published: April 2012

The aim of this study was to examine histological changes in bone morphology after surgical treatment of tibial plateau fractures using calcium phosphate cement as a substitute for autologous bone grafting. A total of 42 patients with tibial plateau fractures were treated with open reduction, internal fixation, and calcium phosphate cement. A further 34 control patients underwent open reduction and internal fixation. Bone samples for histology were obtained during the surgery. Bone healing and functional recovery were assessed. Bone cell counts were significantly higher in samples obtained during the second surgery (81.2) compared with the first surgery (45.4, p < 0.001). Bone healing scores significantly increased with time after surgery ( p < 0.001). Mean Hospital for Special Surgery knee scores were rated “good” for both the calcium phosphate cement group (82.3) and control group (79.4) in 12 months, and were not significantly different between groups. Histological examination of samples obtained during the second surgery revealed well-arranged trabeculae, in addition to new bone and blood vessel formation. These histological, radiological, and functional findings suggest that calcium phosphate cement may be an effective substitute for autologous bone grafting to treat tibial plateau fractures.
“That’s What a Man Is Supposed to Do”
Authors: Sumerau J. Edward
Published: April 2012

In this article, I examine how gay Christian men constructed compensatory manhood acts. Based on more than 450 hours of fieldwork in a southeastern LGBT Christian organization, I analyze how a group of gay men, responding to sexist, heterosexist, and religious stigma, as well as the acquisition of a new pastor, constructed identities as gay Christian men by (1) emphasizing paternal stewardship, (2) stressing emotional control and inherent rationality, and (3) defining intimate relationships in a Christian manner. These subordinated men, regardless of their intentions, collaboratively drew on and reproduced cultural notions that facilitate and justify the subordination of women and sexual minorities. Specifically, their compensatory manhood acts symbolically positioned them as superior to supposedly promiscuous, self-centered, and effeminate others. In conclusion, I draw out implications for understanding how groups of gay Christian men engage in compensatory manhood acts, and the consequences these actions have for the reproduction of inequality.
When Death is Good for Life
Authors: Vail Kenneth E. , Juhl Jacob , Arndt Jamie , Vess Matthew , Routledge Clay , Rutjens Bastiaan T.
Published: April 2012

Research derived from terror management theory (TMT) has shown that people’s efforts to manage the awareness of death often have deleterious consequences for the individual and society. The present article takes a closer look at the conceptual foundations of TMT and considers some of the more beneficial trajectories of the terror management process. The awareness of mortality can motivate people to enhance their physical health and prioritize growth-oriented goals; live up to positive standards and beliefs; build supportive relationships and encourage the development of peaceful, charitable communities; and foster open-minded and growth-oriented behaviors. The article also tentatively explores the potential enriching impact of direct encounters with death. Overall, the present analysis suggests that although death awareness can, at times, generate negative outcomes, it can also function to move people along more positive trajectories and contribute to the good life.
Perceived Benefits and E-Commerce Adoption by SME Travel Agents in Developing Countries
Authors: Abou-Shouk Mohamed , Megicks Phil , Lim Wai Mun
Published: April 2012

Small and medium-sized enterprises (SMEs), particularly in developing countries, are regarded as slow adopters of technology, especially e-commerce. Travel agents are a typical category of SMEs, experiencing changes in the travel market structure, caused by the use of e-commerce. E-Commerce adoption is a means of supporting agents’ future survival and competitiveness at a time when many are facing the threat of disintermediation from the global travel market. The investigation of e-commerce adoption by SMEs in developing countries represents an emerging area of research, with only a limited number of studies undertaken to date. This research aims to examine the perceived benefits of an advanced level e-commerce adoption by Egyptian travel agents. Structural equation modeling is used to categorize a set of perceived benefit factors for e-commerce adoption, and establish a relationship with the level of adoption. Results indicate that marketing and competition benefits, essential benefits that support strategy and development, and business efficiency benefits all positively contribute to decisions that lead to an advanced level of e-commerce being adopted.
Improving Survey Methods With Cognitive Interviews in Small- and Medium-Scale Evaluations
Authors: Ryan Katherine , Gannon-Slater Nora , Culbertson Michael J.
Published: April 2012

Findings derived from self-reported, structured survey questionnaires are commonly used in evaluation and applied research to inform policy-making and program decisions. Although there are a variety of issues related to the quality of survey evidence (e.g., sampling precision), the validity of response processes–how respondents process thoughts and perceptions when answering questionnaires–is crucial. We assess the extent to which cognitive interviews, used to test survey questions as part of the process of questionnaire design and refinement, can strengthen the quality of survey evidence for small- and medium-scale evaluations. To illustrate how cognitive interviews can reveal respondents' response processes and improved questionnaire interpretations, we present excerpts from two types of evaluations (e.g., needs assessment) in two domains (e.g., education). The paper concludes with a brief summary about how the use of cognitive interviews can be augmented in survey development, refinement, and adaptation to improve survey questionnaire interpretations in evaluations with limited resources.
Prevalence of feline leukemia virus infection in domestic cats in Rio de Janeiro
Authors: de Almeida Nadia R , Danelli Maria G M , da Silva Lucia H P , Hagiwara Mitika K , Mazur Carlos
Published: April 2012

Peripheral blood smears of 1094 domestic cats were collected and tested by indirect immunofluorescence antibody assay for p27 antigen in cells to study the prevalence and risk factors for feline leukemia virus (FeLV) in the state of Rio de Janeiro. Sex, age, breed, outdoor access, neutering status, type of habitation (household, shelter, veterinary clinics and other places), number of household cats and clinical signs were registered on a form. Among the tested samples, 11.52% were positive. Risk factors for FeLV infection included outdoor access, age range between 1 and 5 years old, and cohabitation with numerous cats.