bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimum Configuration of an Expanding-Contracting-Nozzle for Thrust Enhancement by Bubble Injection
Authors: Singh Sowmitra , Choi Jin-Keun , Chahine Georges
Published: February 2012

This paper addresses the concept of thrust augmentation through bubble injection into an expanding-contracting nozzle. Two-phase models for bubbly flow in an expanding-contracting nozzle are developed, in parallel with laboratory experiments and used to ascertain the geometry configuration for the nozzle that would lead to maximum thrust enhancement upon bubble injection. For preliminary optimization of experimental setup’s design, a quasi 1-D approach is used. Averaged flow quantities (such as velocities, pressures, and void fractions) in a cross section are used for the analysis. The mixture continuity and momentum equations are numerically solved simultaneously along with equations for bubble dynamics, bubble motion, and an equation for conservation of the total bubble number. Various geometric parameters such as the exit and inlet areas, the area of the bubble injection section, the presence of a throat and its location, the length of the diffuser section and the length of the contraction section are varied, and their effects on thrust enhancement are studied. Investigation on the effect of the injected void fraction is also carried out. The key objective function of the optimization is the normalized thrust parameter, which is the thrust with bubble injection minus the thrust with liquid only divided by the inlet liquid momentum. An approximate analytical expression for the normalized thrust parameter was also derived starting from the mixture continuity and momentum equations. This analytical expression involved flow variables only at three locations; inlet section, injection section, and outlet section, and the expression is simple enough to produce a quick concept design of the diffuser-nozzle thruster. The numerical and analytical approaches are verified against each other and the limitations of the analytical approach are discussed.
A Study on the Effects of Covered Stents on Tissue Prolapse
Authors: Weaver Jason D. , Ku D. N.
Published: February 2012

Polyvinyl alcohol (PVA) cryogel covered stents may reduce complications from thrombosis and restenosis by decreasing tissue prolapse. Finite element analysis was employed to evaluate the effects of PVA cryogel layers of varying thickness on tissue prolapse and artery wall stress for two common stent geometries and two vessel diameters. Additionally, several PVA cryogel covered stents were fabricated and imaged with an environmental scanning electron microscope. Finite element results showed that covered stents reduced tissue prolapse up to 13% and artery wall stress up to 29% with the size of the reduction depending on the stent geometry, vessel diameter, and PVA cryogel layer thickness. Environmental scanning electron microscope images of expanded covered stents showed the PVA cryogel to completely cover the area between struts without gaps or tears. Overall, this work provides both computational and experimental evidence for the use of PVA cryogels in covered stents.
Characterization of epitaxial ZnTe layers grown on GaAs substrates by transmission electron microscopy and photoluminescence
Authors: Zhang Fabi , Ikoma Yoshifumi , Zhang Jinping , Xu Ke , Saito Katsuhiko , Guo Qixin
Published: February 2012

The authors have investigated the effects of a low-temperature ZnTe buffer layer on structural and optical properties of ZnTe epilayers grown on (100) GaAs substrates by transmission electron microscopy and photoluminescence measurements. It has been found that the low-temperature ZnTe buffer layer can reduce the defects such as disordered region in the ZnTe buffer layer and suppress the dislocations at the ZnTe surface region, resulting in the formation of a high quality ZnTe epilayer grown on the low-temperature buffer layer.
Growth of Aerobic Ripening Bacteria at the Cheese Surface Is Limited by the Availability of Iron
Authors: Monnet Christophe , Back Alexandre , Irlinger Françoise
Published: February 2012

The microflora on the surface of smear-ripened cheeses is composed of various species of bacteria and yeasts that contribute to the production of the desired organoleptic properties. The objective of the present study was to show that iron availability is a limiting factor in the growth of typical aerobic ripening bacteria in cheese. For that purpose, we investigated the effect of iron or siderophore addition in model cheeses that were coinoculated with a yeast and a ripening bacterium. Both iron and the siderophore desferrioxamine B stimulated the growth of ripening bacteria belonging to the genera
Arthrobacter
,
Corynebacterium
, and
Brevibacterium
. The extent of stimulation was strain dependent, and generally, the effect of desferrioxamine B was greater than that of iron. Measurements of the expression of genes related to the metabolism of iron by
Arthrobacter arilaitensis
Re117 by real-time reverse transcription-PCR showed that these genes were transcribed during growth in cheese. The addition of desferrioxamine B increased the expression of two genes encoding iron-siderophore ABC transport binding proteins. The addition of iron decreased the expression of siderophore biosynthesis genes and of part of the genes encoding iron-siderophore ABC transport components. It was concluded that iron availability is a limiting factor in the growth of typical cheese surface bacteria. The selection of strains with efficient iron acquisition systems may be useful for the development of defined-strain surface cultures. Furthermore, the importance of iron metabolism in the microbial ecology of cheeses should be investigated since it may result in positive or negative microbial interactions.
Biodegradation of Trichloroethylene by an Endophyte of Hybrid Poplar
Authors: Kang Jun Won , Khan Zareen , Doty Sharon L.
Published: February 2012

We isolated and characterized a novel endophyte from hybrid poplar. This unique endophyte, identified as
Enterobacter
sp. strain PDN3, showed high tolerance to trichloroethylene (TCE). Without the addition of inducers, such as toluene or phenol, PDN3 rapidly reduced TCE levels in medium from 72.4 μM to 30.1 μM in 24 h with a concurrent release of 127 μM chloride ion, and nearly 80% of TCE (55.3 μM) was dechlorinated by PDN3 in 5 days with 166 μM chloride ion production, suggesting TCE degradation.
Genome Scanning for Conditionally Essential Genes in Salmonella enterica Serotype Typhimurium
Authors: Khatiwara Anita , Jiang Tieshan , Sung Sam-Sun , Dawoud Turki , Kim Jeong Nam , Bhattacharya Dhruva , Kim Hee-Bal , Ricke Steven C. , Kwon Young Min
Published: February 2012

As more whole-genome sequences become available, there is an increasing demand for high-throughput methods that link genes to phenotypes, facilitating discovery of new gene functions. In this study, we describe a new version of the Tn-seq method involving a modified EZ:Tn
5
transposon for genome-wide and quantitative mapping of all insertions in a complex mutant library utilizing massively parallel Illumina sequencing. This Tn-seq method was applied to a genome-saturating
Salmonella enterica
serotype Typhimurium mutant library recovered from selection under 3 different
in vitro
growth conditions (diluted Luria-Bertani [LB] medium, LB medium plus bile acid, and LB medium at 42°C), mimicking some aspects of host stressors. We identified an overlapping set of 105 protein-coding genes in
S
. Typhimurium that are conditionally essential under at least one of the above selective conditions. Competition assays using 4 deletion mutants (
pyrD
,
glnL
,
recD
, and STM14_5307) confirmed the phenotypes predicted by Tn-seq data, validating the utility of this approach in discovering new gene functions. With continuously increasing sequencing capacity of next generation sequencing technologies, this robust Tn-seq method will aid in revealing unexplored genetic determinants and the underlying mechanisms of various biological processes in
Salmonella
and the other approximately 70 bacterial species for which EZ:Tn
5
mutagenesis has been established.
Efficacy of Biocides Used in the Modern Food Industry To Control Salmonella enterica, and Links between Biocide Tolerance and Resistance to Clinically Relevant Antimicrobial Compounds
Authors: Condell Orla , Iversen Carol , Cooney Shane , Power Karen A. , Walsh Ciara , Burgess Catherine , Fanning Séamus
Published: February 2012

Biocides play an essential role in limiting the spread of infectious disease. The food industry is dependent on these agents, and their increasing use is a matter for concern. Specifically, the emergence of bacteria demonstrating increased tolerance to biocides, coupled with the potential for the development of a phenotype of cross-resistance to clinically important antimicrobial compounds, needs to be assessed. In this study, we investigated the tolerance of a collection of susceptible and multidrug-resistant (MDR)
Salmonella enterica
strains to a panel of seven commercially available food-grade biocide formulations. We explored their abilities to adapt to these formulations and their active biocidal agents, i.e., triclosan, chlorhexidine, hydrogen peroxide, and benzalkonium chloride, after sequential rounds of
in vitro
selection. Finally, cross-tolerance of different categories of biocidal formulations, their active agents, and the potential for coselection of resistance to clinically important antibiotics were investigated. Six of seven food-grade biocide formulations were bactericidal at their recommended working concentrations. All showed a reduced activity against both surface-dried and biofilm cultures. A stable phenotype of tolerance to biocide formulations could not be selected. Upon exposure of
Salmonella
strains to an active biocidal compound, a high-level of tolerance was selected for a number of
Salmonella
serotypes. No cross-tolerance to the different biocidal agents or food-grade biocide formulations was observed. Most tolerant isolates displayed changes in their patterns of susceptibility to antimicrobial compounds. Food industry biocides are effective against planktonic
Salmonella
. When exposed to sublethal concentrations of individual active biocidal agents, tolerant isolates may emerge. This emergence was associated with changes in antimicrobial susceptibilities.
Moraxella Species Are Primarily Responsible for Generating Malodor in Laundry
Authors: Kubota Hiromi , Mitani Asako , Niwano Yu , Takeuchi Kohei , Tanaka Atsushi , Yamaguchi Noriko , Kawamura Yoshiaki , Hitomi Jun
Published: February 2012

Many people in Japan often detect an unpleasant odor generated from laundry that is hung to dry indoors or when using their already-dried laundry. Such an odor is often described as a “wet-and-dirty-dustcloth-like malodor” or an “acidic or sweaty odor.” In this study, we isolated the major microorganisms associated with such a malodor, the major component of which has been identified as 4-methyl-3-hexenoic acid (4M3H). The isolates were identified as
Moraxella osloensis
by morphological observation and biochemical and phylogenetic tree analyses.
M. osloensis
has the potential to generate 4M3H in laundry. The bacterium is known to cause opportunistic infections but has never been known to generate a malodor in clothes. We found that
M. osloensis
exists at a high frequency in various living environments, particularly in laundry in Japan. The bacterium showed a high tolerance to desiccation and UV light irradiation, providing one of the possible reasons why they survive in laundry during and even after drying.
Cellular, Biochemical, and Molecular Changes during Encystment of Free-Living Amoebae
Authors: Fouque Emilie , Trouilhé Marie-Cécile , Thomas Vincent , Hartemann Philippe , Rodier Marie-Hélène , Héchard Yann
Published: February 2012

Free-living amoebae are protozoa found in soil and water. Among them, some are pathogenic and many have been described as potential reservoirs of pathogenic bacteria. Their cell cycle is divided into at least two forms, the trophozoite and the cyst, and the differentiation process is named encystment. As cysts are more resistant to disinfection treatments than trophozoites, many studies focused on encystment, but until recently, little was known about cellular, biochemical, and molecular modifications operating during this process. Important signals and signaling pathways at play during encystment, as well as cell responses at the molecular level, have been described. This review summarizes our knowledge and focuses on new findings.
Comparative Analysis of the First Complete Enterococcus faecium Genome
Authors: Lam Margaret M. C. , Seemann Torsten , Bulach Dieter M. , Gladman Simon L. , Chen Honglei , Haring Volker , Moore Robert J. , Ballard Susan , Grayson M. Lindsay , Johnson Paul D. R. , Howden Benjamin P. , Stinear Timothy P.
Published: February 2012

Vancomycin-resistant enterococci (VRE) are one of the leading causes of nosocomial infections in health care facilities around the globe. In particular, infections caused by vancomycin-resistant
Enterococcus faecium
are becoming increasingly common. Comparative and functional genomic studies of
E. faecium
isolates have so far been limited owing to the lack of a fully assembled
E. faecium
genome sequence. Here we address this issue and report the complete 3.0-Mb genome sequence of the multilocus sequence type 17 vancomycin-resistant
Enterococcus faecium
strain Aus0004, isolated from the bloodstream of a patient in Melbourne, Australia, in 1998. The genome comprises a 2.9-Mb circular chromosome and three circular plasmids. The chromosome harbors putative
E. faecium
virulence factors such as enterococcal surface protein, hemolysin, and collagen-binding adhesin. Aus0004 has a very large accessory genome (38%) that includes three prophage and two genomic islands absent among 22 other
E. faecium
genomes. One of the prophage was present as inverted 50-kb repeats that appear to have facilitated a 683-kb chromosomal inversion across the replication terminus, resulting in a striking replichore imbalance. Other distinctive features include 76 insertion sequence elements and a single chromosomal copy of Tn
1549
containing the
vanB
vancomycin resistance element. A complete
E. faecium
genome will be a useful resource to assist our understanding of this emerging nosocomial pathogen.
Re-evaluation of serological criteria for early syphilis treatment efficacy: progression to neurosyphilis despite therapy
Authors: Zhou Pingyu , Gu Xin , Lu Haikong , Guan Zhifang , Qian Yihong
Published: February 2012

Objectives

To study 17 cases of secondary syphilis that progressed to neurosyphilis despite appropriate treatments and whose rapid plasma reagin (RPR) titres showed a fourfold decrease within 6 months but did not revert to negative.

Methods

Secondary syphilis patients with the following criteria were analysed: (1) RPR titres declined fourfold within 3 months after therapy, (2) patients denied high-risk sexual behaviours following treatment, (3) RPR titre remained serofast 24 months after treatment, (4) reactive cerebrospinal fluid (CSF)–venereal disease research laboratory (VDRL) and CSF–Treponema pallidumParticle Agglutination Test (TPPA) and (5) HIV antibody negative.

Results

14 male and three female patients met the criteria. 13 patients were asymptomatic. The CSF leucocyte count was elevated in 10 patients of whom nine also had elevated CSF–proteins. The RPR titres following secondary syphilis treatments were ≥1:32 in five cases, 1:16 in four cases, 1:8 in six cases and 1:4 in two cases. Following treatments for neurosyphilis, four cases with neurological or psychiatric manifestations resolved or improved, nine cases with raised CSF–white blood cells returned to normal and nine of 12 cases with raised CSF–protein declined to normal.

Conclusions

Neurosyphilis may be detected in immunocompetent patients despite appropriate therapy for early-stage syphilis and appropriate serological responses. Clinicians should consider a CSF examination in any treated patient with evidence of disease progression irrespective of prior treatment history and serological response.
Prevalence of respiratory signs and identification of risk factors for respiratory morbidity in Swedish Yorkshire terriers
Authors: Madsen M. F. , Toft N. , Houe H. , Granström S. , Willesen J. L. , Koch J.
Published: February 2012

Yorkshire terriers may be prone to respiratory disease; however, limited epidemiological information is available. A cross‐sectional study design was used to compare the prevalence of respiratory signs in Yorkshire terriers with the prevalence in a population of dogs in general and to identify risk factors for respiratory clinical signs within the Swedish population of Yorkshire terriers. Data on clinical signs and risk factors were obtained from a questionnaire. The prevalence of respiratory signs in general (RS) was significantly higher among Yorkshire terriers compared with control dogs (RS 56.3 per cent and 23.0 per cent), and likewise more frequent respiratory signs (FRS) (26.0 per cent and 5.0 per cent). Age, sex and breed were shown to be significant risk factors, and an interaction between age and sex was discovered. The study indicated a sex ratio reversal in the prevalence of RS – the probability of females having RS increased with advancing age, while the probability for males was fairly constant.
TESTING THE FLYBY ANOMALY WITH THE GNSS CONSTELLATION
Authors: BERTOLAMI ORFEU , FRANCISCO FREDERICO , GIL PAULO J. S. , PÁRAMOS JORGE
Published: February 2012

We propose the concept of a space mission to probe the so called flyby anomaly, an unexpected velocity change experienced by some deep-space probes using earth gravity assists. The key feature of this proposal is the use of GNSS systems to obtain an increased accuracy in the tracking of the approaching spacecraft, mainly near the perigee. Two low-cost options are also discussed to further test this anomaly: an add-on to an existing spacecraft and a dedicated mission.
LOCALLY SUPPORTED WAVELETS FOR THE SEPARATION OF SPHERICAL VECTOR FIELDS WITH RESPECT TO THEIR SOURCES
Authors: GERHARDS C.
Published: February 2012

We provide a space domain-oriented separation of magnetic fields into parts generated by sources in the exterior and sources in the interior of a given sphere. The separation itself is well-known in geomagnetic modeling, usually in terms of a spherical harmonic analysis or a wavelet analysis that is spherical harmonic-based. In contrast to these frequency-oriented methods, we use a more spatially-oriented approach in this paper. We derive integral representations with explicitly known convolution kernels. Regularizing these singular kernels allows a multiscale representation of the internal and external contributions to the magnetic field with locally supported wavelets. This representation is applied to a set of CHAMP data for crustal field modeling.
RADIAL CENTROID CURVE FOR AFFINE INVARIANT FEATURES EXTRACTION
Authors: YANG JIANWEI , LAN RUSHI , TANG YUAN YAN , CHEN YUNJIE
Published: February 2012

The extraction of affine invariant features plays an important role in many fields of computer vision. Contour-based wavelet methods are unapplicable to objects with several separable components. In this paper, a method is proposed by converting the object into a closed curve, which is called radial centroid curve (RCC). Point on this curve is the centroid of radial line segment from centroid of the object. It is shown that the RCC derived from the affine transformed object is the same affine transformed version as that of the original object. An affine invariant function (AIF) is constructed by applying stationary wavelet transform (SWT) to the derived RCC. This scheme is applicable to objects with several separable components. Several experiments have been conducted to evaluate the performance of the proposed method.
Inhibiting NF-κB in the developing lung disrupts angiogenesis and alveolarization
Authors: Iosef Cristiana , Alastalo Tero-Pekka , Hou Yanli , Chen Chihhsin , Adams Eloa S. , Lyu Shu-Chen , Cornfield David N. , Alvira Cristina M.
Published: February 2012

Bronchopulmonary dysplasia (BPD), a chronic lung disease of infancy, is characterized by arrested alveolar development. Pulmonary angiogenesis, mediated by the vascular endothelial growth factor (VEGF) pathway, is essential for alveolarization. However, the transcriptional regulators mediating pulmonary angiogenesis remain unknown. We previously demonstrated that NF-κB, a transcription factor traditionally associated with inflammation, plays a unique protective role in the neonatal lung. Therefore, we hypothesized that constitutive NF-κB activity is essential for postnatal lung development. Blocking NF-κB activity in 6-day-old neonatal mice induced the alveolar simplification similar to that observed in BPD and significantly reduced pulmonary capillary density. Studies to determine the mechanism responsible for this effect identified greater constitutive NF-κB in neonatal lung and in primary pulmonary endothelial cells (PEC) compared with adult. Moreover, inhibiting constitutive NF-κB activity in the neonatal PEC with either pharmacological inhibitors or RNA interference blocked PEC survival, decreased proliferation, and impaired in vitro angiogenesis. Finally, by chromatin immunoprecipitation, NF-κB was found to be a direct regulator of the angiogenic mediator, VEGF-receptor-2, in the neonatal pulmonary vasculature. Taken together, our data identify an entirely novel role for NF-κB in promoting physiological angiogenesis and alveolarization in the developing lung. Our data suggest that disruption of NF-κB signaling may contribute to the pathogenesis of BPD and that enhancement of NF-κB may represent a viable therapeutic strategy to promote lung growth and regeneration in pulmonary diseases marked by impaired angiogenesis.
Intermittent pneumatic leg compressions enhance muscle performance and blood flow in a model of peripheral arterial insufficiency
Authors: Roseguini Bruno T. , Arce-Esquivel Arturo A. , Newcomer Sean C. , Yang Hsiao T. , Terjung Ronald , Laughlin M. H.
Published: February 2012

Despite the escalating prevalence in the aging population, few therapeutic options exist to treat patients with peripheral arterial disease. Application of intermittent pneumatic leg compressions (IPC) is regarded as a promising noninvasive approach to treat this condition, but the clinical efficacy, as well the mechanistic basis of action of this therapy, remain poorly defined. We tested the hypothesis that 2 wk of daily application of IPC enhances exercise tolerance by improving blood flow and promoting angiogenesis in skeletal muscle in a model of peripheral arterial insufficiency. Male Sprague-Dawley rats were subjected to bilateral ligation of the femoral artery and randomly allocated to treatment or sham groups. Animals were anesthetized daily and exposed to 1-h sessions of bilateral IPC or sham treatment for 14–16 consecutive days. A third group of nonligated rats was also studied. Marked increases in treadmill exercise tolerance (∼33%, P < 0.05) and improved muscle performance in situ (∼10%, P < 0.05) were observed in IPC-treated animals. Compared with sham-treated controls, blood flow measured with isotope-labeled microspheres during in situ contractions tended to be higher in IPC-treated animals in muscles composed of predominantly fast-twitch white fibers, such as the plantaris (∼93%, P = 0.02). Capillary contacts per fiber and citrate synthase activity were not significantly altered by IPC treatment. Collectively, these data indicate that IPC improves exercise tolerance in a model of peripheral arterial insufficiency in part by enhancing blood flow to collateral-dependent tissues.
On Uniformly Bazilevic and Related Functions
Authors: Noor Khalida Inayat
Published: February 2012

We introduce a new class of functions analytic in the open unit disc, which contains the class of Bazilevic functions and also generalizes the concept of uniform convexity. We establish univalence criterion for the functions in this class and investigate rate of growth of coefficients, arc length problem, inclusion results, and distortion bounds. Some interesting results are derived as special cases.
Zero Triple Product Determined Matrix Algebras
Authors: Yao Hongmei , Zheng Baodong
Published: February 2012

Let A be an algebra over a commutative unital ring 𝒞. We say that A is zero triple
product determined if for every 𝒞‐module X and every trilinear map {·, ·, ·}, the following
holds: if {x, y, z} = 0 whenever xyz = 0, then there exists a 𝒞‐linear operator T : A3 → X
such that {x, y, z} = T(xyz) for all x, y, z ∈ A. If the ordinary
triple product in the aforementioned definition is replaced by Jordan triple
product, then A is called zero Jordan triple
product determined. This paper mainly shows that matrix algebra Mn(B), n ≥ 3, where
B is any commutative unital algebra even different
from the above mentioned commutative unital algebra 𝒞, is always zero triple product determined, and Mn(F), n ≥ 3, where F
is any field with chF ≠ 2, is also zero Jordan triple product determined.
Concordant Release of Glycolysis Proteins into the Plasma Preceding a Diagnosis of ER+ Breast Cancer
Authors: Amon Lynn M. , Pitteri Sharon J. , Li Christopher I. , McIntosh Martin , Ladd Jon J. , Disis Mary , Porter Peggy , Wong Chee Hong , Zhang Qing , Lampe Paul , Prentice Ross L. , Hanash Samir M.
Published: February 2012

Although the identification of peripheral blood biomarkers would enhance early detection strategies for breast cancer, the discovery of protein markers has been challenging. In this study, we sought to identify coordinated changes in plasma proteins associated with breast cancer based on large-scale quantitative mass spectrometry. We analyzed plasma samples collected up to 74 weeks before diagnosis from 420 estrogen receptor (ER)+ cases and matched controls enrolled in the Women's Health Initiative cohort. A gene set enrichment analysis was applied to 467 quantified proteins, linking their corresponding genes to particular biologic pathways. On the basis of differences in the concentration of individual proteins, glycolysis pathway proteins exhibited a statistically significant difference between cases and controls. In particular, the enrichment was observed among cases in which blood was drawn closer to diagnosis (effect size for the 0–38 weeks prediagnostic group, 1.91; P, 8.3E-05). Analysis of plasmas collected at the time of diagnosis from an independent set of cases and controls confirmed upregulated levels of glycolysis proteins among cases relative to controls. Together, our findings indicate that the concomitant release of glycolysis proteins into the plasma is a pathophysiologic event that precedes a diagnosis of ER+ breast cancer. Cancer Res; 72(8); 1935–42. ©2012 AACR.
Characterization of Gene–Environment Interactions for Colorectal Cancer Susceptibility Loci
Authors: Hutter Carolyn M. , Chang-Claude Jenny , Slattery Martha L. , Pflugeisen Bethann M. , Lin Yi , Duggan David , Nan Hongmei , Lemire Mathieu , Rangrej Jagadish , Figueiredo Jane C. , Jiao Shuo , Harrison Tabitha A. , Liu Yan , Chen Lin S. , Stelling Deanna L. , Warnick Greg S. , Hoffmeister Michael , Küry Sébastien , Fuchs Charles S. , Giovannucci Edward , Hazra Aditi , Kraft Peter , Hunter David J. , Gallinger Steven , Zanke Brent W. , Brenner Hermann , Frank Bernd , Ma Jing , Ulrich Cornelia M. , White Emily , Newcomb Polly A. , Kooperberg Charles , LaCroix Andrea Z. , Prentice Ross L. , Jackson Rebecca D. , Schoen Robert E. , Chanock Stephen J. , Berndt Sonja I. , Hayes Richard B. , Caan Bette J. , Potter John D. , Hsu Li , Bézieau Stéphane , Chan Andrew T. , Hudson Thomas J. , Peters Ulrike
Published: February 2012

Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case–control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 at 18q21 (SMAD7), rs10411210 at 19q13.1 (RHPN2), and rs961253 at 20p12.3 (BMP2)] and select major CRC risk factors (sex, body mass index, height, smoking status, aspirin/nonsteroidal anti-inflammatory drug use, alcohol use, and dietary intake of calcium, folate, red meat, processed meat, vegetables, fruit, and fiber). The strongest statistical evidence for a gene–environment interaction across studies was for vegetable consumption and rs16892766, located on chromosome 8q23.3, near the EIF3H and UTP23 genes (nominal Pinteraction = 1.3 × 10−4; adjusted P = 0.02). The magnitude of the main effect of the SNP increased with increasing levels of vegetable consumption. No other interactions were statistically significant after adjusting for multiple comparisons. Overall, the association of most CRC susceptibility loci identified in initial GWAS seems to be invariant to the other risk factors considered; however, our results suggest potential modification of the rs16892766 effect by vegetable consumption. Cancer Res; 72(8); 2036–44. ©2012 AACR.
Effect of
PON1
Q192R Genetic Polymorphism on Clopidogrel Efficacy and Cardiovascular Events in the Clopidogrel in the Unstable Angina to Prevent Recurrent Events Trial and the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events
Authors: Paré Guillaume , Ross Stephanie , Mehta Shamir R. , Yusuf Salim , Anand Sonia S. , Connolly Stuart J. , Fox Keith A.A. , Eikelboom John W.
Published: February 2012

Background—

A recent report suggested that carriers of the Q allele of the
PON1
Q192R polymorphism had decreased biotransformation of clopidogrel into its active metabolite and decreased efficacy of clopidogrel in preventing cardiovascular events. Furthermore, PON1 has been reported to have a central role in the antioxidant function of high-density lipoprotein, and the Q192R polymorphism has been previously associated with cardiovascular risk in patients not treated with clopidogrel.

Methods and Results—

Patients (n=5059) from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) randomized trial that demonstrated benefits of clopidogrel versus placebo in preventing cardiovascular events in acute coronary syndromes were genotyped for the
PON1
Q192R polymorphism. Clopidogrel compared with placebo significantly reduced the first primary efficacy outcome, irrespective of
PON1
Q192R genotype (
P
=0.07 for heterogeneity). No association was observed between the Q192R polymorphism and cardiovascular events in the overall sample (hazard ratio [HR], 1.09 per allele; 95% confidence interval [CI], 0.95–1.24;
P
=0.23). However, an association was observed between the Q allele and increased cardiovascular events in the placebo group (HR, 1.23 per allele; 95% CI, 1.03–1.47;
P
=0.03) but not in the clopidogrel group (HR, 0.93 per allele; 95% CI, 0.76–1.13;
P
=0.46). In 1156 atrial fibrillation patients from the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events, there was no evidence of interaction between
PON1
genotype and clopidogrel for any outcome or for an association between genotype and cardiovascular events.

Conclusions—

In conclusion, our study shows that
PON1
Q192R genotype does not modify the efficacy and safety of clopidogrel in patients with acute coronary syndromes. Further studies are needed to confirm or refute the association of the Q allele with adverse cardiovascular events independent of clopidogrel in secondary prevention patients.
Predictors of Long-Term Survival After Coronary Artery Bypass Grafting Surgery
Authors: Shahian David M. , O'Brien Sean M. , Sheng Shubin , Grover Frederick L. , Mayer John E. , Jacobs Jeffrey P. , Weiss Jocelyn M. , DeLong Elizabeth R. , Peterson Eric D. , Weintraub William S. , Grau-Sepulveda Maria V. , Klein Lloyd W. , Shaw Richard E. , Garratt Kirk N. , Moussa Issam D. , Shewan Cynthia M. , Dangas George D. , Edwards Fred H.
Published: February 2012

Background—

Most survival prediction models for coronary artery bypass grafting surgery are limited to in-hospital or 30-day end points. We estimate a long-term survival model using data from the Society of Thoracic Surgeons Adult Cardiac Surgery Database and Centers for Medicare and Medicaid Services.

Methods and Results—

The final study cohort included 348 341 isolated coronary artery bypass grafting patients aged ≥65 years, discharged between January 1, 2002, and December 31, 2007, from 917 Society of Thoracic Surgeons–participating hospitals, randomly divided into training (n=174 506) and validation (n=173 835) samples. Through linkage with Centers for Medicare and Medicaid Services claims data, we ascertained vital status from date of surgery through December 31, 2008 (1- to 6-year follow-up). Because the proportional hazards assumption was violated, we fit 4 Cox regression models conditional on being alive at the beginning of the following intervals: 0 to 30 days, 31 to 180 days, 181 days to 2 years, and >2 years. Kaplan-Meier–estimated mortality was 3.2% at 30 days, 6.4% at 180 days, 8.1% at 1 year, and 23.3% at 3 years of follow-up. Harrell's C statistic for predicting overall survival time was 0.732. Some risk factors (eg, emergency status, shock, reoperation) were strong predictors of short-term outcome but, for early survivors, became nonsignificant within 2 years. The adverse impact of some other risk factors (eg, dialysis-dependent renal failure, insulin-dependent diabetes mellitus) continued to increase.

Conclusions—

Using clinical registry data and longitudinal claims data, we developed a long-term survival prediction model for isolated coronary artery bypass grafting. This provides valuable information for shared decision making, comparative effectiveness research, quality improvement, and provider profiling.
Effects of Catecholamine Stress on Diastolic Function and Myocardial Energetics in Obesity
Authors: Rider Oliver J. , Francis Jane M. , Ali Mohammed K. , Holloway Cameron , Pegg Tammy , Robson Matthew D. , Tyler Damian , Byrne James , Clarke Kieran , Neubauer Stefan
Published: February 2012

Background—

Obesity is characterized by impaired cardiac energetics, which may play a role in the development of diastolic dysfunction and inappropriate shortness of breath. We assessed whether, in obesity, derangement of energetics and diastolic function is further altered during acute cardiac stress.

Methods and Results—

Normal-weight (body mass index, 22±2 kg/m
2
; n=9–17) and obese (body mass index, 39±7 kg/m
2
; n=17–46) subjects underwent assessment of diastolic left ventricular function (cine magnetic resonance imaging volume-time curve analysis) and cardiac energetics (phosphocreatine/ATP ratio;
31
P-magnetic resonance spectroscopy) at rest and during dobutamine stress (heart rate increase, 65±22% and 69±14%, respectively;
P
=0.61). At rest, obesity was associated with a 22% lower peak filling rate (
P
<0.001) and a 15% lower phosphocreatine/ATP ratio (1.73±0.40 versus 2.03±0.28;
P
=0.048). Peak filling rate correlated with fat mass, left ventricular mass, leptin, waist-to-hip ratio, and phosphocreatine/ATP ratio. On multivariable analysis, phosphocreatine/ATP was the only independent predictor of peak filling rate (β=0.50;
P
=0.03). During stress, a further reduction in phosphocreatine/ATP occurred in obese (from 1.73±0.40 to 1.53±0.50;
P
=0.03) but not in normal-weight (from 1.98±0.24 to 2.04±0.34;
P
=0.50) subject. For similar levels of inotropic stress, there were smaller increases in peak filling rate in obesity (38% versus 70%;
P
=0.01).

Conclusions—

In obesity, cardiac energetics are further deranged during inotropic stress, in association with continued diastolic dysfunction. Myocardial energetics may play a key role in the impairment of diastolic function in obesity.
Changing Epidemiology of Abdominal Aortic Aneurysms in England and Wales
Authors: Choke Edward , Vijaynagar Badri , Thompson John , Nasim Akhtar , Bown Matthew J. , Sayers Robert D.
Published: February 2012

Background—

Recent studies from Australia, New Zealand, and Sweden have reported declines in abdominal aortic aneurysm (AAA) incidence, prevalence, and mortality. This finding may have important implications for screening programs. This study determined trends in AAA incidence and mortality in England and Wales.

Methods and Results—

Cause-specific mortality data for England and Wales were obtained from UK Office for National Statistics, and hospital admissions and procedures data for England were obtained from Hospital Episode Statistics from 2001 to 2009. Poisson regression models were constructed to estimate the relative change over time. Age-standardized rates for AAA mortality in England and Wales fell significantly by 35.7% from 2001 to 2009, which was largely due to a 35.3% drop in age-standardized ruptured AAA deaths. During the same period, ruptured AAA admissions and emergency AAA repairs in England declined by 29.3% and 35.5%, respectively. In contrast, nonruptured AAA admissions remained static, and nonemergency AAA repairs increased by 17.2%. The average ages for hospital admissions for nonruptured AAAs and ruptured AAAs increased by 0.19 years of age per annum (
P
<0.001) and 0.09 years of age per annum (
P
<0.001), respectively. Nonruptured AAA admissions increased by 21.4% in age band 75 years or more but declined by 11.7% in ages <75 years.

Conclusions—

AAA mortality, ruptured AAA admission, and emergency AAA repair have declined in England and Wales. However, nonruptured AAA admission has remained steady, with an increasing rate in older population offsetting a decreasing rate in younger population. This suggests a shift in AAA presentation to the older population. Present screening strategies may need reassessment to include consideration for increasing the age at which to screen men for AAAs.
Endothelial Cells Overexpressing Interleukin-8 Receptors Reduce Inflammatory and Neointimal Responses to Arterial Injury
Authors: Xing Dongqi , Li Peng , Gong Kaizheng , Yang Zhengqin , Yu Hao , Hage Fadi G. , Oparil Suzanne , Chen Yiu-Fai
Published: February 2012

Background—

Interleukin-8 (IL8) receptors IL8RA and IL8RB on neutrophil membranes bind to IL8 and direct neutrophil recruitment to sites of inflammation, including acutely injured arteries. This study tested whether administration of IL8RA- and/or IL8RB-transduced rat aortic endothelial cells (ECs) accelerates adhesion of ECs to the injured surface, thus suppressing inflammation and neointima formation in balloon-injured rat carotid arteries. We tested the hypothesis that targeted delivery of ECs by overexpressing IL8RA and IL8RB receptors prevents inflammatory responses and promotes structural recovery of arteries after endoluminal injury.

Methods and Results—

Young adult male rats received balloon injury of the right carotid artery and were transfused intravenously with ECs (total, 1.5×10
6
cells at 1, 3, and 5 hours after injury) transduced with adenoviral vectors carrying IL8RA, IL8RB, and IL8RA/RB (dual transduction) genes, AdNull (empty vector), or vehicle (no EC transfusion). ECs overexpressing IL8Rs inhibited proinflammatory mediators expression significantly (by 60% to 85%) and reduced infiltration of neutrophils and monocytes/macrophages into injured arteries at 1 day after injury, as well as stimulating a 2-fold increase in reendothelialization at 14 days after injury. IL8RA-EC, IL8RB-EC, and IL8RA/RB-EC treatment reduced neointima formation dramatically (by 80%, 74%, and 95%) at 28 days after injury.

Conclusions—

ECs with overexpression of IL8RA and/or IL8RB mimic the behavior of neutrophils that target and adhere to injured tissues, preventing inflammation and neointima formation. Targeted delivery of ECs to arteries with endoluminal injury provides a novel strategy for the prevention and treatment of cardiovascular disease.
An Admission Bioclinical Score to Predict 1-Year Outcomes in Patients Undergoing Aneurysm Coiling
Authors: Degos Vincent , Apfel Christian C. , Sanchez Paola , Colonne Chantal , Renuit Isabelle , Clarençon Frédéric , Nouet Aurélien , Boch Anne Laure , Pourmohamad Tony , Kim Helen , Gourraud Pierre Antoine , Young William L. , Puybasset Louis
Published: February 2012

Background and Purpose—

A number of scores were developed to predict outcomes after clipping for subarachnoid hemorrhages, yet there is no score for patients undergoing endovascular treatment. Our goal was to develop, compare, and validate a predictive score for 1-year outcomes in patients with coiled subarachnoid hemorrhage.

Methods—

We studied 526 patients for 1 year after intensive care unit discharge. We developed an admission bioclinical score (ABC score), which integrated biomarkers such as troponin I and S100β, with the Glasgow Coma Scale. Using the receiver operating characteristic curve (95% CI), the ABC score was compared with the Glasgow Coma Scale, World Federation of Neurosurgical Societies score, and Fisher score in the derivation cohort and further validated in an independent cohort.

Results—

In the derivation cohort (from 2003–2007, n=368), multivariate logistic regression analysis showed that only Glasgow Coma Scale (
P
<0.001), high S100β (
P
<0.001), and high troponin (
P
<0.02) were independently associated with 1-year mortality. Troponin, S100β, and Glasgow Coma Scale were thus integrated to derive the ABC score. In the derivation cohort, the ABC score reached an receiver operating characteristic curve of 0.82 (0.77–0.88,
P
<0.001) and was significantly greater than the receiver operating characteristic curves of the Glasgow Coma Scale, World Federation of Neurosurgical Societies, and Fisher scores for predicting 1-year mortality. In the validation cohort (from 2008–2009, n=158), the ABC score's receiver operating characteristic curve of 0.76 (0.67–0.86,
P
<0.001) remained superior to the 3 other scores for predicting 1-year mortality.

Conclusions—

The ABC score improves 1-year outcome prediction at admission for patients with coiled subarachnoid hemorrhage. Our study provides large cohort-based evidence supporting integration of individual biomarkers and clinical characteristics to predict outcomes.

Clinical Trial Registration—

URL:
www.clinicaltrials.gov
. Unique identifier: NCT01357057.
Improved Generative Semisupervised Learning Based on Finely Grained Component-Conditional Class Labeling
Authors: Miller David J. , Raghuram Jayaram , Kesidis George , Collins Christopher M.
Published: February 2012

We introduce new inductive, generative semisupervised mixtures with more finely grained class label generation mechanisms than in previous work. Our models combine advantages of semisupervised mixtures, which achieve label extrapolation over a component, and nearest-neighbor (NN)/nearest-prototype (NP) classification, which achieve accurate classification in the vicinity of labeled samples or prototypes. For our NN-based method, we propose a novel two-stage stochastic data generation, with all samples first generated using a standard finite mixture and then all class labels generated, conditioned on the samples and their components of origin. This mechanism entails an underlying Markov random field, specific to each mixture component or cluster. We invoke the pseudo-likelihood formulation, which forms the basis for an approximate generalized expectation-maximization model learning algorithm. Our NP-based model overcomes a problem with the NN-based model that manifests at very low labeled fractions. Both models are advantageous when within-component class proportions are not constant over the feature space region “owned by” a component. The practicality of this scenario is borne out by experiments on UC Irvine data sets, which demonstrate significant gains in classification accuracy over previous semisupervised mixtures and also overall gains, over KNN classification. Moreover, for very small labeled fractions, our methods overall outperform supervised linear and nonlinear kernel support vector machines.
Size and shape of the caudate nucleus in individuals with bipolar affective disorder
Authors: Ong Daniel , Walterfang Mark , Malhi Gin S , Styner Martin , Velakoulis Dennis , Pantelis Christos
Published: February 2012

Objective: The caudate nucleus (CN) is a crucial component of the ventral striatum, which is part of a prefrontal-striatal-thalamic circuit that is modulated by limbic structures to subserve emotional processing. Bipolar disorder is thought to be underpinned by dysfunctional anterior limbic networks, although MRI studies examining the CN have shown equivocal results. As gross volumetric analyses may not detect subtle regional change, we aimed to clarify the role of the CN in bipolar disorder by undertaking shape analysis to detect regional reductions.

Methods: The CN was manually traced on MRI scans from 27 patients with bipolar-I disorder and 24 matched controls. A non-parametric spherical harmonic shape analysis was undertaken using the SPHARM toolkit.

Results: Whilst the left CN volume was consistently larger in the sample, there was no effect of group or gender or significant interactions between these variables. Volume did not correlate with illness duration or lithium dosage, but was larger in those with a history of psychosis at trend level. However, left caudate shape differed significantly between groups, with deflation in an area along the ventromedial surface (connecting to dorsolateral prefrontal regions) in bipolar patients. Psychotic patients showed increases in the dorsal head and body at trend level overall, in regions connecting to medial and orbitofrontal regions.

Conclusions: These findings suggest that subtle rather than gross structural changes occur in the CN, which may not be detectable by volumetric analysis alone, and reflect alterations in specific frontostriatal circuitry in the disorder.
If You’re Against Them You’re With Us
Authors: Albertus Michael , Menaldo Victor
Published: February 2012

This article advances a theory of why some dictators weaken the elite through expropriation whereas others do not. When the organization that launches a new dictator into power is uncertain about whether he will remain loyal to them, a dictator’s decision to expropriate the preexisting elite may contribute to political stability by signaling his exclusive reliance on this group. The authors corroborate this claim empirically. Using new data compiled on land, resource, and bank expropriations in Latin America from 1950 to 2002, the authors show that large-scale expropriation helps dictators survive in power. Furthermore, expropriation tends to occur early in a dictator’s tenure, and its effect on leader survival decays over time, providing additional evidence for its signaling value. The history of autocracy in Mexico between 1911 and 2000 further illustrates the importance of expropriation in promoting autocratic survival as well as how the codification of new property rights can transform a dictator’s launching organization into a new economic elite.