bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous versus Intermittent Infusion of Oxacillin for Treatment of Infective Endocarditis Caused by Methicillin-Susceptible
Staphylococcus aureus
Authors: Hughes Darrel W. , Frei Christopher R. , Maxwell Pamela R. , Green Kay , Patterson Jan E. , Crawford George E. , Lewis James S.
Published: March 2009

Infective endocarditis (IE) is the fourth leading cause of life-threatening infection in the United States and imposes significant morbidity and mortality. The American Heart Association guidelines for the diagnosis and treatment of IE do not address continuous-infusion (CI) oxacillin. This retrospective study compares outcomes between CI oxacillin and intermittent-infusion (II) oxacillin in the treatment of IE caused by methicillin-susceptible
Staphylococcus aureus
(MSSA). A total of 709 medical records were reviewed for inpatients with definitive IE treated between 1 January 2000 and 31 December 2007. Continuous data were analyzed by Student's
t
test or the Wilcoxon rank sum test. The chi-square test or Fisher's exact test was used to compare nominal data. A multivariate logistic model was constructed. One hundred seven patients met eligibility criteria for inclusion into the study. Seventy-eight patients received CI oxacillin, whereas 28 received II oxacillin. CI and II groups were similar with respect to 30-day mortality (8% versus 10%,
P
= 0.7) and length of stay (20 versus 25 days,
P
= 0.4) but differed in 30-day microbiological cure (94% versus 79%,
P
= 0.03). Sixty-three patients received synergistic gentamicin, whereas 44 did not. The gentamicin and no-gentamicin groups were similar with respect to 30-day mortality (11% versus 4%,
P
= 0.2) and 30-day microbiological cure (90% versus 89%,
P
= 0.8); however, times to defervescence (4 versus 2 days,
P
= 0.02) were significantly different. CI oxacillin is an effective alternative to II oxacillin for the treatment of IE caused by MSSA and may improve microbiological cure. This convenient and pharmacodynamically optimized dosing regimen for oxacillin deserves consideration for patients with IE caused by MSSA.
Does the Activity of the Combination of Imipenem and Colistin In Vitro Exceed the Problem of Resistance in Metallo-β-Lactamase-Producing
Klebsiella pneumoniae
Isolates?
Authors: Souli Maria , Rekatsina Panagiota Danai , Chryssouli Zoi , Galani Irene , Giamarellou Helen , Kanellakopoulou Kyriaki
Published: March 2009

Using time-kill methodology, we investigated the interactions of an imipenem-colistin combination against 42 genetically distinct
Klebsiella pneumoniae
clinical isolates carrying a
bla
VIM-1
-type gene. Irrespective of the imipenem MIC, the combination was synergistic (50%) or indifferent (50%) against colistin-susceptible strains, while it was antagonistic (55.6%) and rarely synergistic (11%) against non-colistin-susceptible strains (with synergy being observed only against strains with colistin MICs of 3 to 4 μg/ml). The combination showed improved bactericidal activity against isolates susceptible either to both agents or to colistin.
Population Pharmacokinetics of Lopinavir Predict Suboptimal Therapeutic Concentrations in Treatment-Experienced Human Immunodeficiency Virus-Infected Children
Authors: Rakhmanina Natella , van den Anker John , Baghdassarian Aline , Soldin Steven , Williams Keetra , Neely Michael N.
Published: March 2009

In adult protease inhibitor (PI)-experienced patients, a lopinavir (LPV) phenotypic inhibitory quotient (PIQ) of >15 has been associated with a higher likelihood of viral suppression. The aims of this study were to develop a population pharmacokinetic (PK) model of LPV in children and to estimate the probability of achieving a PIQ of >15. HIV-infected, PI-experienced children receiving LPV were intensively sampled for 12 h to measure plasma LPV. The data were fitted to candidate PK models (using MM-USCPACK software), and the final model was used to simulate 1,000 children to determine the probability of achieving an LPV PIQ of >15. In 50 patients (4 to 18 years old), the median LPV plasma 12-hour-postdose concentration was 5.9 mg/liter (range, 0.03 to 16.2 mg/liter) lower than that reported in adults. After a delay, LPV was absorbed linearly into a central compartment whose size was dependent on the weight and age of the patient. Elimination was dependent on weight. The regression line of observed versus predicted LPV had an
R
2
of 0.99 and a slope of 1.0. Visual predictive checks against all available measured concentrations showed good predictive ability of the model. The probability of achieving an LPV PIQ of >15 was >90% for wild-type virus but <10% for even moderately resistant virus. The currently recommended dose of LPV/ritonavir appears to be adequate for children infected with wild-type virus but is unlikely to provide adequate inhibitory concentrations for even moderately resistant human immunodeficiency virus (HIV). PI-experienced HIV-infected children will likely benefit from longitudinal, repeated LPV measurement in plasma to ensure that drug exposure is most often near the maximal end of the observed safe range.
Extended-Spectrum Cephalosporinases in
Pseudomonas aeruginosa
Authors: Rodríguez-Martínez José-Manuel , Poirel Laurent , Nordmann Patrice
Published: March 2009

The characterization of AmpC-type β-lactamases was performed in a collection of 32 clinical
Pseudomonas aeruginosa
isolates with intermediate susceptibility or resistance to imipenem and ceftazidime. Twenty-one out of those 32 isolates overexpressed AmpC β-lactamase, and the MICs of ceftazidime and imipenem were reduced after cloxacillin addition. Cloning and sequencing identified 10 AmpC β-lactamase variants. Reduced susceptibility to imipenem, ceftazidime, and cefepime was observed only with recombinant
P. aeruginosa
strains expressing an AmpC β-lactamase that had an alanine residue at position 105. The catalytic efficiencies (
k
cat
/

K
m

) of the AmpC variants possessing this residue were increased against oxyiminocephalosporins and imipenem. In addition, we show here that those AmpC variants constitute a favorable background for the in vitro selection of imipenem-resistant strains. This report identified a novel resistance mechanism that may contribute to imipenem resistance in
P. aeruginosa
.
Tetracyclines Modulate Protease-Activated Receptor 2-Mediated Proinflammatory Reactions in Epidermal Keratinocytes
Authors: Ishikawa Chika , Tsuda Tatsuya , Konishi Hiroe , Nakagawa Noboru , Yamanishi Kiyofumi
Published: March 2009

In addition to their antibiotic effects, tetracyclines have anti-inflammatory action that is often beneficial in the control of inflammatory skin disorders. In this study, we examined the effects of tetracycline (TET) and two of its derivatives, doxycycline (DOX) and minocycline (MIN), on the production of interleukin-8 (IL-8) elicited by the activation of protease-activated receptor 2 (PAR2) in normal human epidermal keratinocytes (NHEK). In NHEK, the production of IL-8 stimulated by an agonist peptide of PAR2, SLIGKIV-NH2, at 100 μM was significantly reduced by TET, DOX, or MIN at 5 and 10 μM, concentrations that are noncytotoxic. The tumor necrosis factor alpha (TNF-α)-induced production of IL-8 was synergistically augmented by SLIGKIV-NH2, and that synergistic increase in the production of IL-8 was suppressed by 100 nMPAR2-specific small interfering RNA. It was also suppressed by TET, DOX, or MIN but not by the 14-membered-ring macrolide antibiotics erythromycin, roxithromycin, and clarithromycin, which also have anti-inflammatory activities, at 10 μM. These results suggest that tetracyclines attenuate the PAR2-IL-8 axis in keratinocytes and thereby effectively modulate proinflammatory responses in the skin.
Identification and Characterization of Mefloquine Efficacy against JC Virus In Vitro
Authors: Brickelmaier Margot , Lugovskoy Alexey , Kartikeyan Ramya , Reviriego-Mendoza Marta M. , Allaire Norm , Simon Kenneth , Frisque Richard J. , Gorelik Leonid
Published: March 2009

Progressive multifocal leukoencephalopathy (PML) is a rare but frequently fatal disease caused by the uncontrolled replication of JC virus (JCV), a polyomavirus, in the brains of some immunocompromised individuals. Currently, no effective antiviral treatment for this disease has been identified. As a first step in the identification of such therapy, we screened the Spectrum collection of 2,000 approved drugs and biologically active molecules for their anti-JCV activities in an in vitro infection assay. We identified a number of different drugs and compounds that had significant anti-JCV activities at micromolar concentrations and lacked cellular toxicity. Of the compounds with anti-JCV activities, only mefloquine, an antimalarial agent, has been reported to show sufficiently high penetration into the central nervous system such that it would be predicted to achieve efficacious concentrations in the brain. Additional in vitro experiments demonstrated that mefloquine inhibits the viral infection rates of three different JCV isolates, JCV(Mad1), JCV(Mad4), and JCV(M1/SVEΔ), and does so in three different cell types, transformed human glial (SVG-A) cells, primary human fetal glial cells, and primary human astrocytes. Using quantitative PCR to quantify the number of viral copies in cultured cells, we have also shown that mefloquine inhibits viral DNA replication. Finally, we demonstrated that mefloquine does not block viral cell entry; rather, it inhibits viral replication in cells after viral entry. Although no suitable animal model of PML or JCV infection is available for the testing of mefloquine in vivo, our in vitro results, combined with biodistribution data published in the literature, suggest that mefloquine could be an effective therapy for PML.
Conditioning of Uropathogenic
Escherichia coli
for Enhanced Colonization of Host
Authors: Bower Jean M. , Gordon-Raagas Hannah B. , Mulvey Matthew A.
Published: March 2009

While in transit within and between hosts, uropathogenic
Escherichia coli
(UPEC) encounters multiple stresses, including substantial levels of nitric oxide and reactive nitrogen intermediates. Here we show that UPEC, the primary cause of urinary tract infections, can be conditioned to grow at higher rates in the presence of acidified sodium nitrite (ASN), a model system used to generate nitrosative stress. When inoculated into the bladder of a mouse, ASN-conditioned UPEC bacteria are far more likely to establish an infection than nonconditioned bacteria. Microarray analysis of ASN-conditioned bacteria suggests that several NsrR-regulated genes and other stress- and polyamine-responsive factors may be partially responsible for this effect. Compared to K-12 reference strains, most UPEC isolates have increased resistance to ASN, and this resistance can be substantially enhanced by addition of the polyamine cadaverine. Nitrosative stress, as generated by ASN, can stimulate cadaverine synthesis by UPEC, and growth of UPEC in cadaverine-supplemented broth in the absence of ASN can also promote UPEC colonization of the bladder. These results suggest that UPEC interactions with polyamines or stresses such as reactive nitrogen intermediates can in effect reprogram the bacteria, enabling them to better colonize the host.
Listeria monocytogenesσBModulates PrfA-Mediated Virulence Factor Expression
Authors: Ollinger Juliane , Bowen Barbara , Wiedmann Martin , Boor Kathryn J. , Bergholz Teresa M.
Published: March 2009

Listeria monocytogenesσBand positive regulatory factor A (PrfA) are pleiotropic transcriptional regulators that coregulate a subset of virulence genes. A positive regulatory role for σBinprfAtranscription has been well established; therefore, observations of increased virulence gene expression and hemolytic activity in a ΔsigBstrain initially appeared paradoxical. To test the hypothesis thatL. monocytogenesσBcontributes to a regulatory network critical for appropriate repression as well as induction of virulence gene expression, genome-wide transcript profiling and follow-up quantitative reverse transcriptase PCR (qRT-PCR), reporter fusion, and phenotypic experiments were conducted usingL. monocytogenes prfA*,prfA* ΔsigB, ΔprfA, and ΔprfAΔsigBstrains. Genome-wide transcript profiling and qRT-PCR showed that in the presence of active PrfA (PrfA*), σBis responsible for reduced expression of the PrfA regulon. σB-dependent modulation of PrfA regulon expression reduced the cytotoxic effects of a PrfA* strain in HepG2 cells, highlighting the functional importance of regulatory interactions between PrfA and σB. The emerging model of the role of σBin regulating overall PrfA activity includes a switch from transcriptional activation at the P2prfApromoter (e.g., in extracellular bacteria when PrfA activity is low) to posttranscriptional downregulation of PrfA regulon expression (e.g., in intracellular bacteria when PrfA activity is high).
Staphylococcus aureusSuperantigens Elicit Redundant and Extensive Human Vβ Patterns
Authors: Thomas Damien , Dauwalder Olivier , Brun Virginie , Badiou Cedric , Ferry Tristan , Etienne Jerome , Vandenesch François , Lina Gerard
Published: March 2009

Staphylococcus aureuscan produce a wide variety of exotoxins, including toxic shock syndrome toxin 1 (TSST-1), staphylococcal enterotoxins, and staphylococcal enterotoxin-like toxins. These toxins share superantigenic activity. To investigate the β chain (Vβ) specificities of each of these toxins, TSST-1 and all knownS. aureusenterotoxins and enterotoxin-like toxins were produced as recombinant proteins and tested for their ability to induce the selective in vitro expansion of human T cells bearing particular Vβ T-cell receptors (TCR). Although redundancies were observed between the toxins and the Vβ populations, each toxin induced the expansion of distinct Vβ subsets, including enterotoxin H and enterotoxin-like toxin J. Surprisingly, the Vβ signatures were not associated with a specific phylogenic group of toxins. Interestingly, each human Vβ analyzed in this study was stimulated by at least one staphylococcal superantigen, suggesting that the bacterium derives a selective advantage from targeting the entire human TCR Vβ panel.
Protection against Pneumococcal Colonization and Fatal Pneumonia by a Trivalent Conjugate of a Fusion Protein with the Cell Wall Polysaccharide
Authors: Lu Ying-Jie , Forte Sophie , Thompson Claudette M. , Anderson Porter W. , Malley Richard
Published: March 2009

Cell wall polysaccharide (CWPS), pneumolysin, and surface adhesin A (PsaA) are antigens common to virtually all serotypes of
Streptococcus pneumoniae
(pneumococcus), and all have been studied separately for use in protection. Previously we showed that protection against nasopharyngeal (NP) colonization by intranasal vaccination of mice with killed pneumococci is mediated by T
H
17 cells and correlates with interleukin-17A (IL-17A) expression by T cells in vitro; we have also shown that CWPS and other species-common antigens protect against colonization by a similar mechanism. Here we made a fusion protein of PsaA with the pneumolysin nontoxic derivative PdT and then coupled CWPS to the fusion protein, aiming to enhance immune responses to all three antigens. When given intranasally with cholera toxin adjuvant, the fusion conjugate induced higher serum antibody titers and greater priming for IL-17A responses than an equimolar mixture of the three antigens. The conjugate administered intranasally protected mice against experimental NP colonization by a strain of serotype 6B, while mice immunized with the mixture or with bivalent conjugates were not protected. Subcutaneous immunization with the conjugate and alum adjuvant likewise induced higher antibody titers than the mixture, primed for IL-17A responses, and reduced colonization. The conjugate, but not the antigen mixture, fully protected mice from fatal pneumonia caused by a highly virulent serotype 3 strain. Thus, a covalent construct of three antigens common to all serotypes exhibits protection with both mucosal and systemic administration.
How the Microbial World Saved Evolution from the Scylla of Molecular Biology and the Charybdis of the Modern Synthesis
Authors: Woese Carl R. , Goldenfeld Nigel
Published: March 2009

In this commentary, we provide a personal overview of the conceptual history of microbiology and molecular biology over the course of the last hundred years, emphasizing the relationship of these fields to the problem of evolution. We argue that despite their apparent success, all three reached an impasse that arose from the influence of dogmatic or overly narrow perspectives. Finally, we describe how recent developments in microbiology are realizing Beijerinck's vision of a field that is fully integrated with molecular biology, microbial ecology, thereby challenging and extending current thinking in evolution.
A Gripping Tale of Ribosomal Frameshifting: Extragenic Suppressors of Frameshift Mutations Spotlight P-Site Realignment
Authors: Atkins John F. , Björk Glenn R.
Published: March 2009

Mutants of translation components which compensate for both −1 and +1 frameshift mutations showed the first evidence for framing malleability. Those compensatory mutants isolated in bacteria and yeast with altered tRNA or protein factors are reviewed here and are considered to primarily cause altered P-site realignment and not altered translocation. Though the first sequenced tRNA mutant which suppressed a +1 frameshift mutation had an extra base in its anticodon loop and led to a textbook “yardstick” model in which the number of anticodon bases determines codon size, this model has long been discounted, although not by all. Accordingly, the reviewed data suggest that reading frame maintenance and translocation are two distinct features of the ribosome. None of the −1 tRNA suppressors have anticodon loops with fewer than the standard seven nucleotides. Many of the tRNA mutants potentially affect tRNA bending and/or stability and can be used for functional assays, and one has the conserved C74 of the 3′ CCA substituted. The effect of tRNA modification deficiencies on framing has been particularly informative. The properties of some mutants suggest the use of alternative tRNA anticodon loop stack conformations by individual tRNAs in one translation cycle. The mutant proteins range from defective release factors with delayed decoding of A-site stop codons facilitating P-site frameshifting to altered EF-Tu/EF1α to mutant ribosomal large- and small-subunit proteins L9 and S9. Their study is revealing how mRNA slippage is restrained except where it is programmed to occur and be utilized.
Pivotal Roles of the Outer Membrane Polysaccharide Export and Polysaccharide Copolymerase Protein Families in Export of Extracellular Polysaccharides in Gram-Negative Bacteria
Authors: Cuthbertson Leslie , Mainprize Iain L. , Naismith James H. , Whitfield Chris
Published: March 2009

Many bacteria export extracellular polysaccharides (EPS) and capsular polysaccharides (CPS). These polymers exhibit remarkably diverse structures and play important roles in the biology of free-living, commensal, and pathogenic bacteria. EPS and CPS production represents a major challenge because these high-molecular-weight hydrophilic polymers must be assembled and exported in a process spanning the envelope, without compromising the essential barrier properties of the envelope. Emerging evidence points to the existence of molecular scaffolds that perform these critical polymer-trafficking functions. Two major pathways with different polymer biosynthesis strategies are involved in the assembly of most EPS/CPS: the Wzy-dependent and ATP-binding cassette (ABC) transporter-dependent pathways. They converge in an outer membrane export step mediated by a member of the outer membrane auxiliary (OMA) protein family. OMA proteins form outer membrane efflux channels for the polymers, and here we propose the revised name outer membrane polysaccharide export (OPX) proteins. Proteins in the polysaccharide copolymerase (PCP) family have been implicated in several aspects of polymer biogenesis, but there is unequivocal evidence for some systems that PCP and OPX proteins interact to form a trans-envelope scaffold for polymer export. Understanding of the precise functions of the OPX and PCP proteins has been advanced by recent findings from biochemistry and structural biology approaches and by parallel studies of other macromolecular trafficking events. Phylogenetic analyses reported here also contribute important new insight into the distribution, structural relationships, and function of the OPX and PCP proteins. This review is intended as an update on progress in this important area of microbial cell biology.
Biochemical Features and Functional Implications of the RNA-Based T-Box Regulatory Mechanism
Authors: Gutiérrez-Preciado Ana , Henkin Tina M. , Grundy Frank J. , Yanofsky Charles , Merino Enrique
Published: March 2009

The T-box mechanism is a common regulatory strategy used for modulating the expression of genes of amino acid metabolism-related operons in gram-positive bacteria, especially members of the Firmicutes. T-box regulation is usually based on a transcription attenuation mechanism in which an interaction between a specific uncharged tRNA and the 5′ region of the transcript stabilizes an antiterminator structure in preference to a terminator structure, thereby preventing transcription termination. Although single T-box regulatory elements are common, double or triple T-box arrangements are also observed, expanding the regulatory range of these elements. In the present study, we predict the functional implications of T-box regulation in genes encoding aminoacyl-tRNA synthetases, proteins of amino acid biosynthetic pathways, transporters, and regulatory proteins. We also consider the global impact of the use of this regulatory mechanism on cell physiology. Novel biochemical relationships between regulated genes and their corresponding metabolic pathways were revealed. Some of the genes identified, such as the quorum-sensing gene luxS, in members of the Lactobacillaceae were not previously predicted to be regulated by the T-box mechanism. Our analyses also predict an imbalance in tRNA sensing during the regulation of operons containing multiple aminoacyl-tRNA synthetase genes or biosynthetic genes involved in pathways common to more than one amino acid. Based on the distribution of T-box regulatory elements, we propose that this regulatory mechanism originated in a common ancestor of members of the Firmicutes, Chloroflexi, Deinococcus-Thermus group, and Actinobacteria and was transferred into the Deltaproteobacteria by horizontal gene transfer.
Environmental Proteomics: a Paradigm Shift in Characterizing Microbial Activities at the Molecular Level
Authors: Keller Martin , Hettich Robert
Published: March 2009

The increase in sequencing capacity led to a new wave of metagenomic projects, enabling and setting the prerequisite for the application of environmental proteomics technologies. This review describes the current status of environmental proteomics. It describes sample preparation as well as the two major technologies applied within this field: two-dimensional electrophoresis-based environmental proteomics and liquid chromatography-mass spectrometry-based environmental proteomics. It also highlights current publications and describes major scientific findings. The review closes with a discussion of critical improvements in the area of integrating experimental mass spectrometry technologies with bioinformatics as well as improved sample handling.
Eukaryotic Translesion Polymerases and Their Roles and Regulation in DNA Damage Tolerance
Authors: Waters Lauren S. , Minesinger Brenda K. , Wiltrout Mary Ellen , D'Souza Sanjay , Woodruff Rachel V. , Walker Graham C.
Published: March 2009

DNA repair and DNA damage tolerance machineries are crucial to overcome the vast array of DNA damage that a cell encounters during its lifetime. In this review, we summarize the current state of knowledge about the eukaryotic DNA damage tolerance pathway translesion synthesis (TLS), a process in which specialized DNA polymerases replicate across from DNA lesions. TLS aids in resistance to DNA damage, presumably by restarting stalled replication forks or filling in gaps that remain in the genome due to the presence of DNA lesions. One consequence of this process is the potential risk of introducing mutations. Given the role of these translesion polymerases in mutagenesis, we discuss the significant regulatory mechanisms that control the five known eukaryotic translesion polymerases: Rev1, Pol ζ, Pol κ, Pol η, and Pol ι.
Incidence rates of surgically treated idiopathic carpal tunnel syndrome in blue- and white-collar workers and housewives in Tuscany, Italy
Authors: Mattioli S , Baldasseroni A , Curti S , Cooke R M T , Mandes A , Zanardi F , Farioli A , Buiatti E , Campo G , Violante F S
Published: March 2009

Objectives:

Rates of surgically treated carpal tunnel syndrome (CTS) among blue- and white-collar workers and housewives in the general population were compared.

Methods:

Surgically treated cases of idiopathic CTS were investigated among 25–59-year-old residents of Tuscany, Italy, during 1997–2000, based on obligatory discharge records from all Italian public/private hospitals, archived according to residence on Tuscany’s regional database. Population data were extracted from the 2001 census.

Results:

After excluding repeat admissions, 8801 eligible cases were identified. Age-standardised rates (per 100 000 person-years) of surgical CTS were: “blue-collar women”, 367.8; “white-collar women”, 88.1; “housewives”, 334.5; “blue-collar men”, 73.5; and “white-collar men”, 15.3. Compared with reference categories (same-sex white-collar workers): female blue-collar workers experienced a 4.2-fold higher standardised rate; housewives, a 3.8-fold excess; and male blue-collar workers, a 4.8-fold excess (all p<0.001). Male and female blue-collar workers showed approximately three to sevenfold higher age-specific rates compared to their white-collar counterparts (all p<0.001). Housewives’ rates were similar to those of blue-collar female workers up to 40–44 years of age, after which they were significantly lower (p<0.002). At all ages, housewives’ rates were much higher (p<0.001) than those of white-collar women.

Conclusions:

Surgically treated CTS was three to seven times more common (depending on age/gender) in blue-collar than in white-collar workers, which is difficult to explain by differences in body weight or other individual factors. Thus, occupational risk factors seem relevant throughout working life. The high rates for full-time housewives suggest that domestic chores should be investigated as a possible risk factor for CTS.
Mortality among British asbestos workers undergoing regular medical examinations (1971–2005)
Authors: Harding A-H , Darnton A , Wegerdt J , McElvenny D
Published: March 2009

Objectives:

The Great Britain Asbestos Survey was established to monitor mortality among workers covered by regulations to control occupational exposure to asbestos. This study updates the estimated burden of asbestos-related mortality in the cohort, and identifies risk factors associated with mortality.

Methods:

From 1971, workers were recruited during initially voluntary and later statutory medical examinations. A brief questionnaire was completed during the medical, and participants were flagged for death registrations. Standardised mortality ratios (SMRs) and proportional mortality ratios (PMRs) were calculated for deaths occurring before 2006. Poisson regression analyses were undertaken for diseases with significant excess mortality.

Results:

There were 15 496 deaths among 98 117 workers followed-up for 1 779 580 person-years. The SMR for all cause mortality was 141 (95% CI 139 to 143) and for all malignant neoplasms 163 (95% CI 159 to 167). The SMRs for cancers of the stomach (166), lung (187), peritoneum (3730) and pleura (968), mesothelioma (513), cerebrovascular disease (164) and asbestosis (5594) were statistically significantly elevated, as were the corresponding PMRs. In age and sex adjusted analysis, birth cohort, age at first exposure, year of first exposure, duration of exposure, latency and job type were associated with the relative risk of lung, pleural and peritoneal cancers, asbestosis and mesothelioma mortality.

Conclusions:

Known associations between asbestos exposure and mortality from lung, peritoneal and pleural cancers, mesothelioma and asbestosis were confirmed, and evidence of associations with stroke and stomach cancer mortality was observed. Limited evidence suggested that asbestos-related disease risk may be lower among those first exposed in more recent times.
An analysis of latent semantic term self-correlation
Authors: Park Laurence A. F. , Ramamohanarao Kotagiri
Published: March 2009

Latent semantic analysis (LSA) is a generalized vector space method that uses dimension reduction to generate term correlations for use during the information retrieval process. We hypothesized that even though the dimension reduction establishes correlations between terms, the dimension reduction is causing a degradation in the correlation of a term to itself (self-correlation). In this article, we have proven that there is a direct relationship to the size of the LSA dimension reduction and the LSA self-correlation. We have also shown that by altering the LSA term self-correlations we gain a substantial increase in precision, while also reducing the computation required during the information retrieval process.
Textual analysis of stock market prediction using breaking financial news
Authors: Schumaker Robert P. , Chen Hsinchun
Published: March 2009

Our research examines a predictive machine learning approach for financial news articles analysis using several different textual representations: bag of words, noun phrases, and named entities. Through this approach, we investigated 9,211 financial news articles and 10,259,042 stock quotes covering the S&P 500 stocks during a five week period. We applied our analysis to estimate a discrete stock price twenty minutes after a news article was released. Using a support vector machine (SVM) derivative specially tailored for discrete numeric prediction and models containing different stock-specific variables, we show that the model containing both article terms and stock price at the time of article release had the best performance in closeness to the actual future stock price (MSE 0.04261), the same direction of price movement as the future price (57.1% directional accuracy) and the highest return using a simulated trading engine (2.06% return). We further investigated the different textual representations and found that a Proper Noun scheme performs better than the de facto standard of Bag of Words in all three metrics.
Conception and Experimentation of a Communication Device with Adaptive Scanning
Authors: Ghedira Souhir , Pino Pierre , Bourhis Guy
Published: March 2009

For some people with motor disabilities and speech disorders, the only way to communicate and to have some control over their environment is through the use of a controlled scanning system operated by a single switch. The main problem with these systems is that the communication process tends to be exceedingly slow, since the system must scan through the available choices one at a time until the desired message is reached. One way of raising the speed of message selection is to optimize the elementary scanning delay in real time so that it allows the user to make selections as quickly as possible without making too many errors. With this objective in mind, this article presents a method for optimizing the scanning delay, which is based on an analysis of the data recorded in “log files” while applying the EDiTH system [Digital Teleaction Environment for People with Disabilities]. This analysis makes it possible to develop a human-machine interaction model specific to the study, and then to establish an adaptive algorithm for the calculation of the scanning delay. The results obtained with imposed scenarios and then in ecological situations provides a confirmation that our algorithms are effective in dynamically adapting a scan speed. The main advantage offered by the procedure proposed is that it works on timing information alone and thus does not require any knowledge of the scanning device itself. This allows it to work with any scanning device.
Evaluating the STANDUP Pun Generating Software with Children with Cerebral Palsy
Authors: Waller Annalu , Black Rolf , O’Mara David A. , Pain Helen , Ritchie Graeme , Manurung Ruli
Published: March 2009

The interactive STANDUP software was developed to provide children who use augmentative and alternative communication (AAC) with a “language playground.” The software provides appropriate functionality for users with physical, speech, and language impairments to generate and tell novel punning riddles at different levels of complexity. STANDUP was evaluated with nine children with cerebral palsy during an eight-week study. Results show that the participants were able to generate and tell novel jokes with minimal or no support. The use of STANDUP impacted favorably on general AAC use. The study results also suggested that STANDUP could potentially have a positive effect on social and pragmatic skills. Further research to investigate the impact of STANDUP on communication skills is proposed. Suggestions for future software development include providing users with opportunities to complete jokes and to integrate online dictionaries when new vocabulary is encountered.
A type system for data-flow integrity on Windows Vista
Authors: Chaudhuri Avik , Naldurg Prasad , Rajamani Sriram
Published: March 2009

The Windows Vista operating system implements an interesting model of multi-level integrity. We observe that in this model, trusted code must participate in any information-flow attack. Thus, it is possible to eliminate such attacks by statically restricting trusted code. We formalize this model by designing a type system that can efficiently enforce data-flow integrity on Windows Vista. Typechecking guarantees that objects whose contents are statically trusted never contain untrusted values, regardless of what untrusted code runs in the environment. Some of Windows Vista's runtime access checks are necessary for soundness; others are redundant and can be optimized away.
Verified enforcement of stateful information release policies
Authors: Swamy Nikhil , Hicks Michael
Published: March 2009

Many organizations specify information release policies to describe the terms under which sensitive information may be released to other organizations. This paper presents a new approach for ensuring that security-critical software correctly enforces its information release policy. Our approach has two parts. First, an information release policy is specified as a security automaton written in a new language called AIR. Second, we enforce an AIR policy by translating it into an API for programs written in lAIR, a core formalism for a functional programming language. lAIR uses a novel combination of dependent, affine, and singleton types to ensure that the API is used correctly. As a consequence we can certify that programs written in lAIR meet the requirements of the original AIR policy specification.
Programming languages and program analysis for security
Authors: Pistoia Marco , Erlingsson Úlfar
Published: March 2009

Software security has been traditionally enforced at the level of operating systems. However, operating systems have become increasingly large and complex, and it is very difficult--if not impossible--to enforce software security solely through them. Moreover, operating-system security allows dealing primarily with access-control policies on resources such as files and network connections. However, attacks may happen at both lower and higher levels of abstraction, and may target the internal behavior of applications, such as today's Web-based applications. Therefore, defenses must offer protection at the level of applications. Language-based security is the area of research that studies how to enforce application-level security using programming-language and program-analysis techniques. This area of research has become very active with the advent of Web applications. In 2006, the ACM SIGPLAN has introduced a new yearly forum entirely dedicated to the discussion of language-based-security research: Programming Languages and Analysis for Security (PLAS). This paper is a three-year survey of PLAS papers that discusses the progress made in the area of language-based security.
Frequency of Myocardial Bridges and Dynamic Compression of Epicardial Coronary Arteries
Authors: Kim Pyung Jin , Hur Gham , Kim Su Young , Namgung June , Hong Seong Wan , Kim Yong Hoon , Lee Won Ro
Published: March 2009

Background—

The objective of the present study was to describe the relative frequency of myocardial bridging and dynamic compression of the coronary arteries as assessed by CT angiography and conventional angiography.

Methods and Results—

A total of 311 patients (208 men, 103 women; mean age 63 years) who received both 64-section CT angiography and conventional angiography were reviewed retrospectively for myocardial bridging of the left anterior descending coronary artery. Myocardial bridging was considered when the left anterior descending coronary artery was within the interventricular gorge and was classified as either myocardial bridging with partial encasement or myocardial bridging with full encasement, according to the extent of vessel encasement by the myocardium. The length, location, and depth of myocardial bridging were correlated with the presence, length, and degree of dynamic compression observed at conventional angiography. Among the 300 patients studied (11 were excluded), myocardial bridging was observed at CT angiography in 174 (58%) as partial encasement (n=57) or full encasement (n=117). Conventional angiography revealed dynamic compression in 40 patients (13.3%; partial encasement in 1 patient and full encasement in 39). The length of the dynamic compression was considerably longer than the respective tunneled segment in all patients. Total length correlated (
P
=0.003) with the dynamic compression, but depth did not (
P
=0.283).

Conclusions—

The frequency of myocardial bridging observed by CT angiography was 58%, and conventional angiography revealed dynamic compression in 13.3% of total patients. Dynamic compression occurred almost exclusively (97.5% of the time) in patients with full encasement of the left anterior descending coronary artery, regardless of the presence of overlying muscle.
Resolution of Established Cardiac Hypertrophy and Fibrosis and Prevention of Systolic Dysfunction in a Transgenic Rabbit Model of Human Cardiomyopathy Through Thiol-Sensitive Mechanisms
Authors: Lombardi Raffaella , Rodriguez Gabriela , Chen Suet Nee , Ripplinger Crystal M. , Li Wenwen , Chen Junjie , Willerson James T. , Betocchi Sandro , Wickline Samuel A. , Efimov Igor R. , Marian Ali J.
Published: March 2009

Background—

Cardiac hypertrophy, the clinical hallmark of hypertrophic cardiomyopathy (HCM), is a major determinant of morbidity and mortality not only in HCM but also in a number of cardiovascular diseases. There is no effective therapy for HCM and generally for cardiac hypertrophy. Myocardial oxidative stress and thiol-sensitive signaling molecules are implicated in pathogenesis of hypertrophy and fibrosis. We posit that treatment with
N
-acetylcysteine, a precursor of glutathione, the largest intracellular thiol pool against oxidative stress, could reverse cardiac hypertrophy and fibrosis in HCM.

Methods and Results—

We treated 2-year-old β-myosin heavy-chain Q403 transgenic rabbits with established cardiac hypertrophy and preserved systolic function with
N
-acetylcysteine or a placebo for 12 months (n=10 per group). Transgenic rabbits in the placebo group had cardiac hypertrophy, fibrosis, systolic dysfunction, increased oxidized to total glutathione ratio, higher levels of activated thiol-sensitive active protein kinase G, dephosphorylated nuclear factor of activated T cells (NFATc1) and phospho-p38, and reduced levels of glutathiolated cardiac α-actin. Treatment with
N
-acetylcysteine restored oxidized to total glutathione ratio, normalized levels of glutathiolated cardiac α-actin, reversed cardiac and myocyte hypertrophy and interstitial fibrosis, reduced the propensity for ventricular arrhythmias, prevented cardiac dysfunction, restored myocardial levels of active protein kinase G, and dephosphorylated NFATc1 and phospho-p38.

Conclusions—

Treatment with
N
-acetylcysteine, a safe prodrug against oxidation, reversed established cardiac phenotype in a transgenic rabbit model of human HCM. Because there is no effective pharmacological therapy for HCM and given that hypertrophy, fibrosis, and cardiac dysfunction are common and major predictors of clinical outcomes, the findings could have implications in various cardiovascular disorders.
Divergent Tumor Necrosis Factor Receptor–Related Remodeling Responses in Heart Failure
Authors: Hamid Tariq , Gu Yan , Ortines Roger V. , Bhattacharya Chhandashri , Wang Guangwu , Xuan Yu-Ting , Prabhu Sumanth D.
Published: March 2009

Background—

Although preclinical data suggested that tumor necrosis factor-α (TNF) neutralization in heart failure (HF) would be beneficial, clinical trials of TNF antagonists were paradoxically negative. We hypothesized that TNF induces opposing inflammatory and remodeling responses in HF that are TNF-receptor (TNFR) specific.

Methods and Results—

HF was induced in wild-type (WT), TNFR1
−/−
, and TNFR2
−/−
mice via coronary ligation. Compared with WT HF, 4-week postinfarction survival was significantly improved in both TNFR1
−/−
and TNFR2
−/−
HF. Compared with sham, WT HF hearts exhibited significant remodeling with robust activation of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase, and JNK2 and upregulation of TNF, interleukin (IL)-1β, IL-6, and IL-10. Compared with WT HF, TNFR1
−/−
HF exhibited (1) improved remodeling, hypertrophy, and contractile function; (2) less apoptosis; and (3) diminished NF-κB, p38 mitogen-activated protein kinase, and JNK2 activation and cytokine expression. In contrast, TNFR2
−/−
HF showed exaggerated remodeling and hypertrophy, increased border zone fibrosis, augmented NF-κB and p38 mitogen-activated protein kinase activation, higher IL-1β and IL-6 gene expression, greater activated macrophages, and greater apoptosis. Oxidative stress and diastolic function were improved in both TNFR1
−/−
and TNFR2
−/−
HF. In H9c2 cardiomyocytes, sustained NF-κB activation was proapoptotic, an effect dependent on TNFR1 signaling, whereas TNFR2 overexpression attenuated TNF-induced NF-κB activation.

Conclusions—

TNFR1 and TNFR2 have disparate and opposing effects on remodeling, hypertrophy, NF-κB, inflammation, and apoptosis in HF: TNFR1 exacerbates, whereas TNFR2 ameliorates, these events. However, signaling through both receptors is required to induce diastolic dysfunction and oxidative stress. TNFR-specific effects in HF should be considered when therapeutic anti-TNF strategies are developed.
Impact of Proteinuria and Glomerular Filtration Rate on Risk of Thromboembolism in Atrial Fibrillation
Authors: Go Alan S. , Fang Margaret C. , Udaltsova Natalia , Chang Yuchiao , Pomernacki Niela K. , Borowsky Leila , Singer Daniel E.
Published: March 2009

Background—

Atrial fibrillation (AF) substantially increases the risk of ischemic stroke, but this risk varies among individual patients with AF. Existing risk stratification schemes have limited predictive ability. Chronic kidney disease is a major cardiovascular risk factor, but whether it independently increases the risk for ischemic stroke in persons with AF is unknown.

Methods and Results—

We examined how chronic kidney disease (reduced glomerular filtration rate or proteinuria) affects the risk of thromboembolism off anticoagulation in patients with AF. We estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation and proteinuria from urine dipstick results found in laboratory databases. Patient characteristics, warfarin use, and thromboembolic events were ascertained from clinical databases, with validation of thromboembolism by chart review. During 33 165 person-years off anticoagulation among 10 908 patients with AF, we observed 676 incident thromboembolic events. After adjustment for known risk factors for stroke and other confounders, proteinuria increased the risk of thromboembolism by 54% (relative risk, 1.54; 95% CI, 1.29 to 1.85), and there was a graded, increased risk of stroke associated with a progressively lower level of estimated glomerular filtration rate compared with a rate ≥60 mL · min
−1
· 1.73 m
−2
: relative risk of 1.16 (95% CI, 0.95 to 1.40) for estimated glomerular filtration rate of 45 to 59 mL · min
−1
· 1.73 m
−2
and 1.39 (95% CI, 1.13 to 1.71) for estimated glomerular filtration rate <45 mL · min
−1
· 1.73 m
−2
(
P
=0.0082 for trend).

Conclusions—

Chronic kidney disease increases the risk of thromboembolism in AF independently of other risk factors. Knowing the level of kidney function and the presence of proteinuria may improve risk stratification for decision making about the use of antithrombotic therapy for stroke prevention in AF.
Effects of Regional Dysfunction and Late Gadolinium Enhancement on Global Right Ventricular Function and Exercise Capacity in Patients With Repaired Tetralogy of Fallot
Authors: Wald Rachel M. , Haber Idith , Wald Ron , Valente Anne Marie , Powell Andrew J. , Geva Tal
Published: March 2009

Background—

The underlying mechanisms that contribute to global right ventricular (RV) dysfunction in patients with repaired tetralogy of Fallot are incompletely understood. We therefore sought to quantify regional RV abnormalities and to determine the relationship of these to global RV function and exercise capacity.

Methods and Results—

Clinical and cardiac magnetic resonance data from 62 consecutive patients with repaired tetralogy of Fallot were analyzed (median age at follow-up 23 years [limits 9 to 67 years]). Using cardiac magnetic resonance data, 3D RV endocardial surface models were reconstructed from segmented contours, and a correspondence between end diastole and end systole was computed with a novel algorithm. Regional RV abnormalities were quantified and expressed as segmental ejection fraction, spatial extent of dyskinetic area, displacement of dyskinetic area, and score of extent of late gadolinium enhancement. Regional abnormalities of function and hyperenhancement were greatest in the RV outflow tract (RVOT). These regional RVOT abnormalities correlated with global RV ejection fraction: RVOT ejection fraction
r
=0.64,
P
<0.0001; RVOT dyskinetic area
r
=−0.51,
P
<0.0001; RVOT displacement of dyskinetic area
r
=−0.49,
P
<0.0001; and RVOT late gadolinium enhancement score
r
=−0.33,
P
=0.01. Peak oxygen consumption during exercise correlated best with RVOT ejection fraction (
r
=0.56,
P
=0.0002) compared with the remainder of the RV (
r
=0.35,
P
=0.03). The only cardiac magnetic resonance variable independently predictive of aerobic capacity was RVOT ejection fraction (
P
=0.02).

Conclusion—

A greater extent of regional abnormalities in the RVOT adversely affects global RV function and exercise capacity after tetralogy of Fallot repair. These regional measures may have important implications for patient management, including RVOT reconstruction, at the time of pulmonary valve replacement.