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Showing papers by "University of New South Wales published in 2006"



Journal ArticleDOI
TL;DR: In this article, the superiority of guided instruction is explained in the context of our knowledge of human cognitive architecture, expert-novice differences, and cognitive load, and it is shown that the advantage of guidance begins to recede only when learners have sufficiently high prior knowledge to provide "internal" guidance.
Abstract: Evidence for the superiority of guided instruction is explained in the context of our knowledge of human cognitive architecture, expert–novice differences, and cognitive load. Although unguided or minimally guided instructional approaches are very popular and intuitively appealing, the point is made that these approaches ignore both the structures that constitute human cognitive architecture and evidence from empirical studies over the past half-century that consistently indicate that minimally guided instruction is less effective and less efficient than instructional approaches that place a strong emphasis on guidance of the student learning process. The advantage of guidance begins to recede only when learners have sufficiently high prior knowledge to provide "internal" guidance. Recent developments in instructional research and instructional design models that support guidance during instruction are briefly described.

5,199 citations



Journal ArticleDOI
TL;DR: In this paper, a review of more than 300 publications on membrane bioreactor fouling is presented, and the authors propose updated definitions of key parameters such as critical and sustainable flux, along with standard methods to determine and measure the different fractions of the biomass.

2,113 citations


Journal ArticleDOI
TL;DR: Episodic antiretroviral therapy guided by the CD4+ count significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antireteviral therapy, largely as a consequence of lowering theCD4+ cell count and increasing the viral load.
Abstract: Methods We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. Results A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P = 0.007) and 1.7 (95% CI, 1.1 to 2.5; P = 0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). Conclusions Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352.)

1,999 citations


Journal ArticleDOI
TL;DR: This review describes for the practitioner the essential features of line‐fitting methods for estimating the relationship between two variables: what methods are commonly used, which method should be used when, and how to make inferences from these lines to answer common research questions.
Abstract: Fitting a line to a bivariate dataset can be a deceptively complex problem, and there has been much debate on this issue in the literature. In this review, we describe for the practitioner the essential features of line-fitting methods for estimating the relationship between two variables: what methods are commonly used, which method should be used when, and how to make inferences from these lines to answer common research questions. A particularly important point for line-fitting in allometry is that usually, two sources of error are present (which we call measurement and equation error), and these have quite different implications for choice of line-fitting method. As a consequence, the approach in this review and the methods presented have subtle but important differences from previous reviews in the biology literature. Linear regression, major axis and standardised major axis are alternative methods that can be appropriate when there is no measurement error. When there is measurement error, this often needs to be estimated and used to adjust the variance terms in formulae for line-fitting. We also review line-fitting methods for phylogenetic analyses. Methods of inference are described for the line-fitting techniques discussed in this paper. The types of inference considered here are testing if the slope or elevation equals a given value, constructing confidence intervals for the slope or elevation, comparing several slopes or elevations, and testing for shift along the axis amongst several groups. In some cases several methods have been proposed in the literature. These are discussed and compared. In other cases there is little or no previous guidance available in the literature. Simulations were conducted to check whether the methods of inference proposed have the intended coverage probability or Type I error. We identified the methods of inference that perform well and recommend the techniques that should be adopted in future work.

1,952 citations


Posted Content
TL;DR: In this paper, the short run interdependence of prices and price volatility across three major international stock markets is studied using the autoregressive conditionally heteroskedastic (ARCH) family of statistical models.
Abstract: The short-run interdependence of prices and price volatility across three major international stock markets is studied. Daily opening and closing prices of major stock indexes for the Tokyo, London, and New York stock markets are examined. The analysis utilizes the autoregressive conditionally heteroskedastic (ARCH family of statistical models to explore these pricing relationships. Evidence of price volatility spillovers from New York to Tokyo, London to Tokyo, and New, York to London is observed but no price volatility spillover effects in other directions are found for the pre-October 1987 period.

1,780 citations


Journal ArticleDOI
TL;DR: The evolution of virulence is linked to bacterial sex because rates of evolution have accelerated in pathogenic lineages, culminating in highly virulent organisms whose genomic contents are altered frequently by increased rates of homologous recombination.
Abstract: Summary Pathogenic Escherichia coli cause over 160 million cases of dysentery and one million deaths per year, whereas non-pathogenic E. coli constitute part of the normal intestinal flora of healthy mammals and birds. The evolutionary pathways underlying this dichotomy in bacterial lifestyle were investigated by multilocus sequence typing of a global collection of isolates. Specific pathogen types (enterohaemorrhagic E. coli , enteropathogenic E. coli , enteroinvasive E. coli , K1 and Shigella ) have arisen independently and repeat- edly in several lineages, whereas other lineages con- tain only few pathogens. Rates of evolution have accelerated in pathogenic lineages, culminating in highly virulent organisms whose genomic contents are altered frequently by increased rates of homolo- gous recombination; thus, the evolution of virulence is linked to bacterial sex. This long-term pattern of evolution was observed in genes distributed through- out the genome, and thereby is the likely result of episodic selection for strains that can escape the host immune response.

1,773 citations


Journal ArticleDOI
TL;DR: In a qualitative framework, research based on interviews often seeks to penetrate social life beyond appearance and manifest meanings as mentioned in this paper, which requires the researcher to be immersed in the research field, to establish continuing, fruitful relationships with respondents and through theoretical contemplation to address the research problem in depth.
Abstract: In a qualitative framework, research based on interviews often seeks to penetrate social life beyond appearance and manifest meanings. This requires the researcher to be immersed in the research field, to establish continuing, fruitful relationships with respondents and through theoretical contemplation to address the research problem in depth. Therefore a small number of cases (less than 20, say) will facilitate the researcher’s close association with the respondents, and enhance the validity of fine-grained, in-depth inquiry in naturalistic settings. Epistemologically prior to these considerations, however, is the explanatory status of such research. From a realist standpoint, here concept formation through induction and analysis aims to clarify the nature of some specific situations in the social world, to discover what features there are in them and to account, however partially, for those features being as they are. Since such a research project scrutinizes the dynamic qualities of a situation (rathe...

1,539 citations


Journal ArticleDOI
TL;DR: Cell surface expression of CD127 allows accurate estimation of T reg cell numbers and isolation of pure populations for in vitro studies and should contribute to the understanding of regulatory abnormalities in immunopathic diseases.
Abstract: Abnormalities in CD4+CD25+Foxp3+ regulatory T (T reg) cells have been implicated in susceptibility to allergic, autoimmune, and immunoinflammatory conditions. However, phenotypic and functional assessment of human T reg cells has been hampered by difficulty in distinguishing between CD25-expressing activated and regulatory T cells. Here, we show that expression of CD127, the α chain of the interleukin-7 receptor, allows an unambiguous flow cytometry–based distinction to be made between CD127lo T reg cells and CD127hi conventional T cells within the CD25+CD45RO+RA− effector/memory and CD45RA+RO− naive compartments in peripheral blood and lymph node. In healthy volunteers, peripheral blood CD25+CD127lo cells comprised 6.35 ± 0.26% of CD4+ T cells, of which 2.05 ± 0.14% expressed the naive subset marker CD45RA. Expression of FoxP3 protein and the CD127lo phenotype were highly correlated within the CD4+CD25+ population. Moreover, both effector/memory and naive CD25+CD127lo cells manifested suppressive activity in vitro, whereas CD25+CD127hi cells did not. Cell surface expression of CD127 therefore allows accurate estimation of T reg cell numbers and isolation of pure populations for in vitro studies and should contribute to our understanding of regulatory abnormalities in immunopathic diseases.

1,517 citations


Journal ArticleDOI
TL;DR: Using a sample of U.K. wire makers, a model in which personality and work environment antecedents affect proactive work behavior via cognitive-motivational mechanisms was tested and positive self-reported proactive work behaviors were validated against rater assessments.
Abstract: Using a sample of U.K. wire makers (N = 282), the authors tested a model in which personality and work environment antecedents affect proactive work behavior via cognitive-motivational mechanisms. Self-reported proactive work behaviors (proactive idea implementation and proactive problem solving) were validated against rater assessments for a subsample (n = 60) of wire makers. With the exception of supportive supervision, each antecedent was important, albeit through different processes. Proactive personality was significantly associated with proactive work behavior via role breadth self-efficacy and flexible role orientation, job autonomy was also linked to proactive behavior via these processes, as well as directly; and coworker trust was associated with proactive behavior via flexible role orientation. In further support of the model, the cognitive-motivational processes for proactive work behavior differed from those for the more passive outcome of generalized compliance.

Journal ArticleDOI
TL;DR: These definitions, guidelines, and recommendations, based upon current best evidence and expert opinion are proposed to assist clinicians in the management of IAH and ACS as well as serve as a reference for future clinical and basic science research.
Abstract: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been increasingly recognized in the critically ill over the past decade. In the absence of consensus definitions and treatment guidelines the diagnosis and management of IAH and ACS remains variable from institution to institution. An international consensus group of multidisciplinary critical care specialists convened at the second World Congress on Abdominal Compartment Syndrome to develop practice guidelines for the diagnosis, management, and prevention of IAH and ACS. Prior to the conference the authors developed a blueprint for consensus definitions and treatment guidelines which were refined both during and after the conference. The present article is the second installment of the final report from the 2004 International ACS Consensus Definitions Conference and is endorsed by the World Society of the Abdominal Compartment Syndrome. The prevalence and etiological factors for IAH and ACS are reviewed. Evidence-based medicine treatment guidelines are presented to facilitate the diagnosis and management of IAH and ACS. Recommendations to guide future studies are proposed. These definitions, guidelines, and recommendations, based upon current best evidence and expert opinion are proposed to assist clinicians in the management of IAH and ACS as well as serve as a reference for future clinical and basic science research.

Journal ArticleDOI
01 Jan 2006
TL;DR: Results demonstrate the feasibility of implementing an accelerometry-based, real-time movement classifier using embedded intelligence.
Abstract: The real-time monitoring of human movement can provide valuable information regarding an individual's degree of functional ability and general level of activity. This paper presents the implementation of a real-time classification system for the types of human movement associated with the data acquired from a single, waist-mounted triaxial accelerometer unit. The major advance proposed by the system is to perform the vast majority of signal processing onboard the wearable unit using embedded intelligence. In this way, the system distinguishes between periods of activity and rest, recognizes the postural orientation of the wearer, detects events such as walking and falls, and provides an estimation of metabolic energy expenditure. A laboratory-based trial involving six subjects was undertaken, with results indicating an overall accuracy of 90.8% across a series of 12 tasks (283 tests) involving a variety of movements related to normal daily activities. Distinction between activity and rest was performed without error; recognition of postural orientation was carried out with 94.1% accuracy, classification of walking was achieved with less certainty (83.3% accuracy), and detection of possible falls was made with 95.6% accuracy. Results demonstrate the feasibility of implementing an accelerometry-based, real-time movement classifier using embedded intelligence

Journal ArticleDOI
TL;DR: In this article, the spectral kurtosis (SK) was used to detect and characterize nonstationary signals in the presence of strong masking noise and to detect incipient faults in rotating machines.

Journal ArticleDOI
20 Dec 2006-JAMA
TL;DR: Comparing the incidence of cancer in patients receiving immune suppression after kidney transplantation with incidence in the same population in 2 periods before receipt of immune suppression suggests a broader than previously appreciated role of the interaction between the immune system and common viral infections in the etiology of cancer.
Abstract: ContextImmune suppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer and a few virus-associated cancers. Although it is generally accepted that other cancers do not occur at increased rates, there have been few long-term population-based cohort studies performed.ObjectiveTo compare the incidence of cancer in patients receiving immune suppression after kidney transplantation with incidence in the same population in 2 periods before receipt of immune suppression: during dialysis and during end-stage kidney disease before renal replacement therapy (RRT).Design, Setting, and ParticipantsA population-based cohort study of 28 855 patients with end-stage kidney disease who received RRT, with 273 407 person-years of follow-up. Incident cancers (1982-2003) were ascertained by record linkage between the Australia and New Zealand Dialysis and Transplant Registry and the Australian National Cancer Statistics Clearing House.Main Outcome MeasureStandardized incidence ratios (SIRs) of cancer, using age-specific, sex-specific, calendar year–specific, and state/territory–specific population cancer incidence rates.ResultsThe overall incidence of cancer, excluding nonmelanoma skin cancer and those cancers known to frequently cause end-stage kidney disease, was markedly increased after transplantation (n = 1236; SIR, 3.27; 95% confidence interval [CI], 3.09-3.46). In contrast, cancer incidence was only slightly increased during dialysis (n = 870; SIR, 1.35; 95% CI, 1.27-1.45) and before RRT (n = 689; SIR, 1.16; 95% CI, 1.08-1.25). After transplantation, cancer occurred at significantly increased incidence at 25 sites, and risk exceeded 3-fold at 18 of these sites. Most of these cancers were of known or suspected viral etiology.ConclusionsKidney transplantation is associated with a marked increase in cancer risk at a wide variety of sites. Because SIRs for most types of cancer were not increased before transplantation, immune suppression may be responsible for the increased risk. These data suggest a broader than previously appreciated role of the interaction between the immune system and common viral infections in the etiology of cancer.

Posted Content
TL;DR: The authors examined the information transmission mechanism linking oil futures with stock prices, where they examined the lead and lag cross-correlations of returns in one market with the others and investigated the dynamic interactions between oil futures prices traded on the New York Mercantile Exchange (NYMEX) and US stock prices.
Abstract: This study analyzes the information transmission mechanism linking oil futures with stock prices, where we examine the lead and lag cross-correlations of returns in one market with the others We investigate the dynamic interactions between oil futures prices traded on the New York Mercantile Exchange (NYMEX) and US stock prices, which allows us to examine the effects of energy shocks on financial markets In particular, we examine the extent to which these markets are contemporaneously correlated, with particular attention paid to the association of oil price indexes with the SP 12 major industry stock price indices and 3 individual oil company stock price series We also examine the extent to which price changes or returns in one market dynamically lead returns in the others and whether volatility spillover effects exist across these markets Using VAR model estimates for various time series of returns we find that petroleum industry stock index and our three oil company stocks are the only series where we can reject the null hypothesis that oil futures do not lead Treasury Bill rates and stock returns, while we can reject the hypothesis that oil futures lag these other two series Finally, the return volatility evidence for oil futures leading individual oil company stocks is much weaker than is the evidence for returns themselves

Journal ArticleDOI
TL;DR: Experiments with P. aeruginosa strains indicated that the extracellular DNA is generated via a mechanism which is dependent on acyl homoserine lactone and Pseudomonas quinolone signalling, as well as on flagella and type IV pili.
Abstract: Pseudomonas aeruginosa produces extracellular DNA which functions as a cell-to-cell interconnecting matrix component in biofilms. Comparison of extracellular DNA and chromosomal DNA by the use of polymerase chain reaction and Southern analysis suggested that the extracellular DNA is similar to whole-genome DNA. Evidence that the extracellular DNA in P. aeruginosa biofilms and cultures is generated via lysis of a subpopulation of the bacteria was obtained through experiments where extracellular ?-galactosidase released from lacZ-containing P. aeruginosa strains was assessed. Experiments with the wild type and lasIrhlI, pqsA, pqsL and fliMpilA mutants indicated that the extracellular DNA is generated via a mechanism which is dependent on acyl homoserine lactone and Pseudomonas quinolone signalling, as well as on flagella and type IV pili. Microscopic investigation of flow chamber-grown wild-type P. aeruginosa biofilms stained with different DNA stains suggested that the extracellular DNA is located primarily in the stalks of mushroom-shaped multicellular structures, with a high concentration especially in the outer part of the stalks forming a border between the stalk-forming bacteria and the cap-forming bacteria. Biofilms formed by lasIrhlI, pqsA and fliMpilA mutants contained less extracellular DNA than biofilms formed by the wild type, and the mutant biofilms were more susceptible to treatment with sodium dodecyl sulphate than the wild-type biofilm

Journal ArticleDOI
TL;DR: The fundamental understanding of properties of inorganic nanoparticles in relation to cellular delivery efficiency as the most paramount issue will be highlighted and some key issues in efficient cellular delivery using in organic nanoparticles are highlighted.

Journal ArticleDOI
TL;DR: Compared to fathering, mothering involves not only more overall time commitment but more multitasking, more physical labor, a more rigid timetable, more time alone with children, and more overall responsibility for managing care.
Abstract: This article uses diary data from the most recent Australian Bureau of Statistics Time Use Survey (N > 4,000) to compare by gender total child care time calculated in the measurements of (1) main activity, (2) main or secondary activity, and (3) total time spent in the company of children. It also offers an innovative gender comparison of relative time spent in (1) the activities that constitute child care, (2) child care as double activity, and (3) time with children in sole charge. These measures give a fuller picture of total time commitment to children and how men and women spend that time than has been available in previous time use analyses. The results indicate that compared to fathering, mothering involves not only more overall time commitment but more multitasking, more physical labor, a more rigid timetable, more time alone with children, and more overall responsibility for managing care. These gender differences in the quantity and nature of care apply even when women work full-time.

Journal ArticleDOI
TL;DR: A systematic review was conducted of longitudinal studies of acute hepatitis C infection to improve the precision of the estimated rate of spontaneous viral clearance, and factors associated with viral clearance were female gender and acute clinical hepatitis C study population.
Abstract: A large number of studies have reported on spontaneous viral clearance rates in acute hepatitis C infection, however most have been small, and reported rates have varied quite widely To improve the precision of the estimated rate of spontaneous viral clearance, a systematic review was conducted of longitudinal studies Factors associated with viral clearance were also examined Inclusion criteria for studies were: longitudinal assessment from time of acute hepatitis C; hepatitis C virus RNA analysis as determinant of viral clearance; untreated for acute hepatitis C Information on study population, and factors that may influence viral clearance were extracted from each study Viral clearance was defined among individuals with at least 6 months follow-up following acute hepatitis C The number of subjects with viral clearance was expressed as a proportion for each study and a weighted mean for proportion was calculated A total of 31 studies were examined Study populations included nine studies of post-transfusion hepatitis, 19 of acute clinical hepatitis, and three of sero-incident cases In total, data was available for 675 subjects and the mean study population was 22 (range 4-67) The proportion with viral clearance ranged from 00 to 08, with a weighted mean of 026 (95% CI 022-029) Factors associated with viral clearance were female gender and acute clinical hepatitis C study population Further studies are required to more clearly define predictors of clearance and guide therapeutic intervention strategies

Journal ArticleDOI
TL;DR: In this article, the authors examined the relationship between audit quality and long audit partner tenure and found a lower propensity to issue a going-concern opinion and some evidence of just beating (missing) earnings benchmarks.
Abstract: Rotation of audit partners is one of the main policy initiatives that has been implemented in many jurisdictions around the world to deal with concerns about audit quality. The basis of any requirement limiting the tenure of audit partners is that there is a reduction in audit quality associated with long periods of tenure. Using data from Australia, where the audit partner can be identified and for a period where partner rotation was not mandatory, we examine the association between audit quality and long audit partner tenure. The three measures of audit quality examined are the auditor's propensity to issue a going‐concern audit opinion for distressed companies, the direction and amount of abnormal working capital accruals, and just beating (missing) earnings benchmarks. For long tenure observations we find a lower propensity to issue a going‐concern opinion and some evidence of just beating (missing) earnings benchmarks, consistent with deterioration in audit quality associated with long audit partner ...

Journal ArticleDOI
TL;DR: A new sports injury research framework is proposed, the Translating Research into Injury Prevention Practice framework, or TRIPP, which builds on the fact that only research that can, and will, be adopted by sports participants, their coaches and sporting bodies will prevent injuries.

Journal ArticleDOI
TL;DR: In this paper, the authors investigate the influence of the extent of service employees' display of positive emotions and the authenticity of their emotional labor display on customers' emotional states and subsequently, customers' assessments of the service interaction and their relationship with the service provider.
Abstract: In this study, the authors examine the effects of two facets of employee emotions on customers' assessments of service encounters. Drawing on emotional contagion and emotional labor theories, they investigate the influence of the extent of service employees' display of positive emotions and the authenticity of their emotional labor display on customers' emotional states and, subsequently, on customers' assessments of the service interaction and their relationship with the service provider. To test the study hypotheses, 223 consumers participated in a simulated service encounter in which actors played the roles of service employees. In a 2 × 2 factorial design, the employees varied both the extent of their smiling behavior and their emotional labor display by engaging in surface or deep acting. The results show that the authenticity of employees' emotional labor display directly affects customers' emotional states. However, contrary to expectations, the extent of employee smiling does not influenc...

Journal ArticleDOI
TL;DR: In this article, basic properties and recent developments of Chebyshev expansion-based algorithms and the kernel polynomial method are reviewed, and an illustration on how the k-means algorithm is successfully embedded into other numerical techniques, such as cluster perturbation theory or Monte Carlo simulation, is provided.
Abstract: Efficient and stable algorithms for the calculation of spectral quantities and correlation functions are some of the key tools in computational condensed-matter physics. In this paper basic properties and recent developments of Chebyshev expansion based algorithms and the kernel polynomial method are reviewed. Characterized by a resource consumption that scales linearly with the problem dimension these methods enjoyed growing popularity over the last decade and found broad application not only in physics. Representative examples from the fields of disordered systems, strongly correlated electrons, electron-phonon interaction, and quantum spin systems are discussed in detail. In addition, an illustration on how the kernel polynomial method is successfully embedded into other numerical techniques, such as cluster perturbation theory or Monte Carlo simulation, is provided.

Journal ArticleDOI
TL;DR: In this paper, the application of rare-earth-doped inorganic materials for achieving external quantum efficiencies greater than unity and enhancing the conversion efficiency of silicon solar cells was examined, and the opportunities for the DC of high-energy solar photons to multiple photons with energy greater than the silicon bandgap were discussed.

Journal ArticleDOI
TL;DR: This review addresses the structure, function, and stability of cold-adapted enzymes, highlighting the challenges for immediate and future consideration.
Abstract: By far the largest proportion of the Earth's biosphere is comprised of organisms that thrive in cold environments (psychrophiles). Their ability to proliferate in the cold is predicated on a capacity to synthesize cold-adapted enzymes. These enzymes have evolved a range of structural features that confer a high level of flexibility compared to thermostable homologs. High flexibility, particularly around the active site, is translated into low-activation enthalpy, low-substrate affinity, and high specific activity at low temperatures. High flexibility is also accompanied by a trade-off in stability, resulting in heat lability and, in the few cases studied, cold lability. This review addresses the structure, function, and stability of cold-adapted enzymes, highlighting the challenges for immediate and future consideration. Because of the unique properties of cold-adapted enzymes, they are not only an important focus in extremophile biology, but also represent a valuable model for fundamental researc...

Journal ArticleDOI
TL;DR: It is demonstrated that exposure to SNP greatly enhanced the efficacy of antimicrobial compounds in the removal of established P. aeruginosa biofilms from a glass surface and combined exposure to both NO and antimicrobial agents may offer a novel strategy to control preestablished, persistent P. aerobicaerobic bacteria.
Abstract: Bacterial biofilms at times undergo regulated and coordinated dispersal events where sessile biofilm cells convert to free-swimming, planktonic bacteria. In the opportunistic pathogen Pseudomonas aeruginosa, we previously observed that dispersal occurs concurrently with three interrelated processes within mature biofilms: (i) production of oxidative or nitrosative stress-inducing molecules inside biofilm structures, (ii) bacteriophage induction, and (iii) cell lysis. Here we examine whether specific reactive oxygen or nitrogen intermediates play a role in cell dispersal from P. aeruginosa biofilms. We demonstrate the involvement of anaerobic respiration processes in P. aeruginosa biofilm dispersal and show that nitric oxide (NO), used widely as a signaling molecule in biological systems, causes dispersal of P. aeruginosa biofilm bacteria. Dispersal was induced with low, sublethal concentrations (25 to 500 nM) of the NO donor sodium nitroprusside (SNP). Moreover, a P. aeruginosa mutant lacking the only enzyme capable of generating metabolic NO through anaerobic respiration (nitrite reductase, ΔnirS) did not disperse, whereas a NO reductase mutant (ΔnorCB) exhibited greatly enhanced dispersal. Strategies to induce biofilm dispersal are of interest due to their potential to prevent biofilms and biofilm-related infections. We observed that exposure to SNP (500 nM) greatly enhanced the efficacy of antimicrobial compounds (tobramycin, hydrogen peroxide, and sodium dodecyl sulfate) in the removal of established P. aeruginosa biofilms from a glass surface. Combined exposure to both NO and antimicrobial agents may therefore offer a novel strategy to control preestablished, persistent P. aeruginosa biofilms and biofilm-related infections.

Journal ArticleDOI
TL;DR: Cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference χ2; 1 df; P = 0.43), and the type or site of STK 11/L KB1 mutation did not significantly influence cancer risk.
Abstract: BACKGROUND: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited. EXPERIMENTAL DESIGN: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations. RESULTS: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference chi2 = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk. CONCLUSIONS: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.

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TL;DR: Some of the milestones in research that have led to an increased awareness of the contribution of immune and inflammatory systems to neuropathic pain are reviewed and the role of immune cells and inflammatory mediators are reviewed.

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TL;DR: Research on the behavioral and neurobiological mechanisms of contextual influences on extinction learning and retrieval is reviewed, with particular attention to the effects of recent trials and trial spacing.