Showing papers by "Flinders University published in 2010"

Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update

Abstract: The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel α2-δ ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.

Recent developments in PDMS surface modification for microfluidic devices

Abstract: PDMS is enjoying continued and ever increasing popularity as the material of choice for microfluidic devices due to its low cost, ease of fabrication, oxygen permeability and optical transparency. However, PDMS's hydrophobicity and fast hydrophobic recovery after surface hydrophilization, attributed to its low glass transition temperature of less than -120 degrees C, negatively impacts on the performance of PDMS-based microfluidic device components. This issue has spawned a flurry of research to devise longer lasting surface modifications of PDMS, with particular emphasis on microfluidic applications. This review will present recent research on surface modifications of PDMS using techniques ranging from metal layer coatings and layer-by-layer depositions to dynamic surfactant treatments and the adsorption of amphipathic proteins. We will also discuss significant advances that have been made with a broad palette of gas-phase processing methods including plasma processing, sol-gel coatings and chemical vapor deposition. Finally, we will present examples of applications and future prospects of modified PDMS surfaces in microfluidics, in areas such as molecular separations, cell culture in microchannels and biomolecular detection via immunoassays.

Association of KRAS p.G13D Mutation With Outcome in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer Treated With Cetuximab

Abstract: Context Patients with metastatic colorectal cancer who have KRAS codon 12- or KRAS codon 13-mutated tumors are presently excluded from treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab. Objective To test the hypothesis that KRAS codon 13 mutations are associated with a better outcome after treatment with cetuximab than observed with other KRAS mutations. Design, Setting, and Patients We studied the association between KRAS mutation status (p.G13D vs other KRAS mutations) and response and survival in a pooled data set of 579 patients with chemotherapy-refractory colorectal cancer treated with cetuximab between 2001 and 2008. Patients were included in the CO. 17, BOND, MABEL, EMR202600, EVEREST, BABEL, or SALVAGE clinical trials or received off-study treatment. Univariate and multivariate analyses, adjusting for possible prognostic factors and data set, were performed. The effect of the different mutations was studied in vitro by constructing isogenic cell lines with wild-type KRAS, p.G12V, or p.G13D mutant alleles and treating them with cetuximab. Main Outcome Measures The main efficacy end point was overall survival. Secondary efficacy end points were response rate and progression-free survival. Results In comparison with patients with other KRAS-mutated tumors, patients with p.G13D-mutated tumors (n=32) treated with cetuximab had longer overall survival (median, 7.6 [95% confidence interval {CI}, 5.7-20.5] months vs 5.7 [95% CI, 4.9-6.8] months; adjusted hazard ratio [HR], 0.50; 95% CI, 0.31-0.81; P=.005) and longer progression-free survival (median, 4.0 [95% CI, 1.9-6.2] months vs 1.9 [95% CI, 1.8-2.8] months; adjusted HR, 0.51; 95% CI, 0.32-0.81; P=.004). There was a significant interaction between KRAS mutation status (p.G13D vs other KRAS mutations) and overall survival benefit with cetuximab treatment (adjusted HR, 0.30; 95% CI, 0.14-0.67; P=.003). In vitro and mouse model analysis showed that although p.G12V-mutated colorectal cells were insensitive to cetuximab, p.G13D-mutated cells were sensitive, as were KRAS wild-type cells. Conclusions In this analysis, use of cetuximab was associated with longer overall and progression-free survival among patients with chemotherapy-refractory colorectal cancer with p.G13D-mutated tumors than with other KRAS-mutated tumors. Evaluation of cetuximab therapy in these tumors in prospective randomized trials may be warranted. JAMA. 2010; 304(16): 1812-1820

Recent developments in gravity-wave effects in climate models and the global distribution of gravity-wave momentum flux from observations and models

Abstract: Recent observational and theoretical studies of the global properties of small-scale atmospheric gravity waves have highlighted the global effects of these waves on the circulation from the surface to the middle atmosphere. The effects of gravity waves on the large-scale circulation have long been treated via parametrizations in both climate and weather-forecasting applications. In these parametrizations, key parameters describe the global distributions of gravity-wave momentum flux, wavelengths and frequencies. Until recently, global observations could not define the required parameters because the waves are small in scale and intermittent in occurrence. Recent satellite and other global datasets with improved resolution, along with innovative analysis methods, are now providing constraints for the parametrizations that can improve the treatment of these waves in climate-prediction models. Research using very-high-resolution global models has also recently demonstrated the capability to resolve gravity waves and their circulation effects, and when tested against observations these models show some very realistic properties. Here we review recent studies on gravity-wave effects in stratosphere-resolving climate models, recent observations and analysis methods that reveal global patterns in gravity-wave momentum fluxes and results of very-high-resolution model studies, and we outline some future research requirements to improve the treatment of these waves in climate simulations. Copyright © 2010 Royal Meteorological Society and Crown in the right of Canada

Sensory Processing Subtypes in Autism: Association with Adaptive Behavior

Abstract: Children with autism are frequently observed to experience difficulties in sensory processing. This study examined specific patterns of sensory processing in 54 children with autistic disorder and their association with adaptive behavior. Model-based cluster analysis revealed three distinct sensory processing subtypes in autism. These subtypes were differentiated by taste and smell sensitivity and movement-related sensory behavior. Further, sensory processing subtypes predicted communication competence and maladaptive behavior. The findings of this study lay the foundation for the generation of more specific hypotheses regarding the mechanisms of sensory processing dysfunction in autism, and support the continued use of sensory-based interventions in the remediation of communication and behavioral difficulties in autism.

Ticagrelor Versus Clopidogrel in Acute Coronary Syndromes in Relation to Renal Function Results From the Platelet Inhibition and Patient Outcomes (PLATO) Trial

Abstract: Background—Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates. Methods and Results—Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal ren...

Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma

Abstract: We conducted a genome-wide association study for primary open-angle glaucoma (POAG) in 1,263 affected individuals (cases) and 34,877 controls from Iceland. We identified a common sequence variant at 7q31 (rs4236601[ A], odds ratio (OR) = 1.36, P = 5.0 x 10(-10)). We then replicated the association in sample sets of 2,175 POAG cases and 2,064 controls from Sweden, the UK and Australia (combined OR = 1.18, P = 0.0015) and in 299 POAG cases and 580 unaffected controls from Hong Kong and Shantou, China (combined OR = 5.42, P = 0.0021). The risk variant identified here is located close to CAV1 and CAV2, both of which are expressed in the trabecular meshwork and retinal ganglion cells that are involved in the pathogenesis of POAG.

Will I Stay or Will I Go? Explaining Repatriation by Self-Initiated Expatriates

Abstract: Offering an integrated framework, we sought to explain why and how professionals who self-initiate expatriation repatriate. We measured host country “pull” and “push,” home country pull, “shocks,” ...

The edge of legitimacy: voluntary social and environmental reporting in Rothmans' 1956 - 1999 annual reports

Abstract: Purpose – The purpose of this paper is to examine the voluntary social and environmental disclosures made in the annual reports of Rothmans Ltd between the years of 1955 and 1999. The first part of the paper focuses on defining legitimacy theory as it has been used in accounting research, extending the current model of legitimacy that predominates, and discussing the potential of a resource‐based approach to testing the theory.Design/methodology/approach – A qualitative and quantitative approach to analysing annual report disclosures is presented, and this is one of the few studies to operationalise the variables under study as measures of resource flows.Findings – The paper considers legitimacy theory in light of disclosures made by Rothmans. An initial analysis provides qualitative examples of expected attempts to legitimatise the corporation given the threat posed by the smoking and health debate. Further analysis conducted using a quantitative measure of resource flows controlled by one stakeholder gr...

Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR

Abstract: Around 40-50% of patients with chronic myeloid leukemia (CML) who achieve a stable complete molecular response (CMR; undetectable breakpoint cluster region-Abelson leukemia gene human homolog 1 (BCR-ABL1) mRNA) on imatinib can stop therapy and remain in CMR, at least for several years. This raises the possibility that imatinib therapy may not need to be continued indefinitely in some CML patients. Two possible explanations for this observation are (1) CML has been eradicated or (2) residual leukemic cells fail to proliferate despite the absence of ongoing kinase inhibition. We used a highly sensitive patient-specific nested quantitative PCR to look for evidence of genomic BCR-ABL1 DNA in patients who sustained CMR after stopping imatinib therapy. Seven of eight patients who sustained CMR off therapy had BCR-ABL1 DNA detected at least once after stopping imatinib, but none has relapsed (follow-up 12-41 months). BCR-ABL1 DNA levels increased in all of the 10 patients who lost CMR soon after imatinib cessation, whereas serial testing of patients in sustained CMR showed a stable level of BCR-ABL1 DNA. This more sensitive assay for BCR-ABL1 provides evidence that even patients who maintain a CMR after stopping imatinib may harbor residual leukemia. A search for intrinsic or extrinsic (for example, immunological) causes for this drug-free leukemic suppression is now indicated.

The Internet and Adolescent Girls’ Weight Satisfaction and Drive for Thinness

Abstract: The primary aim of the study was to examine the relationship between media exposure and body image in adolescent girls, with a particular focus on the ‘new’ and as yet unstudied medium of the Internet. A sample of 156 Australian female high school students (mean age = 14.9 years) completed questionnaire measures of media consumption and body image. Internet appearance exposure and magazine reading, but not television exposure, were found to be correlated with greater internalization of thin ideals, appearance comparison, weight dissatisfaction, and drive for thinness. Regression analyses indicated that the effects of magazines and Internet exposure were mediated by internalization and appearance comparison. It was concluded that the Internet represents a powerful sociocultural influence on young women’s lives.

Optimizing Surfactant Concentrations for Dispersion of Single-Walled Carbon Nanotubes in Aqueous Solution

Abstract: The sonication−centrifugation technique is commonly used for dispersing single-walled carbon nanotubes (SWCNTs) in aqueous surfactant solutions However, the methodologies and materials used for this purpose are widely varied, and few dispersive agents have been studied systematically This work describes a systematic study into the ability of some well-known (and some less common) surfactants and polymers to disperse SWCNTs fabricated by two different techniques UV−vis−NIR absorbance spectra of their supernatant solutions showed that the smaller ionic surfactants were generally more effective dispersants, with larger polymer and surfactant molecules exhibiting a reduced performance for ensembles of carbon nanotubes of smaller average diameter Optimal surfactant concentrations were established for dispersions of carbon nanotubes produced by the electric arc method in aqueous solutions of sodium dodecylbenzene sulfonate, sodium deoxycholate, Triton X-405, Brij S-100, Pluronic F-127, and polyvinylpyrrolid

The prediction of drug-glucuronidation parameters in humans: UDP-glucuronosyltransferase enzyme-selective substrate and inhibitor probes for reaction phenotyping and in vitro-in vivo extrapolation of drug clearance and drug-drug interaction potential.

Abstract: Major advances in the characterization of uridine diphosphate (UDP)-glucuronosyltransferase (UGT) enzyme substrate and inhibitor selectivities and the development of experimental paradigms to investigate xenobiotic glucuronidation in vitro now permit the prediction of a range of drug-glucuronidation parameters in humans. In particular, the availability of substrate and inhibitor “probes” for the major hepatic drug metabolizing UGTs together with batteries of recombinant enzymes allow the reaction phenotyping of drug glucuronidation reactions. Additionally, in vitro experimental approaches and scaling strategies have been successfully applied to the quantitative prediction of in vivo clearance via glucuronidation and drug-drug interaction potential.

Inulin - a versatile polysaccharide with multiple pharmaceutical and food chemical uses.

Abstract: b ABSTRACT a-D-glucopyranosyl-(â-D-fructofuranosyl)(n-1)-D-fructofuranoside, commonly referred to as inulin, is a natural plant-derived polysaccharide with a diverse range of food and pharmaceutical applications. It is used by the food industry as a soluble dietary fibre and fat or sugar replacement, and in the pharmaceutical industry as a stabiliser and excipient. It can also be used as a precursor in the synthesis of a wide range of compounds. New uses for inulin are constantly being discovered, with recent research into its use for slow-release drug delivery. Inulin, when in a particulate form, possesses anti-cancer and immune enhancing properties. Given its increasing importance to industry, this review explains how inulin's unique physico-chemical properties bestow it with many useful pharmaceutical applications.

Switching between executive and default mode networks in posttraumatic stress disorder: Alterations in functional connectivity

Abstract: Background Working memory processing and resting-state connectivity in the default mode network are altered in patients with post-traumatic stress disorder (PTSD) Because the ability to effortlessly switch between concentration on a task and an idling state during rest is implicated in both these alterations, we undertook a functional magnetic resonance imaging study with a block design to analyze task-induced modulations in connectivity

Definition of ambulatory blood pressure targets for diagnosis and treatment of hypertension in relation to clinic blood pressure: prospective cohort study

Abstract: Background Twenty-four hour ambulatory blood pressure thresholds have been defined for the diagnosis of mild hypertension but not for its treatment or for other blood pressure thresholds used in the diagnosis of moderate to severe hypertension. We aimed to derive age and sex related ambulatory blood pressure equivalents to clinic blood pressure thresholds for diagnosis and treatment of hypertension. Methods We collated 24 hour ambulatory blood pressure data, recorded with validated devices, from 11 centres across six Australian states (n=8575). We used least product regression to assess the relation between these measurements and clinic blood pressure measured by trained staff and in a smaller cohort by doctors (n=1693). Results Mean age of participants was 56 years (SD 15) with mean body mass index 28.9 (5.5) and mean clinic systolic/diastolic blood pressure 142/82 mm Hg (19/12); 4626 (54%) were women. Average clinic measurements by trained staff were 6/3 mm Hg higher than daytime ambulatory blood pressure and 10/5 mm Hg higher than 24 hour blood pressure, but 9/7 mm Hg lower than clinic values measured by doctors. Daytime ambulatory equivalents derived from trained staff clinic measurements were 4/3 mm Hg less than the 140/90 mm Hg clinic threshold (lower limit of grade 1 hypertension), 2/2 mm Hg less than the 130/80 mm Hg threshold (target upper limit for patients with associated conditions), and 1/1 mm Hg less than the 125/75 mm Hg threshold. Equivalents were 1/2 mm Hg lower for women and 3/1 mm Hg lower in older people compared with the combined group. Conclusions Our study provides daytime ambulatory blood pressure thresholds that are slightly lower than equivalent clinic values. Clinic blood pressure measurements taken by doctors were considerably higher than those taken by trained staff and therefore gave inappropriate estimates of ambulatory thresholds. These results provide a framework for the diagnosis and management of hypertension using ambulatory blood pressure values.

Optimization and uncertainty assessment of strongly nonlinear groundwater models with high parameter dimensionality

Abstract: [1] Highly parameterized and CPU-intensive groundwater models are increasingly being used to understand and predict flow and transport through aquifers. Despite their frequent use, these models pose significant challenges for parameter estimation and predictive uncertainty analysis algorithms, particularly global methods which usually require very large numbers of forward runs. Here we present a general methodology for parameter estimation and uncertainty analysis that can be utilized in these situations. Our proposed method includes extraction of a surrogate model that mimics key characteristics of a full process model, followed by testing and implementation of a pragmatic uncertainty analysis technique, called null-space Monte Carlo (NSMC), that merges the strengths of gradient-based search and parameter dimensionality reduction. As part of the surrogate model analysis, the results of NSMC are compared with a formal Bayesian approach using the DiffeRential Evolution Adaptive Metropolis (DREAM) algorithm. Such a comparison has never been accomplished before, especially in the context of high parameter dimensionality. Despite the highly nonlinear nature of the inverse problem, the existence of multiple local minima, and the relatively large parameter dimensionality, both methods performed well and results compare favorably with each other. Experiences gained from the surrogate model analysis are then transferred to calibrate the full highly parameterized and CPU intensive groundwater model and to explore predictive uncertainty of predictions made by that model. The methodology presented here is generally applicable to any highly parameterized and CPU-intensive environmental model, where efficient methods such as NSMC provide the only practical means for conducting predictive uncertainty analysis.

Attitudes toward Cosmetic Surgery in Middle-Aged Women: Body Image, Aging Anxiety, and the Media.

Abstract: Our study investigated factors that influence attitudes toward cosmetic surgery in middle-aged women. A sample of 108 women, aged between 35 and 55 years, completed questionnaire measures of body dissatisfaction, appearance investment, aging anxiety, media exposure (television and magazine), and attitudes toward cosmetic surgery (delineated in terms of general attitudes, social motivations, and actual consideration). Body dissatisfaction, appearance investment, aging anxiety, and both media variables predicted some facet of attitudes toward cosmetic surgery. Specifically, appearance investment, aging anxiety, and television exposure were unique predictors of endorsement of social motivations for cosmetic surgery, whereas body dissatisfaction, appearance investment, and television exposure were unique predictors of actual consideration of cosmetic surgery. Regression analysis revealed that the effects of media on cosmetic surgery attitudes were primarily direct. We concluded that there are multiple influen...

A short exploration of structural noise

Abstract: [1] “Structural noise” is a term often used to describe model-to-measurement misfit that cannot be ascribed to measurement noise and therefore must be ascribed to the imperfect nature of a numerical model as a simulator of reality. As such, it is often the dominant contributor to model-to-measurement misfit. As the name “structural noise” implies, this type of misfit is often treated as an additive term to measurement noise when assessing model parameter and predictive uncertainty. This paper inquires into the nature of defect-induced model-to-measurement misfit and provides a conceptual basis for accommodating it. It is shown that inasmuch as defect-induced model-to-measurement misfit can be characterized as “noise,” this noise is likely to show a high degree of spatial and temporal correlation; furthermore, its covariance matrix may approach singularity. However, the deleterious impact of structural noise on the model calibration process may be mitigated in a variety of ways. These include adoption of a highly parameterized approach to model construction and calibration (including the strategic use of compensatory parameters where appropriate), processing of observations and their model-generated counterparts in ways that are able to filter out structural noise prior to fitting one to the other, and/or through implementation of a weighting strategy that gives prominence to observations that most resemble predictions required of a model.