ORCID Profile
0000-0002-5454-6450
Current Organisation
QIMR Berghofer Medical Research Institute
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Informa UK Limited
Date: 12-2003
Publisher: Elsevier BV
Date: 03-2000
Publisher: Wiley
Date: 03-1999
Publisher: Public Library of Science (PLoS)
Date: 05-02-2021
DOI: 10.1371/JOURNAL.PNTD.0009121
Abstract: The development of insecticide resistance in mosquitoes can have pleiotropic effects on key behaviours such as mating competition and host-location. Documenting these effects is crucial for understanding the dynamics and costs of insecticide resistance and may give researchers an evidence base for promoting vector control programs that aim to restore or conserve insecticide susceptibility. We evaluated changes in behaviour in a backcrossed strain of Aedes aegypti , homozygous for two knockdown resistance (kdr) mutations (V1016G and S989P) isolated in an otherwise fully susceptible genetic background. We compared biting activity, host location behaviours, wing beat frequency (WBF) and mating competition between the backcrossed strain, and the fully susceptible and resistant parental strains from which it was derived. The presence of the homozygous kdr mutations did not have significant effects on blood avidity, the time to locate a host, or WBF in females. There was, however, a significant reduction in mean WBF in males and a significant reduction in estimated male mating success (17.3%), associated with the isolated kdr genotype. Our results demonstrate a cost of insecticide resistance associated with an isolated kdr genotype and manifest as a reduction in male mating success. While there was no recorded difference in WBF between the females of our strains, the significant reduction in male WBF recorded in our backcrossed strain might contribute to mate-recognition and mating disruption. These consequences of resistance evolution, especially when combined with other pleiotropic fitness costs that have been previously described, may encourage reversion to susceptibility in the absence of insecticide selection pressures. This offers justification for the implementation of insecticide resistance management strategies based on the rotation or alternation of different insecticide classes in space and time.
Publisher: Springer Science and Business Media LLC
Date: 05-03-2016
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 09-01-2019
Publisher: Wiley
Date: 19-03-2014
DOI: 10.1002/WCC.279
Abstract: Engaging the public about mitigating or adapting to climate change threats poses significant challenges for scientists, policy makers, and others responsible for developing communication strategies. In response to these challenges, interest is growing in audience segmentation as a possible strategy to develop more effective communications that are tailored and targeted to subgroups of the public who share similar values, beliefs, behaviors, and/or policy preferences about climate change. In this article, we provide a brief historical overview of audience segmentation and its applications to marketing, health, politics, and most recently climate change. We then critically evaluate several conceptual arguments about whether segmentation is an appropriate strategy for climate change communications, review key methodological considerations associated with conducting segmentation analyses, and make several recommendations about best practice. We conclude that, in principle, audience segmentation and targeted messaging are potentially valuable tools for enhancing climate change communication. But, in practice, there are conceptual and methodological complexities of which practitioners and consumers should be aware when conducting and interpreting the results of segmentation studies. In addition, more research is required, particularly related to tailoring and targeting messages to identified segments, before these strategies can be considered to have a sufficient evidence base to warrant widespread adoption. This article is categorized under: Perceptions, Behavior, and Communication of Climate Change Perceptions of Climate Change
Publisher: Elsevier BV
Date: 07-2022
Publisher: Springer Science and Business Media LLC
Date: 27-09-2018
Publisher: Wiley
Date: 15-06-2011
Publisher: Elsevier BV
Date: 02-2022
Publisher: Cold Spring Harbor Laboratory
Date: 25-08-2020
DOI: 10.1101/2020.08.23.20180422
Abstract: The D-Health Trial aims to determine whether monthly high-dose vitamin D supplementation can reduce the mortality rate and prevent cancer. We did not have adequate statistical power for subgroup analyses, so could not justify the high cost of collecting blood s les at baseline. To enable future exploratory analyses stratified by baseline vitamin D status, we developed a model to predict baseline serum 25 hydroxy vitamin D [25(OH)D] concentration. We used data and serum 25(OH)D concentrations from participants who gave a blood s le during the trial for compliance monitoring and were randomised to placebo. Data were partitioned into training (80%) and validation (20%) datasets. Deseasonalised serum 25(OH)D concentrations were dichotomised using cut-points of 50 nmol/L, 60 nmol/L and 75 nmol/L. We fitted boosted regression tree models, based on 13 predictors, and evaluated model performance using the validation data. The training and validation datasets had 1788 (10.5% nmol/L, 23.1% nmol, 48.8 nmol/L) and 447 (11.9% nmol/L, 25.7% nmol/L, and 49.2% nmol/L) s les, respectively. Ambient UV radiation and total intake of vitamin D were the strongest predictors of ‘low’ serum 25(OH)D concentration. The area under the receiver operating characteristic curves were 0.71, 0.70, and 0.66 for cut-points of nmol/L, nmol/L and nmol/L respectively. We exploited compliance monitoring data to develop models to predict serum 25(OH)D concentration for D-Health participants at baseline. This approach may prove useful in other trial settings where there is an obstacle to exhaustive data collection.
Publisher: Elsevier BV
Date: 11-1998
DOI: 10.1016/S0001-706X(98)00063-1
Abstract: We introduce a new method, activity diaries, in order to evaluate human water contact among fishing communities in an area moderately endemic for Schistosoma japonicum in the Dongting Lake region of Southern China. Two hundred and forty-nine subjects (76% male) were followed prospectively over a 9-month-period in order to verify exposure and reinfection. Exposure was determined crudely with questionnaires, direct 12-h water observations, and more precisely with activity diaries and an adjusted exposure model which took into account the time of day, the duration of contact and the percent body surface area in contact with water. Cohort subjects filled in activity diaries for an average of 85 days as compared with 2 days for the direct water observations. The typical unadjusted mean daily water contact (duration) based on the activity diaries was 53 min with 62% of this time spent in fishing. In contrast, the direct water observations revealed an average daily duration of 149 min with 53% of the time spent in fishing. Human water contact patterns (min/day) by site, activity and body part exposed were examined with the activity diaries. In iduals in the 36-49-year-old age range had the highest degree of water contact. Most of this daily contact occurred by males on the hands (mean+/-S.D. 83.53+/-67.80 min/day) while fishing (mean+/-S.D. 87.84+/-8.88 min/day) on the lake (mean+/-S.D. 85.98+/-69.90 min/day). There was a strong positive log correlation (r=0.95) between the crude and adjusted (based on our derived exposure model) diary outcomes for the entire study s le, however, at higher exposure levels this relationship was differentially weaker (r=0.70). Results from this study suggest that current methods used in evaluating schistosomiasis exposure in China may overestimate and bias measures of the risk of infection. Activity diaries adjusted for the time of day, duration and the percent body surface area exposed are cost-effective and practical instruments to accurately quantify human exposure in the vast lake regions of Southern China where most of the endemic schistosomiasis japonica occurs.
Publisher: Informa UK Limited
Date: 03-2020
DOI: 10.2147/PPA.S236818
Publisher: Cold Spring Harbor Laboratory
Date: 22-08-2018
DOI: 10.1101/397620
Abstract: Colorectal cancer is an epigenetically heterogeneous disease, however the extent and spectrum of the CpG Island Methylator Phenotype (CIMP) is not clear. An unselected cohort of 216 colorectal cancers clustered into five clinically and molecularly distinct subgroups using Illumina 450K DNA methylation arrays. CIMP-High cancers were most frequent in the proximal colons of female patients. These dichotomised into CIMP-Hl and CIMP-H2 based on methylation profile which was supported by over representation of BRAF (74%, P .0001) or KRAS (55%, P .0001) mutation, respectively. Congruent with increasing methylation, there was a stepwise increase in patient age from 62 years in the CI MP-Negative subgroup to 75 years in the CIMP-Hl subgroup (P .0001). There was a striking association between PRC2-marked loci and those subjected to significant gene body methylation in CIMP-type cancers (P .6xl0 78 ). We identified oncogenes susceptible to gene body methylation and Wnt pathway antagonists resistant to gene body methylation. CIMP cluster specific mutations were observed for genes involved in chromatin remodelling, such as in the SWI/SNF and NuRD complexes, suggesting synthetic lethality. There are five clinically and molecularly distinct subgroups of colorectal cancer based on genome wide epigenetic profiling. These analyses highlighted an unidentified role for gene body methylation in progression of serrated neoplasia. Subgroup-specific mutation of distinct epigenetic regulator genes revealed potentially druggable vulnerabilities for these cancers, which may provide novel precision medicine approaches.
Publisher: Wiley
Date: 11-2006
DOI: 10.1111/J.1423-0410.2006.00830.X
Abstract: Concerns about the potential for prions to be retained on chromatography gels during the manufacture of plasma products prompted development of an investigational strategy for detecting infectious prions bound to gels. The objective was to firstly examine methods of implanting gels intracerebrally (IC) in mice, then to examine prion cleaning from a scaled-down version of the DEAE Sepharose column used in a production process to fractionate immunoglobulins and albumin from human plasma. The study consisted of two parts: (i) the pathophysiological impact by IC inoculation of ground gel beads was compared to whole gel beads (ii) the feedstreams to two DEAE Sepharose columns were spiked with scrapie ME7. One column was subjected to the protein loading and elution portions of the chromatography cycle. The other column was subjected to the full cycle of protein loading and elution, followed by regeneration with 0.5 m NaCl, 1 m NaOH and solvent/detergent washes. The gels were unpacked and bioassayed by IC implantation in mice to quantify infectivity. IC inoculation of ground gel beads resulted in unacceptably high pathological impact in the mice whereas whole gel bead inoculation resulted in a reduced affect. Accordingly, the whole bead model system was used to assess prion removal/inactivation from chromatography gels at the pre- and postcleaning stage of the chromatography cycle. Infectious prions were detected on the DEAE Sepharose prior to the cleaning step however, the gel cleaning cycle reduced infectivity by a log reduction factor (LRF) of > or = 2.75, thus reducing infectivity by bioassay to below detectable limits. A model system for assessment of prion inactivation/removal from chromatography gels has been established. Spiked prion infectivity does bind to DEAE Sepharose gel however, the cleaning cycle removed infectivity to levels below that detectable by bioassay.
Publisher: Informa UK Limited
Date: 11-2021
DOI: 10.2147/PPA.S341566
Publisher: Impact Journals, LLC
Date: 15-12-2017
Publisher: Resilience Alliance, Inc.
Date: 2015
Publisher: American Thoracic Society
Date: 02-2022
Publisher: Informa UK Limited
Date: 12-04-2016
DOI: 10.3109/01612840.2016.1149260
Abstract: This study describes and evaluates an innovative program designed to reduce functional decline among seniors, using a participatory care approach and integrated health teams. The evaluation provides older people and community support workers (CSWs) with the opportunity to share their experiences of being involved with an innovative program to reduce functional decline (mobility, skin integrity, nutrition, mental health, continence) of older, community dwelling adults implemented by a Nursing Service in a major capital city in Australia. As part of the program, CSWs were trained to provide care that aimed to reduce functional decline, and improve the quality of life for the care recipients. Data were collected through in-depth interviews with older people receiving care and a focus group (FG) was conducted with CSWs. Seven themes emerged during data analysis: 1) functionality/independence 2) prevention 3) confidence 4) connection 5) the approach 6) care plans and 7) the role of the CSWs. The relationship built between care giver and receiver and the mutual respect facilitated through adopting a participatory care approach was crucial. This relationship-focused care contributed to improved functionality and consequently quality of life for the older person, and for the CSW professional it contributed to their development, improved satisfaction with their role, and increased pride in the difference they make in the lives of their clients. Opportunities for improvement of the program included ensuring that participants understood the rationale for all aspects of the program, including regular reminders, as well as the use of regular reviews of in idual outcomes.
Publisher: Oxford University Press
Date: 26-10-2017
DOI: 10.1093/ACREFORE/9780190228620.013.415
Abstract: Communication with farmers about climate change has proven to be difficult, with relatively low acceptance of anthropogenic climate change or the idea that climate change will negatively affect agriculture. Many farmers have been impervious to climate change communications because of the nature of farming, their worldviews, and the controversies about climate change in the media. Segmentation studies from the agriculture and natural resource management literatures provide evidence of homogeneous farmer groups internationally with respect to climate change attitudes and behaviors in a farming context. Understanding these segments—including their values, beliefs, and behaviors—is important for developing tailored and targeted communications approaches. Based on understanding of commonly observed farmer segments, it is possible to tailor communication strategies to better engage with segments of concern, including which message to use, appropriate sources, as well as alternative communication techniques based on participatory approaches and use of the arts. For certain segments, discussion about human-induced climate change should be avoided given that it is contentious and not critical for how farmers should respond to climate change. Theoretical frameworks from psychology and marketing—such as the theory of planned behavior, the attitude-to-behavior process model, the motivation and opportunity and determinants (MODE) model, motivation to avoid harm, and the elaboration likelihood model—can also be used to inform the design of communication strategies for engaging with farmers. However, a careful analysis of farmer segments, their worldviews, their beliefs, and their position in the consumer decision-making process suggests that the recommendations from these theoretical models should not be implemented uniformly across farmer segments. Rather, the various theoretical models provide a number of strategies that need to be selectively applied based on knowledge of the target segment. While use of theory and understanding of segments will help to improve communications with farmers, it is apparent that changing the beliefs of farmers in some segments about the need to respond to climate change will require more than simply increasing the quantity or quality of communications. Engaging farmers in these segments requires a much richer information set and a much greater effort to show farmers how they should be responding to climate variability and change using practical demonstrations and participatory approaches.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2009
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.DIAGMICROBIO.2017.12.004
Abstract: Very little is known about the natural history of oral HPV infection. Several different methods exist to collect oral specimens and detect HPV, but their respective performance characteristics are unknown. We compared two different methods for oral specimen collection (oral saline rinse and commercial saliva kit) from 96 in iduals and then analyzed the s les for HPV by two different PCR detection methods (single GP5+/6+ PCR and nested MY09/11 and GP5+/6+ PCR). For the oral rinse s les, the oral HPV prevalence was 10.4% (GP+ PCR 10% repeatability) vs 11.5% (nested PCR method 100% repeatability). For the commercial saliva kit s les, the prevalences were 3.1% vs 16.7% with the GP+ PCR vs the nested PCR method (repeatability 100% for both detection methods). Overall the agreement was fair or poor between s les and methods (kappa 0.06-0.36). Standardizing methods of oral s le collection and HPV detection would ensure comparability between future oral HPV studies.
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 06-2021
Publisher: Wiley
Date: 12-2004
Publisher: Wiley
Date: 06-2005
Publisher: Informa UK Limited
Date: 31-03-2017
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.SEIZURE.2018.12.015
Abstract: The clinical utility of EEG in cases of NMDA encephalitis is broad with many findings indicating not just epileptiform activity but also encephalopathy and potentially providing insights into pathophysiologic mechanisms of disease. We aimed to determine the frequency of different abnormalities described on EEG and their association with outcome in patients affected by NMDARE through a systematic review of all cases published. A systematic literature review of PubMed and Embase of all published cases of anti-NMDA receptor encephalitis with EEG results, was performed from inception to January 2018. A total of 446 cases of anti-NMDA receptor encephalitis with reported EEG findings were identified. 373 EEGs were abnormal, and this strongly correlated with ICU admission and time to recovery (p = 0.014 and 0.04 respectively). ICU admission and recovery were also correlated with delta range abnormalities including extreme delta brush (p = 0.007 and 0.03). Electrographic seizures correlated strongly with clinical seizures (p < 0.0001), however only 39 cases had EEG seizures captured, while there were 294 cases with clinical seizures. EEG is useful in the clinical management and prognostication of cases on NMDA encephalitis. This is particularly true of certain findings which portend a higher likelihood of ICU admission or poorer outcome and this may assist in the decision to pursue more aggressive treatment options.
Publisher: MDPI AG
Date: 05-05-2020
Abstract: Chikungunya virus (CHIKV), Ross River virus (RRV), o’nyong nyong virus (ONNV), Mayaro virus (MAYV) and Getah virus (GETV) represent arthritogenic alphaviruses belonging to the Semliki Forest virus antigenic complex. Antibodies raised against one of these viruses can cross-react with other serogroup members, suggesting that, for instance, a CHIKV vaccine (deemed commercially viable) might provide cross-protection against antigenically related alphaviruses. Herein we use human alphavirus isolates (including a new human RRV isolate) and wild-type mice to explore whether infection with one virus leads to cross-protection against viremia after challenge with other members of the antigenic complex. Persistently infected Rag1-/- mice were also used to assess the cross-protective capacity of convalescent CHIKV serum. We also assessed the ability of a recombinant poxvirus-based CHIKV vaccine and a commercially available formalin-fixed, whole-virus GETV vaccine to induce cross-protective responses. Although cross-protection and/or cross-reactivity were clearly evident, they were not universal and were often suboptimal. Even for the more closely related viruses (e.g., CHIKV and ONNV, or RRV and GETV), vaccine-mediated neutralization and/or protection against the intended homologous target was significantly more effective than cross-neutralization and/or cross-protection against the heterologous virus. Effective vaccine-mediated cross-protection would thus likely require a higher dose and/or more vaccinations, which is likely to be unattractive to regulators and vaccine manufacturers.
Publisher: American Medical Association (AMA)
Date: 06-01-2009
Abstract: In the ongoing influenza pandemic, a safe and effective vaccine against 2009 influenza A(H1N1) is needed for infants and children. To assess the immunogenicity and safety of a 2009 influenza A(H1N1) vaccine in children. Randomized, observer-blind, age-stratified, parallel group study assessing 2 doses of an inactivated, split-virus 2009 influenza A(H1N1) vaccine in 370 healthy infants and children aged 6 months to less than 9 years living in Australia. Intramuscular injection of 15 microg or 30 microg of hemagglutinin antigen dose of monovalent, unadjuvanted 2009 influenza A(H1N1) vaccine in a 2-dose regimen, administered 21 days apart. Hemagglutination inhibition assay to estimate the proportion of participants with antibody titers of 1:40 or greater, seroconversion, or a significant antibody titer increase, and factor increase in geometric mean titer. Assessments of solicited adverse events during 7 days and unsolicited adverse events for 21 days after each vaccination. Following the first dose of vaccine, antibody titers of 1:40 or greater were observed in 161 of 174 infants and children in the 15-microg group (92.5% 95% confidence interval [CI], 87.6%-95.6%) and in 168 of 172 infants and children in the 30-microg group (97.7% 95% CI, 94.2%-99.1%). Corresponding seroconversion rates were 86.8% (95% CI, 80.9%-91.0%) and 94.2% (95% CI, 89.6%-96.8%), and factor increases in geometric mean titer were 13.6 (95% CI, 11.8-15.6) and 18.3 (95% CI, 15.7-21.4). All participants demonstrated antibody titers of 1:40 or greater after the second vaccine dose. Immune responses were robust regardless of age, baseline serostatus, or seasonal influenza vaccination status. The majority of adverse events were mild to moderate in severity. One 15-microg dose of vaccine was immunogenic in infants and children starting at 6 months of age and vaccine-associated reactions were mild to moderate in severity. clinicaltrials.gov Identifier: NCT00940108.
Publisher: Elsevier BV
Date: 03-2021
DOI: 10.1016/J.JCF.2021.11.015
Abstract: Improved survival of children with CF has increased our need to understand the relevance of cystic fibrosis-associated liver disease (CFLD). We assessed the impact of liver disease and disease severity on the survival of children with cystic fibrosis. A real life, single center cohort study with 27 years follow up was conducted. Mild CFLD was diagnosed as children with abnormal serum liver function tests and abnormal ultrasound. Advanced CFLD was established by detection of cirrhosis or portal hypertension. A directed acyclic graph, Kaplan-Meier (KM) and Cox regression analysis were used to model survival. 290 patients were enrolled, 48 (16.5%) had mild CFLD and 55 (19%) had advanced CFLD. Ten children with advanced CFLD and 1 with mild CFLD died. Based on the KM analysis, the mean (SE) overall survival age of all CF children was 29.1 years (0.50). The mean (SE) survival among females with advanced CFLD was 24.7 years (1.58) compared to 30.4 years (0.66) for females without advanced CFLD (p = 0.0027). Advanced CFLD was a predictor of decreased survival when adjusted for sex and diabetes (HR 2.54, 95%CI 1.05-6.15, p = 0.039). Mild CFLD was not associated with decreased survival. The effect of advanced CFLD on survival was mainly borne by females (HR = 6.37, 95%CI 1.62-25.06 vs. males, HR = 1.00, 95%CI 0.25-4.01). Advanced but not mild CFLD was associated with an increased risk of death when adjusted for sex and diabetes, and resulted in premature death in females with cystic fibrosis by approximately 6 years.
Publisher: Oxford University Press (OUP)
Date: 05-1998
DOI: 10.1016/S0035-9203(98)90997-X
Abstract: This paper describes a rapid, simple, cost-effective questionnaire for screening school-aged children at risk for Asian schistosomiasis in China. Five hundred and thirty-two children, aged 8-14 years, were selected from 3 schools in an area moderately endemic for Schistosoma japonicum in Hunan province. The questionnaire, comprising 15 multiple-choice questions, was administered by teachers in order to collect both ethnographic and epidemiological data relevant to current S. japonicum infections. This was followed by Kato-Katz thick smear stool examinations, miracidium hatching tests, and soluble egg antigen-enzyme linked immunosorbent assays in order to validate the efficacy of the questionnaire approach. The results from a combination of all 3 procedures indicated that the overall schistosomiasis prevalence in the 3 schools was 29.9% (138/472). Six risk factors (episodes of diarrhoea, frequency of water contact, school grade attained, weakness, past history of S. japonicum infection(s), and whether a subject had been previously treated for schistosomiasis) in the questionnaire were determined by logistic regression to be highly statistically significant predictors of in idual current infection. The sensitivity (93.7%), specificity (91.9%) and low cost (c. US$ 0.6/true positive case) associated with the 6 variables model make the questionnaire approach a very useful diagnostic tool for screening marshland and lake communities at high risk for schistosomiasis in China before selective treatment with praziquantel or diagnostic follow-up. An even simpler 3 variables 'yes/no' model was derived from the questionnaire and found to be nearly as good at predicting in idual infection (sensitivity 86.2% and specificity exceeding 97.6%) and extremely simple to use. If validated in other ecological settings in China the questionnaire, modified or as presented here, could be adopted by the national schistosomiasis control programme.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 09-2013
Publisher: Springer Science and Business Media LLC
Date: 26-02-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-06-2020
DOI: 10.1002/HEP4.1536
Abstract: Although there is evidence that type 2 diabetes mellitus (T2D) impacts adversely on liver‐related mortality, its influence on hospital readmissions and development of complications in patients with cirrhosis, particularly in alcohol‐related cirrhosis (the most common etiological factor among Australian hospital admissions for cirrhosis) has not been well studied. This study aimed to investigate the association between T2D and liver cirrhosis in a population‐based cohort of patients admitted for cirrhosis in the state of Queensland, Australia. A retrospective cohort analysis was conducted using data from the Queensland Hospital Admitted Patient Data Collection, which contains information on all hospital episodes of care for patients with liver cirrhosis, and the Death Registry during 2008‐2017. We used demographic, clinical data, and socioeconomic characteristics. A total of 8,631 patients were analyzed. A higher proportion of patients with T2D had cryptogenic cirrhosis (42.4% vs. 27.3%, respectively P 0.001) or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (13.8% vs. 3.4%, respectively P 0.001) and an admission for hepatocellular carcinoma (18.0% vs. 12.2%, respectively P 0.001) compared to patients without T2D. Patients with liver cirrhosis with T2D compared to those without T2D had a significantly increased median length of hospital stay (6 [range, 1‐11] vs. 5 [range, 1‐11] days, respectively P 0.001), double the rate of noncirrhosis‐related admissions (incidence rate ratios [IRR], 2.03 95% confidence interval [CI], 1.98‐2.07), a 1.35‐fold increased rate of cirrhosis‐related admissions (IRR, 1.35 95% CI, 1.30‐1.41), and significantly lower survival ( P 0.001). Conclusion: Among hospitalized patients with cirrhosis, the cohort with T2D is at higher risk and may benefit from attention to comorbidities and additional support to reduce readmissions.
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S13063-021-05890-6
Abstract: Schizophrenia is a persistent psychotic disorder often accompanied by severe disability and premature mortality. New pharmacological treatments are urgently needed. Sodium benzoate, a common food preservative holds potential to be an effective, accessible treatment for schizophrenia, though the optimal dosing and mechanism of action of the compound requires further investigation. In iduals with persistent treatment-refractory schizophrenia ( n =52) will be recruited. Patients will be randomised in a 1:1:1:1 ratio to receive treatment of one of three active doses (1000, 2000 or 4000 mg daily) of sodium benzoate or placebo for 6 weeks duration. The primary outcome measurement is change in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measurements are PANSS subscales, Global Assessment of Function (GAF), Clinical Global Impression (CGI) and Patient Global Impression (PGI-I). Change in concentrations of peripheral amino acids (D-alanine, L-alanine, D-serine, L-serine, glycine and glutamate), plasma sodium benzoate, plasma catalase, 3-nitrotyrosine, malondialdehyde and high-sensitivity C-reactive protein (hs-CRP) will be determined as tertiary measures. This trial seeks to build upon previous research indicating potential efficacy of sodium benzoate for reduction of symptoms in in iduals with treatment-refractory schizophrenia. The trial aims to improve the understanding of the mechanism of action of the compound. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000327886 . Registered on 23 March 2021.
Publisher: Springer Science and Business Media LLC
Date: 05-12-2018
Publisher: MDPI AG
Date: 08-06-2021
Abstract: The current endoscopy and biopsy diagnosis of esophageal adenocarcinoma (EAC) and its premalignant condition Barrett’s esophagus (BE) is not cost-effective. To enable EAC screening and patient triaging for endoscopy, we developed a microfluidic lectin immunoassay, the EndoScreen Chip, which allows sensitive multiplex serum biomarker measurements. Here, we report the proof-of-concept deployment for the EAC biomarker Jacalin lectin binding complement C9 (JAC-C9), which we previously discovered and validated by mass spectrometry. A monoclonal C9 antibody (m26 3C9) was generated and validated in microplate ELISA, and then deployed for JAC-C9 measurement on EndoScreen Chip. Cohort evaluation (n = 46) confirmed the expected elevation of serum JAC-C9 in EAC, along with elevated total serum C9 level. Next, we asked if the small panel of serum biomarkers improves detection of EAC in this cohort when used in conjunction with patient risk factors (age, body mass index and heartburn history). Using logistic regression modeling, we found that serum C9 and JAC-C9 significantly improved EAC prediction from AUROC of 0.838 to 0.931, with JAC-C9 strongly predictive of EAC (vs. BE OR = 4.6, 95% CI: 1.6–15.6, p = 0.014 vs. Healthy OR = 4.1, 95% CI: 1.2–13.7, p = 0.024). This proof-of-concept study confirms the microfluidic EndoScreen Chip technology and supports the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy. Future work will expand the number of markers on EndoScreen Chip from our list of validated EAC biomarkers.
Publisher: SAGE Publications
Date: 26-08-2009
Abstract: Student evaluation of teaching has been examined in higher education research for over 70 years but there are gaps in our knowledge about the contribution, and relationships between, the relevant constructs. Recent literature encourages researchers to test multivariate models of Teaching Effectiveness. Seven main constructs known to influence Teaching Effectiveness have been variously selected for inclusion in previous literature however, previous multivariate studies have examined only a subset of these constructs, with the majority considering four or fewer constructs. The comprehensive model of Teaching Effectiveness developed in this study examines the main and mediated influence of all seven constructs on Teaching Effectiveness. Data have been collected from undergraduate marketing students. Three constructs (Clear Communication, Delivery Dynamism, and Assessment Fairness) contribute directly to Teaching Effectiveness. Real-World Knowledge, Rapport, Subject Organization, and Subject Difficulty contribute indirectly to Teaching Effectiveness. Consistent with previous research, these findings highlight the importance of personal attributes (communication, delivery, real-world knowledge, and rapport) on Teaching Effectiveness.
Publisher: American Chemical Society (ACS)
Date: 19-07-2021
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.EPLEPSYRES.2021.106708
Abstract: Autoantibodies to central nervous system (CNS) antigens are increasingly identified in patients with epilepsy. Alterations in cytokines and chemokines have also been demonstrated in epilepsy, but this has not been explored in subjects with autoantibodies. If antibody positive and antibody negative subjects show a difference in immune activation, as measured by cytokine levels, this could improve diagnostic and therapeutic approaches, and provide insights into the underlying pathophysiology. We aimed to evaluate serum and CSF cytokines and chemokines in patients with and without autoantibody positivity to identify any differences between the two groups. We studied participants who had undergone serum and CSF testing for CNS autoantibodies, as part of their clinical evaluation. Cases were classified as antibody positive or antibody negative for comparison. Stored CSF and sera were analysed for cytokine and chemokine concentrations. 25 participants underwent testing. 8 were antibody positive, 17 were antibody negative. Significant elevations in the mean concentration of IL-13 and RANTES in CSF were found in the antibody positive cases and significant elevation of CSF VEGF was found in the antibody negative cases. Significant elevations in the mean concentrations of serum TNFβ, INFγ, bNGF, IL-8, and IL-12 were seen in the antibody negative group, and there was poor correlation between the majority of serum and CSF concentrations. Measurement of cytokines and chemokines such as IL-13 and RANTES could be useful in diagnosis of autoimmune associated epilepsy. Such markers might also guide targeted immunotherapy to improve seizure control and provide insights into the underlying pathophysiology of epilepsy associated with CNS autoantibodies.
Publisher: Informa UK Limited
Date: 02-01-2017
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 05-2019
Publisher: Elsevier BV
Date: 2019
Publisher: Wiley
Date: 30-05-2000
DOI: 10.1002/(SICI)1097-0258(20000530)19:10<1295::AID-SIM493>3.0.CO;2-Z
Abstract: A traditional measure of effect size associated with tests for difference between two groups is the variance explained by group membership (R(2)). If exposure to a disease causes a small but long term deficit in performance, however, R(2) does not capture that cumulating effect. We propose an alternative statistic, gamma, based on the probability of an unexposed person outperforming an exposed person. Although gamma is also a point estimate, it more easily conveys what the cumulating effect of a deficit would be. We discuss some of the advantages of this measure.
Publisher: Wiley
Date: 25-07-2011
Publisher: Wiley
Date: 2020
DOI: 10.1111/IMJ.14356
Abstract: Cancer care involves many different healthcare providers. Delayed or inaccurate communication between specialists and general practitioners (GP) may negatively affect care. To describe the pattern and variation of communication between primary healthcare (PHC) services and hospitals and specialists in relation to the patient's cancer care. A retrospective audit of clinical records of Indigenous Australians diagnosed with cancer during 2010-2016 identified through 10 PHC services in Queensland is described. Poisson regression was used to model the dichotomous outcome availability of hospital discharge summary versus not. A total of 138 patient records was audited 115 of those patients visited the PHC service for cancer-related care after cancer diagnosis 40.0% visited the service before a discharge summary was available, and 36.5% of the patients had no discharge summary in their medical notes. While most discharge summaries noted important information about the patient's cancer, 42.4% lacked details regarding the discharge medications regimen. Deficits in communication and information transfer between specialists and GP may adversely affect patient care. Indigenous Australians are a relatively disadvantaged group that experience poor health outcomes and relatively poor access to care. The low proportion of discharge summaries noting discharge medication regimen is of concern among Indigenous Australians with cancer who have high comorbidity burden and low health literacy. Our findings provide an insight into some of the factors associated with quality of cancer care, and may provide guidance for focus areas for further research and improvement efforts.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.IJANTIMICAG.2019.05.020
Abstract: In clinical practice, differing opinions exists regarding the optimal management of patients with penicillin-susceptible Staphylococcus aureus (PSSA) bloodstream infection (BSI). The aim of this study was to compare the 30-day mortality of patients treated with benzylpenicillin or flucloxacillin for PSSA BSI from a large prospectively collected data set from Australia and New Zealand. A logistic regression model and propensity score treatment analysis using inverse probability of treatment weighting were used. A total of 915 patients were included in the study, with an overall mortality rate of 12.9% (118/915) [benzylpenicillin 10.5% (33/315) and flucloxacillin 14.2% (85/600)]. Endocarditis was associated with benzylpenicillin treatment choice, whereas skin and soft-tissue infection was associated with flucloxacillin treatment choice. In the multivariate analysis, increased 30-day mortality was associated with flucloxacillin compared with benzylpenicillin [odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.0-2.5 P = 0.05). When adjusted for treatment choice in the propensity score analysis, flucloxacillin was again associated with increased 30-day mortality (OR = 1.06, 95% CI 1.01-1.1 P = 0.03). An increase in 30-day mortality associated with flucloxacillin use suggests a potential benefit for benzylpenicillin therapy in patients with PSSA BSI.
Publisher: Springer Science and Business Media LLC
Date: 08-01-2021
Publisher: Oxford Brookes University
Date: 26-04-2010
DOI: 10.3794/IJME.83.275
Publisher: Informa UK Limited
Date: 06-2013
Publisher: AME Publishing Company
Date: 05-2019
Publisher: Elsevier BV
Date: 11-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2019
DOI: 10.1097/MAO.0000000000002044
Abstract: To determine the typical proportions of diagnoses for patients presenting with dizziness or vertigo based on clinical speciality and to assess the change in proportions of diagnoses over time. Following PRISMA guidelines, systematic searches of PubMed and CINAHL databases and follow-up reference searches were performed for articles published in English up to October 2016. Analysis of searches yielded 42 studies meeting the criteria of case series of adult patients with dizziness and/or vertigo presenting to general practice, emergency departments or specialist outpatient clinics. Data comprising demographics, diagnostic cases, and the total number of cases were recorded and independently tested, followed by a risk of bias analysis. S le size weighted proportions expressed as percentages with confidence intervals were calculated and compared using χ 2 analysis and a reference proportion formed by the combination of Ear Nose and Throat and Neurotology case series published between 2010 and 2016. Analysis of diagnostic trends over time used Poisson regression with consideration for overdispersion. This systematic review of case series demonstrated significant differences in the proportions of diagnoses for patients presenting with dizziness or vertigo, depending on the specialty making the diagnosis. ENT proportions were dominated by BPPV, Psychogenic and Menière's disease diagnostic categories, whereas emergency proportions were dominated by Other, Cardiac, and Neurological categories. Analysis of case series proportions over time revealed increases in diagnoses such as Benign Paroxysmal Positional Vertigo and Vestibular Migraine, and a corresponding decrease in the diagnoses of Menière's disease.
Publisher: Public Library of Science (PLoS)
Date: 06-08-2015
Publisher: Wiley
Date: 09-2000
Publisher: Cold Spring Harbor Laboratory
Date: 13-12-2021
DOI: 10.1101/2021.12.12.472299
Abstract: T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use s les from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages. We identify a dramatic re-distribution of the Tfh cell compartment with age that is independent of malaria exposure, with Th2-Tfh cells predominating in early childhood, while Th1-Tfh cell gradually increase to adult levels over the first decade of life. Functional antibody acquisition is age-dependent and hierarchical acquired based on parasite stage, with merozoite responses followed by sporozoite and gametocyte antibodies. Antibodies were boosted in children with current infection, and were higher in females. The children with the very highest antibody levels had increased Tfh cell activation and proliferation, consistent with a key role of Tfh cells in antibody development. Together, these data reveal a complex relationship between the circulating Tfh compartment, antibody development and protection from malaria.
Publisher: Informa UK Limited
Date: 30-09-2015
Publisher: Springer Science and Business Media LLC
Date: 03-06-2009
Publisher: Springer Science and Business Media LLC
Date: 02-05-2020
DOI: 10.1007/S00520-019-04821-1
Abstract: The role of general practitioners in cancer care has expanded in recent years. However, little is known about utilization of primary health care (PHC) services by patients with cancer, particularly among socio-economically disadvantaged groups. We describe utilization of PHC services by patients with cancer, and the nature of the care provided. The study focuses on a disadvantaged group in Australia, namely Indigenous Australians. A retrospective audit of clinical records in ten PHC services in Queensland, Australia. Demographic and clinical data of Indigenous Australians diagnosed with cancer during 2010-2016 were abstracted from patient's medical records at the PHC services. The rates of cancer-related visits were calculated using person years at risk as a denominator. A total of 138 patients' records were audited. During 12 months following the cancer diagnosis, patients visited the PHC service on average 5.95 times per year. Frequency of visits were relatively high in remote areas and among socioeconomic disadvantaged patients (IRR = 1.87, 95%CI 1.61-2.17 IRR = 1.79, 95%CI 1.45-2.21, respectively). Over 80% of visits were for seeking attention for symptoms, wound care, and emotional or social support. Patients who did not undergo surgery, had greater comorbidity, received chemotherapy and/or radiotherapy, and male gender had significantly greater rate of visits than their counterparts. The frequency of utilization of PHC services, especially by patients with comorbidities, and the range of reasons for attendance highlights the important role of PHC services in providing cancer care. The reliance on PHC services, particularly by patients in remote and disadvantaged communities, has important implications for appropriate resourcing and support for services in these locations.
Publisher: Informa UK Limited
Date: 05-09-2019
Publisher: Cold Spring Harbor Laboratory
Date: 08-03-2022
DOI: 10.1101/2022.03.07.483250
Abstract: Researching the murine epigenome in disease models has been h ered by the lack of an appropriate and cost-effective DNA methylation array. Until recently, investigators have been limited to the relatively expensive and analysis intensive bisulphite sequencing methods. Here, we performed a comprehensive, comparative analysis between the new Mouse Methylation BeadChip (MMB) and reduced representation bisulphite sequencing (RRBS) in two murine models of colorectal carcinogenesis, providing insight into the utility to each platforms in a real world environment. We captured 1.47×10 6 CpGs by RRBS and 2.64×10 5 CpGs by MMB, mapping to 13,778 and 13,365 CpG islands, respectively. RRBS captured significantly more CpGs per island (median 41 for RRBS versus 2 for MMB). We found that 64.4% of intra-island CpG methylation variability can be captured by measuring approximately one quarter of CpG island (CGI) CpGs. MMB was more precise in measuring DNA methylation, especially at sites that had low RRBS coverage. This impacted differential methylation analysis, with more statistically significantly differentially methylated CpG sites identified by MMB in all experimental conditions, however the difference was minute when appropriate thresholding for the magnitude of methylation change (0.2 beta value difference) was applied, providing confidence that both techniques can identify similar differential DNA methylation. Gene ontology enrichment analysis of differentially hypermethylated gene promoters identified similar biological processes and pathways by both RRBS and MMB across two murine model systems. MMB is an effective tool for profiling the murine methylome that performs comparably to RRBS, identifying similar differentially methylated pathways. Although MMB captures a similar proportion of CpG islands, it does so with fewer CpGs per island. We show that subs ling informative CpGs from CpG islands is an appropriate strategy to capture whole island variation. Choice of technology is experiment dependent and will be predicated on the underlying biology being probed.
Publisher: MDPI AG
Date: 05-01-2022
Abstract: With five-year survival rates as low as 3%, lung cancer is the most common cause of cancer-related mortality worldwide. The severity of the disease at presentation is accredited to the lack of early detection capacities, resulting in the reliance on low-throughput diagnostic measures, such as tissue biopsy and imaging. Interest in the development and use of liquid biopsies has risen, due to non-invasive s le collection, and the depth of information it can provide on a disease. Small extracellular vesicles (sEVs) as viable liquid biopsies are of particular interest due to their potential as cancer biomarkers. To validate the use of sEVs as cancer biomarkers, we characterised cancer sEVs using miRNA sequencing analysis. We found that miRNA-3182 was highly enriched in sEVs derived from the blood of patients with invasive breast carcinoma and NSCLC. The enrichment of sEV miR-3182 was confirmed in oncogenic, transformed lung cells in comparison to isogenic, untransformed lung cells. Most importantly, miR-3182 can successfully distinguish early-stage NSCLC patients from those with benign lung conditions. Therefore, miR-3182 provides potential to be used for the detection of NSCLC in blood s les, which could result in earlier therapy and thus improved outcomes and survival for patients.
Publisher: Informa UK Limited
Date: 02-01-2018
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.AUCC.2021.03.005
Abstract: Pressure injuries are a ubiquitous, yet largely preventable, hospital acquired complication commonly seen in critically ill patients in the intensive care unit. The objectives of this study were to implement targeted evidence-based pressure injury prevention strategies and evaluate their effect through measurement of patient pressure injury observations. A prospective multiphased design was used in the intensive care unit of an Australian tertiary referral hospital using three study periods (period 1, weeks 1-18 period 2, weeks 19-28 and period 3, weeks 29-52). The interventions included staff-focused interventions and patient-focused interventions, with the latter defined in a work unit guideline. Weekly visual observations of critically ill patients' skin integrity were conducted by trained research nurses over 52 weeks from November 2015 to November 2016. The primary outcome measure was a pressure injury of any stage, identified at the weekly observation, and the effect of the intervention was evaluated through logistic regression. Reporting rigour has been demonstrated using the Standards for Quality Improvement Reporting Excellence checklist. Over the whole study, 15.4% (95% confidence interval [CI] = 12.6, 18.2%, 97/631) of patients developed a pressure injury, with the majority of these injuries (73.2%, 95% CI = 64.4%, 82.0%, 71/97) caused by medical devices. After adjustment for covariates known to influence hospital-acquired pressure injury development, pressure injury rates for period 3 compared with period 1 were reduced (odds ratio = 0.41, 95% CI = 0.20-0.97, p = 0.0126). We found the use of defined pressure injury prevention strategies targeted at both staff and patients reduced pressure injury prevalence.
Publisher: Informa UK Limited
Date: 02-11-2017
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.VACCINE.2008.05.077
Abstract: The primary objective was to evaluate the safety and immunogenicity of a prototype inactivated, split-virus H5N1 (avian influenza A) vaccine. A secondary objective was to assess the cross-reactivity of immune responses to two variant clade 2 H5N1 strains. In two randomised, dose comparison, parallel assignment, multicentre trials conducted in Australia, healthy adult volunteers received two doses of 7.5 microg or 15 microg H5 haemagglutinin (HA) vaccine+/-AlPO4 adjuvant (phase I trial N=400) or two doses of 30 microg or 45 microg H5 HA with AlPO4 adjuvant (phase II trial N=400). Revaccination with a booster dose was offered 6 months after dose 2 (phase I trial only). Main outcome measures were the change in immunogenicity at each follow-up visit from baseline, measured using HA inhibition (HI) and virus microneutralisation (MN) assays, and the frequency and nature of adverse events (AEs). Computer generated tables were used to randomly allocate treatments participants and investigators were blinded to treatment allocation. All formulations were well-tolerated no unexpected serious adverse events were reported. Two doses of 30 microg or 45 microg H5 HA adjuvanted formulations elicited the highest immune responses, with considerable MN antibody (>or=1:20) persistence up to 6 months post-vaccination. The 7.5 and 15 microg formulations (+/-adjuvant) were less immunogenic than the higher dose formulations HI and MN antibody titres decreased to near pre-vaccination levels at 6 months but were restored to post-dose 2 levels after the booster dose. Immune responses in the phase I trial demonstrated modest levels of cross-protective MN antibodies against two currently circulating, distinct clade 2 H5N1 strains. Two doses of prototype 30 microg or 45 microg aluminium-adjuvanted, clade 1 H5N1 vaccines were immunogenic and well-tolerated with considerable 6-month antibody persistence. The prototype H5N1 vaccine also elicited modest levels of cross-protective MN antibodies against variant clade 2 H5N1 strains [ClinicalTrials.gov identifiers: NCT00136331, NCT00320346 CSL Limited, Australia].
Publisher: Elsevier BV
Date: 04-2004
Publisher: American Geophysical Union (AGU)
Date: 09-1999
DOI: 10.1029/1999WR900020
Publisher: Springer Science and Business Media LLC
Date: 27-11-2019
DOI: 10.1186/S12905-019-0846-7
Abstract: Health inequities inhibit global development and achievement of the Sustainable Development Goals. One gendered health area, Menstrual Health & Hygiene (MHH), has received increasing attention in Low- and Middle-Income Countries as a barrier to health, wellbeing, and gender equity. Recent anecdotal evidence in Australia highlights that MHH also present challenges to High Income Countries, particularly among underrepresented populations, such as Indigenous Australian peoples, people from low socio-economic backgrounds, or communities that are remotely located. In this article, we chart the emergence of attention to MHH in the Australian context and highlight key considerations for the conduct of research with Aboriginal and Torres Strait Islander Peoples within the culturally- and gender-sensitive area of MHH. Further we draw on insights offered by a partnership between female Aboriginal and Torres Strait Islander leaders, NGO stakeholders, and non-Indigenous researchers. Through a convening (yarning circle) held in March 2018, the group identified multiple socioecological considerations for MHH research and practice, including: affordability and access to menstrual products, barriers to knowledge and culturally sensitive education, infrastructure and supply chain challenges, and the necessity of Indigenous-led research and community-driven data collection methods in addressing the sensitive topic. We draw together these insights to develop recommendations for future research, advocacy, and action in Australia.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.VACCINE.2007.04.017
Abstract: 23 Valent pneumococcal vaccine is provided to the elderly through public health programs in many countries. However there is no clear recommendation regarding its route of administration (subcutaneous or intramuscular). In a randomised, observer blind study of 254 elderly subjects, the immunogenicity of a 23 valent pneumococcal vaccine was not influenced by its route of administration. A low rate of systemic adverse reactions was observed with the vaccine (subcutaneous and intramuscular both 6.3%). Local adverse reaction rates were intramuscular 7.1% and subcutaneous 18.9% and these were predicted by: * Pre-vaccination antibody titres>1 microg/ml, odds ratio 22.4 (8.06-74.84) compared with pre-vaccination antibody titre<1 microg/ml. * Female gender, odds ratio 5.0 (1.85-14.83) compared with male gender. * Subcutaneous injection route, odds ratio 3.20 (1.13-9.13) compared with intramuscular injection route. * Female gender subcutaneous injection route, odds ratio 2.99 (1.10-8.70) compared with female gender intramuscular injection route. These data support the intramuscular injection of 23 valent pneumococcal vaccine, especially in elderly females.
Publisher: Cold Spring Harbor Laboratory
Date: 11-02-2022
DOI: 10.1101/2022.02.11.480021
Abstract: Regorafenib is a multi-kinase inhibitor approved for refractory metastatic colorectal cancer. Previous studies have suggested that combining kinase inhibitors with aspirin may improve patient outcomes. We aimed to determine the effects of aspirin and regorafenib combination treatment in preclinical models of colorectal cancer. SW480, RKO and LIM1215 colorectal cancer cell lines were treated with aspirin and regorafenib to determine effects on proliferation and cytotoxicity. RNA sequencing and Western blotting were performed to explore underlying molecular effects. Aspirin and regorafenib combination treatment was also tested using organoids derived from three human colorectal cancer tissue specimens. For the in vivo study, SW480-derived tumors were established in athymic mice. Tumor volume was measured during treatment with aspirin and regorafenib, followed by immunohistochemical staining for markers of proliferation and apoptosis. Aspirin and regorafenib synergistically inhibited proliferation of colorectal cancer cell lines and patient-derived organoids, irrespective of KRAS or BRAF mutation status. This was associated with inhibition of the PI3K-Akt-mTOR pathway and activation of the AMPK pathway. Aspirin and regorafenib effectively inhibited growth of microsatellite stable KRAS -mutant SW480-derived tumors in vivo . Immunohistochemical staining for Ki67 and cleaved caspase 3 showed that combination treatment elicited a synergistic anti-proliferative effect, in addition to a pro-apoptotic effect that was driven by regorafenib. Aspirin and regorafenib demonstrate synergistic anti-proliferative effects in preclinical models of colorectal cancer. This suggests that combining regorafenib with aspirin may be an improved treatment strategy for patients with refractory metastatic colorectal cancer.
Publisher: Academy of Management
Date: 2013
Publisher: Emerald
Date: 06-02-2009
Publisher: Elsevier BV
Date: 12-2006
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-02-2023
DOI: 10.1097/HC9.0000000000000066
Abstract: Australians with cirrhosis have significant practical and psychosocial needs. This longitudinal study examined the association between supportive care needs and health service use and costs, and patient outcomes from June 2017 to December 2018. The Supportive Needs Assessment tool for Cirrhosis (SNAC), quality of life (Chronic Liver Disease Questionnaire and Short Form 36), and distress (distress thermometer) were self-reported through an interview at recruitment (n=433). Clinical data were obtained from medical records and through linkage, and health service use and costs through linkage. Patients were grouped as by needs status. Rates of hospital admissions (per person days at risk) and costs were assessed by needs status [incidence rate ratios (IRR), Poisson regression]. Multivariable linear regression was used to assess the differences in SNAC scores by quality of life and distress. Multivariable models included Child-Pugh class, age, sex, recruitment hospital, living arrangements, place of residence, comorbidity burden, and primary liver disease etiology. In adjusted analyses, compared with patients with low/no needs, patients with unmet needs had more cirrhosis-related admissions (adjusted IRR=2.11, 95% CI=1.48–3.13 p .001), admissions through the emergency department (IRR=2.99, 95% CI=1.80–4.97, p .001), and emergency presentations (IRR=3.57, 95% CI=1.41–9.02 p .001). Total hospitalization costs for cirrhosis admissions were higher for those with unmet needs ($431,242 per person days at risk) compared with those with met needs ($87,363 per person days at risk, adjusted cost ratio=3.52, 95%CI=3.49–3.54 p .001). In multivariable analysis, increasing overall mean SNAC scores (higher needs) were correlated with poorer quality of life and higher level of distress ( p .001 for all comparisons). Patients with cirrhosis and high unmet psychosocial needs and practical and physical needs have poor quality of life, high distress, and very high service use and costs, highlighting the importance of urgently addressing unmet needs.
Publisher: Wiley
Date: 28-05-2020
Publisher: Wiley
Date: 05-08-2019
DOI: 10.1111/JAN.14085
Abstract: This study aimed to compare the head dose of a cardiologist to scrub and scout nurses during cardiac angiography. A correlational longitudinal quantitative design was used to examine the relationship between the variable of occupational dose to the medical operator when compared with the dose to the scrub and scout nurses. A quantitative analysis was performed on data collected during coronary angiograms (N = 612) for one cardiologist and 22 nurses performing either the scrub or scout role between May 2015 and February 2017. Analysis was based on log-transformed dose levels and reported as geometric means and associated 95% confidence intervals. It was found that scrub nurses received on average 41% more head dose than the cardiologist during diagnostic procedures and 52% higher doses during interventional cases. Nurses working in fluoroscopic cardiovascular procedures should be provided with appropriate training and protective equipment, notably lead skull caps, to minimize their occupational radiation exposure. There is a notable lack of research evaluating the occupational head and eye exposure to nurses involved in fluoroscopic procedures. This study found that during diagnostic coronary angiograms, the scrub nurses received 41% more occupational head dose than the cardiologist and 52% higher head doses during interventional cases. Radial access resulted in higher doses to scrub nurses than femoral artery access. It is advisable that staff wear protective lead glasses and skull caps and use appropriately positioned ceiling mounted lead shields to minimize the risk of adverse effects of occupational exposure to ionizing radiation.
Publisher: Cambridge University Press (CUP)
Date: 17-09-2012
Publisher: SAGE Publications
Date: 12-2005
Publisher: Informa UK Limited
Date: 03-07-2014
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.YPMED.2019.05.005
Abstract: Sunscreen when applied at the recommended concentration (2 mg/cm
Publisher: Elsevier BV
Date: 2021
DOI: 10.2139/SSRN.3778707
Publisher: Massachusetts Medical Society
Date: 17-12-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2019
Publisher: Elsevier BV
Date: 11-2021
Publisher: Emerald
Date: 12-2004
DOI: 10.1108/13527600410797918
Abstract: Detrimental effects of ersity in workgroups has frequently been observed but research identifying the factors that lead to negative or positive effects in heterogeneous groups is lacking. The Perceived Dissimilarity Openness Moderator Model provides one explanation of the process by which ersity influences group affective, behavioral, and cognitive outcomes. Specifically the model identifies in idual, group, and organizational openness as moderating the effects of ersity in workgroups. In this paper evidence is provided from a field study that increased openness to perceived dissimilarity leads to better outcomes in newly formed groups. This study also constitutes a significant building block toward the development of theory concerning the moderating variables of the relationship between ersity and group processes, and outcomes of organizations.
Publisher: Informa UK Limited
Date: 05-11-2013
Publisher: Springer Science and Business Media LLC
Date: 07-10-2021
DOI: 10.1007/S00192-021-04985-7
Abstract: The aim was to develop and validate (internally and externally) a prediction model for the presence and diagnosis of pelvic floor dysfunction (PFD) in women, including pelvic organ prolapse, stress urinary incontinence and/or overactive bladder via a patient-completed online tool. Using a retrospective cohort of women aged >18 years, from multiple tertiary gynaecology units within Queensland, Australia (2014-2018), the prediction model was developed via penalized logistic regression with internal and external validation utilizing multiple clinical predictors (42 questions from the Australian Pelvic Floor Questionnaire and demographics: age, body mass index, parity and mode of delivery). The main outcome measures were the accuracy of the model in predicting a diagnosis of pelvic floor dysfunction and its specific conditions of prolapse and incontinence. A total of 3,501 women were utilized for model development and internal validation and 449 for external validation. On internal validation the model correctly identified those with PFD with 97% sensitivity, 74% specificity and a concordance index (C-index) of 0.96. Predictions of pelvic organ prolapse were also accurate, with 86% sensitivity, 83% specificity, C-index 0.83, as was stress urinary incontinence, 84% sensitivity, 87% specificity, C-index 0.87, and overactive bladder, 76% sensitivity, 77% specificity, C-index 0.77. External validation confirmed the model's accuracy with a similar C-index in all parameters. This model provides an accurate online tool to differentiate between those with and without PFD and diagnoses of common pelvic floor disorders. It serves as a valuable self-assessment for women and primary care providers.
Publisher: SAGE Publications
Date: 10-2002
DOI: 10.1046/J.1440-1614.2002.01070.X
Abstract: Objective: To determine the prevalence and investigate potential predictors of psychological distress in Filipino women living in Queensland, Australia. Methods: The s le of n = 487 women (88% response rate) was drawn from Filipino organization membership lists and supplemented by snowball s ling. Participants were interviewed in their homes or at a community event in 1996/1997. Follow-up in 1997/1998 involved n = 346 women (71% response rate) who were interviewed either in their homes or by telephone. The two surveys included measurement of demographic, immigration, physical health, satisfaction with life in Australia and life event variables. The GHQ-28 was included in the follow-up survey as a measure of psychological distress. Results: The proportion of women having an above threshold score (using the cut-off of 4/5) on the GHQ-28 was 23%. Women who were single, dissatisfied with life in Australia, had reported a major change in their financial situation, their relationship or their health in the year between surveys were significantly more likely to have an above threshold score. Conclusions: The level of mental distress among Filipinas in Queensland appears to be slightly higher than the levels reported in the general population but lower than other migrant groups. The determinants of mental distress in this population contrast with those in the general Australian population and other migrant groups. The social context of these determinants in Filipinas needs to be elicited for an understanding of these differences.
Publisher: IOP Publishing
Date: 10-2020
Abstract: Volatile organic compound (VOC) breath testing of lung and head and neck squamous cell carcinoma (SCC) has been widely studied, however little is known regarding VOC profiles of in-situ SCC. A prospective study of VOC in patients with histologically proven SCC, either in-situ or advanced, and controls. Breath s les were analysed using the E-nose Cyranose ® 320 and by gas chromatography/mass spectroscopy. Predictive models were developed using bootstrap forest using all 32 sensors. Data from 55 participants was analysed: 42 SCC cases comprising 20 bronchial (10 in-situ , 10 advanced) and 22 laryngeal (12 in-situ , 10 advanced), and 13 controls. There were 32 (76%) male SCC cases with mean age 63.6 (SD = 9.5) compared with 11 (85%) male controls with mean age 61.9 (SD = 10.1). Predictive models for in situ cases had good sensitivity and specificity compared to controls (overall, 95% and 69% laryngeal, 100% and 85% bronchial, 77% and 80%). When distinguishing in-situ and advanced tumours, sensitivity and specificity 82% and 75% respectively. For different tumour types (bronchial versus advanced laryngeal) sensitivity and specificity were 100% and 80% respectively. VOCs isolated from in-situ cancers included some previously demonstrated in advanced cancers and some novel VOCs. In-situ bronchial and laryngeal cancer can be detected by VOC analysis. Distinction from normal controls and between the two tumour types could allow screening in high risk groups for these curable lesions.
Publisher: BMJ
Date: 06-07-2022
DOI: 10.1136/GUTJNL-2020-322166
Abstract: Sessile serrated lesions (SSLs) are common across the age spectrum, but the BRAF mutant cancers arising occur predominantly in the elderly. Aberrant DNA methylation is uncommon in SSL from young patients. Here, we interrogate the role of ageing and DNA methylation in SSL initiation and progression. We used an inducible model of Braf mutation to direct recombination of the oncogenic Braf V637E allele to the murine intestine. BRAF mutation was activated after periods of ageing, and tissue was assessed for histological, DNA methylation and gene expression changes thereafter. We also investigated DNA methylation alterations in human SSLs. Inducing Braf mutation in aged mice was associated with a 10-fold relative risk of serrated lesions compared with young mice. There were extensive differences in age-associated DNA methylation between animals induced at 9 months versus wean, with relatively little differential Braf- specific methylation. DNA methylation at WNT pathway genes scales with age and Braf mutation accelerated age-associated DNA methylation. In human SSLs, increased epigenetic age was associated with high-risk serrated colorectal neoplasia. SSLs arising in the aged intestine are at a significantly higher risk of spontaneous neoplastic progression. These findings provide support for a new conceptual model for serrated colorectal carcinogenesis, whereby risk of Braf- induced neoplastic transformation is dependent on age and may be related to age-associated molecular alterations that accumulate in the ageing intestine, including DNA methylation. This may have implications for surveillance and chemopreventive strategies targeting the epigenome.
Publisher: Oxford University Press (OUP)
Date: 07-11-2019
DOI: 10.1111/BJD.18517
Publisher: Elsevier BV
Date: 05-2020
DOI: 10.1016/J.JCF.2019.06.017
Abstract: Current diagnostic methods for the diagnosis of Cystic fibrosis (CF)-associated liver disease (CFLD) are non-specific and assessment of disease progression is difficult prior to the advent of advanced disease with portal hypertension. This study investigated the potential of Supersonic shear-wave elastography (SSWE) to non-invasively detect CFLD and assess hepatic fibrosis severity in children with CF. 125 children were enrolled in this study including CFLD (n = 55), CF patients with no evidence of liver disease (CFnoLD = 41) and controls (n = 29). CFLD was diagnosed using clinical, biochemical and imaging best-practice guidelines. Advanced CFLD was established by the presence of portal hypertension and/or macronodular cirrhosis on ultrasound. Liver stiffness measurements (LSM) were acquired using SSWE and diagnostic performance for CFLD detection was evaluated alone or combined with aspartate aminotransferase-to-platelet ratio index (APRI). LSM was significantly higher in CFLD (8.1 kPa, IQR = 6.7-11.9) versus CFnoLD (6.2 kPa, IQR = 5.6-7.0 P < 0.0001) and Controls (5.3 kPa, IQR = 4.9-5.8 P < 0.0001). LSM was also increased in CFnoLD versus Controls (P = 0.0192). Receiver Operating Characteristic (ROC) curve analysis demonstrated good diagnostic accuracy for LSM in detecting CFLD using a cut-off = 6.85 kPa with an AUC = 0.79 (Sensitivity = 75%, Specificity = 71%, P < 0.0001). APRI also discriminated CFLD (AUC = 0.74, P = 0.004). Classification and regression tree modelling combining LSM + APRI showed 14.8 times greater odds of accurately predicting CFLD (AUC = 0.84). The diagnostic accuracy of SSWE for discriminating advanced disease was excellent with a cut-off = 9.05 kPa (AUC = 0.95 P < 0.0001). SSWE-determined LSM shows good diagnostic accuracy in detecting CFLD in children, which was improved when combined with APRI. SSWE alone discriminates advanced CFLD.
Publisher: Informa UK Limited
Date: 2000
Publisher: Elsevier BV
Date: 11-1998
DOI: 10.1016/S0001-706X(98)00062-X
Abstract: In this study we examine the pathways to schistosomiasis exposure and infection among residents residing on two islands (large, Qingshan small, Niangashan) in the Dongting Lake region (Hunan province) of China. An exposure model, based on activity diaries, was used to quantify an in idual's square-metre-minute (sq.m.min) daily water contact. Subjects living on the small island had a significantly higher (P=0.0002) degree of exposure (mean+/-S.D., 13.2+/-11.0 sq.m.min) than in iduals dwelling on the large island (mean+/-S.D., 5.5+/-7.1 sq.m.min). Participants identified as stool egg positive (mean+/-S.D., 8.3+/-10.4 sq.m.min) had higher exposures than for those never treated (mean+/-S.D., 2.2+/-3.4 sq.m.min) for schistosomiasis, and these high exposures rose steadily to peak at 35-49 years of age and decline after age 50. This exposure pattern differs markedly from those reported for African or South American schistosomiasis. The majority of human water contact occurs on the lake. Egg-positive subjects reported significantly higher (P < 0.05) episodes of water contact on the lake versus their egg-negative counterparts, who reported significantly higher (P < 0.01) exposure at the aquaculture ponds. The results of path analysis revealed that sex, age, island of residence and whether a fisherman or not were the most highly significant independent predictors of lake exposure. This accounted for approximately 40% (R2=0.39) of the total lake exposure. Exposure to lake water was a strong predictor (P=0.0006) of past infection and a modest predictor (P=0.05) of current infection.
Publisher: Elsevier BV
Date: 03-2021
DOI: 10.1016/J.JCF.2021.10.014
Abstract: Cystic fibrosis (CF)-associated liver disease (CFLD) causes significant morbidity and mortality in children with CF. Diagnosis of liver disease prior to development of cirrhosis or portal hypertension (PHT) is challenging. While imaging modalities using Elastography show great promise they are still not widely available to all clinicians. This study investigated gamma-glutamyl transpeptidase-to-platelet ratio (GPR) as a non-invasive biomarker to detect liver disease and stage fibrosis severity in children with CF. 237 children were enroled including 76 with CFLD and 161 with CF and no detectable liver disease (CFnoLD). CFLD was diagnosed using standard clinical, biochemical and imaging practice guidelines. Hepatic fibrosis was staged on liver biopsies available from 54 children with CFLD. Serum liver biochemistry was used to calculate GPR (median, [IQR]) and receiver operating characteristics (ROC) analysis assessed utility to detect liver disease and stage fibrosis severity. GPR was significantly increased in CFLD versus CFnoLD (0.33 [0.19-0.96] vs. 0.15 [0.11-0.21], P<0.0001). GPR demonstrated good diagnostic utility for detecting CFLD with an area under the curve (AUC) of 0.81 (95% confidence Interval [CI] [0.75-0.87] P<0.0001), with sensitivity of 74% and specificity of 73%, using a cut-off of 0.20. GPR increased with increasing hepatic fibrosis stage. GPR discriminated both moderate-advanced (F2-F4) fibrosis vs. F0-F1 (AUC=0.82 95%CI [0.71-0.94] P 0.84 was predictive of PHT at diagnosis of CFLD (AUC=0.81 95%CI [0.67-0.95] P = 0.0003). GPR demonstrates good diagnostic utility for assessing the presence of liver disease, PHT and hepatic fibrosis severity in children with CF. These findings will aid in better identification of patients at risk for CF-related liver involvement and the potential for more targeted and timely follow-up and treatment.
Publisher: American Thoracic Society
Date: 06-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2018
DOI: 10.1161/ATVBAHA.118.310538
Abstract: CSL112 (apolipoprotein A-I [apoA-I human]) is a novel formulation of apoA-I in development for reduction of early recurrent cardiovascular events after acute myocardial infarction. Cholesterol efflux capacity (CEC) is a marker of high-density lipoprotein (HDL) function that is strongly correlated with incident cardiovascular disease. Impaired CEC has been observed in patients with coronary heart disease. Here, we determined whether infused apoA-I improves CEC when administered to patients with stable atherosclerotic disease versus healthy volunteers. Measurements of apoA-I, HDL unesterified cholesterol, HDL esterified cholesterol, pre–β1-HDL, and CEC were determined in s les from patients with stable atherosclerotic disease before and after intravenous administration of CSL112. These measures were compared with 2 prior studies in healthy volunteers for differences in CEC at baseline and after CSL112 infusion. Patients with stable atherosclerotic disease exhibited significantly lower ATP-binding cassette transporter 1–mediated CEC at baseline ( P .0001) despite slightly higher apoA-I levels when compared with healthy in iduals (2 phase 1 studies pooled P ≤0.05), suggesting impaired HDL function. However, no differences were observed in apoA-I pharmacokinetics or in pre–β1-HDL ( P =0.5) or CEC ( P =0.1) after infusion of CSL112. Similar elevation in CEC was observed in patients with low or high baseline HDL function (based on tertiles of apoA-I–normalized CEC P =0.1242). These observations were extended and confirmed using cholesterol esterification as an additional measure. CSL112 shows comparable, strong, and immediate effects on CEC despite underlying cardiovascular disease. CSL112 is, therefore, a promising novel therapy for lowering the burden of atherosclerosis and reducing the risk of recurrent cardiovascular events.
Publisher: Wiley
Date: 12-01-2011
Publisher: Public Library of Science (PLoS)
Date: 06-01-2021
DOI: 10.1371/JOURNAL.PNTD.0008997
Abstract: Scabies, a highly contagious skin disease affecting more than 200 million people worldwide at any time, is caused by the parasitic mite Sarcoptes scabiei . In the absence of molecular markers, diagnosis requires experience making surveillance and control challenging. Superficial microthrombi in the absence of vasculitis in scabies-affected skin are a recognised, yet unexplained histopathological differential of scabies infection. This study demonstrates that a family of Scabies Mite Inactivated Cysteine Protease Paralogues (SMIPP-Cs) excreted by the mites plays a role in formation of scabies-induced superficial microthrombi. A series of in vitro and ex vivo experiments involving two representative recombinant SMIPP-Cs was carried out. In the presence of SMIPP-Cs, the thrombin clotting time (TCT), fibrin formation and plasmin induced fibrinolysis were monitored in vitro . The ultrastructure of the SMIPP-C—modulated fibrin was analysed by Scanning Electron Microscopy (SEM). Immuno-histological analyses were performed ex vivo , to localise the SMIPP-C proteins within scabies infected skin biopsies. SMIPP-Cs displayed pro-coagulant properties. They bound calcium ions, reduced the thrombin clotting time, enhanced the fibrin formation rate and delayed plasmin-induced fibrinolysis. The SMIPP-Cs associated with fibrin clots during fibrinogen polymerisation and did not bind to preformed fibrin. Scanning electron microscopy revealed that the fibrin clots formed in the presence of SMIPP-Cs were aberrant and denser than normal fibrin clots. SMIPP-Cs were detected in microthrombi which are commonly seen in scabietic skin. The SMIPP-Cs are the first scabies mite proteins found in sub-epidermal skin layers and their pro-coagulant properties promote superficial microthrombi formation in scabetic skin. Further research is needed to evaluate their potential as diagnostic or therapeutic target.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-02-2021
DOI: 10.1002/HEP4.1681
Abstract: Patients with cirrhosis have significant physical, psychological, and practical needs. We documented patients’ perceived need for support with these issues and the differences with increasing liver disease severity, etiology, and age. Using the supportive needs assessment tool for cirrhosis (SNAC), we examined the rate of moderate‐to‐high unmet needs (Poisson regression incidence rate ratio [IRR]) and the correlation between needs and sociodemographic/clinical characteristics (multivariable linear regression) in 458 Australians adults with cirrhosis. Primary liver disease etiology was alcohol in 37.6% of patients, chronic viral hepatitis C in 25.5%, and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in 23.8%. A total of 64.6% of patients had Child‐Pugh class A cirrhosis. Most patients (81.2%) had at least one moderate‐to‐high unmet need item more than 25% reported a moderate‐to‐high need for help with “lack of energy,” “sleep poorly,” “feel unwell,” “worry about … illness getting worse (liver cancer),” “have anxiety/stress,” and “difficulty with daily tasks.” Adjusting for key sociodemographic/clinical factors, patients with Child‐Pugh C had a greater rate of “practical and physical needs” (vs. Child‐Pugh A IRR = 2.94, 95% confidence interval [CI] 2.57‐3.37), patients with NAFLD/NASH had a greater rate of needs with “lifestyle changes” (vs. alcohol IRR = 1.81, 95% CI 1.18‐2.77) and “practical and physical needs” (IRR = 1.43, 95% CI 1.23‐1.65), and patients aged ≥65 years had fewer needs overall (vs. 18‐64 years IRR = 0.70, 95% CI 0.64‐0.76). Higher overall SNAC scores were associated with Child‐Pugh B and C (both P 0.001), NAFLD/NASH ( P = 0.028), patients with “no partner, do not live alone” ( P = 0.004), unemployment ( P = 0.039), ascites ( P = 0.022), and dyslipidemia ( P = 0.024) compared with their counterparts. Conclusion: Very high levels of needs were reported by patients with cirrhosis. This information is important to tailor patient‐centered care and facilitate timely interventions or referral to support services.
Publisher: Informa UK Limited
Date: 04-2023
DOI: 10.2147/PPA.S405567
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.JINF.2018.03.005
Abstract: Bloodstream infection results in significant short-term morbidity and mortality. No literature review has studied the long-term outcome following a bloodstream infection. This PROSPERO registered systematic review evaluated studies, which measured the association of a bloodstream infection with long-term morbidity and mortality. Databases were systematically searched for studies of adult patients reporting morbidity and/or mortality one year or more following a bloodstream infection in comparison to a matched cohort without a bloodstream infection. Ten observational studies were included in the final analysis. Five studies assessed only mortality, two assessed morbidity and mortality and three studies assessed morbidity only. The one year mortality ranged from between 8 and 48% for patients with bloodstream infection. The pooled risk ratio of death at one year was significantly higher for patients with bloodstream infection when compared to the matched cohort (RR 4.04 [95% CI 1.84-8.87]). Bloodstream infection was associated with poor long-term outcome measured at one year when compared to matched controls. More evidence is needed to determine if this association is causative.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.VACCINE.2016.08.038
Abstract: Before pandemic H1N1 vaccines were available, the potential benefit of existing seasonal trivalent inactivated influenza vaccines (IIV3s) against influenza due to the 2009 pandemic H1N1 influenza strain was investigated, with conflicting results. This study assessed the efficacy of seasonal IIV3s against influenza due to 2008 and 2009 seasonal influenza strains and against the 2009 pandemic H1N1 strain. This observer-blind, randomized, placebo-controlled study enrolled adults aged 18-64years during 2008 and 2009 in Australia and New Zealand. Participants were randomized 2:1 to receive IIV3 or placebo. The primary objective was to demonstrate the efficacy of IIV3 against laboratory-confirmed influenza. Participants reporting an influenza-like illness during the period from 14days after vaccination until 30 November of each study year were tested for influenza by real-time reverse transcription polymerase chain reaction. Over a study period of 2years, 15,044 participants were enrolled (mean age±standard deviation: 35.5±14.7years 54.4% female). Vaccine efficacy of the 2008 and 2009 IIV3s against influenza due to any strain was 42% (95% confidence interval [CI]: 30%, 52%), whereas vaccine efficacy against influenza due to the vaccine-matched strains was 60% (95% CI: 44%, 72%). Vaccine efficacy of the 2009 IIV3 against influenza due to the 2009 pandemic H1N1 strain was 38% (95% CI: 19%, 53%). No vaccine-related deaths or serious adverse events were reported. Solicited local and systemic adverse events were more frequent in IIV3 recipients than placebo recipients (local: IIV3 74.6% vs placebo 20.4%, p<0.001 systemic: IIV3 46.6% vs placebo 39.1%, p<0.001). The 2008 and 2009 IIV3s were efficacious against influenza due to seasonal influenza strains and the 2009 IIV3 demonstrated moderate efficacy against influenza due to the 2009 pandemic H1N1 strain. Funded by CSL Limited, ClinicalTrials.gov identifier NCT00562484.
Publisher: Public Library of Science (PLoS)
Date: 18-06-2018
Publisher: American Society of Hematology
Date: 18-10-2019
DOI: 10.1182/BLOODADVANCES.2019000453
Abstract: Peg-IFNα is tolerated and induces disease response in patients who relapse after allogeneic SCT. Increased pretreatment MAIT and pDC proportions were associated with better progression-free and overall survival after peg-IFNα treatment.
Publisher: Informa UK Limited
Date: 2003
Publisher: Wiley
Date: 08-2002
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.VACCINE.2014.10.024
Abstract: A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to <18 years of age. Subjects were stratified as follows: Cohort A (≥6 months to <3 years) Cohort B (≥3 years to <9 years) and Cohort C (≥9 years to <18 years). The subject's age and influenza vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1 669.13 vs. 705.61 for H3N2 and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts.
Publisher: Springer Science and Business Media LLC
Date: 18-07-2022
DOI: 10.1038/S41467-022-31880-6
Abstract: T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use s les from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages. We identify a dramatic re-distribution of the Tfh cell compartment with age that is independent of malaria exposure, with Th2-Tfh cells predominating in early childhood, while Th1-Tfh cell gradually increase to adult levels over the first decade of life. Functional antibody acquisition is age-dependent and hierarchical acquired based on parasite stage, with merozoite responses followed by sporozoite and gametocyte antibodies. Antibodies are boosted in children with current infection, and are higher in females. The children with the very highest antibody levels have increased Tfh cell activation and proliferation, consistent with a key role of Tfh cells in antibody development. Together, these data reveal a complex relationship between the circulating Tfh compartment, antibody development and protection from malaria.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2023
Publisher: American Society for Clinical Investigation
Date: 25-07-2019
Publisher: Wiley
Date: 21-10-2014
DOI: 10.1111/IJCS.12066
Publisher: SAGE Publications
Date: 04-2008
Publisher: Elsevier BV
Date: 07-2020
Publisher: Emerald
Date: 20-05-2011
DOI: 10.1108/20442081111129860
Abstract: The purpose of this paper is to develop insight regarding art gallery members' identification with their galleries through the use of segmentation. The antecedents of a member's identification and subsequent involvement with the gallery are explored. Within the four regional art galleries analysed, the authors identify three different segments within the membership groups which illustrate the ways in which gallery members, who identify positively with their gallery, contribute to the organisation through behaviours such as the donation of time and money. A mixed methods approach was used, including 11 in‐depth interviews with gallery staff and members and a survey ( n =433) of gallery members. The in‐depth interviews were interpreted using content analysis and thematic analysis. The survey results were analysed using exploratory factor analysis and cluster analysis. The paper's findings suggest that gallery members can be differentiated in terms of the way that they contribute to their art gallery. Three types were identified: promoters, donors and committee members. A number of constructs were used to distinguish between each of the segments, including: member identification, satisfaction, prestige, visibility, contact quality and domain involvement from the current arts marketing literature. Four other constructs which emerged from the qualitative research were also used to profile the clusters: self‐enhancement, organisational culture, social responsibility and elitism which emerged from the qualitative research. Profiling different segments in the market (membership) using sociodemographics, attitudes and donating behaviours allows marketers and managers to more effectively target the segments who can positively contribute to the organisation. Moreover it provides a greater understanding of the membership base and how various members are engaging with their institution. Current methods of marketing are becoming less ideal to obtain marketing objectives, with diminishing returns to scale on marketing programmes an issue. An understanding of the differences between each of these member types will allow galleries to more efficiently use their finite resources. By tailoring offerings to each of the different segments galleries can maximise the value of their membership base. Further, the use of segmentation enables gallery managers to identify segments where members may be less or not engaged and its causes and potential solutions. Many non‐profit organisations with a membership base, such as the art galleries s led in this research, rely on the contribution of their membership to survive. Therefore understanding the relationship between the institution and the membership is important. The paper is unique in the application of segmentation analysis to examine gallery members. It also furthers the current understanding of identification and its role in the relationship between organisation members and their behaviour as members. That is the role of identification in relationship marketing.
Publisher: MDPI AG
Date: 21-09-2023
Publisher: Informa UK Limited
Date: 2012
Publisher: Springer Science and Business Media LLC
Date: 17-02-2020
DOI: 10.1186/S12939-020-1144-6
Abstract: Indigenous Australians experience greater health disadvantage and have a higher prevalence of many chronic health conditions. Liver diseases leading to cirrhosis are among the most common contributor to the mortality gap between Indigenous and other Australian adults. However, no comparative data exist assessing differences in presentation and patient outcomes between Indigenous and non-Indigenous Australians hospitalised with cirrhosis. Using data from the Hospital Admitted Patient Data Collection and the Death Registry, this retrospective, population-based, cohort study including all people hospitalised for cirrhosis in the state of Queensland during 2008–2017 examined rate of readmission (Poisson regression), cumulative survival (Kaplan–Meier), and assessed the differences in survival (Multivariable Cox regression) by Indigenous status. Predictor variables included demographic, health service characteristics and clinical data. We studied 779 Indigenous and 10,642 non-Indigenous patients with cirrhosis. A higher proportion of Indigenous patients were younger than 50 years (346 [44%] vs. 2063 [19%] non-Indigenous patients), lived in most disadvantaged areas (395 [51%) vs. 2728 [26%]), had alcohol-related cirrhosis (547 [70%] vs. 5041 [47%]), had ascites (314 [40%] vs. 3555 [33%), and presented to hospital via the Emergency Department (510 [68%] vs. 4790 [47%]). Indigenous patients had 3.04 times the rate of non-cirrhosis readmissions (95%CI 2.98–3.10), 1.35 times the rate of cirrhosis-related readmissions (95%CI 1.29–1.41), and lower overall survival (17% vs. 27% unadjusted hazard ratio (HR) = 1.16 95%CI 1.06–1.27), compared to non-Indigenous patients. Most of the survival deficit was explained by Emergency Department presentation (adj-HR = 1.03 95%CI 0.93–1.13), and alcohol-related aetiology (adj-HR = 1.08 95%CI 0.99–1.19). The remaining survival deficit was influenced by the other clinico-demographic and health service factors (final adj-HR = 1.08 95%CI 0.96–1.20). There was evidence of differential presentation, higher rates of readmissions, and poorer survival for Indigenous Australians with cirrhosis, compared to other Australians. The increased prevalence of Emergency Department presentation among Indigenous patients suggests missed opportunities for early intervention to prevent progressive cirrhosis complications and hospital readmissions.
Publisher: Inderscience Publishers
Date: 2006
Publisher: Wiley
Date: 08-2022
DOI: 10.1111/IRV.12107
Publisher: No publisher found
Date: 1997
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-11-2022
DOI: 10.1002/HEP4.1852
Abstract: It remains unclear whether screening for advanced fibrosis in the community can identify the subgroup of people with nonalcoholic fatty liver disease (NAFLD) at higher risk for development of liver‐related complications. We aimed to determine the prognostic value of baseline noninvasive fibrosis tests for predicting liver‐related outcomes and mortality in patients with NAFLD from type 2 diabetes (T2D) clinics or primary care. Patients (n = 243) who were screened for NAFLD with advanced fibrosis by using NAFLD fibrosis score (NFS), fibrosis 4 score (FIB‐4), enhanced liver fibrosis (ELF) test, and liver stiffness measurements (LSMs) were followed up for clinical outcomes by review of electronic medical records. During a median follow‐up of 50 months, decompensated liver disease or primary liver cancer occurred in 6 of 35 (17.1%) patients with baseline LSM 13 kPa, 1 of 17 (5.9%) patients with LSM 9.5‐13 kPa, and in no patients with LSM 9.5 kPa. No patient with low‐risk NFS developed liver decompensation or liver‐related mortality. Following repeat NFSs at the end of follow‐up, all patients with a liver‐related complication were in the high‐risk NFS category. Patients who developed liver‐related complications were also more likely to have baseline high‐risk FIB‐4 scores or ELF test ≥9.8 compared to patients who did not develop liver outcomes. Conclusion: Liver fibrosis risk stratification in non‐hepatology settings can identify the subset of patients at risk of liver‐related complications. Although the rate of development of a decompensation event or hepatocellular carcinoma was low (2.1% per year) in our patients with compensated cirrhosis (LSM 13 kPa), these events are projected to lead to a substantial increase in NAFLD‐related disease burden over the next decade due to the high prevalence of NAFLD in people with obesity and T2D.
Publisher: Elsevier BV
Date: 12-2018
Publisher: Cold Spring Harbor Laboratory
Date: 13-03-2018
DOI: 10.1101/281220
Abstract: Esophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett’s esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance for BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker panel for BE surveillance. Serum glycoprotein biomarker candidates were measured in 301 serum s les collected from Australia (4 states) and USA (1 clinic) using lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS). The area under receiver operating characteristic curve was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multi-marker panel for BE surveillance. Different glycoforms of complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarker candidates for EAC across both cohorts. A panel of 10 serum glycoproteins accurately discriminated BE patients not requiring intervention [BE+/-low grade dysplasia] from those requiring intervention [BE with high grade dysplasia (BE-HGD) or EAC]. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal s les from subjects that have progressed towards EAC, levels of serum C9 glycoforms were increased with disease progression. Further prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted. A first-line BE surveillance blood test may be developed based on these findings. AAL Aleuria aurantia lectin %CV % Co-efficient of variation AUROC Area under receiver operating characteristics curve BE Barrett’s esophagus BE-HGD Barrett’s esophagus with high-grade dysplasia BE-ID Barrett’s esophagus which is indefinite for dysplasia BE-LGD Barrett’s esophagus with low-grade dysplasia BMI Body mass index C1QB Complement C1q subcomponent subunit B C2 Complement C2 C3 Complement C3 C4B Complement C4-B C4BPA C4b-binding protein alpha chain C4BPB C4b-binding protein beta chain C9 Complement component C9 CFB Complement factor B CFI Complement factor I CI Confidence interval CP Ceruloplasmin EAC Esophageal adenocarcinoma EPHA Erythroagglutinin from Phaseolus vulgaris FFPE Formalin-fixed, paraffin-embedded GERD Gastroesophageal reflux disease GSN Gelsolin JAC Jacalin from Artocarpus integrifolia LeMBA Lectin magnetic bead array MRM-MS Multiple reaction monitoring-mass spectrometry NPL Narcissus pseudonarcissus lectin NSE Non-specialized epithelium OR Odds ratio PGLYRP2 N-acetylmuramoyl-L-alanine amidase PON1 Serum paraoxonase/arylesterase 1 PON3 Serum paraoxonase/lactonase 3 RBP4 Retinol-binding protein 4 SERPINA4 Kallistatin SIS Stable isotope-labeled internal standard
Publisher: BMJ
Date: 23-01-2008
Abstract: To assess the prevalence of abnormal anal cytology and high-risk human papilloma virus (HPV)-type infection in HIV-infected people with a CD4 cell count >300 cells/microl. The clinic-based patient population included 126 HIV-infected people: 124 men who have sex with men, and two women (median age 45 years CD4 cell count >300 cells/microl). Anal cytology swabs were placed into liquid-based medium for HPV typing by Hybrid Capture-2 assay and cytological assessment, by a single cytopathologist. 106 (84%) participants were infected with high-risk HPV 17 (14%) had no high-risk types of HPV detected three (2%) had no HPV assay result because of an inadequate s le. Sixteen (13%) participants had cytological evidence of high-grade squamous intraepithelial (HGSIL) changes, 100% of whom had high-risk HPV types detected, and 13 (10%) had atypical squamous cells of undetermined significance with possible high-grade changes (ASCUS-H), 92% of whom had high-risk HPV types detected. Low-grade changes (LSIL) were detected in 24 (19%) participants, 96% of whom had high-risk HPV types, 32 (25%) had ASCUS with 88% high-risk HPV types, 30 (24%) had normal cytology with 73% high-risk HPV types, and 11 (9%) s les were inadequate for cytological assessment. The odds ratio of participants with high-risk HPV having abnormal anal cytology on anal swab was 5.03 (95% CI 1.45 to 17.39). High-risk HPV types are common in this HIV+ population with a CD4 cell count >300 cells/microl. The presence of high-risk HPV types was associated with abnormal anal cytology such as HGSIL and ASCUS-H.
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.VACCINE.2005.11.057
Abstract: In many countries there is no clear recommendation regarding the preferred route of administration of inactivated influenza vaccines. In a randomised, observer blind study of 720 elderly subjects, a split, trivalent influenza vaccine was significantly more immunogenic for both A strains (H3N2 and H1N1, p = 0.0016 and 0.003, respectively) when given intramuscularly compared to subcutaneously. This difference was due entirely to a gender effect, with females in the intramuscular (IM) group having a significantly greater serological response than females in the subcutaneous (SC) group for both of these strains. Similar results were seen with local adverse effects. These data suggest that vaccination practices that ensure intramuscular injection are required for optimal administration of influenza vaccines in the elderly.
Publisher: Elsevier BV
Date: 04-2022
Publisher: Elsevier BV
Date: 2015
Publisher: Elsevier BV
Date: 06-2019
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.GENE.2018.10.002
Abstract: Genetic modifiers contribute to variable disease phenotype in cystic fibrosis (CF). We explored the association between mutations in the hemochromatosis (HFE) gene and disease severity in adults with CF. HFE genotyping was performed in 163 adults with CF attending a single centre. Results were correlated with lung disease severity, prevalence of CF-related diabetes (CFRD) and history of meconium ileus (MI) or distal intestinal obstruction syndrome (DIOS). Subjects with the C282Y substitution in the HFE protein (C282Y mutation) had a lower FEV In subjects with CF, the C282Y HFE substitution was associated with worse lung function, and increased rates of CFRD and gastrointestinal complications. The H63D HFE substitution also impacted on disease phenotype, but to a lesser extent. The results support a role for HFE gene mutations as modifiers of CF phenotype.
Publisher: Frontiers Media SA
Date: 03-06-2021
Abstract: Glioblastoma (GBM) is the most common and aggressive type of tumour arising from the central nervous system. GBM remains an incurable disease despite advancement in therapies, with overall survival of approximately 15 months. Recent literature has highlighted that GBM releases tumoural content which crosses the blood-brain barrier (BBB) and is detected in patients’ blood, such as circulating tumour cells (CTCs). CTCs carry tumour information and have shown promise as prognostic and predictive biomarkers in different cancer types. Currently, there is limited data for the clinical utility of CTCs in GBM. Here, we report the use of spiral microfluidic technology to isolate CTCs from whole blood of newly diagnosed GBM patients before and after surgery, followed by characterization for GFAP, cell-surface vimentin protein expression and EGFR lification. CTCs were found in 13 out of 20 patients (9/20 before surgery and 11/19 after surgery). Patients with CTC counts equal to 0 after surgery had a significantly longer recurrence-free survival (p=0.0370). This is the first investigation using the spiral microfluidics technology for the enrichment of CTCs from GBM patients and these results support the use of this technology to better understand the clinical value of CTCs in the management of GBM in future studies.
Publisher: Wiley
Date: 05-2021
DOI: 10.1111/IMJ.14809
Abstract: The rate of hospital admissions for cirrhosis increased 1.3‐fold during 2008–2016 in Queensland. Alcohol misuse was a contributing factor for cirrhosis in 55% of admissions and 40% of patients had at least one comorbidity. To examine the temporal change in aetiology of liver disease and presence of comorbidity in patients admitted with cirrhosis. Population‐based retrospective cohort study of all people treated in hospital for cirrhosis (10 254 patients) in Queensland during 2008–2016. Data were sourced from Queensland Hospital Admitted Patient Data Collection. The commonest aetiology was alcohol (49.5%), followed by cryptogenic (unspecified cirrhosis 28.5%), hepatitis C virus (19.3%), non‐alcoholic fatty liver disease (NAFLD)/non‐alcoholic steatohepatitis (NASH) (4.8%) and hepatitis B virus (HBV) (4.3%). The prevalence of alcohol‐related ( P = 0.41) and hepatitis C virus ( P = 0.08) remained stable between 2008–2010 and 2014–2016, that of NAFLD/NASH, cryptogenic and HBV‐cirrhosis increased by 67% ( P 0.00001), 27% ( P 0.00001) and 20% ( P = 0.00019), respectively 41.1% of patients had at least one comorbidity. The prevalence of type 2 diabetes nearly doubled (from 13.7% to 25.4% P 0.00001) between 2008–2010 and 2014–2016. Alcohol misuse was the most important aetiology. The importance of NAFLD/NASH, cryptogenic and HBV‐cirrhosis and the burden of comorbidity increased during 2008–2016. Ongoing alcohol misuse and the increasing prevalence of NAFLD/NASH, cryptogenic cirrhosis and comorbid type 2 diabetes among admissions for cirrhosis has implications for public health interventions to reduce the burden of unhealthy lifestyle and metabolic disorders.
Publisher: Oxford University Press (OUP)
Date: 11-2010
DOI: 10.1086/656601
Abstract: When the novel H1N1 influenza A strain appeared in April of 2009, development of novel H1N1 vaccines became a public health priority. We conducted a phase‐2, multicenter, randomized, placebo‐controlled, observer‐blind clinical trial of a 2009 H1N1 vaccine in 1313 young (age, 18-64 years) and older (age, >or=65 years) adults. Participants were randomized 1:4:4:4 to receive 2 doses of placebo or 7.5, 15, or 30 μg of H1N1 hemagglutinin administered 21 days apart. In post hoc analyses, hemagglutination inhibition (HI) titers measured at baseline and after vaccination were analyzed for young adults (age, 18-64 years), "younger elderly" adults (age, 65-74 years), and "very elderly" adults (age, >or=75 years). At baseline, 28.8% of young adults, 43.9% of younger elderly adults, and 62.9% of very elderly adults had HI titers to A/2009 H1N1 of >or=1:40. A single 7.5‐μg dose induced HI titers >or=1:40 in 94.5% (95% confidence interval [CI], 91.8%-96.3%) of all adults. After one 7.5‐μg dose, the geometric mean titers achieved were 326.4 (95% CI, 275.9-386.0) in young adults, 155.4 (95% CI, 123.4-195.8) in "younger elderly" adults, and 243.9 (95% CI, 167.1-356.0) in "very elderly" adults. This large phase-2 trial demonstrated that a single 7.5‐μg dose of a monovalent unadjuvanted H1N1 vaccine induced protective HI antibody levels in adults of all ages, including very elderly adults. Clinicaltrials.gov identifier NCT00958126.
Publisher: SAGE Publications
Date: 11-2013
DOI: 10.1016/J.AUSMJ.2013.09.001
Abstract: Public support for policies that address climate change, in Australia and elsewhere, has become polarised, and has declined in Australia. The polarisation and decline has occurred despite considerable efforts by government, non-government and scientific bodies to raise levels of support. In this research, therefore, we aim to better understand the preferences of politically salient household segments with the objective of more effectively communicating to those segments the desirability of addressing climate change. Replicating an American market segmentation study, we find that 26% of participants fell into the most politically salient household segment, labelled Cautious. This segment is relatively open to changing its views about climate change, and is supportive of both government and opposition policies. These findings suggest that segment members will potentially be influenced by targeted media c aigns by either side of politics. Additional findings relate to effective communication channels, and trusted sources including the use of celebrities.
Publisher: Wiley
Date: 05-06-2021
DOI: 10.1002/JGH3.12580
Abstract: Surveillance and early detection and curative treatment of hepatocellular carcinoma (HCC) are the mainstay of improving survival for patients, but there are several barriers to achieving this goal. We reported the impact of remoteness of residence on receipt of treatment, tumor stage, and survival in patients with HCC in Queensland. We conducted a retrospective cohort study of 1651 HCC patients (147 migrants) from 1 January 2007 to 31 December 2016. We used Wilcoxon rank‐sum test to compare the median age at the time of diagnosis and Bayesian Weibull accelerated failure time regression to identify independent predictors of time to death. The median survival time after HCC diagnosis was 9.0 months (interquartile range 2.0–24.0). Metropolitan residence ( P = 0.02), non‐English language ( P 0.001), foreign country of origin ( P 0.001), and HBV etiology ( P 0.001) were significantly associated with receiving surgical resection for HCC treatment. The strongest predictors of time to death were undifferentiated tumor at presentation (time ratio [TR] = 0.30, 95% credible interval (CrI) 0.23–0.39), age ≥70 years (TR = 0.42, 95% CrI 0.34–0.53), living in remote areas (TR = 0.67, 95% CrI 0.55–0.80), and presence of ≥1 comorbidity (TR = 0.69 95% CrI 0.54–0.90). All the other covariates adjusted, including country of birth (TR = 0.76, 95% CrI 0.49–1.06), did not predict survival time. Patients living in rural and remote areas had late stage clinical presentation and poor survival. Remoteness of residence may limit access to HCC surveillance in at‐risk patients such as those with cirrhosis, and timely curative treatment to improve survival in these patients.
Publisher: Wiley
Date: 25-01-2020
DOI: 10.1111/IJCS.12639
Abstract: Household norms have been shown to influence energy efficiency behaviors, but little is known about the relative influence of household norms when compared to other established drivers of household efficiency behaviors, such as comfort‐seeking, environmental concern and cost sensitivity. This paper unpacks the nature of the influence of household norms on household efficiency behaviors, whether as antecedents, mediating the influence of other drivers or a direct influence on efficiency behaviors. Responses from 775 households in regional Australia were analyzed to test six hypotheses. Results suggest that household norms are among the most important variables influencing household efficiency behaviors. They have a strong and significant influence on curtailment and investment behaviors, mediate the relationship between established drivers of efficiency and efficiency behaviors and influence the drivers of efficiency. These findings demonstrate the importance of household norms for improving the energy efficiency of households.
Publisher: Elsevier BV
Date: 11-2008
DOI: 10.1016/J.VACCINE.2008.08.046
Abstract: Highly pathogenic avian influenza A virus (H5N1) is a leading candidate for the next influenza pandemic, and infants and children may play an important role in transmission in a pandemic. Our objective was to evaluate the safety and immunogenicity of a prototype inactivated, aluminium adjuvanted, split-virus, clade 1 H5N1 vaccine (A/Vietnam/1194/2004/NIBRG-14) in infants and children aged > or =6 months to or =1:20) and HI assays (95-100% > or =1:32), with 80-87% of children having MN antibody persistence (> or =1:20) up to 6 months post-vaccination. Additionally, robust cross-clade HI antibody responses were elicited following two doses. Two doses of prototype 30 microg or 45 microg aluminium-adjuvanted, H5N1 vaccines were highly immunogenic and well-tolerated, with considerable antibody persistence 6 months after the primary vaccination course. Additional cross-clade HI antibody responses and an acceptable safety and tolerability profile support the use of the either candidate vaccine formulations in infants and children in the event of a pandemic.
Publisher: Wiley
Date: 10-12-2021
DOI: 10.1002/JGH3.12462
Abstract: Health‐related quality‐of‐life measurements are important to understand lived experiences of patients who have cirrhosis. These measures also inform economic evaluations by modelling quality‐adjusted life years (QALYs). We aimed to describe health‐related quality of life, specifically multiattribute utility (scale anchors of death = 0.00 and full health = 1.00), across various stages and etiologies of cirrhosis. Face‐to‐face interviews were used to collect Short Form 36 (SF‐36) questionnaire responses from CirCare study participants with cirrhosis (June 2017 to December 2018). The severity of cirrhosis was assessed using the Child‐Pugh score classified as class A (5–6 points), B (7–9), or C (10–15) and by the absence (“compensated”) versus presence (“decompensated”) of cirrhosis‐related complications. Patients ( n = 562, average 59.8 years [SD = 11.0], male 69.9%) had a range of primary etiologies (alcohol‐related 35.2%, chronic hepatitis C 25.4%, non‐alcoholic fatty liver disease (NAFLD) 25.1%, chronic hepatitis B 5.9%, “other” 8.4%). Significantly lower (all P 0.001) mean multiattribute utility was observed in the health states of patients with decompensated (mean = 0.62, SD = 0.15) versus compensated cirrhosis (mean = 0.68, SD = 0.12), Child‐Pugh class C (mean = 0.59, SD = 0.15) or B (mean = 0.63, SD = 0.15) versus A (mean = 0.68, SD = 0.16), and between those of working age (18–64 years mean = 0.64, SD = 0.16) versus those aged 65+ years (mean = 0.70, SD = 0.16). The greatest decrements in health‐related quality of life relative to Australian population norms were observed across physical SF‐36 domains. Persons with more advanced cirrhosis report greater life impacts. Estimates from this study are suitable for informing economic evaluations, particularly cost‐utility modelling, which captures the benefits of effective prevention, surveillance, and treatments on both the quality and quantity of patients' lives.
Publisher: American Society of Civil Engineers (ASCE)
Date: 11-2022
Publisher: Emerald
Date: 30-08-2013
Abstract: Trust is known to have three dimensions: ability/competence, integrity/contractual and benevolence/goodwill. Yet what develops these three dimensions of trust is relatively unknown, particularly at the different stages of the relationship lifecycle. The primary goal of this paper is improving understanding about the development of these three elements of trust. Hence, this research is undertaken within the critical growth phase of the relationship lifecycle. A qualitative approach was deemed most appropriate to achieve the deep understanding needed for this type of exploratory study. Using a relationship dyad, which contained a retail manager and wholesale salesperson as the unit of investigation, 18 in‐depth semi‐structured interviews were conducted. This constituted nine case studies, which were analysed using content and thematic analysis. A purposive case selection method was used to ensure variance of cases and provide rich data. The most interesting findings relate to how trust is developed and how this varies for the different forms of trust. For ability trust, the crucial factors in its development were performance, expertise and communication. With respect to integrity trust, honesty, integral actions and candid response were found to influence the development of trust. For benevolence, trust actions and attitudes emerged as key factors for the development of trust. Trust has been found to be a key component of relationship marketing success. This research extends this through providing understanding of the elements of trust and what drives the development of these elements, thus providing insights at a level more usable for the practitioner. It is generally agreed that trust is a multidimensional construct however there has been limited research on how to develop each of the three elements of trust. This research provides insight into how to develop trust, at a crucial time in the relationship growth stage. It is at this stage that partnerships can flourish or fade, hence trust is vital. Therefore, the development of ability, integrity and benevolence trust is important. This is not an issue that has been researched frequently in the literature this paper helps to provide understanding of the key factors which develop these three elements of trust.
Publisher: American Psychological Association (APA)
Date: 09-1997
Publisher: Elsevier BV
Date: 05-2022
Publisher: Informa UK Limited
Date: 15-05-2022
Publisher: Informa UK Limited
Date: 28-01-2011
Publisher: Informa UK Limited
Date: 06-01-2010
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/186420
Abstract: The measurement of vaccine-induced humoral and CD 4 + and CD 8 + cellular immune responses represents an important correlate of vaccine efficacy. Accurate and reliable assays evaluating such responses are therefore critical during the clinical development phase of vaccines. T cells play a pivotal role both in coordinating the adaptive and innate immune responses and as effectors. During the assessment of cell-mediated immunity (CMI) in subjects participating in a large-scale influenza vaccine trial, we identified the expansion of an IFN- γ -producing CD3 + CD4 - CD8 - γ δ + T cell population in the peripheral blood of 90/610 (15%) healthy subjects. The appearance of CD3 + CD4 - CD8 - γ δ + T cells in the blood of subjects was transient and found to be independent of the study cohort, vaccine group, subject gender and ethnicity, and ex vivo restimulation conditions. Although the function of this population and relevance to vaccination are unclear, their inclusion in the total vaccine-specific T-cell response has the potential to confound data interpretation. It is thus recommended that when evaluating the induction of IFN- γ -producing CD 4 + and CD 8 + immune responses following vaccination, the CD3 + CD4 - CD8 - γ δ + T cells are either excluded or separately enumerated from the overall frequency determination.
Publisher: Edward Elgar Publishing
Date: 31-10-2013
Publisher: Informa UK Limited
Date: 10-2016
Publisher: European Respiratory Society (ERS)
Date: 10-2018
DOI: 10.1183/23120541.00080-2018
Abstract: Expiratory dynamic airways collapse (EDAC) is a condition that affects the central airways it is not well characterised physiologically, with relatively few studies. We sought to characterise impulse oscillometry (IOS) features of EDAC in patients with normal spirometry. Expiratory data were hypothesised to be the most revealing. In addition, we compared IOS findings in chronic obstructive pulmonary disease (COPD) patients with and without EDAC. EDAC was identified at bronchoscopy as 75–100% expiratory closure at the carina or bilateral main bronchi. Four patient groups were compared: controls with no EDAC and normal lung function lone EDAC with normal lung function COPD-only patients and COPD patients with EDAC. 38 patients were studied. Mean IOS data z-scores for EDAC compared to controls showed significantly higher reactance ( X ) values including X at 5 Hz, resonance frequency and area under the reactance curve (A X ). EDAC showed significantly greater expiratory/inspiratory differences in all IOS data compared to controls. Stepwise logistic regression showed that resonant frequency best discriminated between EDAC and normal control, whereas classification and regression tree analysis found A X ≥3.523 to be highly predictive for EDAC in cases with normal lung function (14 out of 15 cases, and none out of eight controls). These data show a new utility of IOS: detecting EDAC in patients with normal lung function.
Publisher: Inderscience Publishers
Date: 2002
Publisher: Informa UK Limited
Date: 10-2011
Publisher: Informa UK Limited
Date: 10-02-2015
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1053/J.GASTRO.2018.07.012
Abstract: Among sessile serrated adenomas (SSAs) with identical histologic features, some never progress, whereas others become dysplastic and develop into invasive cancers. Development of the CpG island methylator phenotype is a feature of SSA progression we examined the CIMP status of 448 SSAs and examined the association with patient clinical data. Overall, 190 SSAs were CpG island methylator phenotype-positive. CpG island methylator phenotype positivity was associated with older patient age (P < .001) and proximal polyp site (P < .001), but not with patient sex (P = .94) or polyp size (P = .34). These results might be used to improve SSA surveillance guidelines.
Publisher: Wiley
Date: 08-2021
DOI: 10.1002/JCSM.12759
Abstract: Falls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to determine whether monthly high‐dose vitamin D supplementation reduces risk and incidence of falls. We used data from the randomized, double‐blind, placebo‐controlled D‐Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60–84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking IU/day supplementary vitamin D were ineligible. Each year, we collected blood s les from ~450 randomly s led participants from each trial arm and measured 25‐hydroxyvitamin D [25(OH)D]. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3‐month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random s les of participants (surveys, n = 16 000 diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention‐to‐treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763) registered 4 July 2013. Mean treatment duration was 4.3 years (standard deviation [SD] = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively approximately half were randomized to vitamin D (surveys: 50.1% diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.95–1.10). There was an interaction with body mass index (BMI) ( P ‐interaction = 0.001) vitamin D increased risk in participants with BMI 25 kg/m 2 (OR 1.25, 95% CI 1.09–1.43), but there was no effect in those with BMI ≥ 25 kg/m 2 (OR 0.95, 95% CI 0.87–1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups. Monthly high‐dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation.
Publisher: Elsevier BV
Date: 03-2023
DOI: 10.1016/J.OPHTHA.2022.09.015
Abstract: Observational studies suggest that higher serum 25-hydroxyvitamin D concentration may be associated with lower risk of cataract. However, no randomized controlled trials (RCTs) have assessed the effect of vitamin D supplementation on the incidence of cataract. We aimed to assess whether vitamin D supplementation reduces the incidence of cataract surgery. We conducted an ancillary study of D-Health Trial, a randomized, double-masked, placebo-controlled trial of monthly vitamin D for the prevention of all-cause mortality conducted from 2014 to 2020 within the Australian general population. We invited 421,207 men and women aged 60-84 years to participate including an additional 1,896 volunteers, 40,824 expressed interest. Those with hypercalcemia, hyperparathyroidism, kidney stones, osteomalacia or sarcoidosis, or who were taking >500 international units (IU) supplemental vitamin D per day were excluded. 21,315 people were randomized. 1,390 participants did not fulfil the eligibility criteria for this analysis (linked data available, no cataract within first 6 months) leaving 19,925 included. The median follow-up was 5 years. . 60,000 IU of vitamin D The primary outcome for this analysis was the first surgical treatment for cataract, ascertained through linkage to universal health insurance records and hospital data. Among 19,925 participants eligible for the analysis of incident cataract (mean age 69.3 years, 46% women) 3,668 (18.4%) underwent cataract surgery during follow-up (n=1,841 (18.5%) of the vitamin D group and n=1,827 (18.3%) of the placebo group). The incidence of cataract surgery was similar between the two groups (incidence rate 41.6 and 41.1 per 1,000 person-years in the vitamin D and placebo groups, respectively hazard ratio 1.02 95% CI 0.95 to 1.09). In pre-specified subgroup analyses, the effect of vitamin D supplementation on the incidence of cataract surgery was not modified by age, sex, body mass index, predicted serum 25-hydroxyvitamin D concentration, or ambient ultraviolet radiation. Routinely supplementing older adults who live in an area with a low prevalence of vitamin D deficiency with high-dose vitamin D is unlikely to reduce the need for cataract surgery.
Publisher: Cambridge University Press (CUP)
Date: 2013
DOI: 10.1017/JMO.2013.4
Abstract: This paper outlines a new approach to cultural awareness training, the In idual Differences Approach to Diversity Awareness (IDADA). IDADA is distinguished from other approaches in three ways: (a) it eliminates the need to characterise cultures, (b) it addresses unfair discrimination of any kind (e.g., weight, height, attractiveness), (c) it teaches employees to become aware of how their attitudes affect organisational performance, and (d) it focuses on job requirements. Initial evidence supports the validity of the model. The paper also introduces a new measure of ersity-openness called the Ideal Employee Inventory. Preliminary reliability and validity evidence for the measure is provided.
Publisher: American Medical Association (AMA)
Date: 11-2021
DOI: 10.1001/JAMANEUROL.2021.3113
Abstract: The literature on neural autoantibody positivity in epilepsy has expanded over the last decade, with an increased interest among clinicians in identifying potentially treatable causes of otherwise refractory seizures. Prior studies have reported a wide range of neural autoantibody positivity rates among various epilepsy populations, with the highest frequency reported in in iduals with focal epilepsy of unknown cause and new-onset seizures. The antibodies in some cases are of uncertain significance, and their presence can cause conundrums regarding therapy. There is likely some role for neural autoantibody assessment in patients with unexplained epilepsy who lack clear evidence of autoimmune encephalitis, but the clinical implications of such testing remain unclear owing to limitations in previous published studies. A framework for study design to bridge the current gaps in knowledge on autoimmune-associated epilepsy is proposed.
Publisher: SAGE Publications
Date: 04-2006
Abstract: Debate over the link between student learning styles and effective teaching has a long tradition, made more interesting by Karns's recent article “Learning Style Differences in the Perceived Effectiveness of Learning Activities.” Fundamentally he asserts, in critiquing Morrison et al. (2003), that marketing educators should not adopt “a high investment strategy” in tailoring curriculum to student learning styles segments but merely “provide a range of learning experiences that tap multiple learning modalities.” This study contends that in developing his research question, Karns has misunderstood the perspective of Morrison et al. about how to adapt teaching styles to influence learning outcomes. In addition, this study reviews Karns's methodology, noting weaknesses in the measurement of learning styles, s ling, and data analysis that the authors expect has influenced his findings and conclusions. Finally, the authors introduce additional data that support their findings rather than his, thus further stimulating this debate.
Publisher: Wiley
Date: 25-03-2023
DOI: 10.1002/IJC.34517
Abstract: Human papillomavirus (HPV)‐related oropharyngeal cancer (OPC) is increasing in incidence, yet very little is known about oral HPV infection in the general population. In this Australian‐based study we assess oral HPV prevalence according to HPV vaccination status. Participants of the Oral Diversity Study were Australian residents, aged 18 to 70 years, who filled out a questionnaire about lifestyle and sexual behaviour, and donated a saliva s le in 2020 to 2021. We obtained permission to access HPV vaccination status through record linkage with the Australian Immunisation Register. Saliva s les were DNA extracted, DNA quality checked and analysed for HPV. We recruited 1023 participants to the Oral Diversity Study. Nine hundred twenty‐one returned a saliva s le for analysis, 911 passed the DNA quality check and were included in the study. The oral HPV prevalence was 7.2%, and was strongly associated with sexual behaviours. We identified 27 different HPV types 53% of participants carried high‐risk HPV types, with no difference between the vaccinated and the unvaccinated groups (53% both, P = .979). Two hundred thirty participants (26%) were HPV vaccinated. The oral prevalence of the nine HPV types included in the nonavalent HPV vaccine was significantly lower in the vaccinated participants compared to the unvaccinated (0.9% vs 3.4% P = .022). These findings suggest that a sizeable minority of Australian residents harbour oral HPV infections, and many of these are high‐risk subtypes. We found some evidence that HPV vaccination resulted in lower prevalence of oral HPV infections of vaccine‐specific types. Larger surveys are required to confirm these findings.
Publisher: Wiley
Date: 22-10-2009
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.CGH.2019.03.015
Abstract: Liver disease develops in 15%-72% of patients with cystic fibrosis, and 5%-10% develop cirrhosis or portal hypertension, usually during childhood. Transient elastography (TE) is a noninvasive method to measure liver stiffness. We aimed to validate its accuracy in detection of liver disease and assessment of fibrosis in children with cystic fibrosis. We performed a cross-sectional study to evaluate the accuracy of TE in analysis of liver disease in 160 consecutive children who presented with cystic fibrosis (9.0 ± 0.4 years old, 53% male) at a tertiary referral pediatric center in Australia, from 2011 through 2016. Patients were classified as having cystic fibrosis-associated liver disease (CFLD) or cystic fibrosis without liver disease (CFnoLD) based on clinical, biochemical, and imaging features. Fibrosis severity was determined from histologic analysis of dual-pass liver biopsies from children with CFLD, as the reference standard. Data from healthy children without cystic fibrosis (n = 64, controls) were obtained from a separate study. Liver stiffness measurements (LSMs) were made by Fibroscan analysis, using the inter-quartile range/median ≤30% of 10 valid measurements. Children with macronodularity or portal hypertension with heterogeneous changes on ultrasound without available biopsy were assigned to the category of stage F3-F4 fibrosis. LSM was made reliably in 86% of children accuracy increased with age. LSMs were significantly higher in children with CFLD (10.7 ± 2.4 kPa, n = 33) than with CFnoLD (4.6 ± 0.1 kPa, n = 105) (P < .0001) or controls (4.1 ± 0.1kPa) (P < .0001) LSMs were higher in children with CFnoLD than controls (P < .05). At a cut-off value of 5.55kPa, LSM identified children with CFLD with an area under the receiver operating characteristic (AUROC) curve of 0.82, 70% sensitivity, and 82% specificity (P < .0001). Classification and regression tree models that combined LSM and aspartate aminotransferase to platelet ratio index (APRI) identified children with CFLD with an AUROC curve of 0.89, 87% sensitivity, and 74% specificity (odds ratio, 18.6). LSMs correlated with fibrosis stage in patients with CFLD (r = 0.67, P = .0001). A cut-off value of 8.7kPa differentiated patients with stage F3-F4 fibrosis from patients with stage F1-F2 fibrosis (AUROC, 0.87 75% sensitivity 100% specificity, P=.0002). The combination of LSMs and APRI improved the differentiation of patients with F3-F4 fibrosis vs F1-F2 fibrosis (AUROC, 0.92 83% sensitivity and 100% specificity (P < .01). LSMs made by TE accurately detect liver disease in children with cystic fibrosis diagnostic accuracy increases when LSMs are combined with APRI. LSMs also differentiate between children with cystic fibrosis with mild-moderate fibrosis vs advanced fibrosis.
Publisher: European Respiratory Society (ERS)
Date: 04-2021
DOI: 10.1183/23120541.00895-2020
Abstract: The difference in patient comfort with conscious sedation versus general anaesthesia for bronchoscopy has not been adequately assessed in a randomised trial. This study aimed to assess if patient comfort during bronchoscopy with conscious sedation is noninferior to general anaesthesia. 96 subjects were randomised to receive conscious sedation or general anaesthesia for bronchoscopy. The primary outcome was subject comfort. Secondary outcomes included willingness to undergo a repeat procedure if necessary and level of sedation assessed clinically and by bispectral index (BIS) monitoring. There was no significant difference between subject comfort scores (difference −0.01, 95% CI −0.63–0.61 on a 10-point scale p=0.97) or willingness to undergo a repeat procedure (97.7% versus 91.8%, 95% CI −4.8–15.5% p=0.37). Deeper levels of sedation in the general anaesthesia cohort was confirmed with both clinical and BIS monitoring. There was no significant difference in diagnostic accuracy (conscious sedation 93.9%, 95% CI 80.4–98.3% versus general anaesthesia 86.5%, 95% CI 72.0–94.1% p=0.43). There were more complications (29.6%, 95% CI 18.2–44.2% versus 6.1%, 95% CI 2.1–16.5% p .01) in the general anaesthesia group. There was no relationship between high BIS scores and subject discomfort. BIS levels during a procedure were associated with increased complications. Conscious sedation is not inferior to general anaesthesia in providing patient comfort during bronchoscopy, despite lighter sedation, and is associated with fewer complications and comparable diagnostic accuracy. BIS monitoring may have a role in preventing complications associated with deeper sedation.
Publisher: Elsevier BV
Date: 07-2008
Publisher: MDPI AG
Date: 02-2022
DOI: 10.3390/BIOMEDICINES10020351
Abstract: Fourier transform infrared (FTIR) spectroscopy provides a (bio)chemical snapshot of the s le, and was recently used in proof-of-concept cohort studies for COVID-19 saliva screening. However, the biological basis of the proposed technology has not been established. To investigate underlying pathophysiology, we conducted controlled infection experiments on Vero E6 cells in vitro and K18-hACE2 mice in vivo. Potentially infectious culture supernatant or mouse oral lavage s les were treated with ethanol or 75% (v/v) Trizol for attenuated total reflectance (ATR)-FTIR spectroscopy and proteomics, or RT-PCR, respectively. Controlled infection with UV-inactivated SARS-CoV-2 elicited strong biochemical changes in culture supernatant/oral lavage despite a lack of viral replication, determined by RT-PCR or a cell culture infectious dose 50% assay. Nevertheless, SARS-CoV-2 infection induced additional FTIR signals over UV-inactivated SARS-CoV-2 infection in both cell and mouse models, which correspond to aggregated proteins and RNA. Proteomics of mouse oral lavage revealed increased secretion of kallikreins and immune modulatory proteins. Next, we collected saliva from a cohort of human participants (n = 104) and developed a predictive model for COVID-19 using partial least squares discriminant analysis. While high sensitivity of 93.48% was achieved through leave-one-out cross-validation, COVID-19 patients testing negative on follow-up on the day of saliva s ling using RT-PCR was poorly predicted in this model. Importantly, COVID-19 vaccination did not lead to the misclassification of COVID-19 negatives. Finally, meta-analysis revealed that SARS-CoV-2 induced increases in the amide II band in all arms of this study and in recently published cohort studies, indicative of altered β-sheet structures in secreted proteins. In conclusion, this study reveals a consistent secretory pathophysiological response to SARS-CoV-2, as well as a simple, robust method for COVID-19 saliva screening using ATR-FTIR.
Publisher: Springer Science and Business Media LLC
Date: 07-08-2020
DOI: 10.1038/S41523-020-0172-0
Abstract: The homologous recombination deficiency (HRD) score was developed using whole-genome copy number data derived from arrays as a way to infer deficiency in the homologous recombination DNA damage repair pathway (in particular BRCA1 or BRCA2 deficiency) in breast cancer s les. The score has utility in understanding tumour biology and may be indicative of response to certain therapeutic strategies. Studies have used whole-exome sequencing to derive the HRD score, however, with increasing use of whole-genome sequencing (WGS) to characterise tumour genomes, there has yet to be a comprehensive comparison between HRD scores derived by array versus WGS. Here we demonstrate that there is both a high correlation and a good agreement between array- and WGS-derived HRD scores and between the scores derived from WGS and downs led WGS to represent shallow WGS. For s les with an HRD score close to threshold for stratifying HR proficiency or deficiency there was however some disagreement in the HR status between array and WGS data, highlighting the importance of not relying on a single method of ascertaining the homologous recombination status of a tumour.
Publisher: Wiley
Date: 10-02-2017
Publisher: Informa UK Limited
Date: 10-2006
Publisher: Wiley
Date: 19-04-2012
No related grants have been discovered for Gunter Hartel.