ORCID Profile
0000-0002-2204-3189
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UNSW Sydney
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Publisher: Informa UK Limited
Date: 11-1991
Publisher: Elsevier BV
Date: 12-2016
Publisher: Informa UK Limited
Date: 18-04-2016
Publisher: Elsevier BV
Date: 12-2013
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.INJURY.2006.07.006
Abstract: Computed tomography (CT) scans are often used in the evaluation of patients with blunt trauma. This study identifies the clinical features associated with further diagnostic information obtained on a CT chest scan compared with a standard chest X-ray in patients sustaining blunt trauma to the chest. A 2-year retrospective survey of 141 patients who attended a Level 1 trauma centre for blunt trauma and had a chest CT scan and a chest X-ray as part of an initial assessment was undertaken. Data extracted from the medical record included vital signs, laboratory findings, interventions and the type and severity of injury. The CT chest scan is significantly more likely to provide further diagnostic information for the management of blunt trauma compared to a chest X-ray in patients with chest wall tenderness (OR=6.73, 95% CI=2.56, 17.70, p<0.001), reduced air-entry (OR=4.48, 95% CI=1.33, 15.02, p=0.015) and/or abnormal respiratory effort (OR=4.05, 95% CI=1.28, 12.66, p=0.017). CT scan was significantly more effective than routine chest X-ray in detecting lung contusions, pneumothoraces, mediastinal haematomas, as well as fractured ribs, scapulas, sternums and vertebrae. In alert patients without evidence of chest wall tenderness, reduced air-entry or abnormal respiratory effort, selective use of CT chest scanning as a screening tool could be adopted. This is supported by the fact that most chest injuries can be treated with simple observation. Intubated patients, in most instances, should receive a routine CT chest scan in their first assessment.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488651
Abstract: Supplementary Methods
Publisher: SAGE Publications
Date: 07-2002
DOI: 10.1177/101053950201400206
Abstract: For many women today work is essential for the economic survival of their families while they also fulfil their role of providing optimum nutrition to their babies through breastfeeding. The objective of the study is to document the effect of returning to work on exclusive breastfeeding by mothers in Kenya. A cross-sectional study of 444 working mothers was undertaken in Nairobi, Kenya. About one half of the mothers were in formal paid employment and the rest were self-employed. The mean number of hours the mothers were away from home due to work was 46.2 hours per week. The prevalence of exclusive breastfeeding was 13.3% at three months. Early introduction of complementary foods was high, with 46.4% of the mothers introducing other foods before one month. Breast milk insufficiency and return to work were the main reasons cited for the cessation of exclusive breastfeeding. In a logistic regression analysis the mode of work (fixed working hours versus shift working hours) was associated with exclusive breastfeeding at one month (OR=0.45) and two months ( OR=0.39). Working mothers were able to continue breastfeeding, although the exclusive breastfeeding rates were low. The early introduction of other foods is of public health importance as it exposes infants to increased risk of infection and poor nutrition, particularly diarrhoeal diseases and may lead to flattening of the growth curve. Shift work makes it impossible for some mothers to exclusively breastfeed their infants. Asia Pac J Public Health 2002 14(2): 85-90.
Publisher: Elsevier BV
Date: 03-2017
Publisher: American Association for Cancer Research (AACR)
Date: 07-2012
DOI: 10.1158/1940-6207.CAPR-11-0577
Abstract: Folate exists as functionally erse species within cells. Although folate deficiency may contribute to DNA hypomethylation in colorectal cancer, findings on the association between total folate concentration and global DNA methylation have been inconsistent. This study determined global, LINE-1, and Alu DNA methylation in blood and colon of healthy and colorectal cancer patients and their relationship to folate distribution. Blood and normal mucosa from 112 colorectal cancer patients and 114 healthy people were analyzed for global DNA methylation and folate species distribution using liquid chromatography tandem mass spectrometry. Repeat element methylation was determined using end-specific PCR. Colorectal mucosa had lower global and repeat element DNA methylation compared with peripheral blood (P & 0.0001). After adjusting for age, sex and smoking history, global but not repeat element methylation was marginally higher in normal mucosa from colorectal cancer patients compared with healthy in iduals. Colorectal mucosa from colorectal cancer subjects had lower 5-methyltetrahydrofolate and higher tetrahydrofolate and formyltetrahydrofolate levels than blood from the same in idual. Blood folate levels should not be used as a surrogate for the levels in colorectal mucosa because there are marked differences in folate species distribution between the two tissues. Similarly, repeat element methylation is not a good surrogate measure of global DNA methylation in both blood and colonic mucosa. There was no evidence that mucosal global DNA methylation or folate distribution was related to the presence of cancer per se, suggesting that if abnormalities exist, they are confined to in idual cells rather than the entire colon. Cancer Prev Res 5(7) 921–9. ©2012 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488654
Abstract: Supplementary Figures S1-S13
Publisher: BMJ
Date: 06-2005
Publisher: Wiley
Date: 17-01-2003
DOI: 10.1002/PATH.1266
Publisher: Wiley
Date: 17-01-2003
DOI: 10.1002/PATH.1265
Publisher: Elsevier BV
Date: 03-2000
Publisher: Springer Science and Business Media LLC
Date: 08-2001
Publisher: American Association for Cancer Research (AACR)
Date: 13-06-2013
DOI: 10.1158/1078-0432.CCR-12-3614
Abstract: Purpose: PIK3CA and PTEN mutations are prevalent in colorectal cancer and potential markers of response to mitogen-activated protein/extracellular signal–regulated kinase inhibitors and anti-EGF receptor antibody therapy. Relationships between phosphoinositide 3-kinase (PI3K) pathway mutation, clinicopathologic characteristics, molecular features, and prognosis remain controversial. Experimental Design: A total of 1,093 stage I–IV colorectal cancers were screened for PIK3CA (exons 9 and 20), KRAS (codons 12–13), BRAF (codon 600) mutations, and microsatellite instability (MSI). PTEN (exons 3–8) and CpG island methylator phenotype (CIMP) status were determined in 744 and 489 cases. PIK3CA data were integrated with 17 previous reports (n = 5,594). Results: PIK3CA and PTEN mutations were identified in 11.9% and 5.8% of colorectal cancers. PTEN mutation was associated with proximal tumors, mucinous histology, MSI-high (MSI-H), CIMP-high (CIMP-H), and BRAF mutation (P & 0.02). PIK3CA mutation was related to older age, proximal tumors, mucinous histology, and KRAS mutation (P & 0.04). In integrated cohort analysis, PIK3CA exon 9 and 20 mutations were overrepresented in proximal, CIMP-low (CIMP-L), and KRAS-mutated cancers (P ≤ 0.011). Comparing PIK3CA exonic mutants, exon 20 mutation was associated with MSI-H, CIMP-H, and BRAF mutation, and exon 9 mutation was associated with KRAS mutation (P ≤ 0.027). Disease-free survival for stage II/III colorectal cancers did not differ by PI3K pathway status. Conclusion: PI3K pathway mutation is prominent in proximal colon cancers, with PIK3CA exon 20 and PTEN mutations associated with features of the sessile-serrated pathway (MSI-H/CIMP-H/BRAFmut), and PIK3CA exon 9 (and to a lesser extent exon 20) mutation associated with features of the traditional serrated pathway (CIMP-L/KRASmut) of tumorigenesis. Our data highlight the PI3K pathway as a therapeutic target in distinct colorectal cancer subtypes. Clin Cancer Res 19(12) 3285–96. ©2013 AACR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
DOI: 10.1038/AJG.2013.292
Abstract: Microsatellite instability (MSI) is an established marker of good prognosis in colorectal cancer (CRC). Chromosomal instability (CIN) is strongly negatively associated with MSI and has been shown to be a marker of poor prognosis in a small number of studies. However, a substantial group of "double-negative" (MSI-/CIN-) CRCs exists. The prognosis of these patients is unclear. Furthermore, MSI and CIN are each associated with specific molecular changes, such as mutations in KRAS and BRAF, that have been associated with prognosis. It is not known which of MSI, CIN, and the specific gene mutations are primary predictors of survival. We evaluated the prognostic value (disease-free survival, DFS) of CIN, MSI, mutations in KRAS, NRAS, BRAF, PIK3CA, FBXW7, and TP53, and chromosome 18q loss-of-heterozygosity (LOH) in 822 patients from the VICTOR trial of stage II/III CRC. We followed up promising associations in an Australian community-based cohort (N=375). In the VICTOR patients, no specific mutation was associated with DFS, but in idually MSI and CIN showed significant associations after adjusting for stage, age, gender, tumor location, and therapy. A combined analysis of the VICTOR and community-based cohorts showed that MSI and CIN were independent predictors of DFS (for MSI, hazard ratio (HR)=0.58, 95% confidence interval (CI) 0.36-0.93, and P=0.021 for CIN, HR=1.54, 95% CI 1.14-2.08, and P=0.005), and joint CIN/MSI testing significantly improved the prognostic prediction of MSI alone (P=0.028). Higher levels of CIN were monotonically associated with progressively poorer DFS, and a semi-quantitative measure of CIN was a better predictor of outcome than a simple CIN+/- variable. All measures of CIN predicted DFS better than the recently described Watanabe LOH ratio. MSI and CIN are independent predictors of DFS for stage II/III CRC. Prognostic molecular tests for CRC relapse should currently use MSI and a quantitative measure of CIN rather than specific gene mutations.
Publisher: Informa UK Limited
Date: 03-10-2014
Publisher: Elsevier BV
Date: 07-2008
Publisher: Wiley
Date: 02-1991
Publisher: Springer Science and Business Media LLC
Date: 2001
Publisher: BMJ
Date: 2007
Publisher: BMJ
Date: 10-2008
Abstract: To increase seat belt restraint use in Guangzhou City, People's Republic of China. Comparison group pre-test, post-test design. Guangzhou City. Interventions to increase the prevalence of seat belt use in high-income countries (enhanced training and enforcement practices along with raising of public awareness) were adapted and implemented in Guangzhou. The prevalence of seat belt use was determined before and after the introduction of the 12-month intervention. Seat belt prevalence was also examined over the same time period in the neighboring city of Nanning, and an incremental cost-effectiveness analysis of the intervention was undertaken. Prevalence rates and incremental cost effectiveness ratios. A 12% increase in seat belt use was observed in Guangzhou over the study period, increasing from a prevalence of 50% before (error range 30-62%) to 62% after (error range 60-67%) (p<0.001) the intervention an absolute change difference between the intervention and reference city of 20% was achieved. The incremental cost-effectiveness ratio of the intervention was yen 3246 (US dollars 418) per disability-adjusted life year saved. This city-wide intervention demonstrates that it is possible to increase the prevalence of seat belt use using similar methods to those used in high-income countries and, importantly, that such an approach is cost-effective.
Publisher: Elsevier BV
Date: 02-2003
Publisher: Elsevier BV
Date: 12-2016
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.AAP.2012.08.002
Abstract: Child restraints protect a young child against injury in crashes but best practice child restraint use is low in Australia, particularly among lower socio-economic groups. We investigated factors associated with restraint use to inform the development of education and distribution programmes to support new Australian legislation on child passengers among families in low socio-economic areas of metropolitan Sydney. We interviewed a parent or carer of 1160 children aged 2-5 years enrolled at one of 28 early childhood centres in low socio-economic areas of urban Sydney. Appropriate child restraint use was defined as a forward facing child restraint (FFCR) for 2-3 year olds and a FFCR or booster seat for children aged 4 years or more. Predictors of self-reported appropriate use were explored using logistic regression. Analysis was conducted on one child from each family in the target age range (2-5 years): 586 (51%) were male and the mean age was 3.5 (Standard Deviation 0.8) years. There were 432 (45%) families with annual income below $60,000, 248 (22%) spoke a language other than English at home and 360 (33%) had 3 or more children. Fifty-four percent of carers indicated that their 2-3 year old children travelled in a FFCR. Inappropriate use among children in this age group was more likely when the carer was <36 years (odds ratio (OR) 1.62, 95% confidence interval (CI) 1.08-2.45), in families with ≥3 children (OR 1.64, 95% CI 1.10-2.44) and when the carer believed that a booster seat was just as safe as a FFCR (OR 2.98, 2.05-4.32). Eight-eight percent of carers of 4-5 year olds reported use of a booster seat or FFCR. Non-use was associated with low household income (OR 3.10, 95% CI 1.67-5.75), in families with ≥3 children (OR 2.03, 95% CI 1.09-3.76) and families where a language other than English is spoken at home (OR 2.39, 95% CI 1.10-5.21). Non-English speaking families had less awareness of the new law and poorer knowledge of safety benefits of child restraints. They also had lower household incomes and more concerns about cost of child restraints and booster seats. These findings can inform development of interventions to promote best practice child restraint use, which will reach non-English speaking families in this region. They also confirm the importance of economic and logistic barriers to best practice child restraint use.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2009
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.AAP.2017.01.016
Abstract: Road freight transport is considered to be one of the most dangerous industries in Australia, accounting for over 30% of all work fatalities. Whilst system reform (i.e., change to policy and practice) is needed, it is not clear what this reform should be, or what approaches should be used to drive it. This article argues that road freight transportation reform should be underpinned by a systems thinking approach. Efforts to understand crash causation should be focused beyond the driver and identify contributing factors at other levels with the road freight system. Accordingly, we present the findings from a study that examined whether Australian Coronial investigations into road freight crashes reflect support appropriate system reform. Content analysis was used to identify the contributing factors and interrelations implicated in the road freight crashes described in publicly available Australian Coroner's inquest reports from the last 10 years (2004-2014 n=21). The results found evidence to suggest that the Coronial inquests provide some understanding of the complex system of factors influencing road freight transportation crashes in Australia. However, there was a lack of evidence to suggest an understanding of system-based reform based on the identification of reductionist-focused recommendations. It is concluded that researchers and practitioners (ie., government and industry) need to work together to develop prevention efforts focused on system reforms. Systems thinking based data collection and analysis frameworks are urgently required to help develop this understanding in road freight transportation.
Publisher: Wiley
Date: 29-10-2003
DOI: 10.1002/JSO.10310
Abstract: Gene promoter hypermethylation is common in colorectal cancer and is associated with transcriptional silencing. However, the clinicopathological significance of p16(INK4a) gene silencing with hypermethylation is unknown. Therefore, the aim of this study was to analyze loss of p16 expression and its relationship to hypermethylation in sporadic colorectal cancer. Tissue from 426 colorectal cancers underwent histological analysis. Immunohistochemistry was performed for p16 expression. Fresh tumor DNA was analyzed for microsatellite instability (MSI) and the presence of K-ras mutations. In addition, DNA was bisulphite-modified and analyzed for p16(INK4a) promoter methylation by methylation-specific PCR. There were 25% of tumors with p16(INK4a) promoter hypermethylation. These tumors were associated with older patients, right-sidedness, MSI and were poorly differentiated, mucinous, and had intraepithelial and peritumoral lymphocytes and a Crohn's-type lymphocytic reaction (P < 0.05). However, only right-sidedness was significant on multivariate analysis (P < 0.001). Only 8.1% of tumors did not express p16, and this was associated with hypermethylation (P < 0.05). p16(INK4a) promoter methylation, although common in colorectal cancer, does not result in a clinicopathologically distinct subgroup of tumors and infrequently results in transcriptional silencing. This suggests that p16(INK4a) gene inactivation does not have an important role in the pathogenesis of sporadic colorectal cancer.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488645
Abstract: Supplementary Tables S1-S11
Publisher: BMJ
Date: 06-2000
Publisher: Springer Science and Business Media LLC
Date: 10-10-2006
Publisher: BMJ
Date: 06-1997
DOI: 10.1136/IP.3.2.89
Abstract: To examine the extent of international differences in children's exposure to traffic as pedestrians or bicyclists. Children's travel patterns were surveyed using a parent-child administered questionnaire. Children were s led via primary schools, using a probability cluster s ling design. Six cities in five countries: Melbourne and Perth (Australia), Montreal (Canada), Auckland (New Zealand), Umeå (Sweden), and Baltimore (USA). Children aged 6 and 9 years. Modes of travel on the school-home journey, total daily time spent walking, and the average daily number of roads crossed. Responses were obtained from the parents of 13423 children. There are distinct patterns of children's travel in the six cities studied. Children's travel in the three Australasian cities, Melbourne, Perth and Auckland, is characterised by high car use, low levels of bicycling, and a steep decline in walking with increasing car ownership. In these cities, over a third of the children s led spent less than five minutes walking per day. In Montreal, walking and public transport were the most common modes of travel. In Umeå, walking and bicycling predominated, with very low use of motorised transport. In comparison with children in the Australasian and North American cities, children in Umeå spend more time walking, with 87% of children walking for more than five minutes per day. There are large international differences in the extent to which children walk and cycle. These findings would suggest that differences in 'exposure to risk' may be an important contributor to international differences in pedestrian injury rates. There are also substantial differences in pedestrian exposure to risk by levels of car ownership-differences that may explain socioeconomic differentials in pedestrian injury rates.
Publisher: American Academy of Pediatrics (AAP)
Date: 11-2009
Abstract: OBJECTIVE: The research aimed to explore associations between participation in 2 education programs for school-based learner drivers and subsequent road traffic offenses and crashes among a large cohort of newly licensed drivers. METHODS: DRIVE is a prospective cohort study of 20822 first-year drivers aged 17 to 24 in New South Wales (NSW), Australia. Participants completed a detailed questionnaire and consented to data linkage in 2003–2004. Questionnaire items included year of participation in 2 specific education programs: a 1-day workshop-only program focusing on driving risks (“driver-focused”) and a whole-of-community program also including a 1-day workshop but also longer term follow-up activities and a broader focus on reducing risk-taking and building resilience (“resilience-focused”). Survey data were subsequently linked to police-reported crash and offense data for 1996–2005. Poisson regression models that adjusted for multiple confounders were created to explore offenses and crashes as a driver (dichotomized as 0 vs ≥1) after program participation. RESULTS: Offenses did not differ between groups however, whereas the driver-focused program was not associated with reduced crash risk, the resilience-focused program was associated with a 44% reduced relative risk for crash (0.56 [95% confidence interval: 0.34–0.93]). CONCLUSIONS: The large effect size observed and complementary findings from a comparable randomized, controlled trial in the United States suggest programs that focus more generally on reducing risks and building resilience have the potential to reduce crashes. A large, representative, randomized, controlled trial is urgently needed to confirm road safety benefits and ensure evidence-based spending and practitioner recommendations in this field.
Publisher: Informa UK Limited
Date: 08-05-2017
DOI: 10.1080/15389588.2017.1288289
Abstract: Statistics indicate that employees commuting or traveling as part of their work are overrepresented in workplace injury and death. Despite this, many organizations are unaware of the factors within their organizations that are likely to influence potential reductions in work-related road traffic injury. This article presents a multilevel conceptual framework that identifies health investment as the central feature in reducing work-related road traffic injury. Within this framework, we explore factors operating at the in idual driver, workgroup supervisor, and organizational senior management levels that create a mutually reinforcing system of safety. The health investment framework identifies key factors at the senior manager, supervisor, and driver levels to cultivating a safe working environment. These factors are high-performance workplace systems, leader-member exchange and autonomy, trust and empowerment, respectively. The framework demonstrates the important interactions between these factors and how they create a self-sustaining organizational safety system. The framework aims to provide insight into the future development of interventions that are strategically aligned with the organization and target elements that facilitate and enhance driver safety and ultimately reduce work-related road traffic injury and death.
Publisher: Elsevier BV
Date: 05-2003
Publisher: Informa UK Limited
Date: 09-2006
Publisher: Elsevier BV
Date: 03-2016
Publisher: BMJ
Date: 06-01-2009
Abstract: To determine the prevalence of colorectal polyps of different types in an unselected population, and to correlate the morphological diagnoses with BRAF mutation analysis. Cases of colorectal polyps diagnosed at endoscopy were retrieved from the files of Southern.IML Pathology. All slides were reviewed and the lesions classified histologically. A diagnosis of sessile serrated adenoma was made even if the characteristic features were present only focally. If there was more than one polyp of a particular type in any patient, one lesion was chosen at random so that the results represent the number of patients with each type of polyp rather than the total number of polyps. A proportion of the polyps was subjected to BRAF mutation analysis. A total of 1479 patients were identified. Non-serrated ("conventional") adenomas were found in 964 patients (65%), hyperplastic polyps in 437 (30%), sessile serrated adenomas in 57 (3.9%), traditional serrated adenomas in 11 (0.7%) and mixed hyperplastic adenomatous polyps in 10 (0.7%). BRAF V600E mutation analysis was performed in 148 selected cases mutations were found in 44/49 (90%) of lesions diagnosed as sessile serrated adenoma, in 10/34 (29%) of hyperplastic polyps of microvesicular type, in 4/11 (36%) of traditional serrated adenomas, in 10/10 (100%) of mixed hyperplastic adenomatous polyps, and in 2/42 (5%) of "conventional" adenomas. Sessile serrated adenomas are encountered commonly in routine endoscopy practice. The histological diagnosis correlates strongly with the presence of BRAF mutation.
Publisher: BMJ
Date: 03-1999
DOI: 10.1136/IP.5.1.26
Abstract: To assess the effectiveness of community/environmental interventions undertaken as part of the Child Pedestrian Injury Prevention Project (CPIPP). Three communities (local government areas) in the Perth metropolitan area, Western Australia. A quasiexperimental community intervention trial was undertaken over three years (1995-97). Three communities were assigned to either: a community/environmental road safety intervention and a school based road edestrian safety education program (intervention group 1) a school based road edestrian safety education program only (intervention group 2) or to no road safety intervention (comparison group). Quantification of the various road safety community/environmental activities undertaken in each community during the trial was measured, and a cumulative community activity index developed. Estimates of the volume and speed of vehicular traffic were monitored over a two year period. Greater road safety activity was observed in intervention group 1 compared with the other groups. A significant reduction in the volume of traffic on local access roads was also observed over the period of the trial in intervention group 1, but not in the remaining groups. The findings indicate that the various community/environmental interventions initiated in collaboration with CPIPP in intervention group 1 contributed, in part, to the observed reduction in the volume of traffic. A combination of community/environmental interventions and education are likely to reduce the rate of childhood pedestrian injury.
Publisher: Elsevier BV
Date: 2010
Publisher: Elsevier BV
Date: 02-2017
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6532782.V1
Abstract: AbstractPurpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC ( i n /i = 333), mucinous borderline ovarian tumors (MBOT, i n /i = 151), and upper GI ( i n /i = 65) and lower GI tumors ( i n /i = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77 95% confidence interval (CI), 1.04–7.41, i P /i = 0.042]. Increased expression of i THBS2 /i and i TAGLN /i was associated with shorter OS in MOC patients (HR, 1.25 95% CI, 1.04–1.51, i P /i = 0.016) and (HR, 1.21 95% CI, 1.01–1.45, i P /i = 0.043), respectively. i ERBB2 /i (HER2) lification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of i THBS2 /i and i TAGLN /i in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC s les clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies. /
Publisher: BMJ
Date: 07-2003
Abstract: To examine the effect of family welfare index (FWI) and maternal education on the probability of infant death. A population based multistage stratified clustered survey. Women of reproductive age in Indonesia between 1983-1997. The 1997 Indonesian Demographic and Health Survey. Infant mortality was associated with FWI and maternal education. Relative to families of high FWI, the risk of infant death was almost twice among families of low FWI (aOR=1.7, 95%CI=0.9 to 3.3), and three times for families of medium FWI (aOR=3.3,95%CI=1.7 to 6.5). Also, the risk of infant death was threefold higher (aOR=3.4, 95% CI=1.6 to 7.1) among mothers who had fewer than seven years of formal education compared with mothers with more than seven years of education. Fertility related indicators such as young maternal age, absence from contraception, birth intervals, and prenatal care, seem to exert significant effect on the increased probability of infant death. The increased probability of infant mortality attributable to family income inequality and low maternal education seems to work through pathways of material deprivation and chronic psychological stress that affect a person's health damaging behaviours. The policies that are likely to significantly reduce the family's socioeconomic inequality in infant mortality are implicated.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.AAP.2016.08.012
Abstract: The aim of this study was to describe the crash characteristics and patient outcomes of a s le of patients admitted to hospital following bicycle crashes. Injured cyclists were recruited from the two major trauma services for the state of Victoria, Australia. Enrolled cyclists completed a structured interview, and injury details and patient outcomes were extracted from the Victorian State Trauma Registry (VSTR) and the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). 186 cyclists consented to participate in the study. Crashes commonly occurred during daylight hours and in clear weather conditions. Two-thirds of crashes occurred on-road (69%) and were a combination of single cyclist-only events (56%) and multi-vehicle crashes (44%). Of the multi-vehicle crashes, a motor vehicle was the most common impact partner (72%) and distinct pre-crash directional interactions were observed between the cyclist and motor vehicle. Nearly a quarter of on-road crashes occurred when the cyclist was in a marked bicycle lane. Of the 31% of crashes that were not on-road, 28 (15%) occurred on bicycle paths and 29 (16%) occurred in other locations. Crashes on bicycle paths commonly occurred on shared bicycle and pedestrian paths (83%) and did not involve another person or vehicle. Other crash locations included mountain bike trails (39%), BMX parks (21%) and footpaths (18%). While differences in impact partners and crash characteristics were observed between crashes occurring on-road, on bicycle paths and in other locations, injury patterns and severity were similar. Most cyclists had returned to work at 6 months post-injury, however only a third of participants reported a complete functional recovery. Further research is required to develop targeted countermeasures to address the risk factors identified in this study.
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.JADOHEALTH.2010.03.010
Abstract: Earlier research demonstrates increased and decreased risk of crash related to psychological distress however, previous literature has almost entirely used retrospective study designs and has not been able to adequately control for important confounders such as exposure to driving, alcohol and drug use, or having had a previous crash. This study aimed to assess the relationship between psychological distress and risk of motor vehicle crashes. The DRIVE study is a prospective cohort study of 20,822 novice drivers aged 17-24 years in Australia. Information on risk factors for motor vehicle crash was collected through online questionnaire and subsequently linked to police-reported crashes. Poisson regression was used to analyze risk of various crash types by low, moderate, high, and very high levels of psychological distress, taking into account other known risk factors for crash. Compared to the referent group with low or no distress, a protective effect against crash was observed for young people who reported a moderate amount of psychological distress in unadjusted (RR = .87 95% CI = .76-1.00) and multivariable analyses (RR = .85 95% CI = .74-.97). Severe psychological distress was not significantly associated with an increase or decrease in the risk of crash. Psychological distress was not significantly associated with an increased risk of single vehicle crash. Earlier studies may have overestimated risk for motor vehicle crashes associated with psychological distress. This study found little convincing evidence to support a strong risk relationship for higher levels of distress and indeed found a modest protective association for low levels of distress.
Publisher: Informa UK Limited
Date: 16-05-2014
DOI: 10.4161/EPI.29222
Publisher: Elsevier BV
Date: 05-1999
DOI: 10.1016/S0022-1759(99)00044-7
Abstract: In vivo panning of peptide libraries in mice has allowed the isolation of peptides which target the vasculature of specific organs. The application of this approach to phage displaying Fab fragments (phage-Fab) could lead to the isolation of antibodies which recognize novel tumor antigens. In this study, we have evaluated the biodistribution of phage-Fab in nude mice. Balb/c nude mice were injected intravenously with 10(9) TU of phage displaying the anti-colon cancer Fab c30.6. Blood s les were collected at nine time points over a period of 72 h and three groups of four mice were sacrificed at 4 min, 24 h and 72 h. Normal tissues (liver, colon, spleen, kidneys, lungs, skeletal muscle) and faeces were collected at these time points and the number of viable phage in each s le was determined. The distribution of phage in tissues was also examined by immunohistochemical analysis of paraffin-embedded tissues. Regression analysis of plasma kinetic data showed that the half-life and the volume of distribution of phage was 3.6 h and 1 ml, respectively. Phage uptake occurred predominantly in lungs, kidneys, spleen and liver. Relatively few phage were distributed to colon and muscle, and phage were eliminated from the circulation by 72 h. Immunohistochemical analysis showed phage to be mainly within the vasculature at 4 min, whereas notable phage extravasation was observed at 24 h and 72 h. In conclusion, this study provides information on the in vivo behavior of phage-Fab which will be useful in the design of in vivo panning strategies. By choosing appropriate time points for tissue collection, it may be possible to isolate novel Fabs against both intra- and extravascular targets.
Publisher: Elsevier BV
Date: 08-2017
Publisher: American Association for Cancer Research (AACR)
Date: 10-2007
DOI: 10.1158/0008-5472.CAN-07-0869
Abstract: Biallelic promoter methylation and transcriptional silencing of the MLH1 gene occurs in the majority of sporadic colorectal cancers exhibiting microsatellite instability due to defective DNA mismatch repair. Long-range epigenetic silencing of contiguous genes has been found on chromosome 2q14 in colorectal cancer. We hypothesized that epigenetic silencing of MLH1 could occur on a regional scale affecting additional genes within 3p22, rather than as a focal event. We studied the levels of CpG island methylation and expression of multiple contiguous genes across a 4 Mb segment of 3p22 including MLH1 in microsatellite-unstable and -stable cancers, and their paired normal colonic mucosa. We found concordant CpG island hypermethylation, H3-K9 dimethylation and transcriptional silencing of MLH1 and multiple flanking genes spanning up to 2.4 Mb in microsatellite-unstable colorectal cancers. This region was interspersed with unmethylated genes, which were also transcriptionally repressed. Expression of both methylated and unmethylated genes was reactivated by methyltransferase and histone deacetylase inhibitors in a microsatellite-unstable colorectal carcinoma cell line. Two genes at the telomeric end of the region were also hypermethylated in microsatellite-stable cancers, adenomas, and at low levels in normal colonic mucosa from older in iduals. Thus, the cluster of genes flanking MLH1 that was specifically methylated in the microsatellite-unstable group of cancers extended across 1.1 Mb. Our results show that coordinate epigenetic silencing extends across a large chromosomal region encompassing MLH1 in microsatellite-unstable colorectal cancers. Simultaneous epigenetic silencing of this cluster of 3p22 genes may contribute to the development or progression of this type of cancer. [Cancer Res 2007 (19):9107–16]
Publisher: Elsevier BV
Date: 10-1997
DOI: 10.1016/S1380-2933(97)00016-X
Abstract: The L-arabinose operon from E. coli contains an inducible promoter PBAD which has been extensively studied for the control of gene expression. PBAD has a number of potential advantages over Plac, and has been used successfully to promote high level expression of recombinant proteins. The aim of this study was to investigate PBAD as an alternative system to Plac for the bacterial expression of recombinant Fabs. The promoter PBAD from the E. coli arabinose operon araBAD and the gene encoding the regulator of this promoter, were cloned into the phagemid expression vector MCO1. Expression of human recombinant tetanus toxoid (TT) and c-erbB2 Fabs under the control of PBAD was compared at two induction temperatures with the same Fabs produced under the control of Plac. Expression of TT and c-erbB2 Fabs under the control of PBAD was comparable to Fab expression from Plac. However, highly expressed TT Fab under the control of PBAD was localised to the soluble periplasmic fraction whereas under the control of Plac, there was greater leakage of Fab into the culture supernatant. In addition, Fab expression from PBAD could be more tightly repressed than from Plac. PBAD is a useful and cheaply inducible alternative to the more commonly used Plac for the rapid expression of soluble recombinant human antibody fragments.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2002
DOI: 10.1007/S10350-004-6266-1
Abstract: AB. B. subset of sporadic colorectal carcinomas show microsatellite instability, usually as a result of biallelic hMLH1 gene promoter methylation. Synchronous tumors occur in up to 5 percent of patients with colorectal cancer, but their cause is poorly understood. We hypothesized that in the setting of sporadic microsatellite instability cancers, synchronicity may reflect a global predisposition of colorectal epithelium toward tumor development because of gene hypermethylation. We identified 14 in iduals with 33 synchronous cancers from a series of 362 patients with 381 sporadic colorectal cancers. We then analyzed the synchronous lesions for microsatellite status, hMLH1 protein expression, and hMLH1 promoter methylation. Seven of 33 synchronous tumors (21 percent) showed microsatellite instability, compared with 36 of 348 solitary tumors (10.3 percent, P = 0.06). The 14 patients with synchronous tumors were significantly older than those with solitary tumors (mean age 79.4 vs. 68.2 years, P = 0.01), and 5 of these patients had at least one microsatellite instability tumor. However, only one patient harbored synchronous tumors that were all of the microsatellite instability type. Methylation of the hMLH1 promoter was seen in 9 synchronous cancers from 27 assessable lesions in 7 patients and was associated with microsatellite instability (P = 0.01), right-sidedness (P = 0.01), and loss of expression of hMLH1 (P = 0.03). Only one case showed methylation in all synchronous tumors, whereas in five cases synchronous tumors showed different methylation status within the one in idual. Our data suggest that synchronous tumors arise as independent events and that the slightly greater frequency of synchronous tumors in in iduals with microsatellite instability cancers is likely to be a chance event reflecting the older age of these in iduals rather than arising from a predisposition toward cancer as a result of global hypermethylation of colorectal epithelium.
Publisher: Mary Ann Liebert Inc
Date: 04-2014
Publisher: Elsevier
Date: 2016
Publisher: Cambridge University Press (CUP)
Date: 12-2002
DOI: 10.1079/PHN2002349
Abstract: In the fast growing city of Nairobi, women often combine the roles of mother and worker in trying to achieve better standards of living. The objective of this study was to document the effect of returning to work on breast-feeding by mothers in Kenya. A cross-sectional survey. Outpatient clinics of two major hospitals in Nairobi, one government hospital in an economically deprived area and one high-fee private hospital. Four hundred and forty-four working mothers from low and higher socio-economic areas in Nairobi. All working mothers with infants aged 4 to 12 months attending during the survey period were invited to participate. The prevalence of breast-feeding at the time of interview was found to be 94.1%. The lower socio-economic group exhibited a higher prevalence of breast-feeding (99%), 10% greater than the higher socio-economic group. The mean number of hours the mothers were away from home due to work was 46.2 hours each week. The majority (54.4%) of the mothers employed a ‘house-girl’ to care for their infant while they were at work, while 28.4% were able to take their infants to work. Most of the breast-feeding mothers (95%) breast-fed their infants at least three times a day and only 23 mothers reported not being able to breast-feed their infants during the day. The lower socio-economic group had a mean of 5.09 breast-feeding times per day while the higher socio-economic group had a mean of 3 times a day. In a logistic regression analysis the mode of work (fixed working hours vs. shift working hours) was associated with exclusive breast-feeding at one month (odds ratio (OR) = 0.45) and two months (OR = 0.39). In Western countries ‘return to work’ is often cited as the reason that breast-feeding is discontinued prematurely. In this study we have shown how mothers in Kenya are able to successfully continue breast-feeding after they have returned to work, often for very long hours.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1053/J.GASTRO.2005.09.003
Abstract: Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by heterozygous germline sequence mutations of DNA mismatch repair genes, most frequently MLH1 or MSH2. A novel molecular mechanism for HNPCC has recently been suggested by the finding of in iduals with soma-wide monoallelic hypermethylation of the MLH1 gene promoter. In this study, we determined the frequency and role of germline epimutations of MLH1 in HNPCC. A cohort of 160 probands from HNPCC families who did not harbor germline sequence mutations in the mismatch repair genes were screened for methylation of the MLH1 and EPM2AIP1 promoters by combined bisulfite and restriction analyses. Allelic expression and family transmission of MLH1 were determined using polymorphisms in intron 4 and the 3' untranslated region. One of 160 in iduals had monoallelic MLH1 hypermethylation in peripheral blood, hair follicles, and buccal mucosa, indicative of a soma-wide alteration. Monoallelic transcription of the paternal MLH1 allele was shown using a heterozygous expressed polymorphism within the 3' untranslated region. The hypermethylated allele was maternally transmitted, however, the mother and siblings who inherited the same maternal homologue were unmethylated at MLH1, suggesting the epimutation arose as a de novo event. Germline MLH1 epimutations are functionally equivalent to an inactivating mutation and produce a clinical phenotype that resembles HNPCC. Inheritance of epimutations is weak, so family history is not a useful guide for screening. Germline epimutations should be suspected in younger in iduals without a family history who present with a microsatellite unstable tumor showing loss of MLH1 expression.
Publisher: Elsevier BV
Date: 08-2000
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1016/J.AAP.2006.09.005
Abstract: The study's objectives were to determine the prevalence and types of distracting activities involved in serious crashes, and to explore the factors associated with such crashes. We interviewed 1367 drivers who attended hospital in Perth, Western Australia between April 2002 and July 2004 following a crash. A structured questionnaire was administered to each driver and supplementary data were collected from ambulance and medical records. Over 30% of drivers (433, 31.7%) cited at least one distracting activity at the time of crashing and driver distraction was reported to have contributed to 13.6% of all crashes. The major distracting activities were conversing with passengers (155, 11.3%), lack of concentration (148, 10.8%) and outside factors (121, 8.9%). Using logistic regression, a distracting activity at the time of a crash was significantly more likely among drivers with shorter driving experience (0-9 years, 38.3% versus >or=30 years, 21.0%, p<0.001). Distracting activities at the time of serious crashes are common and can cause crashes, and the types of activities reported are varied. Increased driver awareness of the adverse consequences of distracted driving with a focus on novice drivers, enforcement of existing laws (e.g. those requiring a driver to maintain proper control of a vehicle), and progress on engineering initiatives (such as collision warning systems) are needed to reduce injury.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.ACRA.2015.07.002
Abstract: Diagnostic imaging is under-represented in medical curricula globally. Adaptive tutorials, online intelligent tutoring systems that provide a personalized learning experience, have the potential to bridge this gap. However, there is limited evidence of their effectiveness for learning about diagnostic imaging. We performed a randomized mixed methods crossover trial to determine the impact of adaptive tutorials on perceived engagement and understanding of the appropriate use and interpretation of common diagnostic imaging investigations. Although concurrently engaged in disparate blocks of study, 99 volunteer medical students (from years 1-4 of the 6-year program) were randomly allocated to one of two groups. In the first arm of the trial on chest X-rays, one group received access to an adaptive tutorial, whereas the other received links to an existing peer-reviewed Web resource. These two groups crossed over in the second arm of the trial, which focused on computed tomography scans of the head, chest, and abdomen. At the conclusion of each arm of the trial, both groups completed an examination-style assessment, comprising questions both related and unrelated to the topics covered by the relevant adaptive tutorial. Online questionnaires were used to evaluate student perceptions of both learning resources. In both arms of the trial, the group using adaptive tutorials obtained significantly higher assessment scores than controls. This was because of higher assessment scores by senior students in the adaptive tutorial group when answering questions related to topics covered in those tutorials. Furthermore, students indicated significantly better engagement with adaptive tutorials than the Web resource and rated the tutorials as a significantly more valuable tool for learning. Medical students overwhelmingly accept adaptive tutorials for diagnostic imaging. The tutorials significantly improve the understanding of diagnostic imaging by senior students.
Publisher: BMJ
Date: 04-2006
Publisher: Elsevier BV
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 11-07-2014
Publisher: American Public Health Association
Date: 04-2015
Abstract: Objectives. We identified the features of a land use–transportation system that optimizes the health and well-being of the population. Methods. We developed a quantitative system dynamics model to represent relationships among land use, transport, economic development, and population health. Simulation experiments were conducted over a 10-year simulation period to compare the effect of different baseline conditions and land use–transport policies on the number of motor vehicle crash deaths and disability-adjusted life years lost. Results. Optimal reduction in the public health burden attributable to land transport was demonstrated when transport safety risk reduction policies were combined with land use and transport polices that minimized reliance on in idual motorized transport and maximized use of active transport modes. The model’s results were particularly sensitive to the level of development that characterized each city at the start of the simulation period. Conclusions. Local, national, and international decision-makers are encouraged to address transport, land use, and health as an integrated whole to achieve the desired societal benefits of traffic safety, population health, and social equity.
Publisher: Elsevier BV
Date: 02-1997
Abstract: Point mutations in the K-ras gene are frequently observed in a variety of human malignancies, including colorectal and pancreatic cancers. In this paper, we describe a sensitive procedure for the detection of point mutations of codon 12 of the K-ras gene. The assay employs a single-tube enriched PCR procedure, coupled to colorimetric detection. In the enriched PCR procedure, the first round of lification introduces a restriction enzyme site in the wild type, but not in mutant K-ras PCR product. The wild type products are then digested and the second round of PCR enriches for the mutant sequences by lifying the resistant products. The second round of lification allows the incorporation of biotin and a substrate binding tag at opposite ends of the mutant product, thus allowing detection of the product by a simple colorimetric assay. The assay has been validated using DNA from a variety of cell lines known to contain either mutant or wild type K-ras. Under these conditions, the assay has proved both reproducible and sensitive, with the ability to detect one mutant molecule in a background of 1000 wild type molecules. The assay allowed discrimination of mutant from wild type K-ras in s les from colonic adenocarcinomas and normal colonic mucosa. The use of a colorimetric detection system reduces observer bias and facilitates analysis of large numbers of s les. As such, the assay may have specific application in the sensitive detection of K-ras mutations in a variety of clinical s les.
Publisher: Wiley
Date: 05-2016
DOI: 10.1111/JGS.14109
Publisher: American Public Health Association
Date: 03-2015
Abstract: Objectives. We sought to identify the program fidelity factors associated with successful implementation of the Buckle-Up Safely program, targeting correct use of age-appropriate child car restraints. Methods. In 2010, we conducted a cluster randomized controlled trial of 830 families with children attending preschools and long day care centers in South West Sydney, New South Wales, Australia. Families received the Buckle-Up Safely program in the intervention arm of the study (13 services). Independent observers assessed the type of restraint and whether it was used correctly. Results. This detailed process evaluation showed that the multifaceted program was implemented with high fidelity. Program protocols were adhered to and messaging was consistently delivered. Results from multilevel and logistic regression analyses show that age-appropriate restraint use was associated with attendance at a parent information session hosted at the center (adjusted odd ratio [AOR] = 3.66 95% confidence interval [CI] = 1.61, 8.29) and adversely affected by the child being aged 2 to 3 years (AOR = 0.14 95% CI = 0.07, 0.30) or being from a family with more than 2 children (AOR = 0.34 95% CI = 0.17, 0.67). Conclusions. Findings highlight the importance of parents receiving hands-on education regarding the proper use of age-appropriate child restraints.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488654.V1
Abstract: Supplementary Figures S1-S13
Publisher: Elsevier BV
Date: 2011
Publisher: Wiley
Date: 15-03-1997
DOI: 10.1002/(SICI)1097-0142(19970315)79:6<1106::AID-CNCR8>3.0.CO;2-D
Abstract: Association between hypoplastic left heart syndrome and valvular pulmonary stenosis is very rare. Severity of valvular pulmonary stenosis in this setting limits management options. Consequently, patients with this condition are considered poor candidates for Norwood stage one reconstruction. Herein, we describe a newborn with hypoplastic left heart syndrome and significantly dysplastic pulmonary valve who successfully underwent the Norwood procedure with neoaortic valve reconstruction. Therefore, the Norwood procedure with neoaortic valve reconstruction might be an option for this difficult condition.
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.AAP.2009.03.005
Abstract: Most previous literature on urban/rural differences in road crashes has a primary focus on severe injuries or deaths, which may be largely explained by variations of medical resources. Little has been reported on police-reported crashes by geographical location, or crash type and severity, especially among young drivers. DRIVE is a prospective cohort study of 20,822 drivers aged 17-24 in NSW, Australia. Information on risk factors was collected via online questionnaire and subsequently linked to police-reported crashes. Poisson regression was used to analyse risk of various crash types by three levels of rurality of residence: urban, regional (country towns and surrounds) and rural. Compared to urban drivers, risk of crash decreased with increasing rurality (regional adjusted RR: 0.7, 95% CI 0.6-0.9 rural adjusted RR: 0.5, 95% CI 0.3-0.7). Among those who crashed, risk of injurious crash did not differ by geographic location however, regional and rural drivers had significantly higher risk of a single versus multiple vehicle crash (regional adjusted RR 1.8, 95% CI 1.3-2.5 rural adjusted RR: 2.0, 95% CI 1.1-3.6), which was explained by speeding involvement and road alignment at the time or site of crash. Although young urban drivers have a higher crash risk overall, rural and regional residents have increased risk of a single vehicle crash. Interventions to reduce single vehicle crashes should aim to address key issues affecting such crashes, including speeding and specific aspects of road geometry.
Publisher: BMJ
Date: 02-2006
Publisher: Elsevier BV
Date: 09-2004
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-04-2015
DOI: 10.5664/JCSM.4594
Publisher: SAGE Publications
Date: 29-09-2009
Abstract: Mild traumatic brain injury (mTBI) is an emerging public health issue in high-contact sports. Understanding the incidence along with the risk and protective factors of mTBI in high-contact sports such as rugby is paramount if appropriate preventive strategies are to be developed. To estimate the incidence and identify the risk and protective factors of mTBI in Australian nonprofessional rugby players. Cohort study Level of evidence, 2. A cohort of 3207 male nonprofessional rugby players from Sydney, Australia, was recruited and followed over 1 or more playing seasons. Demographic information, history of recent concussion, and information on risk and protective factors were collected. The incidence of mTBI was estimated and the putative risk and protective factors were modeled in relation to mTBI. The incidence of mTBI was 7.97 per 1000 player game hours, with 313 players (9.8%) sustaining 1 or more mTBIs during the study. Players who reported always wearing protective headgear during games were at a reduced risk (incident rate ratio [IRR], 0.57 95% confidence interval [CI], 0.40–0.82) of sustaining an mTBI. In contrast, the likelihood of mTBI was almost 2 times higher among players who reported having sustained either 1 (IRR, 1.75 95% CI, 1.11–2.76) or more mTBIs (IRR, 1.65 95% CI, 1.11–2.45) within the 12 months before recruitment. Nonprofessional rugby has a high incidence of mTBI, with the absence of headgear and a recent history of mTBI associated with an increased risk of subsequent mTBI. These findings highlight that both use of headgear and the management of prior concussion would likely be beneficial in reducing the likelihood of mTBI among nonprofessional rugby players, who compose more than 99% of rugby union players in Australia.
Publisher: Massachusetts Medical Society
Date: 15-02-2007
DOI: 10.1056/NEJMOA064522
Publisher: American Society of Clinical Oncology (ASCO)
Date: 15-10-2003
Abstract: Purpose: DNA methylation is an important biologic event in colorectal cancer and in some cases is associated with the development of microsatellite instability (MSI). In this study, we sought to determine the prognostic significance of DNA methylation, both in univariate analysis and in concert with other clinicopathologic factors known to influence outcome. Patients and Methods: Fresh tissue (625 cancers) was obtained from 605 in iduals (age range, 29 to 99 years) undergoing curative surgery for colorectal cancer at one institution during a period of 8 years. Clinicopathologic details were recorded for all tumors, including stage, grade, type, vascular space invasion, and clinical follow-up to 5 years. Microsatellite status was assessed using standard markers. Methylation of p16 and hMLH1 promoters was determined by methylation-specific polymerase chain reaction (PCR), whereas methylation at methylated-in-tumor loci (MINT)1, MINT2, MINT12, and MINT31 loci were assessed by bisulfite-PCR. Results: Patients with microsatellite unstable tumors (12%) had better disease-specific survival than those with microsatellite stable (MSS) tumors (univariate analysis: hazard ratio [HR], 0.53 95% CI, 0.27 to 1.0). Overall survival of in iduals with MSS tumors was influenced by three independently significant factors: tumor stage (HR, 7.3 95% CI, 5.1 to 10.4), heavy tumor methylation (HR, 2.1 95% CI, 1.1 to 4.0), and vascular space invasion (HR, 1.9 95% CI, 1.3 to 2.9). In MSS tumors, methylation at any single site was not independently predictive of survival. Neither methylation nor microsatellite status predicted a favorable response to chemotherapy. Conclusion: DNA methylation is associated with a worse outcome in colorectal cancer, but this adverse prognostic influence is lost in those methylated tumors showing MSI. The mechanisms of these events warrant additional investigation.
Publisher: Informa UK Limited
Date: 04-04-2008
Publisher: Springer Science and Business Media LLC
Date: 26-03-2010
Abstract: Heavy vehicle transportation continues to grow internationally yet crash rates are high, and the risk of injury and death extends to all road users. The work environment for the heavy vehicle driver poses many challenges conditions such as scheduling and payment are proposed risk factors for crash, yet the precise measure of these needs quantifying. Other risk factors such as sleep disorders including obstructive sleep apnoea have been shown to increase crash risk in motor vehicle drivers however the risk of heavy vehicle crash from this and related health conditions needs detailed investigation. The proposed case control study will recruit 1034 long distance heavy vehicle drivers: 517 who have crashed and 517 who have not. All participants will be interviewed at length, regarding their driving and crash history, typical workloads, scheduling and payment, trip history over several days, sleep patterns, health, and substance use. All participants will have administered a nasal flow monitor for the detection of obstructive sleep apnoea. Significant attention has been paid to the enforcement of legislation aiming to deter problems such as excess loading, speeding and substance use however, there is inconclusive evidence as to the direction and strength of associations of many other postulated risk factors for heavy vehicle crashes. The influence of factors such as remuneration and scheduling on crash risk is unclear so too the association between sleep apnoea and the risk of heavy vehicle driver crash. Contributory factors such as sleep quality and quantity, body mass and health status will be investigated. Quantifying the measure of effect of these factors on the heavy vehicle driver will inform policy development that aims toward safer driving practices and reduction in heavy vehicle crash protecting the lives of many on the road network.
Publisher: SAGE Publications
Date: 13-02-2015
Abstract: Each year, an estimated 270,000 pedestrians die from road traffic-related injuries, (worldwide) and children are among the most vulnerable. Child pedestrian injuries occur primarily in residential areas, often on the same street or in close proximity to the child’s home, and 90% of injured child pedestrians are unaccompanied by an adult at the time of the injury. The cause of these injuries is a complex combination of factors related not only to characteristics of the child but also the built environment, the road configuration, features of the motor vehicle that might reduce injury, and driver behavior. Accordingly, effective interventions must incorporate education, technology, and improved infrastructure. The medical practitioner can not only provide the necessary education but can also be a powerful voice for changes in pedestrian infrastructure that make walking safer. This article explores the current state of childhood pedestrian injuries using ex les from the United States and Australia. Pedestrian interventions and the role that primary care and lifestyle practitioners play in promoting safe pedestrian behaviors among their patients and their families are discussed.
Publisher: Elsevier BV
Date: 06-2014
Abstract: The study aimed to examine the difference in response rates between opt-out and opt-in participant recruitment in a population-based study of heavy-vehicle drivers involved in a police-attended crash. Two approaches to subject recruitment were implemented in two different states over a 14-week period and response rates for the two approaches (opt-out versus opt-in recruitment) were compared. Based on the eligible and contactable drivers, the response rates were 54% for the opt-out group and 16% for the opt-in group. The opt-in recruitment strategy (which was a consequence of one jurisdiction's interpretation of the national Privacy Act at the time) resulted in an insufficient and potentially biased s le for the purposes of conducting research into risk factors for heavy-vehicle crashes. Australia's national Privacy Act 1988 has had a long history of inconsistent practices by state and territory government departments and ethical review committees. These inconsistencies can have profound effects on the validity of research, as shown through the significantly different response rates we reported in this study. It is hoped that a more unified interpretation of the Privacy Act across the states and territories, as proposed under the soon-to-be-released Australian Privacy Principles(1) will reduce the recruitment challenges outlined in this study.
Publisher: Elsevier BV
Date: 05-1994
Abstract: Well-characterized human glomerular mesangial cells were stimulated in vitro with interferon-gamma (IFN-gamma), interleukin-1, and tumor necrosis factor alpha (TNF-alpha) to determine the influence of these cytokines on the expression of class I and II HLA antigens. IFN-gamma induced a dose-dependent increase in expression of both class I and class II HLA antigens. TNF-alpha induced only class I antigens when used alone, but acted synergistically with IFN-gamma in the expression of class I and II antigens. Interleukin-1 had little effect on HLA antigen expression. These results raise the possibility that stimulated mesangial cells may act as antigen-presenting cells and may mediate local immune reactions in the glomerulus.
Publisher: Elsevier BV
Date: 11-2008
Publisher: CMA Joule Inc.
Date: 16-11-2009
DOI: 10.1503/CMAJ.090459
Publisher: BMJ
Date: 08-2006
Publisher: Elsevier BV
Date: 04-2003
Publisher: American Public Health Association
Date: 09-2009
Abstract: Objectives. We explored the risky driving behaviors and risk perceptions of a cohort of young novice drivers and sought to determine their associations with crash risk. Methods. Provisional drivers aged 17 to 24 (n = 20 822) completed a detailed questionnaire that included measures of risk perception and behaviors 2 years following recruitment, survey data were linked to licensing and police-reported crash data. Poisson regression models that adjusted for multiple confounders were created to explore crash risk. Results. High scores on questionnaire items for risky driving were associated with a 50% increased crash risk (adjusted relative risk = 1.51 95% confidence interval = 1.25, 1.81). High scores for risk perception (poorer perceptions of safety) were also associated with increased crash risk in univariate and multivariate models however, significance was not sustained after adjustment for risky driving. Conclusions. The overrepresentation of youths in crashes involving casualties is a significant public health issue. Risky driving behavior is strongly linked to crash risk among young drivers and overrides the importance of risk perceptions. Systemwide intervention, including licensing reform, is warranted.
Publisher: BMJ
Date: 12-07-2005
Publisher: Informa UK Limited
Date: 21-01-2017
Publisher: Springer Science and Business Media LLC
Date: 18-02-2014
DOI: 10.1038/BJC.2014.31
Publisher: Oxford University Press (OUP)
Date: 13-05-2003
DOI: 10.1093/JAC/DKG254
Publisher: American Academy of Pediatrics (AAP)
Date: 02-2010
Publisher: Elsevier BV
Date: 09-1997
Publisher: Wiley
Date: 20-05-2001
DOI: 10.1046/J.1445-5994.2001.00051.X
Abstract: Improvements in cancer care have historically been predicated on significant scientific and technological advances, such as antisepsis in surgery, and the discovery of the therapeutic benefits of radiation and chemotherapeutic drugs. The past 30 years have seen an exponential increase in our knowledge of the biology and genetics of cancer, built on a massive and sustained research effort worldwide. Yet over the same period, significant changes in cancer outcomes have occurred largely as a result of public health measures and through incremental advances in existing technologies. The present paper examines the extent to which the new knowledge of cancer genetics has impacted on current patient care. It considers some of the issues that may have served to lessen this impact, as well as some of the reasons for this apparent imbalance between action and outcome.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2013
Publisher: BMJ
Date: 02-2009
Publisher: BMJ
Date: 26-04-2010
Abstract: In order to determine the accuracy of self-report of on-road crashes and traffic offences among participants in the DRIVE study, 2991 young drivers in New South Wales, Australia who completed the follow-up questionnaire were asked whether they had been involved in an on-road crash or were convicted for a traffic offence while driving during the year prior to the survey. This information was linked to police crash data to determine the level of accuracy of self-report of on-road crashes. There was a high level of accuracy in young drivers' self-report of police recorded crashes (85.1% 95% CI 78.2% to 92.1%) and of police recorded traffic offences (83.0% 95% CI 79.4% to 86.6%). Results suggest that surveys may be useful tools for estimating the incidence of on-road crashes and traffic offences in young drivers. The findings are particularly relevant to jurisdictions where access to administrative data is limited.
Publisher: Springer Science and Business Media LLC
Date: 22-10-2013
DOI: 10.1038/ONC.2012.486
Publisher: Springer US
Date: 2005
Publisher: BMJ
Date: 20-12-2012
Publisher: American Association for Cancer Research (AACR)
Date: 07-10-2022
DOI: 10.1158/1078-0432.CCR-22-1206
Abstract: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) lification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC s les clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.
Publisher: BMJ
Date: 29-01-2014
Publisher: BMJ
Date: 02-2005
Publisher: American Public Health Association
Date: 12-2012
Abstract: Objectives. We evaluated an education, distribution, and fitting program for increasing age-appropriate and correct child restraint use. Methods. We performed a cluster randomized trial involving 28 early childhood education centers in low socioeconomic status areas in Sydney, Australia. The main outcome was optimal restraint use defined as age-appropriate restraints, installed into the vehicle correctly and used correctly. Results. One service withdrew after randomization, so data are presented for 689 child passengers, aged 3 to 5 years, from 27 centers. More children attending intervention centers were optimally restrained (43% vs 31% P = .01 allowing for clustering). More 3-year-olds were using forward-facing seats rather than booster seats, more 4- to 5-year-olds were using booster seats instead of seat belts alone, and there were fewer errors in use at intervention centers. Among non–English-speaking families, more children attending intervention centers were optimally restrained (43% vs 17% P = .002 allowing for clustering). Conclusions. The program increased use of age-appropriate restraints and correct use of restraints, which translates to improved crash injury protection. Multifaceted education, seat distribution, and fitting enhanced legislation effects, and the effect size was larger in non–English-speaking families.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 10-07-2013
Abstract: Molecular screening techniques are available to identify hereditary Lynch syndrome in people with newly diagnosed colorectal cancer (CRC). We aimed to determine whether decisions of patients or clinicians reduced detection of Lynch syndrome. A prospective cohort of 245 consecutive in iduals with mismatch repair–deficient CRC recruited from a population-based molecular screening program of all incident patient cases of CRC in a health care region of 1.2 million inhabitants. All incident CRCs were analyzed for mismatch repair protein loss, supported by BRAF mutation and microsatellite instability testing. Advice regarding referral for germline testing was provided to treating surgeons. The mean age of patients was 72.5 ± standard deviation of 12 years 64% were women 65% had BRAF-mutant cancers. Consent for germline testing was received from 194 patients (79%): 120 with low and 74 with high likelihood of Lynch syndrome based on tumor molecular profile. Of patients who consented, 143 provided s les for germline analysis, with 12 of 143 showing a mutation (8.4% 95% CI, 4.4% to 14.2%). Among the 102 patients who chose not to provide a s le or did not consent, an estimated 5.3 of 102 had germline mutations (5.2% 95% CI, 2.0% to 17.5%). A universal screening strategy for Lynch syndrome is potentially effective because the overall estimate of germline mutations was 17.3 of 245 patient cases (7.1% 95% CI, 2.8% to 18.2%). However, the true value of screening is likely to be greatly limited by the decisions and circumstances of patients in taking up germline testing.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1038/MODPATHOL.2010.212
Abstract: Epigenetic silencing of cancer-related genes by promoter methylation is a frequent event in sporadic colorectal cancer. The CpG island methylator phenotype (CIMP+), in which discrete genes throughout the genome are simultaneously methylated, and long-range epigenetic silencing, whereby multiple genes within contiguous chromosomal regions are methylated, have been described in subsets of colorectal cancer. We previously reported the concurrent methylation of the mismatch repair gene MLH1 with a cluster of flanking genes in chromosome region 3p22 in sporadic colorectal carcinoma exhibiting microsatellite instability and the BRAF V600E mutation. Herein, we aimed to determine whether methylation of MLH1 and neighbouring 3p22 genes, singly or concomitantly, correlate with the germline c.-93G>A SNP within the MLH1 promoter, CIMP+ and other clinicopathological and molecular features of the tumours. By studying a cohort of 946 sporadic colorectal cancer cases, we show a strong association between concordant methylation of ≥ 3 of five 3p22 genes with CIMP+ and the BRAF V600E mutation (P<0.001). These associations were independent of microsatellite instability, as concomitant methylation of 3p22 genes other than MLH1 was found in microsatellite stable cancers. These findings show that long-range epigenetic silencing across 3p22 occurs in the context of CIMP+ and the BRAF V600E mutation, and only gives rise to microsatellite instability when this process encompasses MLH1. Furthermore, the strong relationship between long-range epigenetic silencing of 3p22 and CIMP+ provides further evidence that these two purportedly distinct epigenetic phenotypes represent a single entity with a common aetiology. Low-level methylation of MLH1 and flanking 3p22 genes, as well as the BRAF V600E mutation, were detected in the apparently normal colonic mucosa of a small number of cases whose tumours showed a similar molecular profile, suggesting that these concurring genetic and epigenetic events can occur as a field defect in neoplastic development.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488651.V1
Abstract: Supplementary Methods
Publisher: Oxford University Press
Date: 15-04-2010
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.INJURY.2011.02.013
Abstract: Helicopter Emergency Medical Services (HEMS) have been incorporated into modern health systems for their speed and coverage. In the state of New South Wales (NSW), nine HEMS operate from various locations around the state and currently there is no clear picture of their resource implications. The aim of this study was to assess the cost of HEMS in NSW and investigate the factors linked with the variation in the costs, coverage and activities of HEMS. We undertook a survey of HEMS costs, structures and operations in NSW for the 2008/2009 financial year. Costs were estimated from annual reports and contractual agreements. Data related to the structure and operation of services was obtained by face-to-face interviews, from operational data extracted from in idual HEMS, from the NSW Ambulance Computer Aided Despatch system and from the Aeromedical Operations Centre database. In order to estimate population coverage for each HEMS, we used GIS mapping techniques with Australian Bureau of Statistics census information. Across HEMS, cost per mission estimates ranged between $9300 and $19,000 and cost per engine hour estimates ranged between $5343 and $15,743. Regarding structural aspects, six HEMS were run by charities or not-for-profit companies (with partial government funding) and three HEMS were run (and fully funded) by the state government through NSW Ambulance. Two HEMS operated as 'hub' services in conjunction with three associated 'satellite' services and in contrast, four services operated independently. Variation also existed between the HEMS in the type of helicopter used, the clinical staffing and the hours of operation. The majority of services undertook both primary scene responses and secondary inter-facility transfers, although the proportion of each type of transport contributing to total operations varied across the services. This investigation highlighted the cost of HEMS operations in NSW which in total equated to over $50 million per annum. Across services, we found large variation in the cost estimates which was underscored by variation in the structure and operations of HEMS.
Publisher: Elsevier BV
Date: 2002
DOI: 10.1080/00313020220147122
Abstract: Gastrointestinal stromal tumours (GISTs), once assumed to be of smooth muscle origin, generally express CD117 and CD34, similar to the interstitial cells of Cajal. Assessment of malignant potential in GISTs is problematic, especially on small biopsies. Some recent data indicate that mutations in the juxtamembrane domain (exon 11) of the c-kit (CD117) proto-oncogene may be associated with a worse prognosis. In this study, the frequency of c-kit exon 11 mutations has been determined in a series of 18 gut stromal tumours. Immunophenotype was assessed by immunoperoxidase stains for smooth muscle actin, desmin, S100, CD34 and CD117, and each tumour classified as being of low, uncertain (intermediate) or high malignant potential based on standard histological criteria. DNA from each tumour was extracted from fresh (n = 5) or formalin-fixed, paraffin-embedded (n= 13) tissues using the direct lysis method. Exon 11 was lified by PCR and sequencing of both sense and antisense strands was performed on two occasions using an ABI 377 sequencer. Mutations in exon 11 were detected in three of 14 confirmed GISTs, two being point mutations at codon 560 and one a 3-bp deletion resulting in the in-frame deletion of glutamine at codon 561. All three tumours were of high or intermediate malignant potential histologically. Three other 'high risk' primary GISTs and a metastatic GIST deposit were negative for exon 11 mutations. Data on this relatively small cohort of Australian patients indicate that c-kit exon 11 mutation analysis does not correlate well with histological assessment of malignant potential, and cannot be regarded as a reliable objective marker for poor prognosis in GISTs.
Publisher: Oxford University Press (OUP)
Date: 18-12-2013
DOI: 10.1093/AJE/KWT305
Abstract: Heavy-vehicle driving involves a challenging work environment and a high crash rate. We investigated the associations of sleepiness, sleep disorders, and work environment (including truck characteristics) with the risk of crashing between 2008 and 2011 in the Australian states of New South Wales and Western Australia. We conducted a case-control study of 530 heavy-vehicle drivers who had recently crashed and 517 heavy-vehicle drivers who had not. Drivers' crash histories, truck details, driving schedules, payment rates, sleep patterns, and measures of health were collected. Subjects wore a nasal flow monitor for 1 night to assess for obstructive sleep apnea. Driving schedules that included the period between midnight and 5:59 am were associated with increased likelihood of crashing (odds ratio = 3.42, 95% confidence interval: 2.04, 5.74), as were having an empty load (odds ratio = 2.61, 95% confidence interval: 1.72, 3.97) and being a less experienced driver (odds ratio = 3.25, 95% confidence interval: 2.37, 4.46). Not taking regular breaks and the lack of vehicle safety devices were also associated with increased crash risk. Despite the high prevalence of obstructive sleep apnea, it was not associated with the risk of a heavy-vehicle nonfatal, nonsevere crash. Scheduling of driving to avoid midnight-to-dawn driving and the use of more frequent rest breaks are likely to reduce the risk of heavy-vehicle nonfatal, nonsevere crashes by 2-3 times.
Publisher: Elsevier BV
Date: 2002
Publisher: Springer Science and Business Media LLC
Date: 09-01-2010
DOI: 10.1007/S10689-009-9314-0
Abstract: Lynch syndrome is an autosomal dominant cancer susceptibility syndrome characterized by the early development of microsatellite unstable colorectal, endometrial and other cancers. Lynch syndrome is caused by germline heterozygous loss-of-function sequence mutations within the mismatch repair genes MLH1, MSH2, MSH6 or PMS2. Some in iduals with Lynch syndrome have constitutional epimutations, characterized by promoter methylation and transcriptional inactivation of a single allele in normal somatic tissues, while others lack identifiable pathogenic changes in the germline. We hypothesized that analysis of the relative levels of allelic expression of MLH1 would assist in the identification of cryptic pathogenic defects of MLH1 in five presumed Lynch syndrome cases whose tumours demonstrated MLH1 loss, but whose causative mutation remained unidentified. We exploited the common benign c.655A>G SNP (rs1799977) within MLH1 exon 8 to distinguish between the two genetic alleles in heterozygous in iduals and to study their transcriptional activity, using quantitative pyrosequencing assays. In one of the five patients we detected loss of expression of one allele and deletion of the other allele in the tumour, prompting renewed germline screening. A novel intronic splice mutation was subsequently identified, which resulted in loss of an entire exon from the transcript. This pyrosequencing assay also proved useful in demonstrating the gradual reversal of a constitutional MLH1 epimutation during lymphoblastoid cell culture, suggesting this defect may not be stably maintained in immortalized cells. Our findings illustrate that the study of allelic behaviour can complement conventional molecular analyses by providing new insight into the genetic or epigenetic mechanisms underlying disease.
Publisher: BMJ
Date: 21-09-2015
Publisher: BMJ
Date: 12-10-2010
Abstract: Previous studies that found increased crash risks for young drivers of low socioeconomic status (SES) have failed to adjust for factors such as driving exposure and rural residence. This aim of this study is to examine the independent effect of SES on crash risk, adjusting for such factors, and to examine the relationship between injury severity following a crash and SES. Information on risk factors for crash collected from 20,822 newly licenced drivers aged 17-24 years in New South Wales, Australia, as part of the DRIVE Study was prospectively linked to hospitalisation data. SES was classified as high, moderate or low based on the Australia 2001 Socio-Economic Index for Areas. Poisson regression was used to model risk of crash-related hospitalisation by SES, adjusting for confounders. Two measures of injury severity--urgency of treatment and length of hospital stay--were examined by SES. Results of multivariable analysis showed that drivers from low SES areas had increased relative risk (RR 1.8, 95% CI 1.1 to 3.1) of crash-related hospitalisation compared to drivers from high SES areas. This increased risk remained when adjusting for confounders including driving exposure and rurality (RR 1.9, 95% CI 1.1 to 3.2). No significant association was found between injury severity and SES. The higher risk of crash-related hospitalisation for young drivers from low SES areas is independent of driving exposure and rural-urban differences. This finding may help improve and better target interventions for youth of low SES.
Publisher: BMJ
Date: 10-2003
Publisher: BMJ
Date: 12-2006
Publisher: Elsevier BV
Date: 12-2008
Publisher: Elsevier
Date: 2008
Publisher: BMJ
Date: 03-2001
DOI: 10.1136/IP.7.1.10
Abstract: The research was undertaken to describe the injury severity score (ISS) and the new injury severity score (NISS) and to illustrate their statistical properties. Descriptive analysis and assessment of the distribution of these scales. Three data sources--the National Pediatric Trauma Registry the Massachusetts Uniform Hospital Discharge Data Set and a trauma registry from an urban level I trauma center in Massachusetts--were used to describe the distribution of the ISS and NISS among injured patients. The ISS/NISS was found to have a positively skewed distribution and transformation did not improve their skewness. The findings suggest that for statistical or analytical purposes the ISS/ NISS should not be considered a continuous variable, particularly if ISS/NISS is treated as a continuous variable for correlation with an outcome measure.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.22488645.V1
Abstract: Supplementary Tables S1-S11
Publisher: BMJ
Date: 10-04-2011
Abstract: This study reports the time to sustain a mild traumatic brain injury (mTBI) among a cohort of community rugby union players. Demographic and player characteristics were collected and players followed up for between one and three playing seasons. 7% of the cohort sustained an mTBI within 10 h of game time, increasing twofold to 14% within 20 h. The mean time to first mTBI was 8 h with an SD of 6.2 (median 6.8 h IQR: 2.9-11.7 h). Players reporting a recent history of concussion were 20% more likely to sustain an mTBI after 20 h of game time compared with those with no recent history of concussion. Players were likely to sustain an mTBI in shorter time if they trained for <3 h/week (HR=1.48, p=0.03) or had a body mass index <27 (HR=1.77, p=0.007). The findings highlight modifiable characteristics to reduce the likelihood of shortened time to mTBI.
Publisher: Elsevier BV
Date: 03-2003
DOI: 10.1016/S0959-8049(02)00633-0
Abstract: Colorectal cancers with microsatellite instability (MSI) typically show increased numbers of intraepithelial lymphocytes (IEL) in comparison to microsatellite stable (MSS) cancers. The aim of this study was to determine the phenotype of this unique lymphocyte population in MSI and MSS colorectal cancers. Twenty-four in iduals with sporadic colorectal cancer (17 MSI, 7 MSS) were included in this study. Intraepithelial and stromal lymphocytes were detected using immunohistochemistry with anti-CD8 and anti-CD103 antibodies, and two observers independently quantified the numbers of lymphocytes. CD103+ (alpha E beta 7+) IELs detected within tumour tissue co-expressed CD8+ while the stromal lymphocytes were phenotypically heterogeneous, with respect to CD8+ and CD103+ expression. MSI colorectal cancers harboured increased numbers of CD8+ CD103+ IELs, as well as CD8+ CD103- and CD8+ CD103+ stromal lymphocytes, when compared with MSS colorectal cancers. CD103+ IELs were found at 27-fold greater numbers in the tumour epithelium than in normal epithelium from the same patient (P = 0.001, Wilcoxon matched pairs test). From our findings, we have proposed a mechanism for the homing of these alpha E beta 7+ lymphocytes to tumour tissue in MSI and MSS colorectal cancers.
Publisher: Wiley
Date: 2002
DOI: 10.1002/PATH.1071
Abstract: Microsatellite instability is a well-recognised phenomenon. Ten to 15% of sporadic colorectal cancers with a high level of MSI form a well defined group with distinct clinicopathological features. The set of tumours with low level of microsatellite instability (MSI-low), though widely referred to, is not a clearly defined group. The definitions of MSI-low have varied among groups and between different studies from the same group. Some studies have found associations between the MSI-L phenotype and molecular features, notably a higher frequency of K-ras mutations, and, possibly, methylation of methylguanine methyltransferase. Two recent independent studies, however, showed respectively that 68% and 79%, non-MSI-H cancers showed some MSI and could therefore be classed nominally as MSI-L. There was no evidence for a qualitatively discrete MSI-L group, but quantitative differences in the level of MSI were found.
Publisher: Elsevier BV
Date: 09-2015
Publisher: American Association for Cancer Research (AACR)
Date: 02-2014
DOI: 10.1158/2159-8290.CD-13-0285
Abstract: The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells that survive genome doubling demonstrate increased tolerance to chromosome aberrations. Tetraploid cells do not exhibit increased frequencies of structural or numerical CIN per chromosome. However, the tolerant phenotype in tetraploid cells, coupled with a doubling of chromosome aberrations per cell, allows chromosome abnormalities to evolve specifically in tetraploids, recapitulating chromosomal changes in genomically complex colorectal tumors. Finally, a genome-doubling event is independently predictive of poor relapse-free survival in early-stage disease in two independent cohorts in multivariate analyses [discovery data: hazard ratio (HR), 4.70, 95% confidence interval (CI), 1.04–21.37 validation data: HR, 1.59, 95% CI, 1.05–2.42]. These data highlight an important role for the tolerance of genome doubling in driving cancer genome evolution. Significance: Our work sheds light on the importance of whole-genome–doubling events in colorectal cancer evolution. We show that tetraploid cells undergo rapid genomic changes and recapitulate the genetic alterations seen in chromosomally unstable tumors. Furthermore, we demonstrate that a genome-doubling event is prognostic of poor relapse-free survival in this disease type. Cancer Discov 4(2) 175–85. ©2014 AACR. This article is highlighted in the In This Issue feature, p. 131
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.AAP.2017.02.007
Abstract: It has been estimated that one-third of all work-related deaths occur while driving for work-related purposes. Despite this, many organisations are unaware of the practices, beyond those that identify and control the impact of unforeseen events (i.e., risk management), that predispose drivers to risk. This study addresses the issue by identifying the management practices operationalised as, High Performance Workplace Systems (HPWS) that influence safe driver behaviour. The study also explores the value given to safety by senior level management as a moderator of the relationship between HPWS practices and driver behaviour. Each factor was tested within a two level hierarchical model consisting of 911 drivers, nested within 161 supervisors and 83 organisations. The findings highight that under conditions of high investment in job and work design, communication and selection practices, drivers reported poorer driving behaviour. An interaction effect also demonstrated that under conditions of high investment in remuneration, drivers reported safer behaviour, but only when they perceived that managers valued and prioritised safety. The findings challenge current thinking in the management of workplace road safety.
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.CELREP.2014.10.059
Abstract: Loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC). We identify Rad21 as a gatekeeper of LOH and a β-catenin target gene and provide evidence that Wnt pathway activation drives RAD21 expression in human CRC. Genome-wide analyses identified Rad21 as a key transcriptional regulator of critical CRC genes and long interspersed element (LINE-1 or L1) retrotransposons. Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic CRC, implicating cohesin-mediated L1 expression in global genomic instability and gene dysregulation in cancer.
Publisher: BMJ
Date: 08-2008
Abstract: Little is known about the burden or causes of injury in rural villages in India. To examine injury-related mortality and morbidity in villages in the state of Andhra Pradesh, India. A verbal-autopsy-based mortality surveillance study was used to collect mortality data on all ages from residents in 45 villages in 2003-2004. In early 2005, a morbidity survey in adults was carried out using stratified random s ling in 20 villages. Participants were asked about injuries sustained in the preceding 12 months. Both fatal and non-fatal injuries were coded using classification methods derived from ICD-10. Response rates for the mortality surveillance and morbidity survey were 98% and 81%, respectively. Injury was the second leading cause of death for all ages, responsible for 13% (95% CI 11% to 15%) of all deaths. The leading causes of fatal injury were self-harm (36%), falls (20%), and road traffic crashes (13%). Non-fatal injury was reported by 6.7% of survey participants, with the leading causes of injury being falls (38%), road traffic crashes (25%), and mechanical forces (16.1%). Falls were more common in women, with most (72.3%) attributable to slipping and tripping. Road traffic injuries were sustained mainly by men and were primarily the result of motorcycle crashes (48.8%). Injury is an important contributor to disease burden in rural India. The leading causes of injury-falls, road traffic crashes, and suicides-are all preventable. It is important that effective interventions are developed and implemented to minimize the impact of injury in this region.
Publisher: American Association for Cancer Research (AACR)
Date: 15-01-2013
DOI: 10.1158/0008-5472.CAN-12-2706
Abstract: Activation of the canonical TGF-β signaling pathway provides growth inhibitory signals in the normal intestinal epithelium. Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear. A cohort of 744 primary CRCs and 36 CRC cell lines were sequenced for SMAD4, SMAD2, and SMAD3 and analyzed for allelic loss by single-nucleotide polymorphism (SNP) microarray analysis. Mutation spectra were compared between the genes, the pathogenicity of mutations was assessed, and relationships with clinicopathologic features were examined. The prevalence of SMAD4, SMAD2, and SMAD3 mutations in sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744), respectively. A significant overrepresentation of two genetic hits was detected for SMAD4 and SMAD3, consistent with these genes acting as tumor suppressors. SMAD4 mutations were associated with mucinous histology. The mutation spectra of SMAD2 and SMAD3 were highly similar to that of SMAD4, both in mutation type and location within the encoded proteins. In silico analyses suggested the majority of the mutations were pathogenic, with most missense changes predicted to reduce protein stability or hinder SMAD complex formation. The latter altered interface residues or disrupted the phosphorylation-regulated Ser-Ser-X-Ser motifs within SMAD2 and SMAD3. Functional analyses of selected mutations showed reductions in SMAD3 transcriptional activity and SMAD2–SMAD4 complex formation. Joint biallelic hits in SMAD2 and SMAD3 were overrepresented and mutually exclusive to SMAD4 mutation, underlining the critical roles of these three proteins within the TGF-β signaling pathway. Cancer Res 73(2) 725–35. ©2012 AACR.
Publisher: Springer Science and Business Media LLC
Date: 08-2002
DOI: 10.1007/S00432-002-0361-2
Abstract: Identification of germline mutations in mismatch repair genes is increasingly being used to guide clinical practice in hereditary non-polyposis colon cancer. The aim of this study was to retrospectively assess the clinical utility of immunostaining and microsatellite instability testing in a group of in iduals in whom germline testing of hMSH2 and hMLH1 had already been performed. In iduals were identified from the records of family cancer clinics. A total of thirty-eight tumour blocks were retrieved from 28 kindreds. DNA was extracted and PCR lification of six microsatellite markers was performed. Immunostaining was used to examine the expression of hMSH2 and hMLH1 protein. Of the 32 assessable tumours, 24 (75%) showed microsatellite instability. Most of the MSI-H cancers (92%) failed to express either hMLH1 or hMSH2. Deleterious germline mutations were identified in the proband in 12 of 28 families. Missense mutations were identified in 11 cases and no mutations in six probands. The use of germline genetic testing is indicated for a highly selected group of in iduals. MSI testing and immunostaining are extremely useful tools which significantly improve the clinical interpretation of germline results. Ambiguity regarding the significance of missense mutations in hereditary bowel cancer suggests that these findings should be interpreted with caution.
Publisher: Wiley
Date: 03-1996
DOI: 10.1080/09595239600185691
Abstract: In this paper we present a review of practices surrounding the consumption of khat (Catha edulis) within recent migrant communities in Melbourne from East Africa. Cultures in East Africa and the Arabian Peninsular have used khat as a stimulant since the seventh century and the practice of coming together to chew the leaves of the khat plant has acquired unique cultural importance. Based on focus-group interviews the research examines transformations taking place in the meaning of khat for East African communities within their experiences of displacement and considers how the arrival of khat might be managed in the Australian context. Emphasis is given to indigenous models and the cultural context of practices surrounding khat. This anthropology of khat use in Melbourne summarizes issues such as who chews it, traditional settings for khat gatherings, culturally defined effects of the leaf, health effects, beliefs and attitudes, levels of use, gendered attitudes and questions of dependence. These issues raise questions regarding the reception of indigenous substance use within a state that claims to be multicultural.
Publisher: American Medical Association (AMA)
Date: 07-2013
DOI: 10.1001/JAMAPEDIATRICS.2013.1429
Abstract: Short sleep duration is common in adolescents and young adults, and short sleep duration is a risk factor for motor vehicle crash. To assess the association between hours of sleep and the risk for motor vehicle crash, including the time of day of crash and types of crash (single, multiple vehicle, run off road, and intersection). Prospective cohort study. New South Wales, Australia. Questionnaire responses were obtained from 20,822 newly licensed drivers aged 17 to 24 years. Participants held a first-stage provisional license between June 2003 and December 2004 prospectively linked to licensing and police-reported crash data, with an average of 2 years of follow-up. Analyses were conducted on a subs le of 19,327 participants for which there was full information. Sleeping 6 or fewer hours per night. The main outcome variable was police-reported crash. Multivariable Poisson regression models were used to investigate the role of sleep duration on the risk for crash. On average, those who reported sleeping 6 or fewer hours per night had an increased risk for crash compared with those who reported sleeping more than 6 hours (relative risk [RR], 1.21 95% CI, 1.04-1.41). Less weekend sleep was significantly associated with an increased risk for run-off-road crashes (RR, 1.55 95% CI, 1.21-2.00). Crashes for in iduals who had less sleep per night (on average and on weekends) were significantly more likely to occur between 8 pm and 6 am (RR, 1.86 95% CI, 1.11-3.13, for midnight to 5:59 am and RR, 1.66 95% CI, 1.15-2.39, for 8:00 pm to 11:59 pm). Less sleep per night significantly increased the risk for crash for young drivers. Less sleep on weekend nights increased the risk for run-off-road crashes and crashes occurring in the late-night hours. This provides rationale for governments and health care providers to address sleep-related crashes among young drivers.
Publisher: BMJ
Date: 06-2001
DOI: 10.1136/GUT.48.6.821
Abstract: In this study, we prospectively examined the clinical significance of the microsatellite instability (MSI) phenotype in sporadic colorectal cancer, and investigated methods for effective identification of these tumours in routine pathology practice. DNA was extracted from 310 tumours collected from 302 consecutive in iduals undergoing curative surgery for sporadic colorectal cancer. Microsatellite status was determined by polymerase chain reaction lification using standard markers, while immunostaining was used to examine expression of MLH1, MSH2, and p53. Eleven per cent of tumours showed high level instability (MSI-H), 6.8% had low level instability (MSI-L), and the remainder were stable. MSI-H tumours were significantly more likely to be of high histopathological grade, have a mucinous phenotype, and to harbour increased numbers of intraepithelial lymphocytes. They were also more likely to be right sided, occur in women, and be associated with improved overall survival. In total, 25 (8%) tumours showed loss of staining for MLH1 and a further three tumours showed absence of staining for MSH2. The positive and negative predictive value of immunohistochemistry in the detection of MSI-H tumours was greater than 95%. We conclude that the MSI-H phenotype constitutes a pathologically and clinically distinct subtype of sporadic colorectal cancer. Immunohistochemical staining for MLH1 and MSH2 represents an inexpensive and accurate means of identifying such tumours.
Publisher: Springer Science and Business Media LLC
Date: 06-01-2011
Publisher: Elsevier BV
Date: 12-2016
Publisher: Springer Science and Business Media LLC
Date: 25-08-2015
DOI: 10.1038/BJC.2015.296
Publisher: Proceedings of the National Academy of Sciences
Date: 06-03-2003
Abstract: Genetic alterations in tumor cells often lead to the emergence of growth-stimulatory autocrine and paracrine signals, involving overexpression of secreted peptide growth factors, cytokines, and hormones. Increased levels of these soluble proteins may be exploited for cancer diagnosis and management or as points of therapeutic intervention. Here, we combined the use of controlled vocabulary terms and sequence-based algorithms to predict genes encoding secreted proteins from among ≈12,500 sequences represented on oligonucleotide microarrays. Expression of these genes was queried in 150 carcinomas from 10 anatomic sites of origin and compared with 46 normal tissues derived from the corresponding sites of tumor origin and other body tissues and organs. Of 74 different genes identified as overexpressed in cancer tissues, several encode proteins with demonstrated clinical diagnostic application, such as α-fetoprotein in liver carcinoma, and kallikreins 6 and 10 in ovarian cancer, or therapeutic utility, such as gastrin-releasing peptide/bombesin in lung carcinomas. We show that several of the other candidate genes encode proteins with high levels of tumor-associated expression by immunohistochemistry on tissue microarrays and further demonstrate significantly elevated levels of another novel candidate protein, macrophage inhibitory cytokine 1, a distant member of the tranforming growth factor-β superfamily, in the serum of patients with metastatic prostate, breast, and colorectal carcinomas. Our results suggest that the combination of annotation rotein sequence analysis, transcript profiling, immunohistochemistry, and immunoassay is a powerful approach for delineating candidate biomarkers with potential clinical significance and may be broadly applicable to other human diseases.
Publisher: Elsevier BV
Date: 12-2008
Publisher: American Association for Cancer Research (AACR)
Date: 15-10-2008
DOI: 10.1158/1078-0432.CCR-08-0701
Abstract: Purpose: Identification of biologically and clinically distinct breast cancer subtypes could improve prognostic assessment of primary tumors. The characteristics of “molecular” breast cancer subtypes suggest that routinely assessed histopathologic features in combination with limited biomarkers may provide an informative classification for routine use. Experimental Design: Hierarchical cluster analysis based on components of histopathologic grade (tubule formation, nuclear pleomorphism, and mitotic score), expression of ER, cytokeratin 5/6, and HER2 lification identified four breast cancer subgroups in a cohort of 270 cases. Cluster subgroup membership was compared with observed and Adjuvant! Online predicted 10-year survival. Survival characteristics were confirmed in an independent cohort of 300 cases assigned to cluster subgroups using a decision tree model. Results: Four distinct breast cancer cluster subgroups (A-D) were identified that were analogous to molecular tumor types and showed a significant association with survival in both the original and validation cohorts (P & 0.001). There was a striking difference between survival for patients in cluster subgroups A and B with ER+ breast cancer (P & 0.001). Outcome for all tumor types was well estimated by Adjuvant! Online, with the exception of cluster B ER+ cancers where Adjuvant! Online was too optimistic. Conclusions: Breast cancer subclassification based on readily accessible pathologic features could improve prognostic assessment of ER+ breast cancer.
Publisher: Informa UK Limited
Date: 28-03-2014
DOI: 10.1080/15389588.2013.833328
Abstract: To conduct a process and impact evaluation of a multifaceted education-based pilot program targeting correct use of age-appropriate restraints in a regional setting with a high proportion of Aboriginal and Torres Strait Islander families. The program was delivered in 2010 in 3 early learning centers where 31 percent of the children were of Aboriginal and Torres Strait Islander descent. Each component of the program was assessed for message consistency and uptake. To measure program effectiveness, participating children were matched 1:1 by age, language spoken at home, and annual household income with 71 children from the control arm of a contemporaneous trial. The outcome measure in the control and program centers (a 4-category ordinal scale of restraint use) was compared using ordinal logistic regression accounting for age of the parent. Process evaluation found that though program components were delivered with a consistency of message, uptake was affected by turnover of all staff at one center and by parents experiencing difficulty in paying for subsidized restraints at each of the centers. Impact evaluation found that children from the centers receiving the program had nearly twice the odds of being in a better restraint category than children matched from the control group (adjusted odds ratio [ORadj] = 2.06, 95% confidence interval [CI], 1.09-3.90). This was a pragmatic study reflecting the real-life issues of implementing a program in preschools where 57 percent of families had a low income and turnover of staff was high. Despite these issues, impact evaluation showed that the integrated educational program showed promise in increasing correct use of age-appropriate restraints. The findings from this pilot study support the use of an integrated educational program that includes access to subsidized restraints to promote best practice child restraint use among communities that include a high proportion of Aboriginal and Torres Strait Islander families in New South Wales. Future trials in similar settings should consider offering more support in centers with high turnover of staff and offering alternative methods of payment when families experience financial difficulties in purchasing the subsidized restraints. If proven in larger trials, this approach could reduce death and injuries in child passengers in this vulnerable group.
Publisher: Springer Science and Business Media LLC
Date: 20-02-2007
Publisher: Elsevier BV
Date: 09-2012
Publisher: Oxford University Press (OUP)
Date: 15-12-2002
DOI: 10.1086/342691
Abstract: The incidence of Clostridium difficile-associated diarrhea (CDAD) has increased dramatically in hospitals worldwide during the past 2 decades. In Western Australia, this increase was most obvious during the 1980s, when there was also an increase in the use of third-generation cephalosporin antibiotics. A study of the epidemiology of CDAD and the use of third-generation cephalosporins during 1993-2000 was undertaken. From 1993 through 1998, the incidence of CDAD remained relatively stable (2-3 cases per 1000 discharges annually). Then, a significant decrease in the incidence occurred, from 2.09 cases per 1000 discharges (95% confidence interval [CI], 1.71-2.47) in 1998 to 0.87 cases per 1000 discharges (95% CI, 0.63-1.11) in 1999 (P<.0001) this decrease persisted into 2000. A decrease in third-generation cephalosporin use occurred during the period of the study because of changes in the prescribing policy. These findings suggest that a reduction in the use of third-generation cephalosporins can reduce the occurrence of CDAD.
Publisher: BMJ
Date: 23-02-2012
DOI: 10.1136/INJURYPREV-2011-040261
Abstract: Despite the fact that the A6 mortality reporting system has been operating for almost 20 years in Vietnam, there has been no systematic evaluation of the system. This study assesses the completeness, sensitivity and positive predictive value of the system in relation to injury related mortality. Evaluation of the A6 system was undertaken in three (geographically distributed) provinces in Vietnam. Deaths identified in the A6 system were compared with deaths identified by an independent consensus panel to determine the per cent completeness of the A6 system. Verbal autopsies (VA) were conducted for all identified deaths from the consensus panels, and the sensitivity and positive predictive value of the A6 system were assessed using the VAs as the reference. 5273 deaths were identified from the A6 system with a further 340 cases identified by the independent consensus panel (total n=5613). Injury related deaths accounted for 13.6% (n=763) of all deaths with an overall injury mortality rate of 55.3 per 100 000 person years. The per cent completeness of the A6 system in relation to injury deaths was 93.9% with a sensitivity of 75.4%, specificity of 98.4% and positive predictive value of 88.4%. The A6 mortality reporting system is embedded within the commune health system and is the lead mortality reporting system for the Ministry of Health. The system performs well in relation to its completeness and classification of injury related deaths. With further enhancements and ongoing support from government and donor agencies, the A6 system will be a valuable resource for identifying and planning preventive strategies targeting the leading causes of injury related deaths in Vietnam.
Publisher: Oxford University Press (OUP)
Date: 04-2012
DOI: 10.5665/SLEEP.1726
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2012
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.AAP.2017.06.019
Abstract: As cycling-related injury rates are on the rise, there is a need to understand the long term outcomes of these patients in order to quantify the burden of injury and to inform injury prevention strategies. This study aimed to investigate predictors of return to work and functional recovery in a cohort of cyclists hospitalised for orthopaedic trauma from crashes occurring on-road. A retrospective analysis of data from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) was conducted for patients who were hospitalised for orthopaedic trauma following a cycling crash that occurred on-road between July 2007 and June 2015. There were 1787 injured cyclists admitted at the participating hospitals. Most cyclists were male (79%), resided in major cities (89%) and were in the highest socioeconomic quintile (52%). The majority of crashes were either non-collisions (41%) or collisions with a motor vehicle (35%). A smaller proportion of cyclists who collided with motor vehicles had returned to work and had returned to pre-injury functional levels at 12 months post-injury, when compared to collisions with other impact counterparts and non-collisions. Mixed effects logistic regression models revealed that compensable patients demonstrated lower odds of complete functional recovery and return to work when compared with non-compensable patients. Cyclists who collided with motor vehicles had worse outcomes compared to crashes with other impact counterparts and non-collision events. These findings provide support for reducing the potential for interaction between cyclists and motor vehicles.
Publisher: Springer Science and Business Media LLC
Date: 12-1996
DOI: 10.1007/BF01209124
Abstract: Studying the changes in the microstructure of polyester (PET) in water and non-aqueous solvents is important to understand the swelling mechanism of PET, which can help to reduce water pollution during the dyeing process. This study uses molecular models of PET, water, and decamethyl-cyclopentasiloxane (D5) and employs molecular dynamics method to simulate the influence of solvents on the microstructure of PET. The results show that the glass transition temperature (T
Publisher: Elsevier BV
Date: 10-1997
DOI: 10.1016/S1380-2933(97)00013-4
Abstract: Phage display technology allows the isolation of novel human monoclonal antibodies. The technology relies on the construction of a recombinant antibody library and its display on phage particles. The quality of an antibody library is affected by several factors including the size, ersity and source of immunoglobulin genes. The aim of the project was to determine the best tissue source for the construction of antibody libraries. Three tissue sources were used in this study: peripheral blood mononuclear cells from a healthy donor, Epstein-Barr virus (EBV) transformed peripheral blood mononuclear cells and lymph node tissue from in iduals with breast cancer. The quality of each tissue source was assessed using two criteria: (1) the number of mature and activated B cells in each source (2) the amount of immunoglobulin heavy and light chain genes lifiable by polymerase chain reaction (PCR). EBV-transformed peripheral blood mononuclear cells and lymph node tissue were shown to contain more B cells than peripheral blood mononuclear cells. A relatively larger amount of immunoglobulin gene products could be lified from EBV-transformed peripheral blood mononuclear cells and the lymph node. However, immunoglobulin containing gamma 1 chains could not be lified from EBV-transformed mononuclear cells, and the resultant pattern of gene lification suggests a possible selection bias. This study indicates that among the three tissue sources examined, lymph node tissue is the most suitable source for the construction of antibody libraries.
Publisher: Informa UK Limited
Date: 07-2006
Publisher: Elsevier BV
Date: 11
DOI: 10.1016/J.AAP.2007.03.004
Abstract: There is evidence that mobile phone use while driving (including hands-free) is associated with motor vehicle crashes. However, whether the effects of mobile phone use differ from that of passengers in the vehicle remains unclear. The aim of this research was to estimate the risk of crash associated with passenger carriage and compare that with mobile phone use. A case-control study ('passenger study') was performed in Perth, Western Australia in 2003 and 2004. Cases were 274 drivers who attended hospital following a motor vehicle crash and controls were 1096 drivers (1:4 matching) recruited at service stations matched to the location and time and day of week of the crash. The results were compared with those of a case-crossover study ('mobile phone study') undertaken concurrently (n=456) 152 cases were common to both studies. Passenger carriage increased the likelihood of a crash (adjusted odds ratio (adj. OR), 95% confidence interval (95% CI), 1.6, 1.1-2.2). Drivers carrying two or more passengers were twice as likely to crash as unaccompanied drivers (adj. OR 2.2, 95% CI 1.3-3.8). By comparison, driver's use of a mobile phone within 5 min before a crash was associated with a fourfold increased likelihood of crashing (OR 4.1, 95% CI 2.2-7.7). Passenger carriage and increasing numbers of passengers are associated with an increased likelihood of crash, though not to the same extent as mobile phone use. Further research is needed to investigate the factors underlying the increased risks.
Publisher: Elsevier BV
Date: 12-2016
Publisher: Wiley
Date: 04-2014
DOI: 10.1071/HE13075
Publisher: Wiley
Date: 27-02-2015
DOI: 10.1002/GCC.22243
Abstract: The progression of benign colorectal adenomas into cancer is associated with the accumulation of chromosomal aberrations. Even though patterns and frequencies of chromosomal aberrations have been well established in colorectal carcinomas, corresponding patterns of aberrations in adenomas are less well documented. The aim of this study was to profile chromosomal aberrations across colorectal adenomas and carcinomas to provide a better insight into key changes during tumor initiation and progression. Single nucleotide polymorphism array analysis was performed on 216 colorectal tumor/normal matched pairs, comprising 60 adenomas and 156 carcinomas. While many chromosomal aberrations were specific to carcinomas, those with the highest frequency in carcinomas ( lification of chromosome 7, 13q, and 20q deletion of 17p and chromosome 18 LOH of 1p, chromosome 4, 5q, 8p, 17p, chromosome 18, and 20p) were also identified in adenomas. Hierarchical clustering using chromosomal aberrations revealed three distinct subtypes. Interestingly, these subtypes were only partially dependent on tumor staging. A cluster of colorectal cancer patients with frequent chromosomal deletions had the least favorable prognosis, and a number of adenomas (n = 9) were also present in the cluster suggesting that, at least in some tumors, the chromosomal aberration pattern is determined at a very early stage of tumor formation. Finally, analysis of LOH events revealed that copy-neutral/gain LOH (CN/G-LOH) is frequent (>10%) in carcinomas at 5q, 11q, 15q, 17p, chromosome 18, 20p, and 22q. Deletion of the corresponding region is sometimes present in adenomas, suggesting that LOH at these loci may play an important role in tumor initiation.
Publisher: American Association for Cancer Research (AACR)
Date: 04-2023
DOI: 10.1158/1078-0432.C.6532782
Abstract: AbstractPurpose: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. Experimental Design: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC ( i n /i = 333), mucinous borderline ovarian tumors (MBOT, i n /i = 151), and upper GI ( i n /i = 65) and lower GI tumors ( i n /i = 55). Results: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77 95% confidence interval (CI), 1.04–7.41, i P /i = 0.042]. Increased expression of i THBS2 /i and i TAGLN /i was associated with shorter OS in MOC patients (HR, 1.25 95% CI, 1.04–1.51, i P /i = 0.016) and (HR, 1.21 95% CI, 1.01–1.45, i P /i = 0.043), respectively. i ERBB2 /i (HER2) lification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). Conclusions: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of i THBS2 /i and i TAGLN /i in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC s les clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies. /
Publisher: Informa UK Limited
Date: 10-2011
DOI: 10.1080/15389588.2011.591856
Abstract: This study separately examined the impact of the outcomes of a practical on-road driving test and a hazard perception test on the likelihood of traffic crashes among a cohort of newly licensed young drivers in New South Wales (NSW), Australia. The DRIVE study is a prospective cohort study of drivers aged 17 to 24 years holding their first-year provisional driver license in NSW. Information obtained from 20,822 participants in a detailed baseline questionnaire was linked to information on the number of attempts at a mandatory practical on-road driving test and hazard perception test as well as police-reported traffic crashes. After controlling for a number of sociodemographic and behavioral factors as well as factors related to driver learning experiences, multivariate analysis showed that those who failed the practical on-road test at least 4 times had an increased risk of involvement in a traffic crash compared to those who passed the test at first attempt (relative risk [RR]: 1.79, 95% confidence interval [CI]: 1.20-2.65). The crash risk among those who failed the practical on-road test at least 4 times was particularly high in females (RR: 2.10, 95% CI: 1.20-3.68). Similarly, those who failed the hazard perception test at least twice had an increased risk of involvement in a traffic crash (RR: 1.83, 95% CI: 1.27-2.63) compared to those who passed the test on the first attempt. The crash risk of those who failed the hazard perception test at least twice was particularly high in males (RR: 2.5, 95% CI: 1.5-4.1) and among those from rural and remote areas (RR: 5.53, 95% CI: 1.63-18.71). The findings have implications on licensing practices and suggest the need for adequate strategies to assist young drivers with multiple failures in the driving and hazard perception tests.
Publisher: BMJ
Date: 12-1999
DOI: 10.1136/IP.5.4.254
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1038/MODPATHOL.2009.130
Abstract: O(6)-methylguanine DNA methyltransferase (MGMT) is a DNA repair protein that restores mutagenic O(6)-methylguanine to guanine. MGMT methylation is frequently observed in sporadic colorectal cancer and was recently correlated with the C>T allele at SNP rs16906252, within the transcriptional enhancer element of the promoter. MGMT methylation has also been associated with KRAS mutations, particularly G>A transitions. We studied 1123 colorectal carcinoma to define the molecular and clinicopathological profiles associated with MGMT methylation. Furthermore, we assessed factors contributing to MGMT methylation in the development of colorectal cancer by studying the allelic pattern of MGMT methylation using SNP rs16906252, and the methylation status of neighbouring genes within 10q26 in selected tumours and matched normal colonic mucosa. MGMT methylation was detected by combined bisulphite restriction analysis in 28% of tumours and was associated with a number of characteristics, including CDKN2A methylation, absent lymphovascular space invasion and KRAS mutations (but not specifically with KRAS G>A transitions). In a multivariate analysis adjusted for age and sex, MGMT methylation was associated with the T allele of SNP rs16906252 (P T SNP. We show that the T allele at SNP rs16906252 is a key determinant in the onset of MGMT methylation in colorectal cancer, whereas the association of methylation at MGMT and CDKN2A suggests that these loci may be targets of a common mechanism of epigenetic dysregulation.
Publisher: Elsevier BV
Date: 09-1996
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.AAP.2016.09.014
Abstract: In Australia, more than 30% of the traffic volume can be attributed to work-related vehicles. Although work-related driver safety has been given increasing attention in the scientific literature, it is uncertain how well this knowledge has been translated into practice in industry. It is also unclear how current practice in industry can inform scientific knowledge. The aim of the research was to use a benchmarking tool developed by the National Road Safety Partnership Program to assess industry maturity in relation to risk management practices. A total of 83 managers from a range of small, medium and large organisations were recruited through the Victorian Work Authority. Semi-structured interviews aimed at eliciting information on current organisational practices, as well as policy and procedures around work-related driving were conducted and the data mapped onto the benchmarking tool. Overall, the results demonstrated varying levels of maturity of risk management practices across organisations, highlighting the need to build accountability within organisations, improve communication practices, improve journey management, reduce vehicle-related risk, improve driver competency through an effective workplace road safety management program and review organisational incident and infringement management. The findings of the study have important implications for industry and highlight the need to review current risk management practices.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2014
Publisher: American Association for Cancer Research (AACR)
Date: 15-10-2004
DOI: 10.1158/0008-5472.CAN-03-3978
Abstract: Colorectal cancers with widespread CpG island methylation display a number of distinct clinicopathological features, and it has been suggested that the condition has an inheritable genetic component. To address this possibility, histories of cancer were obtained from 562 in iduals undergoing curative surgery for unselected colorectal cancer at one institution. Microsatellite status and methylation at p16, MINT1, 2, 12, and 31 loci were determined on fresh tumor tissue using standard methods. Fifty-five of 562 probands in this study provided a personal history of at least one other colorectal cancer, 10 reported at least one extracolonic cancer of hereditary nonpolyposis colorectal cancer type, and 84 in iduals had another type of cancer. Age was strongly associated with the risk of multiple cancers, but there was no evidence that microsatellite instability or the CpG island methylator phenotype were independent risk factors for their development, either in the colorectum or elsewhere. Of the 547 in iduals with knowledge of their family history, 80 (14.6%) reported a family history of colorectal cancer in a first-degree relative, and 60% of in iduals reported a history of any cancer in a first-degree relative. Neither tumor CpG island methylator phenotype status nor microsatellite instability was predictive of a positive history of cancer in first- or second-degree relatives. The probability of a positive family or personal history of cancer did not increase with increasing number of methylated loci. Epigenetic silencing of multiple genes seen in some tumors is at best rarely the result of an inherited defect in the methylation apparatus. There is no justification for altering the personal or family cancer screening recommendations on the basis of tumor CpG island methylator phenotype status.
Publisher: Wiley
Date: 12-2005
DOI: 10.1002/PATH.1851
Abstract: This study prospectively examines the accuracy of immunohistochemical staining in the identification of mismatch repair defective (MMRD) colorectal cancer in routine clinical practice. The potential impact of this information on decisions regarding adjuvant treatment and germline testing were quantified. A consecutive series of fresh tissue (836 cancers) was obtained from 786 in iduals undergoing curative surgery for colorectal cancer at one institution. As part of normal practice, each tumour was screened for the expression of MLH1 and MSH2 by immunohistochemical staining (IHC) and relevant clinicopathological details were documented. Microsatellite instability (MSI) was assessed using standard markers. Overall, 108 (13%) tumours showed loss of staining for either MLH1 (92 tumours) or MSH2 (16 tumours). The positive predictive value of mismatch repair IHC when used alone in the detection of MSI tumours was 88%, and the negative predictive value was 97%. Specificity and positive predictive value were improved by correlation with microsatellite status. Tumour stage (HR 3.5, 95% CI 2.0-6.0), vascular space invasion (HR 1.9, 95% CI 1.2-3.0) and mismatch repair deficiency (HR 0.2, 95% CI 0.05-0.87) were independent prognostic factors in stages II and III disease. Screening by mismatch repair IHC could reasonably have been expected to prevent ineffective treatment in 3.6% of stage II and 7.6% of stage III patients. The frequency of germline mismatch repair mutations was 0.8%, representing six unsuspected hereditary non-polyposis colorectal cancer (HNPCC) cases. Routine screening of colorectal cancers by mismatch repair IHC identifies in iduals at low risk of relapse, and can prevent unnecessary adjuvant treatments in a significant number of in iduals. Abnormal immunohistochemistry should be confirmed by microsatellite testing to ensure that false-positive results do not adversely impact on treatment decisions.
Publisher: Elsevier BV
Date: 09-1991
Publisher: Elsevier BV
Date: 05-2006
Publisher: American Association for Cancer Research (AACR)
Date: 14-09-2018
DOI: 10.1158/1078-0432.CCR-17-3678
Abstract: Purpose: MLH1 is a major tumor suppressor gene involved in the pathogenesis of Lynch syndrome and various sporadic cancers. Despite their potential pathogenic importance, genomic regions capable of regulating MLH1 expression over long distances have yet to be identified. Experimental Design: Here, we use chromosome conformation capture (3C) to screen a 650-kb region flanking the MLH1 locus to identify interactions between the MLH1 promoter and distal regions in MLH1-expressing and nonexpressing cells. Putative enhancers were functionally validated using luciferase reporter assays, chromatin immunoprecipitation, and CRISPR-Cas9–mediated deletion of endogenous regions. To evaluate whether germline variants in the enhancer might contribute to impaired MLH1 expression in patients with suspected Lynch syndrome, we also screened germline DNA from a cohort of 74 patients with no known coding mutations or epimutations at the MLH1 promoter. Results: A 1.8-kb DNA fragment, 35 kb upstream of the MLH1 transcription start site enhances MLH1 gene expression in colorectal cells. The enhancer was bound by CTCF and CRISPR-Cas9–mediated deletion of a core binding region impairs endogenous MLH1 expression. A total of 5.4% of suspected Lynch syndrome patients have a rare single-nucleotide variant (G & A rs143969848 2.5% in gnomAD European, non-Finnish) within a highly conserved CTCF-binding motif, which disrupts enhancer activity in SW620 colorectal carcinoma cells. Conclusions: A CTCF-bound region within the MLH1-35 enhancer regulates MLH1 expression in colorectal cells and is worthy of scrutiny in future genetic screening strategies for suspected Lynch syndrome associated with loss of MLH1 expression. Clin Cancer Res 24(18) 4602–11. ©2018 AACR.
Publisher: Elsevier BV
Date: 1996
DOI: 10.1016/0022-1759(95)00231-6
Abstract: A combinatorial human IgG1, kappa gene library of 2 x 10(7) clones was constructed from a pericolic lymph node using the phagemid vector pComb3H. Fabs with binding activity against tetanus toxoid (TT) and keyhole limpet hemocyanin (KLH) were isolated from this library, and one such TT binding Fab was used to further evaluate a new phagemid vector for the display of recombinant antibody fragments (MCO1). This vector was designed to incorporate a cleavage site for the enzyme Genenase I, a myc peptide tag, and an amber codon between the heavy chain cloning site and the truncated M13 phage gene III. When MCO1 phage displaying an anti-TT Fab were bound to TT on a solid substrate, elution with Genenase I at concentrations of 5-10 micrograms/ml proved as effective as acid elution in releasing bound phage. Furthermore, enzymatic elution with Genenase I was comparable to acid elution in the enrichment of a TT binding Fab from the pericolic library subcloned into the vector MCO1. Importantly, the use of enzymatic or acid elutions resulted in the retrieval of different anti-TT Fabs from this same library. We conclude that panning of phage-displayed combinatorial antibody libraries can be successfully performed using enzymatic elution, and that this offers a useful alternative to currently available phage elution techniques.
Publisher: BMJ
Date: 12-1997
DOI: 10.1136/IP.3.4.282
Abstract: The objectives were first, to modify the PRECEDE-PROCEED model and to use it is as a basis for planning a three year intervention trial that aims to reduce injury to child pedestrians. A second objective was to assess the suitability of this process for planning such a relatively complex program. The project was carried out in 47 primary schools in three local government areas, in the Perth metropolitan area. The program was developed, based on extensive needs assessment incorporating formative evaluations. Epidemiological, psychosocial, environmental, educational, and demographic information was gathered, organised, and prioritised. The PRECEDE-PROCEED model was used to identify the relevant behavioural and environmental risk factors associated with child pedestrian injuries in the target areas. Modifiable causes of those behavioural and environmental factors were delineated. A description of how the model facilitated the development of program objectives and subobjectives which were linked to strategy objectives, and strategies is provided. The process used to plan the child pedestrian injury prevention program ensured that a critical assessment was undertaken of all the relevant epidemiological, behavioural, and environmental information. The gathering, organising, and prioritising of the information was facilitated by the process. The use of a model such as PRECEDE-PROCEED can enhance the development of a child injury prevention program. In particular, the process can facilitate the identification of appropriate objectives which in turn facilitates the development of suitable interventions and evaluation methods.
Publisher: Informa UK Limited
Date: 14-06-2010
DOI: 10.1080/15389581003614888
Abstract: To examine differences in risky driving behavior and likelihood of traffic crash according to the country of birth of recently licensed young drivers. The groups examined include those born in Australia, those born in Asia, and those born in other countries. The DRIVE study is a prospective cohort study of drivers aged 17-24 years holding their first-year provisional driver license in New South Wales, Australia. Information obtained from 20,822 participants who completed a baseline questionnaire was linked to police-reported traffic crashes. Self-reported risky driving behaviors and police-reported traffic crashes in young drivers. Young drivers who were born in Asian countries were less likely to report engaging in risky driving behaviors than their Australian-born counterparts. The proportion of participants reporting a high level of risky driving was 31.5 percent (95% confidence intervale [CI], 30.8-32.1) among Australian-born drivers compared to 25.6 percent (95% CI, 23.1-28.2) among Asian-born drivers and 30.4 percent (95% CI, 28.4-32.5) among those born in other regions. Asian-born participants had half the risk of a crash as a driver than their Australian-born counterparts (relative risk [RR] 0.55 95% CI, 0.41-0.75) after adjusting for a number of demographic factors and driving and risk-taking behaviors. The comparative risk was even lower among those aged 17 years (RR 0.29 95% CI, 0.29-0.75). Risk estimates for people born in other regions did not differ to those for Australian-born respondents. The study highlights the lower level of risky driving and significantly reduced crash risk for Australian drivers born in Asian countries relative to those born locally. Further research is needed to examine factors underlying this reduced risk and the impact of the length of residence in the host country.
Publisher: BMJ
Date: 18-03-2013
DOI: 10.1136/BMJ.F1140
Abstract: To determine whether there is an association between use of substances that contain caffeine and the risk of crash in long distance commercial vehicle drivers. Case-control study. New South Wales (NSW) and Western Australia (WA), Australia. 530 long distance drivers of commercial vehicles who were recently involved in a crash attended by police (cases) and 517 control drivers who had not had a crash while driving a commercial vehicle in the past 12 months. The likelihood of a crash associated with the use of substances containing caffeine after adjustment for factors including age, health disorders, sleep patterns, and symptoms of sleep disorders as well as exposures such as kilometres driven, hours slept, breaks taken, and night driving schedules. Forty three percent of drivers reported consuming substances containing caffeine, such as tea, coffee, caffeine tablets, or energy drinks for the express purpose of staying awake. Only 3% reported using illegal stimulants such as hetamine ("speed") 3,4 methylenedioxymeth hetamine (ecstasy) and cocaine. After adjustment for potential confounders, drivers who consumed caffeinated substances for this purpose had a 63% reduced likelihood of crashing (odds ratio 0.37, 95% confidence interval 0.27 to 0.50) compared with drivers who did not take caffeinated substances. Caffeinated substances are associated with a reduced risk of crashing for long distance commercial motor vehicle drivers. While comprehensive mandated strategies for fatigue management remain a priority, the use of caffeinated substances could be a useful adjunct strategy in the maintenance of alertness while driving.
Publisher: Informa UK Limited
Date: 26-09-2014
DOI: 10.1080/15389588.2014.935356
Abstract: Pedestrian road trauma is significant in Australia and requires in-depth understanding to improve or inform new countermeasures. Analyses on single data sources can be limited. This study investigated demographic, behavioral, environmental, and collision characteristics of pedestrian injury in Victoria, Australia, over a 5-year period using multiple data sources. Victorian state police, hospital presentation, hospital admission, and coronial data sets were analyzed and compared for the years 2004 to 2008. Analyses identified 3,702 police-recorded pedestrian casualties (deaths and injuries, of which 256 were deaths), 5,008 pedestrian traffic-related hospital presentations, and 2,802 pedestrian admissions. Trend analyses showed significant increases in police casualty and hospitalization rates per 100,000 population. Age groups most commonly involved were those aged 18-24 especially on weekends, 75+ especially on weekday days, and 13- to 17-year-olds especially at school commute times. Proportionally more cases were male in all data sets. One quarter of coroner-examined deaths involved alcohol and one third involved drugs. Two thirds of police-recorded casualties occurred on weekdays, and 45% of weekend casualties occurred at night. Most casualties occurred in urban areas (95%), in lower-speed zones (78%) however, 79% of rural casualties occurred in high-speed zones, of which more were fatal. Over half did not occur at intersections. The most common injuries were fractures as well as multiple injuries, which together with intracranial injuries, were most common among fatalities (50 and 34%, respectively). Serious injury was more likely in older pedestrians, in males, in rural areas, in 60-80 km/h zones, in areas with poor lighting, while crossing a carriageway, not at an intersection, and when struck by a heavy vehicle. Findings indicate pedestrian serious injury rates are increasing and identify targets for countermeasures. Inherent limitations present in each relevant data collection require mutliple data sets to be explored and results contrasted. Jurisdictions seeking to determine pedestrian injury risk factors should aim to link police and hospital data for a complete analysis.
Publisher: Elsevier BV
Date: 06-1999
DOI: 10.1016/S0198-8859(99)00003-8
Abstract: The HER-2/neu protein is overexpressed in approximately 20% of human adenocarcinomas and is a defined tumor antigen in breast cancer. The purpose of this study was to evaluate the endogenous HER-2/neu specific antibody response in 57 patients with colorectal cancer. HER-2/neu specific antibodies, titer > or = 1:100, were detected in 14% (8/57) of patients with colorectal cancer compared to none of the normal control population (0/200). Furthermore, detection of HER-2/neu specific antibodies in the cancer population correlated significantly with HER-2/neu protein overexpression in the patients' tumor (p < 0.01). 46% of patients with HER-2/neu overexpressing tumors (6/13) and 5% of HER-2/neu negative tumors (2/44) had detectable HER-2/neu specific antibodies. The endogenous HER-2/neu antibody response in these patients was predominantly IgG or IgA.
No related grants have been discovered for Nicholas Hawkins.