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ItemNo Preview AvailableGata-3 Negatively Regulates the Tumor-Initiating Capacity of Mammary Luminal Progenitor Cells and Targets the Putative Tumor Suppressor Caspase-14(AMER SOC MICROBIOLOGY, 2011-11)The transcription factor Gata-3 is a definitive marker of luminal breast cancers and a key regulator of mammary morphogenesis. Here we have explored a role for Gata-3 in tumor initiation and the underlying cellular mechanisms using a mouse model of "luminal-like" cancer. Loss of a single Gata-3 allele markedly accelerated tumor progression in mice carrying the mouse mammary tumor virus promoter-driven polyomavirus middle T antigen (MMTV-PyMT mice), while overexpression of Gata-3 curtailed tumorigenesis. Through the identification of two distinct luminal progenitor cells in the mammary gland, we demonstrate that Gata-3 haplo-insufficiency increases the tumor-initiating capacity of these progenitors but not the stem cell-enriched population. Overexpression of a conditional Gata-3 transgene in the PyMT model promoted cellular differentiation and led to reduced tumor-initiating capacity as well as diminished angiogenesis. Transcript profiling studies identified caspase-14 as a novel downstream target of Gata-3, in keeping with its roles in differentiation and tumorigenesis. A strong association was evident between GATA-3 and caspase-14 expression in preinvasive ductal carcinoma in situ samples, where GATA-3 also displayed prognostic significance. Overall, these studies identify GATA-3 as an important regulator of tumor initiation through its ability to promote the differentiation of committed luminal progenitor cells.
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ItemProlonged Eyelid Closure Episodes during Sleep Deprivation in Professional Drivers(AMER ACAD SLEEP MEDICINE, 2016)STUDY OBJECTIVES: Real life ocular measures of drowsiness use average blink duration, amplitude and velocity of eyelid movements to reflect drowsiness in drivers. However, averaged data may conceal the variability in duration of eyelid closure episodes, and more prolonged episodes that indicate higher levels of drowsiness. The current study aimed to describe the frequency and duration of prolonged eyelid closure episodes during acute sleep deprivation. METHODS: Twenty male professional drivers (mean age ± standard deviation = 41.9 ± 8.3 years) were recruited from the Transport Workers Union newsletter and newspaper advertisements in Melbourne, Australia. Each participant underwent 24 hours of sleep deprivation and completed a simulated driving task (AusEd), the Psychomotor Vigilance Task, and the Karolinska Sleepiness Scale. Eyelid closure episodes during the driving task were recorded and analyzed manually from digital video recordings. RESULTS: Eyelid closure episodes increased in frequency and duration with a median of zero s/h of eyelid closure after 3 h increasing to 34 s/h after 23 h awake. Eyelid closure episodes were short and infrequent from 3 to 14 h of wakefulness. After 17 h of sleep deprivation, longer and more frequent eyelid closure episodes began to occur. Episodes lasting from 7 seconds up to 18 seconds developed after 20 h of wakefulness. Length of eyelid closure episodes was moderately to highly correlated with the standard deviation of lateral lane position, braking reaction time, crashes, impaired vigilance, and subjective sleepiness. CONCLUSIONS: The frequency and duration of episodes of prolonged eyelid closure increases during acute sleep deprivation, with very prolonged episodes after 17 hours awake. Automated devices that assess drowsiness using averaged measures of eyelid closure episodes need to be able to detect prolonged eyelid closure episodes that occur during more severe sleep deprivation.
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ItemNo Preview AvailableIncidence and seroprevalence of dengue virus infections in Australian travellers to Asia(SPRINGER, 2012-06)The purpose of this study was to estimate the incidence density and prevalence of dengue virus infection in Australian travellers to Asia. We conducted a multi-centre prospective cohort study of Australian travellers over a 32-month period. We recruited 467 travellers (≥ 16 years of age) from three travel clinics who intended to travel Asia, and 387 (82.9%) of those travellers completed questionnaires and provide samples pre- and post-travel for serological testing for dengue virus infection. Demographic data, destination countries and history of vaccinations and flavivirus infections were obtained. Serological testing for dengue IgG and IgM by enzyme-linked immunosorbent assay (ELISA) (PanBio assay) was performed. Acute seroconversion for dengue infection was demonstrated in 1.0% of travellers, representing an incidence of 3.4 infections per 10,000 days of travel (95% confidence interval [CI]: 0.9-8.7). The seroprevalence of dengue infection was 4.4% and a greater number of prior trips to Asia was a predictor for dengue seroprevalence (p = 0.019). All travellers experienced subclinical dengue infections and had travelled to India (n = 3) and China (n = 1). This significant attack rate of dengue infection can be used to advise prospective travellers to dengue-endemic countries.
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ItemNo Preview AvailablePrevalence and risk factors for symptoms of common mental disorders in early and late pregnancy in Vietnamese women: A prospective population-based study(Elsevier, 2013-04-05)BACKGROUND: Little is known about the prevalence of and risk factors for common mental disorders (CMD) in pregnant women in low-income countries. The aim of this study was to establish the prevalence of and psychosocial risk factors for clinically significant symptoms of CMD in early and late pregnancy in women in rural Viet Nam. METHODS: A population-based sample of women was surveyed in early and late pregnancy. CMD were assessed by the Edinburgh Postnatal Depression Scale-Viet Nam Validation and psychosocial risks by study-specific structured interviews. RESULTS: In total 497/523 (97%) eligible women were recruited and 419 (84%) provided complete data. Prevalence of CMD only in early pregnancy was 22.4% (95% CI 18.4-26.4); only in late pregnancy was 10.7% (95% CI 7.8-13.7) and at both assessment waves was 17.4% (95% CI 13.8-21.1). Non-economic and economic coincidental life adversity, intimate partner violence, past pregnancy loss, and childhood abuse were positively associated with persistent antenatal CMD. Older age, having a preference for the baby's sex, and nulli- or primiparity were risk factors for CMD in early pregnancy. CONCLUSIONS: Persistent antenatal CMD are prevalent in rural areas of Viet Nam. Psychosocial risk factors play a major role in this significant public health problem.
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ItemNo Preview AvailableIntimate partner violence and perinatal common mental disorders among women in rural Vietnam(Oxford University Press, 2013-03-01)INTRODUCTION: Intimate partner violence against women (IPV) is regarded increasingly as a public health problem worldwide. The overall aim of this study was to examine the associations between different exposures to IPV and women's mental health during pregnancy and after childbirth in rural Vietnam. METHODS: This was a secondary analysis of data generated in a community-based longitudinal investigation in which a cohort of pregnant women were recruited and followed until 6 months after childbirth. Different forms of IPV were measured by the Intimate Partner Violence section of the WHO Multi-Country Study on Women's Health and Domestic Violence Against Women questionnaire. The Edinburgh Postnatal Depression Scale-Vietnam Validation was used to assess symptoms of the common perinatal mental disorders of depression and anxiety (CPMD). RESULTS: Overall, 497 women were recruited and complete data were available from 417 (83.9%). Exposure to either lifetime or perinatal IPV including emotional abuse, physical violence and sexual violence was associated with increased CPMD symptoms (adjusted odds ratio, OR, ranges 1.3-14.3) and suicidal thoughts (OR ranges 4.7-6.1) in women during pregnancy and after childbirth. Experiencing more than one form of IPV increased the magnitude of the association between IPV and CPMD symptoms and thoughts of suicide. CONCLUSION: It is clearly essential in this and other resource-constrained settings to address emotional, physical and sexual violence perpetrated by an intimate partner in any strategies to reduce the risk of perinatal mental health problems in women.
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ItemValidation of the Intimate Bonds Measure for women who are pregnant or have recently given birth in Vietnam(WILEY, 2014-03)INTRODUCTION: Sensitive, valid measures to assess the quality of the intimate partner relationship are necessary for both clinical practice and research. The aim of this study was to examine the validity of the Intimate Bonds Measure (IBM) in women who were pregnant or had recently given birth in Vietnam. METHODS: The IBM was translated and culturally verified in a step-by-step process with Vietnamese health workers, researchers and community members. The validation study was nested within two larger community-based cross-sectional investigations: the first in 2006, which recruited 199 pregnant women and 165 mothers of newborns, and the second in 2010, which recruited 419 pregnant women. Internal structure was assessed by factor analysis and Cronbach's alpha and construct validity by comparison with relevant factors. RESULTS: Exploratory factor analyses revealed an identical factor structure to the one reported by the measure's developers in an Anglophone Australian population more than 20 years ago. The two factors replicate exactly the Care and Control subscales and Cronbach's alpha (from 0.68 to 0.83) indicates high internal consistency in both sub-scales. Mean scores of the Care-V and Control-V sub-scales were associated significantly and in expected directions with whether a woman could confide in, felt supported by or was frightened of her partner, or had experienced intimate partner violence and measures of mental health status. DISCUSSION: The Vietnamese version of the IBM (IBM-V) is comprehensible, meaningful and appears to be a valid measure the construct of quality of relationship with an intimate partner among women in this setting.
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ItemA multilevel study of neighborhood disadvantage, individual socioeconomic position, and body mass index: Exploring cross-level interaction effects(ELSEVIER, 2019-06)This study examined associations between neighborhood disadvantage and body mass index (BMI), and tested whether this differed by level of individual socioeconomic position (SEP). Data were from 9953 residents living in 200 neighborhoods in Brisbane, Australia in 2007. Multilevel linear regression analyses were undertaken by gender to determine associations between neighborhood disadvantage, individual SEP (education, occupation and household income) and BMI (from self-reported height and weight); with cross-level interactions testing whether the relationship between neighborhood disadvantage and BMI differed by level of individual SEP. Both men (Quintile 4, where Quintile 5 is the most disadvantaged β = 0.66 95%CI 0.20, 1.12) and women (Quintile 5 β = 1.32 95%CI 0.76, 1.87) from more disadvantaged neighborhoods had a higher BMI. BMI was significantly higher for those with lower educational attainment (men β = 0.71 95%CI 0.36, 1.07 and women β = 1.66 95%CI 0.78, 1.54), and significantly lower for those in blue collar occupations (men β = -0.67 95%CI -1.09, -0.25 and women β = -0.71 95%CI -1.40, -0.01). Among men, those with a lower income had a significantly lower BMI, while the opposite was found among women. None of the interaction models had a significantly better fit than the random intercept models. The relationship between neighborhood disadvantage and BMI did not differ by level of education, occupation, or household income. This suggests that individual SEP is unlikely to be an effector modifier of the relationship between neighborhood disadvantage and BMI. Further research is required to assist policy-makers to make more informed decisions about where to intervene to counteract BMI-inequalities.
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ItemPrevalence of chlamydia, gonorrhoea, syphilis and trichomonas in Aboriginal and Torres Strait Islander Australians: a systematic review and meta-analysis(CSIRO PUBLISHING, 2016)Higher notification rates of sexually transmissible infections (STIs) are reported among Aboriginal and Torres Strait Islander (Aboriginal) compared with non-Aboriginal people in Australia. The aim of this study is to estimate the pooled prevalence of chlamydia, gonorrhoea, syphilis and trichomonas among Aboriginal people in Australia by sex, age-group, setting (clinic vs population/community-based) and population group [adults, pregnant females, young people (12-29 years) and prisoners]. The databases Medline, PubMed and Web of Science were searched in May 2015. A meta-analysis was conducted to estimate the pooled prevalence of the four STIs in Aboriginal people and if possible, by gender, age-group, setting and population group. A total of 46 studies were included. The pooled prevalence was 11.2% (95%CI: 9.4-13.0%) for chlamydia (36 studies), 12.5% (95%CI: 10.5-14.6%) for gonorrhoea (28 studies), 16.8% (95%CI: 11.0-22.6%) for syphilis (13 studies) and 22.6% (95%CI: 18.5-26.7%) for trichomonas (11 studies); however, there was significant heterogeneity between studies (I(2) <97.5%, P<0.01). In the subgroup analysis, a higher pooled prevalence occurred in females than males for chlamydia (12.7% vs 7.7%) and gonorrhoea (10.7% vs 8.1%). The prevalence of chlamydia was 12.4% in clinic-based compared with 4.3% in population-based studies. The highest pooled prevalence by population group was among pregnant females (16.8%) and young people (16.2%) for chlamydia, pregnant females (25.2%) for trichomonas; and young people for gonorrhoea (11.9%). This review highlights the need to decrease the prevalence of STIs among Aboriginal people through community-based programs that target asymptomatic young people.
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ItemHuman papillomavirus vaccination and genital warts in young Indigenous Australians: national sentinel surveillance data(Australasian Medical Publishing Company, 2017-03-20)OBJECTIVES: To examine the impact of the national human papillomavirus (HPV) vaccination program (available to girls and women [12-26 years] since 2007 and to boys [12-15 years] since 2013) on the number of diagnoses of genital warts in Australian Aboriginal and Torres Strait Islander (Indigenous) people. DESIGN, SETTING, PARTICIPANTS: Analysis of routinely collected data from patients attending 39 sexual health clinics (SHCs) in the Genital Warts Surveillance Network for the first time.Major outcome: The average annual proportion of Indigenous and non-Indigenous SHC patients diagnosed with genital warts during the pre-vaccination (2004-2007) and vaccination periods (2008-2014), stratified by age group and sex. RESULTS: 7.3% of the 215 599 Australian-born patients with known Indigenous status and seen for the first time at participating SHCs during 2004-2014 were Indigenous Australians. The average proportion of female Indigenous patients diagnosed with warts was lower during the vaccination period than during the pre-vaccination period (in those under 21, summary rate ratio [SRR], 0.12; 95% CI, 0.07-0.21; P < 0.001); in 21-30-year olds: SRR, 0.41; 95% CI, 0.27-0.61; P < 0.001); there was no significant difference for women over 30 (SRR, 0.84; 95% CI, 0.51-1.36; P = 0.47). The proportion of male Indigenous heterosexual SHC patients under 21 diagnosed with warts was also lower during the vaccination period (SRR, 0.25; 95% CI, 0.12-0.49; P < 0.001), with no significant changes among older Indigenous men over 30. CONCLUSIONS: There were marked declines in the proportions of diagnoses of genital warts in young Indigenous women and men attending SHCs after the introduction of the HPV vaccination program. If high levels of HPV vaccine coverage are sustained, HPV-related cancer rates should also decline.
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ItemAlterations in Retinal Microvascular Geometry in Young Type 1 Diabetes(AMER DIABETES ASSOC, 2010-06)OBJECTIVE: To describe retinal microvascular geometric parameters in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes (aged 12-20 years) had clinical assessments and retinal photography following standardized protocol at a tertiary-care hospital in Sydney. Retinal microvascular geometry, including arteriolar and venular tortuosity, branching angles, optimality deviation, and length-to-diameter ratio (LDR), were measured from digitized photographs. Associations of these geometric characteristics with diabetes duration, A1C level, systolic blood pressure (SBP), and other risk factors were assessed. RESULTS: Of 1,159 patients enrolled, 944 (81.4%) had gradable photographs and 170 (14.7%) had retinopathy. Older age was associated with decreased arteriolar (P = 0.024) and venular (P = 0.002) tortuosity, and female subjects had larger arteriolar branching angle than male subjects (P = 0.03). After adjusting for age and sex, longer diabetes duration was associated with larger arteriolar branching angle (P 8.5 vs.