354 results on '"Jane Halliday"'
Search Results
102. Effect of reduced pH on physiology and shell integrity of juvenile
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Vonda J, Cummings, Abigail M, Smith, Peter M, Marriott, Bryce A, Peebles, and N Jane, Halliday
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Ecology ,pH ,Ocean acidification ,Climate Change Biology ,Shell thickness ,Juvenile ,Marine Biology ,CO2 ,Mollusc ,Biogeochemistry ,Coastal marine ,Warming - Abstract
The New Zealand pāua or black footed abalone, Haliotis iris, is one of many mollusc species at potential risk from ocean acidification and warming. To investigate possible impacts, juvenile pāua (~24 mm shell length) were grown for 4 months in seawater pH/pCO2 conditions projected for 2100. End of century seawater projections (pHT 7.66/pCO2 ~1,000 μatm) were contrasted with local ambient conditions (pHT 8.00/pCO2 ~400 μatm) at two typical temperatures (13 and 15 °C). We used a combination of methods (morphometric, scanning electron microscopy, X-ray diffraction) to investigate effects on juvenile survival and growth, as well as shell mineralogy and integrity. Lowered pH did not affect survival, growth rate or condition, but animals grew significantly faster at the higher temperature. Juvenile pāua were able to biomineralise their inner nacreous aragonite layer and their outer prismatic calcite layer under end-of-century pH conditions, at both temperatures, and carbonate composition was not affected. There was some thickening of the nacre layer in the newly deposited shell with reduced pH and also at the higher temperature. Most obvious was post-depositional alteration of the shell under lowered pH: the prismatic calcite layer was thinner, and there was greater etching of the external shell surface; this dissolution was greater at the higher temperature. These results demonstrate the importance of even a small (2 °C) difference in temperature on growth and shell characteristics, and on modifying the effects at lowered pH. Projected CO2-related changes may affect shell quality of this iconic New Zealand mollusc through etching (dissolution) and thinning, with potential implications for resilience to physical stresses such as predation and wave action.
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- 2019
103. A minimum estimate of the prevalence of 22q11 deletion syndrome and other chromosome abnormalities in a combined prenatal and postnatal cohort
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Lisa Hui, A Howden, Debbie Nisbet, J Harraway, Melody Menezes, B. Hutchinson, Michael T. Bethune, R. McCoy, L. Gugasyan, A Poulton, A Kulkarni, E Kluckow, Jane Halliday, Ricardo Palma-Dias, Anthea Lindquist, Zeffie Poulakis, Mark D. Pertile, L Bonacquisto, Fabricio da Silva Costa, and Nicole Martin
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Adult ,medicine.medical_specialty ,22q11 Deletion Syndrome ,Population ,Prenatal diagnosis ,Prenatal care ,Miscarriage ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,education ,Child ,Chromosome Aberrations ,education.field_of_study ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics ,Rehabilitation ,Australia ,Infant, Newborn ,Obstetrics and Gynecology ,medicine.disease ,Reproductive Medicine ,Cohort ,Chromosome abnormality ,Female ,business ,Cohort study - Abstract
STUDY QUESTION What is the frequency of major chromosome abnormalities in a population-based diagnostic data set of genomic tests performed on miscarriage, fetal and infant samples in a state with >73 000 annual births? SUMMARY ANSWER The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826), with a significant decrease in the detection of major chromosome abnormalities with later developmental stage, from 50.9% to 21.3% to 15.6% of tests in the miscarriage, prenatal and postnatal cohorts, respectively. WHAT IS KNOWN ALREADY Over the past decade, technological advances have revolutionized genomic testing at every stage of reproduction. Chromosomal microarrays (CMAs) are now the gold standard of chromosome assessment in prenatal diagnosis and pediatrics. STUDY DESIGN, SIZE, DURATION A population-based cohort study including all chromosome analysis was performed in the Australian state of Victoria during a 24-month period from January 2015 to December 2016. All samples obtained via invasive prenatal diagnosis and postnatal samples from pregnancy tissue and infants ≤12 months of age were included. PARTICIPANTS/MATERIALS, SETTING, METHODS A research collaboration of screening and diagnostic units in the Australian state of Victoria was formed (the Perinatal Record Linkage collaboration), capturing all instances of prenatal and postnatal chromosome testing performed in the state. Victoria has over 73 000 births per annum and a median maternal age of 31.5 years. We analyzed our population-based diagnostic data set for (i) chromosome assessment of miscarriage, prenatal diagnosis and postnatal samples; (ii) testing indications and diagnostic yields for each of these cohorts; (iii) and the combined prenatal/infant prevalence of 22q11.2 deletion syndrome (DS) as a proportion of all births ≥20 weeks gestation. MAIN RESULTS AND THE ROLE OF CHANCE During the 24-month study period, a total of 8826 chromosomal analyses were performed on prenatal and postnatal specimens in Victoria. The vast majority (91.2%) of all chromosome analyses were performed with CMA. The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826). There was a significant decreasing trend in the percentage of chromosome abnormalities with later developmental stage from 50.9% to 21.3% to 15.6% in the miscarriage, prenatal and postnatal cohorts, respectively (χ2 trend = 790.0, P LIMITATIONS, REASONS FOR CAUTION Clinical information was missing on 11.6% of postnatal samples, and gestational age was rarely provided on the miscarriage specimens. We were unable to obtain rates of termination of pregnancy and stillbirth in our cohort due to incomplete data provided by clinical referrers. We therefore cannot make conclusions on pregnancy or infant outcome following diagnostic testing. Childhood and adult diagnoses of 22q11 DS were not collected. WIDER IMPLICATIONS OF THE FINDINGS Our study marks a complete transition in genomic testing from the G-banded karyotype era, with CMA now established as the first line investigation for pregnancy losses, fetal diagnosis and newborn/infant assessment in a high-income setting. Integration of prenatal and postnatal diagnostic data sets provides important opportunities for estimating the prevalence of clinically important congenital syndromes, such as 22q11 DS. STUDY FUNDING/COMPETING INTEREST(S) L.H. is funded by a National Health and Medical Research Council Early Career Fellowship (1105603); A.L. was funded by a Mercy Perinatal Research Fellowship; J.H. was funded by a National Health and Medical Research Council Senior Research Fellowship (10121252). The funding bodies had no role in the conduct of the research or the manuscript. Discretionary funding from the Murdoch Children’s Research Institute has supported the prenatal diagnosis data collection and reporting over the years. Dr Ricardo Palma-Dias reports a commercial relationship with Roche Diagnostics, personal fees from Philips Ultrasound, outside the submitted work. Debbie Nisbet reports a commercial relationship with Roche Diagnostics, outside the submitted work. TRIAL REGISTRATION NUMBER NA
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- 2018
104. Improving women’s knowledge about prenatal screening in the era of non-invasive prenatal testing for Down syndrome – development and acceptability of a low literacy decision aid
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Michelle Peate, Rajneesh Kaur, Jane Halliday, Mariana S. Sousa, Lyndal Trevena, Kristine Barlow-Stewart, Alec W. Welsh, Sharon Lewis, Tatiane Yanes, Bettina Meiser, Margot Barclay, Michelle Wong, Antonia Cai, and Sian K Smith
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Adult ,Down syndrome ,medicine.medical_specialty ,Trisomy 21 ,Teaching Materials ,1110 Nursing, 1114 Paediatrics and Reproductive Medicine, 1117 Public Health and Health Services ,Low literacy ,Reproductive medicine ,Health literacy ,Prenatal diagnosis ,Prenatal testing ,lcsh:Gynecology and obstetrics ,Access to Information ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,medicine ,Humans ,030212 general & internal medicine ,Obstetrics & Reproductive Medicine ,lcsh:RG1-991 ,Qualitative Research ,030219 obstetrics & reproductive medicine ,business.industry ,Informed decision-making ,Australia ,Obstetrics and Gynecology ,Prenatal screening ,medicine.disease ,Health Literacy ,3. Good health ,Decision aid ,Telephone interview ,Family medicine ,Non-invasive prenatal testing (NIPT) ,Female ,Pamphlets ,Pregnant Women ,Down Syndrome ,business ,Research Article ,Qualitative research - Abstract
Background Access to information about prenatal screening is important particularly in light of new techniques such as non-invasive prenatal testing (NIPT). This study aimed to develop and examine the acceptability of a low literacy decision aid (DA) about Down syndrome screening among pregnant women with varying education levels and GPs. Methods We developed a DA booklet providing information about first-trimester combined testing, maternal serum screening, and NIPT. GPs and women participated in a telephone interview to examine the acceptability of the DA and measure screening knowledge before and after reading the DA. The knowledge measure was designed to assess whether women had understood the gist of the information presented in the decision aid. It comprised conceptual questions (e.g. screening tells you the chance of having a baby with Down syndrome) and numeric questions (e.g. the accuracy of different screening tests). Results Twenty-nine women and 18 GPs participated. Regardless of education level, most women found the booklet ‘very’ clearly presented (n = 22, 76%), and ‘very’ informative (n = 23, 80%). Overall, women’s conceptual and numeric knowledge improved after exposure to the DA, from 4% having adequate knowledge to 69%. Women’s knowledge of NIPT also improved after receiving the decision aid, irrespective of education. Most GPs found it ‘very’ clearly presented (n = 13, 72%), and that it would ‘very much’ facilitate decision-making (n = 16, 89%). Conclusions The DA was found to be acceptable to women as well as GPs. A comprehensive evaluation of the efficacy of the decision aid compared to standard information is an important next step. Strategies are needed on how to implement the tool in practice. Electronic supplementary material The online version of this article (10.1186/s12884-018-2135-0) contains supplementary material, which is available to authorized users.
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- 2018
105. Natural history of conservatively managed Rathke's cysts: a retrospective analysis of a single centre experience
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Jane Halliday, Christine May, Robin Joseph, Simon Cudlip, Aparna Pal, Sergios Gargalas, Lia Anguelova, and Bahram Jafar-Mohammadi
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Natural history ,medicine.medical_specialty ,Single centre ,business.industry ,General surgery ,Retrospective analysis ,Medicine ,business - Published
- 2018
106. A rare case of prolactin secreting pituitary carcinoma with extra-cranial metastasis
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Olaf Ansorge, Jane Halliday, Aparna Pal, Tamar Saeed, Christine May, Bahram Jafar-Mohammadi, and Simon Cudlip
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Pathology ,medicine.medical_specialty ,business.industry ,Rare case ,Pituitary carcinoma ,Medicine ,business ,medicine.disease ,Prolactin ,Metastasis - Published
- 2018
107. Characterisation of paediatric craniopharyngiomas in a single centre study - analysis of factors affecting recurrence rates
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Tina Foord, Dawn-Marie Davies, Aparna Pal, Bahram Jafar-Mohammadi, Miranda Rogers, Anne Marland, and Jane Halliday
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Single centre ,Pediatrics ,medicine.medical_specialty ,business.industry ,Medicine ,Study analysis ,business - Published
- 2018
108. Which types of conditions should be included in reproductive genetic carrier screening? Views of parents of children with a genetic condition
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Sharon Lewis, Jane Halliday, Felicity K. Boardman, Kristine Barlow-Stewart, John Massie, Alison D Archibald, Edwin P. Kirk, Lauren A Thomas, Martin B. Delatycki, and Belinda J McClaren
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Adult ,Male ,Parents ,0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Hearing loss ,Decision Making ,Population ,Genetic Carrier Screening ,030105 genetics & heredity ,Genetic Condition ,03 medical and health sciences ,Reproductive Techniques ,Intellectual disability ,Genetics ,Humans ,Medicine ,Outpatient clinic ,education ,Genetics (clinical) ,Aged ,education.field_of_study ,business.industry ,Genetic Diseases, Inborn ,General Medicine ,Middle Aged ,medicine.disease ,030104 developmental biology ,Attitude ,Female ,Personalized medicine ,medicine.symptom ,RB ,business ,Carrier screening - Abstract
Reproductive genetic carrier screening identifies couples with an increased chance of having children with autosomal and X-linked recessive conditions. Initially only offered for single conditions to people with a high priori risk, carrier screening is becoming increasingly offered to individuals/couples in the general population for a wider range of genetic conditions. Despite advances in genomic testing technology and greater availability of carrier screening panels, there is no consensus around which types of conditions to include in carrier screening panels. This study sought to identify which types of conditions parents of children with a genetic condition believe should be included in carrier screening. Participants (n = 150) were recruited through Royal Children's Hospital (RCH) Melbourne outpatient clinics, the Genetic Support Network of Victoria (GSNV) and a databank of children with hearing loss (VicCHILD). This study found that the majority of participants support offering carrier screening for: neuromuscular conditions (n = 128/134, 95.5%), early fatal neurodegenerative conditions (n = 130/141, 92.2%), chronic multi-system disorders (n = 124/135, 91.9%), conditions which cause intellectual disability (n = 128/139, 92.1%) and treatable metabolic conditions (n = 120/138, 87.0%). Views towards the inclusion of non-syndromic hearing loss (n = 88/135, 65.2%) and preventable adult-onset conditions (n = 75/135, 55.6%) were more mixed. Most participants indicated that they would use reproductive options to avoid having a child with the more clinically severe conditions, but most would not do so for clinically milder conditions. A recurring association was observed between participants’ views towards carrier screening and their lived experience of having a child with a genetic condition.\ud \ud
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- 2020
109. Maternal micronutrient consumption periconceptionally and during pregnancy: a prospective cohort study
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Peter J. Anderson, Sharon Lewis, Stephen C. Bowden, Jane Halliday, Michelle Livock, and Evelyne Muggli
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Victoria ,Population ,Nutritional Status ,Medicine (miscellaneous) ,Gestational Age ,Prenatal care ,Reference Daily Intake ,Eating ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,Humans ,Micronutrients ,Prospective Studies ,030212 general & internal medicine ,education ,Prospective cohort study ,Demography ,education.field_of_study ,030109 nutrition & dietetics ,Nutrition and Dietetics ,Obstetrics ,business.industry ,Nutritional Requirements ,Public Health, Environmental and Occupational Health ,Gestational age ,Prenatal Care ,Maternal Nutritional Physiological Phenomena ,Micronutrient ,medicine.disease ,Research Papers ,Diet ,Logistic Models ,Dietary Supplements ,Cohort ,Female ,Preconception Care ,business - Abstract
ObjectiveTo examine overall micronutrient intake periconceptionally and throughout pregnancy in a population-based cohort of Australian women.DesignIn a prospective cohort study, micronutrient dosages were extracted from self-reported maternal supplement use, recorded pre-conception, and for each trimester of pregnancy. A food frequency scale (DQESv2) captured usual maternal diet for gestational weeks 14–26. The influence of sociodemographic and lifestyle factors associated with supplement use was examined using logistic regression, and changes in micronutrient intakes prior to and throughout pregnancy were assessed using repeated-measures ANOVA analyses.SettingMetropolitan hospital sites in Melbourne, Australia.SubjectsWomen with a viable singleton pregnancy were recruited at less than 19 weeks’ gestation (n2146).ResultsCompared with non-users, women using supplements during pregnancy were more likely to have planned their pregnancy, be >25 years old, primiparous, Caucasian, non-smokers, have a tertiary education and be consuming a folate-rich diet. Intakes of folate, Fe and Zn were significantly lower in the periconceptional period, compared with other periods (PConclusionsThe study highlights the need for improved public health education on nutritional needs during pregnancy, especially among women with lower educational achievements and income.
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- 2016
110. Socioeconomic Differences in Informed Decisions About Down Syndrome Screening: A Systematic Review and Research Agenda
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Mariana S. Sousa, Mirjam P. Fransen, Marie-Louise Essink-Bot, Jane Halliday, Sian K Smith, Michelle Peate, Public and occupational health, and APH - Amsterdam Public Health
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Gerontology ,Health (social science) ,MEDLINE ,Health literacy ,CINAHL ,PsycINFO ,Library and Information Sciences ,Choice Behavior ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Pregnancy ,law ,Informed consent ,Numeracy ,Prenatal Diagnosis ,Humans ,Medicine ,030212 general & internal medicine ,Socioeconomic status ,Randomized Controlled Trials as Topic ,Informed Consent ,030219 obstetrics & reproductive medicine ,business.industry ,Communication ,Public Health, Environmental and Occupational Health ,Socioeconomic Factors ,0807 Library and Information Studies, 1117 Public Health and Health Services, 2001 Communication and Media Studies ,Female ,Public Health ,Down Syndrome ,business ,Social psychology - Abstract
Supporting pregnant women to make informed choices about Down syndrome screening is widely endorsed. We reviewed the literature on: (a) the association between socioeconomic position and informed choices and decision-making about Down syndrome screening, and (b) the possible mediating variables (e.g., health literacy, numeracy skills, behavioral and communication variables) that might explain the relationship. EMBASE, MEDLINE, PubMed, CINAHL, and PsycINFO were searched from January 1999 to September 2014. The methodological quality of studies was determined by predefined criteria regarding the research aims, study design, study population and setting, measurement tools, and statistical analysis. A total of 33 studies met the inclusion criteria. Women from lower socioeconomic groups experience greater difficulties making informed choices about Down syndrome screening compared to women from higher socioeconomic groups. Most studies focus on individual dimensions of informed decision-making rather than assessing elements in conjunction with one another. Few studies have explored why there are socioeconomic differences in women's ability to make informed screening decisions. Future work is needed to identify mediating variables in this pathway. Systematic evidence-based intervention development to improve communication, understanding, and decision-making about Down syndrome screening is needed to ensure that women have an equal opportunity to make an informed choice about screening regardless of their socioeconomic position.
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- 2016
111. Experiences of prenatal diagnosis and decision‐making about termination of pregnancy: A qualitative study
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Penelope Pitt, Melody Menezes, Chriselle Hickerton, Jane Halliday, Jan Hodgson, Sylvia A Metcalfe, Jane Fisher, Belinda J McClaren, and Kerry Petersen
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Adult ,Male ,Parents ,medicine.medical_specialty ,Adolescent ,media_common.quotation_subject ,Decision Making ,Prenatal diagnosis ,Empathy ,Abortion ,Congenital Abnormalities ,Interviews as Topic ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,medicine ,Humans ,Patient Navigation ,030212 general & internal medicine ,Young adult ,Psychiatry ,Qualitative Research ,media_common ,030219 obstetrics & reproductive medicine ,business.industry ,Communication ,Australia ,Obstetrics and Gynecology ,General Medicine ,Middle Aged ,medicine.disease ,Feeling ,Family medicine ,Female ,Thematic analysis ,business ,Abortion, Eugenic ,Qualitative research - Abstract
Background Advances in genetic technologies and ultrasound screening techniques have increased the ability to predict and diagnose congenital anomalies during pregnancy. As a result more prospective parents than ever before will receive a prenatal diagnosis of a fetal abnormality. Little is known about how Australian women and men experience receiving a prenatal diagnosis and how they make their decision about whether or not to continue the pregnancy. Aims This qualitative study aims to describe parental experiences and examine how best to provide support after a prenatal diagnosis. Results Individual in-depth interviews were conducted with 102 women and men approximately six weeks post-diagnosis of fetal abnormality. Data were elicited using a narrative, chronological approach and women (n = 75) and a sample of male partners (n = 27) were separately interviewed. Thematic analysis, involving a rigorous process of qualitative coding, enabled iterative development and validation of emergent themes. Participants identified that the shock of the diagnosis can be lessened when good care is delivered, by provision of: clear, accurate and respectful communication; empathic, non-judgemental, professional support; timely access to further testing and appointments; seamless interactions with services and administration; appropriate choices about invasive testing; acknowledgment of the enormity and unexpected nature of the diagnosis, and of the subsequent decision-making challenges; and discussion of the myriad feelings likely to emerge throughout the process. Conclusions This study has demonstrated the importance of providing timely access to accurate information and supportive, non-judgemental care for women and their partners following prenatal diagnosis of a fetal abnormality.
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- 2016
112. Lung function in adults conceived by assisted reproductive technologies
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Joanne Kennedy, Liam Welsh, John McBain, Jane Halliday, Sarath Ranganathan, Sharon Lewis, and Markus Juonala
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Spirometry ,Pediatrics ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Reproductive technology ,Lung Clearance Index ,Nitrogen washout ,FEV1/FVC ratio ,Health problems ,Functional residual capacity ,Medicine ,business ,Lung function - Abstract
Background: Approximately 4% of babies born in Australia are conceived by assisted reproductive technologies (ART). The artificial procedures used during ART raises the risk profile of adult-onset chronic health problems, including respiratory conditions, compared with naturally conceived children. Our aim was to determine whether adults conceived by ART have altered lung function compared with age- and sex-matched controls. Methods: As part of a large cohort study in Victoria, Australia, participants performed spirometry and multiple breath nitrogen washout (MBNW) according to current ATS/ERS guidelines. These measures were done with the clinician blinded to the case or control status of the participant. Results: 165 ART-conceived participants (94 female) and 79 naturally conceived controls (53 female) completed spirometry and a subgroup of 71 (48 ART) completed MBNW. There were no differences in mean (sd) age (27.3 (2.9) vs 27.3 (2.5) years, p=0.97) or mean (sd) BMI (25.4 (5.1) vs 25.6 (4.9) kg/m2, p=0.77) between the ART and control groups. There were no significant differences between ART and control participants for any lung function measurements. ART and control participants had similar FEV1 z-scores (mean difference (95%CI) (-0.15 (-0.39 to 0.10)), FVC z-scores (-0.08 (-0.33 to 0.16)), lung clearance index (0.37 (-0.01 to 0.73)) and functional residual capacity (0.27 (-0.20 to 0.74)). Conclusions: ART-conceived adults have comparable lung function to age- and sex-matched controls.
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- 2018
113. Engaging pregnant women in observational research: a qualitative exploratory study
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Helen Curd, Jane Halliday, Cate Nagle, Evelyne Muggli, and Della Forster
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Health Knowledge, Attitudes, Practice ,Alcohol Drinking ,Perinatal research ,Exploratory research ,Population health ,lcsh:Gynecology and obstetrics ,03 medical and health sciences ,0302 clinical medicine ,Social skills ,Nursing ,Pregnancy ,Humans ,Medicine ,Childbirth ,030212 general & internal medicine ,Alcohol use in pregnancy ,lcsh:RG1-991 ,Qualitative Research ,030219 obstetrics & reproductive medicine ,business.industry ,Patient Selection ,Obstetrics and Gynecology ,Observational Studies as Topic ,Female ,Observational study ,Recruitment ,Pregnant Women ,Descriptive research ,business ,Research Article ,Qualitative research - Abstract
Background Recruitment of pregnant women to population health research can be challenging, especially if the research topic is sensitive. While many pregnant women may be inherently interested in research about pregnancy, there is the possibility that the nature and timing of the project may give rise to anxiety in some women, especially if the topic is sensitive or it brings about new awareness of potential pregnancy complications. Research staff undertaking recruitment need to be skilled at strategies to manage the environment, and have well developed communication and interpersonal skills to explain and promote the study and facilitate each woman’s informed decision-making regarding participation. However, the skills needed by recruitment staff to successfully engage pregnant women with a research topic are not well understood. This study aimed to address this evidence gap by providing insight into the dynamics between a pregnant woman and recruitment staff at the time of the offer to participate in an observational study about alcohol use in pregnancy. Methods Naturalistic inquiry guided a qualitative exploratory descriptive approach. Experienced recruitment staff from the Asking Questions about Alcohol in Pregnancy (AQUA) study (Muggli et al., BMC Pregnancy Childbirth 14:302, 2014) participated in individual semi-structured interviews and were asked about their experiences and approaches to engaging pregnant women. Interviews were transcribed verbatim and analysed using inductive content analysis. Results Pregnant women brought with them an inherent interest or disinterest in alcohol research, or in research in general, which formed the basis for engagement. Women responded favourably to the invitation to participate being delivered without pressure, and as part of a two-way conversation. Engagement with a sensitive topic such as alcohol use in pregnancy was facilitated by a non-judgmental and non-targeted approach. Influences such as privacy, distractions, partner’s opinion, time factors and level of clinical support either facilitated or hindered a woman’s engagement with the research. Conclusions These results provide an in-depth explanation of barriers and enablers to recruitment of pregnant women in antenatal clinics to studies that may inform strategies and the training of recruitment staff.
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- 2018
114. Intra-Tumoral CD8+ T-Cells in Follicular Lymphoma Contain Large Clonal Expansions That Are Amenable to Dual-Checkpoint Blockade
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Frank Vari, Sarah-Jane Halliday, Joshua W.D. Tobin, Jay Gunawardana, Soi Cheng Law, Mohamed Shanavas, Karthik Nath, Donna Cross, Muhammed B. Sabdia, Maher K. Gandhi, Colm Keane, Robert Bird, Annette Hernandez, and Lilia Merida de Long
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0301 basic medicine ,education.field_of_study ,Repertoire ,Immunology ,Population ,T-cell receptor ,Follicular lymphoma ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,03 medical and health sciences ,CTL ,030104 developmental biology ,0302 clinical medicine ,medicine ,Cytotoxic T cell ,education ,Diffuse large B-cell lymphoma ,CD8 ,030215 immunology - Abstract
Introduction. Intra-tumoral T-cell infiltration is associated with R-CHOP responsiveness in aggressive B-cell lymphoma (Keane, Lancet Haem 2015). These patients also have a broad (i.e. diverse) intra-tumoral T-cell receptor (TCR) repertoire with a ~20% superior survival compared to those with a narrow (i.e. clonal) repertoire after R-CHOP therapy. Here, the major contributor to the TCR clonal expansion were CD8+ T cells (Keane, CCR 2017). Paradoxically, our recent results in Follicular Lymphoma (FL) (Tobin, JCO in press) found that clonal T-cell expansions were markedly enriched in those patients that experienced progression of disease within 24 months (POD24). Given that FL is a histological subtype associated with a tumor microenvironment distinct from DLBCL including numerous CD4+ T-follicular helper cells (TFH), we now expand upon these findings by comparing TCR repertoires across histological subtypes. We then established whether the TCR repertoire in FL is related to differential TCR clonal expansions between different T-cell subsets and immune checkpoints. Finally, the overlap between tissue and blood TCR repertoires was investigated. Methods. Firstly, unbiased, high-throughput TCRβ sequencing (ImmunoSEQ, Adaptive Biotechnologies) was compared in 164 FFPE tissues (12 healthy nodes, 40 FL, 88 DLBCL, and as a comparator tumor known to be sensitive to checkpoint blockade and to have a high neoantigen burden, 24 melanoma tissues). Next, to determine the contribution of individual T-cell subsets to overall clonality, a further 21 fresh de-aggregated/cryopreserved FL tumor samples were FACS sorted into four T-cell groupings: CD8+ cytotoxic T-lymphocytes (CTLs), CD4+ TFH, CD4+ regulatory T-cells (TREGs) and 'other' (non-TFH/TREG) CD4+ T-cells. Flow cytometry quantified the expression of the checkpoints LAG3, TIM3 and PD1. Then, 5 FL paired tissue/blood samples were tested for shared TCR clones. Results. FL exhibited strikingly reduced TCR repertoire clonality (higher diversity) compared to DLBCL, melanoma and healthy lymph nodes (Fig 1A). Analysis of de-aggregated sorted nodal T-cells revealed a more complex TCR repertoire. The outcome measure was median clonality index (CIx ranging from '0' or minimal, to '1' or maximal clonality). Large T-cell clones in FL (CIx=0.12) predominantly resided within the CTL subset (34% all T-cells). By contrast, there was marked T-cell diversity in TFH (CIx=0.04; 27% all T-cells), TREG (CIx=0.02; 7% all T-cells) and 'other' CD4+ T-cells (CIx=0.02; 32% all T-cells) (Fig 1B). The CTL population had a bimodal expression for PD1 (+51%/-49%), a marker in FL that has been shown to remain functionally active unless co-expressed with LAG3 and/or TIM3 (Yang, Oncotarget 2017). These dual-checkpoint expressing CTLs have reduced capacity to produce cytokines or lytic granules (i.e. they are 'exhausted'). Notably, 54% of the PD1+ CTLs co-expressed either LAG3 or TIM3. Put together, these results are consistent with expanded CTL clones that are frequently functionally exhausted. In contrast, TFH, TREG and 'other' CD4+ T-cells had a low expression of LAG3 and TIM3, although PD1 was frequently found (as expected, particularly in the TFH cells). Finally, in paired tissue/blood samples, there was weak overlap between the circulating and intra-tumoral TCR repertoire in CTLs and TFH T-cells. Conclusion. Although FL has a markedly less clonal TCR repertoire compared to DLBCL, melanoma and even healthy nodes, this result is misleading. Detailed analysis on sorted intra-tumoral T-cell subsets in FL revealed large clonal expansions in CTLs, with approximately half of these classified as functionally exhausted (dual-positive for PD1 and LAG3 and/or TIM3), a state potentially amenable to reversal by dual-checkpoint blockade. The explanation for TCR repertoire diversity lies in CD4+ T-cells (representing approximately two-thirds of T-cells, including the large TFH subset). T-cells in blood did not reflect FL tissue T-cell clones, further highlighting the need for sorted intra-tumoral nodal tissues to accurately assess TCR repertoires in FL. Further characterization of the neo-antigenic targets that CTL clones potentially recognize is required. These results have implications for therapeutic vaccine design and selective recruitment of patients for immune checkpoint blockade. Disclosures Keane: MSD: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Roche: Consultancy, Other: Travel Grant; BMS: Research Funding. Gandhi:Roche: Honoraria, Other: Travel Support; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Research Funding.
- Published
- 2019
115. Prenatal and preimplantation genetic diagnosis for single gene disorders: A population-based study from 1977 to 2016
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Sharon Lewis, Jane Halliday, A Poulton, and Lisa Hui
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0301 basic medicine ,Pediatrics ,medicine.medical_specialty ,Databases, Factual ,Victoria ,Population ,Prenatal diagnosis ,Single gene ,030105 genetics & heredity ,Preimplantation genetic diagnosis ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Statistical significance ,Prenatal Diagnosis ,medicine ,Humans ,Genetic Testing ,education ,Genetics (clinical) ,Preimplantation Diagnosis ,Genetic testing ,Retrospective Studies ,education.field_of_study ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Genetic Diseases, Inborn ,Obstetrics and Gynecology ,Retrospective cohort study ,medicine.disease ,Female ,business - Abstract
OBJECTIVE: To examine the statewide utilisation of prenatal diagnosis (PNDx) and preimplantation genetic diagnosis (PGT-M) for single gene disorders. METHODS: Population-based study of all women utilising PNDx in the Australian state of Victoria from 1977 to 2016. Single gene disorders were categorised using a systematic approach that aimed to reflect aspects of the PNDx decision-making process. Data on PGT-M for single gene disorders from 2005 to 2016 were similarly examined for comparison. Statistical significance testing was performed with χ2 test. RESULTS: Following an initial uptake period, annual PNDx rates for single gene disorders stabilised between 1.3 and 2.2 per 1000 births after the year 2000. The majority of PNDx (72%) was performed for disorders that primarily impair physical ability, while PNDx for adult onset conditions was rare (3%). PGT-M for single gene disorders has seen rapid growth since its introduction, and annual numbers now equal that of PNDx. In contrast to PNDx, one quarter of PGT-M tests were performed for adult onset conditions. CONCLUSIONS: Our population-wide analysis has demonstrated a steady demand for PNDx for single gene disorders over the past decade, in contrast to the rapidly increasing utilisation of PGT-M. PGT-M appears to be the preferred testing modality for adult onset disorders.
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- 2018
116. A comparison of Australian and French families affected by sarcoma: perceptions of genetics and incidental findings
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Jane Halliday, Jean-Yves Blay, Mary-Anne Young, Pierre Meeus, Muriel Rogasik, Eveline Niedermayr, Magali Girodet, Marie-Pierre Sunyach, Olivia Bally, Mandy L. Ballinger, Victoria Rasmussen, Isabelle Ray-Coquard, Paul A. James, Mehdi Brahmi, Laura E Forrest, and David Thomas
- Subjects
0301 basic medicine ,Adult ,Male ,Health Knowledge, Attitudes, Practice ,Referral ,media_common.quotation_subject ,Decision Making ,030105 genetics & heredity ,03 medical and health sciences ,Perception ,Surveys and Questionnaires ,Country group ,medicine ,Genetics ,Humans ,Family ,Genetic Testing ,Genetic testing ,media_common ,Pharmacology ,Incidental Findings ,medicine.diagnostic_test ,Information seeking ,Australia ,Social environment ,Sarcoma ,General Medicine ,Middle Aged ,medicine.disease ,Preference ,Molecular Medicine ,Female ,France ,Psychology ,Attitude to Health ,Confidentiality - Abstract
Aim: To compare Australian and French perceptions of genetics and preferences regarding the return of incidental findings. Methods: Participants from the International Sarcoma Kindred Study received a survey at intake to cancer referral units. A total of 1442 Australian and 479 French individuals affected by sarcoma and their unaffected family members responded to four hypothetical scenarios depicting hereditary conditions of varying treatability and severity. Results: Australians’ preference for the return of incidental findings was consistently higher than French for all scenarios. Country group differences were significant for two scenarios when individual characteristics were controlled through multivariable analyses. Conclusion: Findings support the need for guidelines that are sensitive to sociocultural context and promote autonomous decision-making.
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- 2018
117. OC06.04: Population‐based prevalence of 22q11 deletion syndrome and other chromosome abnormalities in a combined prenatal and postnatal cohort
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Debbie Nisbet, Jane Halliday, F. da Silva Costa, A Howden, E Kluckow, Marcos Roberto de Menezes, Anthea Lindquist, Zeffie Poulakis, J Harraway, A Poulton, L Bonacquisto, Mark D. Pertile, Michael T. Bethune, Lisa Hui, L. Gugasyan, A Kulkarni, R. McCoy, B. Hutchinson, Ricardo Palma-Dias, and Nicole Martin
- Subjects
Genetics ,22q11 Deletion Syndrome ,Reproductive Medicine ,Radiological and Ultrasound Technology ,business.industry ,Cohort ,Obstetrics and Gynecology ,Medicine ,Chromosome ,Radiology, Nuclear Medicine and imaging ,General Medicine ,Population based ,business - Published
- 2019
118. OC01.03: State‐wide performance of traditional and cell‐free DNA‐based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study
- Author
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J Harraway, Jane Halliday, F. da Silva Costa, M. Behune, A Howden, L Bonacquisto, Nicole Martin, R. McCoy, Debbie Nisbet, E Kluckow, A Poulton, Ricardo Palma-Dias, Anthea Lindquist, B. Hutchinson, Zeffie Poulakis, Mark D. Pertile, L. Gugasyan, A Kulkarni, and Lisa Hui
- Subjects
education.field_of_study ,medicine.medical_specialty ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,business.industry ,Obstetrics ,Population ,Obstetrics and Gynecology ,Aneuploidy ,Prenatal diagnosis ,Retrospective cohort study ,General Medicine ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Reproductive Medicine ,Cell-free fetal DNA ,Products of conception ,Chromosome abnormality ,Medicine ,Radiology, Nuclear Medicine and imaging ,030212 general & internal medicine ,business ,Trisomy ,education - Abstract
OBJECTIVES: Women's choices of prenatal screening and diagnostic pathways have increased in complexity since the introduction of cell-free DNA (cfDNA) screening and chromosomal microarrays. We performed individual record-linkage of women undergoing screening with cfDNA, combined first trimester screening (CFTS), second trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing to (i) obtain population-based estimates on women's utilization of screening and diagnosis, (ii) analyse the performance of different screening strategies, and (iii) report the residual risks of any major chromosome abnormality following a low risk aneuploidy screen. METHODS: Retrospective study of women resident in Victoria, Australia, undergoing screening or prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false negative screening results and atypical chromosome abnormalities. Individual record-linkage was performed with LinkageWizTM and statistical analyses with STATA v14.0. RESULTS: There were 79,140 births during the study period; 66,166 women (83.4%) underwent at least one form of aneuploidy screening. Linkage data were complete for 92.4% of women undergoing screening (n=61,911) and of these, 73.1% (n=45,275) used CFTS alone, 20.2% (n=12,520) used cfDNA alone; 5.3% (n=3268) used STSS alone, 1.3% (n=813) used both CFTS and cfDNA, and
- Published
- 2019
119. What do pregnant women eat, and are they meeting the recommended dietary requirements for pregnancy?
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Jane Halliday, Sharon Lewis, Amelia Lee, Della Forster, Evelyne Muggli, and Elisabeth Gasparini
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0301 basic medicine ,Adult ,medicine.medical_specialty ,Victoria ,Population ,Prenatal care ,Overweight ,Midwifery ,Nutrition Policy ,Food group ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Pregnancy ,Environmental health ,Surveys and Questionnaires ,Maternity and Midwifery ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,education ,education.field_of_study ,030109 nutrition & dietetics ,business.industry ,Public health ,Nutritional Requirements ,Obstetrics and Gynecology ,Prenatal Care ,Feeding Behavior ,medicine.disease ,Obesity ,Food ,Female ,medicine.symptom ,business ,Energy Intake ,Cohort study - Abstract
Objective To compare the dietary intake of pregnant women to the 2013 Australian Dietary Guidelines and explore factors associated with inadequate intake. Design Dietary intake data were collected between July 2011 and July 2012 (n = 1570) using a 74-item food frequency questionnaire. Setting Metropolitan public health hospitals in Melbourne, Australia. Participants Pregnant women, at least 16 years of age, with a singleton pregnancy, and literate in English. Measurements and Findings The highest proportion of women met the recommended daily servings for fruit (65.7%), followed by dairy products (55.2%), meat/meat alternatives (31.1%), vegetables (10.3%), and then grain foods (1.8%). A majority of women (83.8%) regularly consumed up to 2.5 serves of discretionary foods per day. Only one woman met the minimum recommended daily servings for all five food groups. Women who were obese were more likely to consume an inadequate diet (Adj. OR 2.13, 95% CI 1.53, 2.95); and having a university degree was associated with a lower odds of consuming an inadequate diet (Adj. OR 0.63, 95% CI 0.50, 0.78). Key Conclusions and Implications for Practice Pregnancy care providers need to be aware of women’s low compliance with the national dietary guidelines, particularly regarding the poor intake of vegetables and grain foods; targeted as well as population-based approaches may be required.
- Published
- 2017
120. Prenatal diagnostic testing and atypical chromosome abnormalities following combined first-trimester screening: implications for contingent models of non-invasive prenatal testing
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Jane Halliday, A Poulton, Lisa Hui, and Anthea Lindquist
- Subjects
Adult ,medicine.medical_specialty ,Down syndrome ,DNA Copy Number Variations ,Victoria ,Population ,Prenatal diagnosis ,Risk Assessment ,Ultrasonography, Prenatal ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Pregnancy ,Prevalence ,Medicine ,Humans ,Mass Screening ,Pregnancy-Associated Plasma Protein-A ,Radiology, Nuclear Medicine and imaging ,Chorionic Gonadotropin, beta Subunit, Human ,030212 general & internal medicine ,education ,Mass screening ,Retrospective Studies ,education.field_of_study ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,business.industry ,Maternal Serum Screening Tests ,Obstetrics ,Obstetrics and Gynecology ,Retrospective cohort study ,General Medicine ,medicine.disease ,Pregnancy Trimester, First ,Reproductive Medicine ,Cohort ,Female ,Down Syndrome ,business ,Trisomy - Abstract
To investigate by means of a population-based analysis of a cohort of women who underwent combined first-trimester screening (CFTS), changes in uptake of invasive prenatal diagnosis according to risk of trisomy 21 (T21) on CFTS, and prevalence and methods for ascertainment of atypical chromosome abnormalities.This was a retrospective cohort study using state-wide prenatal datasets from Victoria, Australia. A three-step approach was taken to analyze the data: (1) linkage of records between serum screening and diagnostic results; (2) comparison of rates of diagnostic testing according to CFTS T21 risk result category in a 2014-2015 cohort with those of a historical 2002-2004 cohort; (3) detailed analysis of atypical abnormalities in the 2014-2015 group according to CFTS T21 risk result, individual serum analyte level and other indications for invasive diagnostic testing.In 2014-2015, there were 100 418 CFTS results issued for 146 776 births (68.4%). The overall prevalence of atypical chromosome abnormalities in the entire CFTS cohort was 0.10% and was highest in those with CFTS T21 risk 1 in 10 (4.6%), or serum analyte levels 0.2 multiples of the median (MoM) (6.9% for pregnancy-associated plasma protein-A (PAPP-A) and 5.2% for beta-human chorionic gonadotropin (β-hCG)). Almost half (49.2%) of women with PAPP-A 0.2 MoM had a risk for T21 on CFTS of less than 1 in 100. The majority (55%) of atypical abnormalities occurred in women with CFTS T21 risk below 1 in 300, and were most commonly detected on ultrasound examination (47.1%).Concerns regarding missed diagnoses of atypical chromosome abnormalities when non-invasive prenatal testing is offered after a result of high risk on CFTS can be mitigated if invasive diagnostic testing is offered to those women with CFTS T21 risk of 1 in 100, serum PAPP-A or β-hCG 0.2 MoM, or ultrasound-detected abnormality. This has implications for contingent models of screening. Copyright © 2017 ISUOG. Published by John WileySons Ltd.
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- 2017
121. Outcomes of a randomised controlled trial of a complex genetic counselling intervention to improve family communication
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MaryAnne Aitken, Susan Donath, Martin B. Delatycki, Sylvia A Metcalfe, Jan Hodgson, Loane Skene, Jane Halliday, Ingrid Winship, and Clara Gaff
- Subjects
Male ,0301 basic medicine ,Proband ,medicine.medical_specialty ,Genetic counseling ,Genetic Counseling ,030105 genetics & heredity ,Article ,law.invention ,03 medical and health sciences ,Randomized controlled trial ,law ,Intervention (counseling) ,Genetics ,Humans ,Medicine ,Family ,Genetics (clinical) ,Genetic testing ,medicine.diagnostic_test ,business.industry ,Communication ,Case-control study ,Odds ratio ,Middle Aged ,Confidence interval ,Case-Control Studies ,Family medicine ,Female ,business - Abstract
When an inherited genetic condition is diagnosed in an individual it has implications for other family members. Privacy legislation and ethical considerations can restrict health professionals from communicating directly with other family members, and so it is frequently the responsibility of the first person in a family to receive the diagnosis (the proband) to share this news. Communication of genetic information is challenging and many at-risk family members remain unaware of important information that may be relevant to their or their children's health. We conducted a randomised controlled trial in six public hospitals to assess whether a specifically designed telephone counselling intervention improved family communication about a new genetic diagnosis. Ninety-five probands/parents of probands were recruited from genetics clinics and randomised to the intervention or control group. The primary outcome measure was the difference between the proportion of at-risk relatives who contacted genetics services for information and/or genetic testing. Audit of the family genetic file after 18 months revealed that 25.6% of intervention group relatives compared with 20.9% of control group relatives made contact with genetic services (adjusted odds ratio (OR) 1.30, 95% confidence interval 0.70–2.42, P=0.40). Although no major difference was detected overall between the intervention and control groups, there was more contact in the intervention group where the genetic condition conferred a high risk to offspring (adjusted OR 24.0, 95% confidence interval 3.4–168.5, P=0.001). The increasing sophistication and scope of genetic testing makes it imperative for health professionals to consider additional ways of supporting families in communicating genetic information.
- Published
- 2015
122. Population-based trends in prenatal screening and diagnosis for aneuploidy: a retrospective analysis of 38 years of state-wide data
- Author
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Jane Halliday, Evelyne Muggli, and Lisa Hui
- Subjects
Adult ,medicine.medical_specialty ,Victoria ,Pregnancy-associated plasma protein A ,Population ,Aneuploidy ,Gestational Age ,Prenatal diagnosis ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Pregnancy ,Prenatal Diagnosis ,medicine ,Humans ,Pregnancy-Associated Plasma Protein-A ,Chorionic Gonadotropin, beta Subunit, Human ,Genetic Testing ,030212 general & internal medicine ,education ,Retrospective Studies ,Genetic testing ,Gynecology ,education.field_of_study ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,business.industry ,Obstetrics ,Australia ,Infant, Newborn ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,Abortion, Spontaneous ,Predictive value of tests ,Amniocentesis ,Female ,alpha-Fetoproteins ,Down Syndrome ,Nuchal Translucency Measurement ,Trisomy ,business ,Biomarkers ,Maternal Age - Abstract
Objective To analyse population-based trends over the entire history of prenatal testing for aneuploidy. Design Retrospective analysis of state-wide data sets. Setting Australian state of Victoria with ~70 000 annual births. Population All pregnant women undergoing invasive prenatal testing at
- Published
- 2015
123. Age when learning about mode of conception and well-being among young adults conceived with ART
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Jane Fisher, Jane Halliday, Karin Hammarberg, John McBain, and Cate Wilson
- Subjects
Assisted reproductive technology ,Offspring ,medicine.medical_treatment ,Obstetrics and Gynecology ,Reproductive technology ,Developmental psychology ,Reproductive Medicine ,Quality of life ,Pediatrics, Perinatology and Child Health ,Well-being ,Structured interview ,medicine ,Young adult ,Psychology ,Association (psychology) ,General Psychology - Abstract
Objective: To investigate the age at which young adults recalled learning about being assistive reproductive technologies (ART)-conceived and the association with subjective well-being and parental relationship. Background: The use of ART is increasing. Parents are encouraged to tell children about the way they were conceived when they are young. Little is known about whether age when learning about being ART-conceived influences adult well-being. Methods: A structured interview was conducted with women who gave birth as a result of ART in Victoria, Australia 1982–1992 and their young adult offspring. The young adults’ interview included questions about age when learning about ART conception and perceived quality of the parental relationship, and a standardised measure of subjective well-being. Results: 547/594 (92%) young adults agreed to participate. Of these, 10.6% (n = 58) were conceived with donor gametes; 77% had been informed about their ART-conception before the age of 12, 18% when they were betwe...
- Published
- 2015
124. Increasing accurate self-report in surveys of pregnancy alcohol use
- Author
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Mph Evelyne Muggli, Jane Halliday, Della Forster, Brendan Cook, and Colleen O'Leary
- Subjects
Adult ,medicine.medical_specialty ,Alcohol Drinking ,Victoria ,Binge drinking ,Context (language use) ,Truth Disclosure ,Survey methodology ,Pregnancy ,Surveys and Questionnaires ,Maternity and Midwifery ,Humans ,Medicine ,Psychiatry ,business.industry ,Obstetrics and Gynecology ,Focus Groups ,medicine.disease ,Focus group ,Substance abuse ,Reporting bias ,Anxiety ,Female ,Pregnant Women ,Self Report ,medicine.symptom ,business ,Qualitative research - Abstract
Background pregnancy alcohol research relies on self-reports of alcohol consumption. Reporting bias may contribute to ambiguous and conflicting findings on fetal effects of low to moderate pregnancy alcohol exposure. Objective this study aimed to identify the determinants which would enable women to provide accurate data in surveys of alcohol use in pregnancy. Design and participants six focus groups were held with a total of 26 pregnant women and new mothers. Participants reviewed a set of alcohol survey questions followed by a guided discussion. Transcripts were analysed using inductive content analysis. Setting public hospital antenatal clinics and Mother & Child Health Centres, Melbourne, Victoria, Australia. Findings women׳s emotional responses were generally favourable, although the potential for anxiety and fear of judgement was acknowledged. Barriers to accurate self-report were recall, complexity and use of subjective language. Facilitators were appropriate drink choices, occasional drinking options and contextualising of questions. Confidentiality and survey method, including a preference for methods other than face-to face, were also important factors. Key conclusions and implications for practice questions embedded in clear context may reduce anxiety around questions about alcohol use in pregnancy. Methods using shorter recall periods, a list of drinks choices, measures of special occasion drinking and minimising complex and subjective language will increase accurate self-report. A setting perceived as confidential and anonymous may reduce a desire to provide socially acceptable answers.
- Published
- 2015
125. Offering pregnant women different levels of genetic information from prenatal chromosome microarray: a prospective study
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Sian K Smith, Susan P. Walker, Mark D. Pertile, Fiona Norris, Cécile Muller, Jane Halliday, Susan Donath, Taryn Charles, Melody Menezes, Zornitza Stark, Bettina Meiser, Della Forster, Joanne Kennedy, David J. Amor, George McGillivray, and Sharon Lewis
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Health Knowledge, Attitudes, Practice ,Chorionic villus sampling ,Prenatal diagnosis ,Chromosome Disorders ,030105 genetics & heredity ,Choice Behavior ,Article ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,Genetics ,medicine ,Humans ,Genetic Testing ,Prospective cohort study ,Genetics (clinical) ,Genetic testing ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,Obstetrics ,business.industry ,Odds ratio ,medicine.disease ,Confidence interval ,Amniocentesis ,Female ,business - Abstract
This study aimed to examine the choice pregnant women make about the amount of fetal genetic information they want from chromosome microarray. Women having invasive prenatal testing in the absence of fetal structural abnormality were recruited in Victoria, Australia. A decision aid for women described ‘targeted’ analysis as reporting only copy number variants implicated in a highly penetrant and well-described phenotype and ‘extended’ as additionally reporting variants of uncertain or unknown significance. Participant’s choice and demographics were collected by survey before chorionic villus sampling or amniocentesis; psychological data were also collected then and again about 10 days after receiving results. High-resolution single-nucleotide polymorphism array analysis was performed, and a clinical review committee assessed variants for reporting before returning results to participants. Sixty-six participants (59.5%) chose extended analysis and 45 (40.5%) targeted. Choosing extended information was associated with (1) indication for prenatal diagnosis: maternal age alone (adjusted odds ratio (adjOR) 9.6, 95% confidence interval (CI): 1.4–66.0, p= 0.02), or ‘other’ indication (adjOR 7.1, 95% CI: 1.5–33.1, p= 0.01)); (2) >12 months to conceive (adjOR 4.1, 95% CI: 1.0–17.7, p= 0.05); and (3) Asian background (adjOR 4.67, 95% CI: 1.0–21.0, p= 0.04). No adverse psychological impact occurred in either group. We conclude that offering pregnant women different levels of fetal genetic analysis is warranted, alongside decision support.
- Published
- 2017
126. Clinical review of 24-35 year olds conceived with and without in vitro fertilization: study protocol
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David J. Amor, Susan Donath, Sarath Ranganathan, Jane Halliday, Robert I McLachlan, Michael Cheung, Markus Juonala, Sharon Lewis, John McBain, David Burgner, Richard Saffery, Karin Hammarberg, Joanne Kennedy, and Lex W. Doyle
- Subjects
0301 basic medicine ,Adult ,Epigenomics ,Male ,medicine.medical_specialty ,Pediatrics ,Reproductive Techniques, Assisted ,Metabolic health ,Reproductive medicine ,Blood Pressure ,Reproductive technology ,Disease ,lcsh:Gynecology and obstetrics ,Carotid Intima-Media Thickness ,Cohort Studies ,03 medical and health sciences ,Study Protocol ,0302 clinical medicine ,In vitro fertilization ,Auxology ,Medicine ,Humans ,Adults ,Respiratory function ,Young adult ,lcsh:RG1-991 ,030219 obstetrics & reproductive medicine ,business.industry ,Respiratory health ,Obstetrics and Gynecology ,DNA Methylation ,Cardiovascular health ,3. Good health ,030104 developmental biology ,Reproductive Medicine ,Cardiovascular Diseases ,Cohort ,Physical therapy ,Female ,Assisted reproductive technologies ,business ,Cohort study - Abstract
Background Children conceived by assisted reproductive technologies (ART) currently comprise 4% of Australian births. The manipulation of biological parameters related to fertilization and implantation are integral to successful ART but potentially pose a risk to the longer-term health of the offspring. There is consensus that many common adult health problems (particularly cardiovascular, metabolic and respiratory conditions) have their origins in early life, possibly before birth, and that risk trajectories track through childhood until clinical disease manifests in adulthood. Early life epigenetic variation may play a role in this process. However little is known about the long-term health of individuals conceived by ART. In a previous study, based on telephone-interviews, we found that young adults conceived by in vitro fertilization (IVF) had significantly more maternal reported atopic respiratory, endocrine, nutritional, and metabolic conditions than non-IVF conceived matched controls. Here we outline the protocol for a follow-up biomedical assessment of this cohort and a questionnaire to obtain information on potential confounders. Methods We are conducting a clinical review of an existing, well characterised cohort comprising 547 IVF-conceived adults and 549 matched controls. We are measuring cardiovascular intermediate phenotypes, metabolic parameters and respiratory function, complemented by epigenome-wide DNA methylation analysis. A pilot study demonstrated the feasibility of our proposed protocol and its acceptability to participants. Participants attend a 2–3 h clinical assessment and complete a study-specific online questionnaire. Measurements include: 1) cardiovascular phenotypes: carotid artery intima-media thickness and distensibility, retinal vascular calibre, resting blood pressure, pulse wave velocity and pulse wave analysis; 2) respiratory function: spirometry, plethysmography, multiple breath washout; 3) auxology: height, weight, waist circumference, bio-impedance. Blood is collected for 4) biomarkers of cardiometabolic profile including inflammatory markers and 5) epigenetic analysis. Discussion Recruitment for this clinical review is challenging as many of the participants have moved to regional, interstate or international locations. Additionally, many female participants are pregnant or breastfeeding, and are therefore ineligible. Nevertheless, comprehensive strategies have been developed to optimize recruitment. Given the increasing use of IVF and related technologies, the potential long-term consequences for risk of common adult diseases is an important clinical and public health issue.
- Published
- 2017
127. Association Between Prenatal Alcohol Exposure and Craniofacial Shape of Children at 12 Months of Age
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Anthony J. Penington, Evelyne Muggli, Jeffrey M. Craig, Jane Halliday, Harold Matthews, Elizabeth J Elliott, Colleen O'Leary, Peter Claes, Susan Donath, Della Forster, Catherine Nagle, Susan M. White, Sharon Lewis, and Peter J. Anderson
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Craniofacial abnormality ,Fetal alcohol syndrome ,Binge drinking ,Binge Drinking ,Cohort Studies ,Craniofacial Abnormalities ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,medicine ,Prevalence ,Humans ,030212 general & internal medicine ,Prospective Studies ,Craniofacial ,Prospective cohort study ,Child ,Nose ,Original Investigation ,business.industry ,Skull ,Australia ,Facies ,Infant ,medicine.disease ,medicine.anatomical_structure ,PSI_MIC ,Fetal Alcohol Spectrum Disorders ,Anesthesia ,Prenatal Exposure Delayed Effects ,Pediatrics, Perinatology and Child Health ,Female ,business ,Tomography, X-Ray Computed ,030217 neurology & neurosurgery ,Cohort study - Abstract
IMPORTANCE: Children who receive a diagnosis of fetal alcohol spectrum disorder may have a characteristic facial appearance in addition to neurodevelopmental impairment. It is not well understood whether there is a gradient of facial characteristics of children who did not receive a diagnosis of fetal alcohol spectrum disorder but who were exposed to a range of common drinking patterns during pregnancy. OBJECTIVE: To examine the association between dose, frequency, and timing of prenatal alcohol exposure and craniofacial phenotype in 12-month-old children. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was performed from January 1, 2011, to December 30, 2014, among mothers recruited in the first trimester of pregnancy from low-risk, public maternity clinics in metropolitan Melbourne, Australia. A total of 415 white children were included in this analysis of 3-dimensional craniofacial images taken at 12 months of age. Analysis was performed with objective, holistic craniofacial phenotyping using dense surface models of the face and head. Partial least square regression models included covariates known to affect craniofacial shape. EXPOSURES: Low, moderate to high, or binge-level alcohol exposure in the first trimester or throughout pregnancy. MAIN OUTCOMES AND MEASURES: Anatomical differences in global and regional craniofacial shape between children of women who abstained from alcohol during pregnancy and children with varying levels of prenatal alcohol exposure. RESULTS: Of the 415 children in the study (195 girls and 220 boys; mean [SD] age, 363.0 [8.3] days), a consistent association between craniofacial shape and prenatal alcohol exposure was observed at almost any level regardless of whether exposure occurred only in the first trimester or throughout pregnancy. Regions of difference were concentrated around the midface, nose, lips, and eyes. Directional visualization showed that these differences corresponded to general recession of the midface and superior displacement of the nose, especially the tip of the nose, indicating shortening of the nose and upturning of the nose tip. Differences were most pronounced between groups with no exposure and groups with low exposure in the first trimester (forehead), moderate to high exposure in the first trimester (eyes, midface, chin, and parietal region), and binge-level exposure in the first trimester (chin). CONCLUSIONS AND RELEVANCE: Prenatal alcohol exposure, even at low levels, can influence craniofacial development. Although the clinical significance of these findings is yet to be determined, they support the conclusion that for women who are or may become pregnant, avoiding alcohol is the safest option. Muggli E., Matthews H., Penington A., Claes P., O'Leary C., Forster D., Donath S., Anderson P.J., Lewis S., Nagle C., Craig J.M., Whilte S.M., Eliott E.J., Halliday J., ''Association between prenatal alcohol exposure and craniofacial shape of children at 12 months of age'', JAMA pediatrics, vol. 171, no. 8, pp. 771-780, 2017. ispartof: JAMA Pediatrics vol:171 issue:8 pages:771-780 ispartof: location:United States status: published
- Published
- 2017
128. Alcohol consumption in a general antenatal population and child neurodevelopment at 2 years
- Author
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Della Forster, Catherine Nagle, Jane Halliday, Susan Donath, Jeffrey M. Craig, David J. Amor, Evelyne Muggli, Elizabeth J Elliott, Sharon Lewis, Peter J. Anderson, Colleen O'Leary, Family Medicine, and RS: CAPHRI - R6 - Promoting Health & Personalised Care
- Subjects
Adult ,Pediatrics ,medicine.medical_specialty ,Alcohol Drinking ,Epidemiology ,Population ,Emotions ,Binge drinking ,Gestational Age ,SPECTRUM DISORDERS ,Prenatal care ,Bayley Scales of Infant Development ,Binge Drinking ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Child Development ,Cognition ,Pregnancy ,SOCIAL-EMOTIONAL PROBLEMS ,medicine ,Humans ,KNOWLEDGE ,030212 general & internal medicine ,Prospective Studies ,Toddler ,education ,Child ,PRENATAL EXPOSURE ,RISK ,education.field_of_study ,030219 obstetrics & reproductive medicine ,business.industry ,Public Health, Environmental and Occupational Health ,Infant ,Prenatal Care ,Child development ,LIGHT DRINKING ,PREVALENCE ,Social deprivation ,COGNITIVE DEFICITS ,Neurodevelopmental Disorders ,Child, Preschool ,Population Surveillance ,Prenatal Exposure Delayed Effects ,Female ,business ,MENTAL-HEALTH ,Cohort study - Abstract
BackgroundPrenatal alcohol exposure (PAE) is a community health problem with up to 50% of pregnant women drinking alcohol. The relationship between low or sporadic binge PAE and adverse child outcomes is not clear. This study examines the association between PAE in the general antenatal population and child neurodevelopment at 2 years, accounting for relevant contributing factors.MethodsThis prospective population-based cohort recruited 1570 pregnant women, providing sociodemographic, psychological and lifestyle information and alcohol use for five time periods. PAE categories were ‘low’, ‘moderate/high’, ‘binge’, in trimester 1 or throughout pregnancy. Measures of cognitive, language and motor development (Bayley Scales of Infant and Toddler Development) were available for 554 children, while measures of sensory processing (Infant/Toddler Sensory Profile) and social–emotional development (Brief Infant Toddler Social Emotional Assessment) were available for 948.ResultsA positive association in univariate analysis with low-level PAE throughout pregnancy and cognition (β=4.1, 95% CI −0.02 to 8.22, p=0.05) was attenuated by adjusting for environmental/social deprivation risk factors (β=3.06 (−1.19 to 7.30), p=0.16). Early binge drinking, plus continued PAE at lower levels, was associated with the child being more likely to score low in sensation avoidance (adjusted OR 1.88 (1.03 to 3.41), p=0.04).ConclusionEarly binge exposure, followed by lower-level PAE, demonstrated an increase in sensation-avoiding behaviour. There were, however, no significant associations between PAE and neurodevelopment following adjustment for important confounders and modifiers. Follow-up is paramount to investigate subtle or later onset problems.
- Published
- 2017
129. Population-based impact of noninvasive prenatal screening on screening and diagnostic testing for fetal aneuploidy
- Author
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Jane Halliday, A Poulton, Lisa Hui, and B. Hutchinson
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Victoria ,Population ,Aneuploidy ,Prenatal diagnosis ,Chromosome Disorders ,030105 genetics & heredity ,Ultrasonography, Prenatal ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Prenatal Diagnosis ,Databases, Genetic ,medicine ,Humans ,Genetic Testing ,education ,Genetics (clinical) ,Genetic testing ,education.field_of_study ,030219 obstetrics & reproductive medicine ,medicine.diagnostic_test ,Obstetrics ,business.industry ,Ultrasound ,medicine.disease ,Pregnancy Trimester, First ,Cell-free fetal DNA ,Population Surveillance ,Female ,Trisomy ,business - Abstract
PurposeTo assess the population-wide impact of noninvasive prenatal screening (NIPS) on combined first-trimester screening (CFTS), early ultrasound (11-13 weeks), and invasive prenatal diagnosis in a state with over 73,000 births per year.MethodsAnalysis of population-based data from 2000 to 2015 including (i) invasive prenatal tests, (ii) CFTS uptake, and (iii) total births. Utilization of early ultrasound was analyzed before and after NIPS (2010-2015).ResultsInvasive testing decreased significantly by 39.6% from 2012 to 2015 despite steady births. More than half of all confirmed cases of trisomy 21 were ascertained by NIPS in 2015, despite NIPS comprising only 11.7% of total indications for invasive testing. CFTS uptake declined significantly from 77.5% in 2013 to 68.1% in 2015, but 11- to 13-week ultrasounds did not. In 2015, ultrasound abnormality replaced CFTS as the most common indication for invasive testing and chromosomal microarray was performed for 85.3% of all prenatal karyotypes.ConclusionPrenatal testing is now unequivocally in the genomic era. NIPS is now the screening test that precedes the majority of confirmed diagnoses of trisomy 21. The contributions of NIPS, early ultrasound, and chromosome microarray have led to unprecedented detection rates of major chromosome abnormalities, now found in 20% of all invasive tests.
- Published
- 2017
130. Prenatally detected de novo apparently balanced chromosomal rearrangements: the effect on maternal worry, family functioning and intent of disclosure
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Jane Halliday, Ingrid B. Sinnerbrink, Amanda Sherwen, Edwin P. Kirk, Elizabeth Evans, Felicity Rea, Elizabeth Waters, Bettina Meiser, David J. Amor, and Belinda Rahman
- Subjects
medicine.medical_specialty ,Pregnancy ,medicine.diagnostic_test ,business.industry ,media_common.quotation_subject ,Obstetrics and Gynecology ,Retrospective cohort study ,Prenatal diagnosis ,medicine.disease ,Mental health ,Clinical research ,medicine ,Anxiety ,medicine.symptom ,Worry ,Psychiatry ,business ,Genetics (clinical) ,Genetic testing ,media_common - Abstract
Objective This study aims to assess the impact of prenatal diagnosis of de novo apparently balanced chromosome rearrangements (ABCRs) on maternal stress, family functioning and maternal plans of disclosure of genetic information to their child. Methods All liveborn children with prenatally detected de novo ABCRs in two Australian states over a 10-year period (1994–2003) were retrospectively ascertained. Of 39 eligible cases, 16 (41%) participated in the study. Mothers of these children completed a questionnaire using standardized measures to assess family functioning, parental distress, parent–child interaction and child characteristics, with open-ended questions regarding disclosure. Results The majority of mothers appeared to experience normal levels of parenting stress, quality of parent–child interaction and healthy family functioning. However, most mothers recalled experiencing a significant degree of worry at the time of receiving their prenatal test results, and some mothers (4/15) reported receiving uncertain or conflicting results. Most mothers (13/15) conveyed an understanding of the importance of disclosing this genetic information to their child, and 12/15 conveyed their intention to make this disclosure. Conclusion Most mothers reported normal parenting stress and family functioning, despite experiencing significant worry upon receiving results. Some children are at risk of nondisclosure of their carrier status. © 2014 John Wiley & Sons, Ltd.
- Published
- 2014
131. Investigating the Vascular Phenotype of Subcutaneously and Orthotopically Propagated PC3 Prostate Cancer Xenografts Using Combined Carbogen Ultrasmall Superparamagnetic Iron Oxide MRI
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Simon P. Robinson, Lauren C.J. Baker, Yann Jamin, John C. Waterton, Jake S. Burrell, Jane Halliday, Simon Walker-Samuel, and Jessica K.R. Boult
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,tumor ,vasculature ,Hemodynamics ,Blood volume ,Ferric Compounds ,Neovascularization ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,In vivo ,Carbogen ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Particle Size ,Magnetite Nanoparticles ,Review Articles ,medicine.diagnostic_test ,Neovascularization, Pathologic ,business.industry ,ultrasmall superparamagnetic iron oxide ,Prostatic Neoplasms ,Magnetic resonance imaging ,Carbon Dioxide ,medicine.disease ,Magnetic Resonance Imaging ,3. Good health ,Oxygen ,Disease Models, Animal ,030104 developmental biology ,030220 oncology & carcinogenesis ,drug delivery ,Breathing ,Heterografts ,medicine.symptom ,business - Abstract
The aim of this study was to use the combined carbogen-ultrasmall superparamagnetic iron oxide (CUSPIO) magnetic resonance imaging (MRI) method, which uses spatial correlations in independent susceptibility imaging biomarkers, to investigate and compare the impact of tumor size and anatomical site on vascular structure and function in vivo. Mice bearing either subcutaneous or orthotopic PC3 LN3 prostate tumors were imaged at 7 T, using a multi-gradient echo sequence to quantify R2∗, before and during carbogen (95% O2/5% CO2) breathing, and subsequently following intravenous administration of USPIO particles. Carbogen and USPIO-induced changes in R2∗ were used to inform on hemodynamic vasculature and fractional blood volume (%), respectively. The CUSPIO imaging data were also segmented to identify and assess five categories of R2∗ response. Small and large subcutaneous and orthotopic tumor cohorts all exhibited significantly (P
- Published
- 2016
132. Effect of reduced pH on physiology and shell integrity of juvenileHaliotis iris(pāua) from New Zealand
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Bryce A. Peebles, Abigail M. Smith, Peter M. Marriott, N. Jane Halliday, and Vonda J. Cummings
- Subjects
0106 biological sciences ,010504 meteorology & atmospheric sciences ,Shell (structure) ,Juvenile ,lcsh:Medicine ,engineering.material ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Growth rate ,Dissolution ,0105 earth and related environmental sciences ,Calcite ,biology ,pH ,Ocean acidification ,010604 marine biology & hydrobiology ,General Neuroscience ,Aragonite ,lcsh:R ,General Medicine ,Haliotis iris ,Coastal marine ,biology.organism_classification ,chemistry ,Environmental chemistry ,engineering ,CO2 ,Seawater ,Mollusc ,General Agricultural and Biological Sciences - Abstract
The New Zealand pāua or black footed abalone,Haliotis iris, is one of many mollusc species at potential risk from ocean acidification and warming. To investigate possible impacts, juvenile pāua (~24 mm shell length) were grown for 4 months in seawater pH/pCO2conditions projected for 2100. End of century seawater projections (pHT7.66/pCO2~1,000 μatm) were contrasted with local ambient conditions (pHT8.00/pCO2~400 μatm) at two typical temperatures (13 and 15 °C). We used a combination of methods (morphometric, scanning electron microscopy, X-ray diffraction) to investigate effects on juvenile survival and growth, as well as shell mineralogy and integrity. Lowered pH did not affect survival, growth rate or condition, but animals grew significantly faster at the higher temperature. Juvenile pāua were able to biomineralise their inner nacreous aragonite layer and their outer prismatic calcite layer under end-of-century pH conditions, at both temperatures, and carbonate composition was not affected. There was some thickening of the nacre layer in the newly deposited shell with reduced pH and also at the higher temperature. Most obvious was post-depositional alteration of the shell under lowered pH: the prismatic calcite layer was thinner, and there was greater etching of the external shell surface; this dissolution was greater at the higher temperature. These results demonstrate the importance of even a small (2 °C) difference in temperature on growth and shell characteristics, and on modifying the effects at lowered pH. Projected CO2-related changes may affect shell quality of this iconic New Zealand mollusc through etching (dissolution) and thinning, with potential implications for resilience to physical stresses such as predation and wave action.
- Published
- 2019
133. Elevated LAG-3 Expression in the Tumor Microenvironement of Patients with DLBCL Is Associated with a Non-GCB Phenotype and Poor Prognosis
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Annette Hernadez, Clare Gould, Joshua W.D. Tobin, Sara Gabreilli, Santiyagu M. Savarimuthu Francis, Simone Birch, Soi Cheng Law, William Stevenson, Anthony J. Gill, Mark P. Hertzberg, Robert Bird, Emad Uddin Abro, Sanjiv Jain, Colm Keane, Dipti Talaulikar, Sarah-Jane Halliday, Donna Cross, Maher K. Gandhi, and Grace Gifford
- Subjects
0301 basic medicine ,Poor prognosis ,business.industry ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Phenotype ,03 medical and health sciences ,030104 developmental biology ,Cancer research ,Medicine ,business ,health care economics and organizations - Abstract
LAG3 is an immune checkpoint expressed on a variety of immune cells including a sub-population of 'exhausted' effector T cells and TREGs. Early-phase studies of anti-LAG3 mAb show promise in solid and haematological cancers. We have previously demonstrated LAG3 is enriched within the tumor microenvironment in Hodgkin Lymphoma (Gandhi et al. Blood 2006). Data in the aggressive B-cell lymphoma DLBCL is lacking. We used a conventional discovery/ validation approach in two population based Australian cohorts (discovery: Brisbane/Canberra; validation: Sydney) totalling 250 patients treated with R-CHOP with >4 year follow-up. Digital gene expression (NanoString) using a consistent LAG3 cut-off showed inferior 5-year overall survival (OS) in both cohorts (discovery: 54% vs. 82%, HR 3.13, p=0.003; validation: 63% vs. 86%, HR 2.95, p=0.025 respectively). In a multivariate model, LAG3HI(p=0.001) was a predictor of OS independent of R-IPI and Cell-of-Origin (by NanoString LST assay). PD-L1 expression was also a predictor of survival though to a lesser degree than LAG3. Notably, LAG3 expression stratified PD-L1HIpatients into two sub-groups with differential survival, with dual LAG3 and PD-L1 positivity conferring particularly poor OS (PD-L1HI/LAG3HI39% vs. 81% PD-L1HI/LAG3LO, HR 3.65, p=0.023). Next, the discovery/validation cohorts were combined with 129 additional DLBCL cases from the ALLG biobank (in whom tissue but no outcome data was available), to test for biological associations and correlations. In these 379 cases, LAG3HIwas enriched in the ABC/UC (66%) subtype vs. LAG3LO(p=0.003). LAG3 was positively correlated with numerous immune checkpoints/effectors including CD4, CD8, PD-1, PD-L1, PD-L2, TIM-3 and CD163 (all p LAG3 gene expression was highly correlated with protein expression by tissue microarray based immunohistochemistry (r=0.79, p Finally, levels of soluble LAG3 (sol-LAG3) were quantified within paired plasma of patients enrolled into the ALLG NHL21 PET-adapted prospective DLBCL study. Samples taken pre-therapy and following 4 cycles of R-CHOP (at the time of interim-PET) were compared. Sol-LAG3 levels were higher in patients with DLBCL at diagnosis compared to healthy controls (p In conclusion, high expression of LAG3 in DLBCL is enriched in the non-GCB phenotype, and is associated with poor outcome independent of clinical and biological prognosticators. Dual PD-L1HI/LAG3HIexpression confers particularly poor outcome after conventional front-line immuno-chemotherapy. Intratumoral LAG3 expression is high on PD-1+ CD8+ and TREG subsets. Sol-LAG3 appears to a circulating disease response biomarker. The results combined indicate a key role for LAG3 within the immunobiology of DLBCL and provide a strong rationale for early phase clinical trials utilising anti-LAG3 and anti-PD1 mAb combinations. Disclosures Keane: BMS: Research Funding; Roche: Other: Education Support, Speakers Bureau; Celgene: Consultancy, Research Funding; Takeda: Other: Educational Meeting; Merck: Consultancy. Gould:Novo Nordisk: Other: Educational Travel. Abro:Novartis: Consultancy; Amgen: Other: education support congress attendance; Janssen: Other: education support congress attendance; Bristol-Myers Squibb: Speakers Bureau; Celgene: Other: education support congress attendance. Tobin:Celgene: Research Funding; Amgen: Other: Educational Travel. Birch:Medadvance: Equity Ownership. Talaulikar:Novartis: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Takeda: Research Funding; Roche: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria. Bird:Amgen, Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hertzberg:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees. Gandhi:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Takeda: Honoraria; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding.
- Published
- 2018
134. A Critical Role for Intratumoral and Circulating LAG3 in Classical Hodgkin Lymphoma: Analysis from the Rathl Prospective Phase III International Clinical Trial
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Richard A. Anderson, Donna Cross, Joshua W.D. Tobin, Jay Gunawardana, Colm Keane, Simone Birch, Sarah-Jane Halliday, Judith Trotman, Muhammed B. Sabdia, Leanne Berkahn, Emad Uddin Abro, Annette Hernandez, Soi Cheng Law, Devinder Gill, Robert Bird, Anne L Saunderson, W P Law, Maher K. Gandhi, Peter Johnson, and Michael J. Fulham
- Subjects
Oncology ,Clinical trial ,medicine.medical_specialty ,LAG3 ,business.industry ,Internal medicine ,Immunology ,medicine ,Classical Hodgkin lymphoma ,Cell Biology ,Hematology ,business ,Biochemistry - Abstract
In classical Hodgkin lymphoma (CHL) the tumor microenvironment (TME) is enriched in T cells that modulate antitumor immunity. PD1 blockade partially restores anti-tumoral T cell function, to induce impressive responses in a proportion of patients with relapsed/refractory CHL (Chen et al JCO 2017). Further characterisation of T cell immune evasion mechanisms in CHL will permit the rational development of enhanced immunotherapeutic strategies. Lymphocyte-activation gene 3 (LAG3) is a cell surface molecule known to be expressed on a subset of immune effector T cells and intratumoral regulatory T cells (Tregs) in solid-organ tumors, with combination PD1/LAG3 mAb blockade showing early promise (Ascierto et al 2017 JCO abst 9520). In contrast, data in haematological malignancies is limited, although it is known that LAG3+ T cells suppress anti-tumoral immunity in CHL and B-CLL (Gandhi et al Blood 2006; Shapiro et al Haematologica 2017). Interestingly, in B-CLL LAG3 is found on both T cells and malignant B cells. Whether Hodgkin Reed-Sternberg (HRS) cells express LAG3 is unknown. To characterise in detail intratumoral and circulating LAG3 in CHL we used a conventional discovery / validation approach. The local institutional discovery cohort was drawn from Princess Alexandra Hospital in Brisbane (Australia), and validated in samples from the prospective randomised phase III international "RATHL" trial (Johnson et al NEJM 2016). Firstly, LAG3 gene expression (GEP) was digitally quantified by NanoString in FFPE tissues in the discovery cohort and compared to normal control nodes and DLBCL tissues. Normalised LAG3 mRNA counts were 5-10-fold higher in CHL than in controls (P < 0.001) and 3-5-fold higher than in DLBCL (P < 0.001), whereas PD1 and TIM3 mRNA counts did not differ. In CHL samples LAG3 mRNA counts were markedly increased compared to PD-1 axis molecules and TIM3 (P < 0.001) (Figure 1a). Higher levels of LAG3 mRNA counts were correlated with infiltration by T cells (CD4 r = 0.55; P < 0.00001; CD8 r = 0.51, P < 0.0001), and macrophages (CD68 r = 0.45; P = 0.002). Findings were replicated in the RATHL cohort. Next, intratumoral LAG3 cellular distribution was established. Flow cytometry was used to quantify LAG3 in T cell subsets and CD30+CD3- HRS cells in 6 de-aggregated freshly frozen CHL nodes (TILs). LAG3 was evenly distributed between CD8+ T cells, CD127LOCD25HI natural-Tregs (nTregs) and CD127LOCD25LO induced-Tregs (iTregs), but with minimal expression on CD4 non-Tregs, with the latter constituting the majority of intratumoral T cells. LAG3+ T cells typically co-expressed PD1 and/or TIM3. LAG3 was expressed on CD30+CD3+ cells but not on CD30+CD3- cells, consistent with LAG3 expression on activated T cells. Multispectral immunofluorescence (mIF) image analysis confirmed these findings in histological tumor samples (Figure 1b). Also, there was negligible expression of LAG3 on HRS-lines. Finally, the potential role of soluble LAG3 (sLAG3) as a rapid-turnaround circulating biomarker applicable to the routine diagnostic laboratory, was assessed in serum samples using the MSD R-PLEX assay. In the discovery cohort sLAG3 was 3-4-fold increased at pre-therapy compared to controls and 3-6M post-therapy serum (P = 0.001). Results from pre-therapy RATHL serum samples were similar (P < 0.05). Notably in RATHL samples at interim restaging after 2 ABVD cycles sLAG3 had reduced by ~5-fold compared to pre-therapy (P < 0.0001) in patients with PET/CT responsive disease (Figures 1 c + d). Twelve months post therapy sLAG remained significantly lower than pre-therapy (P < 0.05) and was equivalent to control samples. Pre-therapy serum sLAG3 demonstrated a modest correlation with tissue LAG3 mRNA counts (r = 0.45; P = 0.02). In conclusion in CHL, LAG3 mRNA expression was markedly increased relative to control and DLBCL tissues. Within CHL tissues LAG3 mRNA was markedly increased compared to other immune checkpoint molecules. Interrogation of the TME using flow cytometry of TILs and mIF demonstrated LAG3 is evenly distributed between CD8+, nTregs and iTRreg. In tumor samples we did not find evidence of LAG3 expression on HRS cells. To our knowledge this is the first study to demonstrate sLAG3 as a cell free circulating disease response biomarker in CHL. Taken together these findings provide a convincing rationale for further exploration of single and/or combined checkpoint blockade incorporating LAG3 inhibition to treat CHL. Disclosures Abro: Bristol-Myers Squibb: Speakers Bureau; Janssen: Other: education support congress attendance; Celgene: Other: education support congress attendance; Novartis: Consultancy; Amgen: Other: education support congress attendance. Keane:BMS: Research Funding; Roche: Other: Education Support, Speakers Bureau; Celgene: Consultancy, Research Funding; Takeda: Other: Educational Meeting; Merck: Consultancy. Birch:Medadvance: Equity Ownership. Tobin:Amgen: Other: Educational Travel; Celgene: Research Funding. Johnson:Kite: Consultancy; Celgene: Honoraria; Eisai: Research Funding; Incyte: Consultancy; Takeda: Honoraria, Travel, accommodations, expenses; Janssen: Consultancy, Research Funding; Genmab: Consultancy; Novartis: Honoraria; Zenyaku Kogyo: Other: Travel, accommodations, expenses; Bristol-Myers Squibb: Honoraria; Boeringher Ingelheim: Consultancy; Epizyme: Consultancy, Honoraria, Research Funding. Trotman:F. Hoffman-La Roche: Other: Travel to meeting, Unremunerated member of Ad Board, Research Funding; PCYC: Research Funding; Janssen: Other: Unremunerated member of Ad Board, Research Funding; Takeda: Other: Unremunerated member of Ad Board; Celgene: Other: Unremunerated member of Ad Board, Research Funding; Beigene: Research Funding. Bird:Amgen, Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gill:Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau. Gandhi:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Takeda: Honoraria; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding.
- Published
- 2018
135. OC02.01: The evolution of ultrasound-indicated prenatal diagnosis over the past two decades: a state-wide retrospective cohort study from 1994-2016
- Author
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Lisa Hui, A Poulton, Emily Lostchuck, and Jane Halliday
- Subjects
Pediatrics ,medicine.medical_specialty ,Reproductive Medicine ,Radiological and Ultrasound Technology ,business.industry ,Ultrasound ,medicine ,Obstetrics and Gynecology ,Radiology, Nuclear Medicine and imaging ,Retrospective cohort study ,Prenatal diagnosis ,General Medicine ,business - Published
- 2018
136. Long-term health and development of children diagnosed prenatally with a de novo apparently balanced chromosomal rearrangement
- Author
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Edwin P. Kirk, Elizabeth Waters, Jane Halliday, Belinda Rahman, Amanda Sherwen, Elizabeth Evans, Bettina Meiser, Ingrid B. Sinnerbrink, Felicity Rea, and David J. Amor
- Subjects
Pediatrics ,medicine.medical_specialty ,education.field_of_study ,Pregnancy ,business.industry ,Population ,MEDLINE ,Obstetrics and Gynecology ,Prenatal diagnosis ,Retrospective cohort study ,medicine.disease ,Mental health ,Child development ,Test (assessment) ,medicine ,education ,business ,Genetics (clinical) - Abstract
Objective This study aimed to determine if liveborn children with prenatally detected de novo apparently balanced chromosome rearrangements (ABCR) have more long-term health, developmental or behavioural concerns compared with children in a normal Australian population. Methods This was a retrospective ascertainment of all liveborn children with prenatally detected de novo ABCRs in two Australian states over a 10-year period (1994–2003). Child health, development and behaviour were assessed by maternal report using standardised measures; educational ability and achievement were measured by direct child assessment. Data were compared with relevant population norms, and one sample t-test performed to test for statistical differences. Results Of 39 eligible cases, 16 (41%) participated in the study. One child (6%) was born with a congenital anomaly, and two children (12.5%) reported a chronic health concern. Compared with population norms, no significant differences were observed with respect to intelligence, mental health, child development and educational ability; children had significantly higher scores indicative of better functioning on bodily pain, social–emotional behaviour and physical functioning. No child satisfied the criteria for having a special health care need. Conclusion Children in this study with a prenatally detected de novo ABCR have similar long-term health, developmental and behavioural outcomes compared with population norms. © 2013 John Wiley & Sons, Ltd.
- Published
- 2013
137. Constitutive and Relative Facultative Skin Pigmentation among Victorian Children Including Comparison of Two Visual Skin Charts for Determining Constitutive Melanin Density
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Robyn M. Lucas, Jane Halliday, Justine A. Ellis, William Siero, Angela Pezic, Terence Dwyer, Christine Rodda, Anne-Louise Ponsonby, and Fergus J. Cameron
- Subjects
Male ,medicine.medical_specialty ,Victoria ,Ultraviolet Rays ,Skin Pigmentation ,Absorption (skin) ,Biology ,Biochemistry ,White People ,vitamin D deficiency ,Melanin ,Asian People ,Eye color ,medicine ,Humans ,Nevus ,Physical and Theoretical Chemistry ,Child ,Hair Color ,Ultraviolet radiation ,Skin ,Melanins ,Sunlight ,Nevus, Pigmented ,Facultative ,Eye Color ,integumentary system ,General Medicine ,medicine.disease ,Dermatology ,Phenotype ,Spectrophotometry ,Child, Preschool ,Female ,sense organs - Abstract
Our aim was to examine the association between ethnicity, phenotype, sun behavior and other characteristics, and constitutive and relative facultative skin pigmentation. A total of 191 participants were recruited, with a mean age of 7.6 years (SD 3.4), during 2009-2011 from Maternal and Child Health Centres (MCHC) and schools in Melbourne, Australia. Parental questionnaire data were obtained on sun behavior and examination consisted of noting the child's natural skin, hair and eye color, ethnicity, nevi count and spectrophotometric melanin density (MD). Constitutive skin pigmentation was estimated from buttock MD. Relative facultative skin pigmentation was estimated by hand compared with buttock absorption. Ethnicity, hair color and skin color were associated with constitutive and facultative skin pigmentation on univariate analysis. Higher ambient ultraviolet radiation (UVR) in the past month, greater freckling, greater nevi and increased sun exposure over the past year were related to darker facultative skin pigmentation. Sun exposure over the life course was not. The two skin charts accounted for 39.7% and 21.4% of buttock MD, respectively. Relative facultative skin pigmentation is associated with recent UVR levels, not life-course sun exposure. Relative facultative skin pigmentation may not be a useful measure of sun exposure over the early life course. Skin color charts can be used to assess constitutive skin pigmentation if spectrophotometry is not available.
- Published
- 2013
138. Exploring ΔR2* and ΔR1as imaging biomarkers of tumor oxygenation
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Jake S. Burrell, Jane Halliday, Simon P. Robinson, Yann Jamin, Simon Walker-Samuel, John C. Waterton, Jessica K.R. Boult, and Lauren C.J. Baker
- Subjects
medicine.diagnostic_test ,Tumor hypoxia ,business.industry ,Magnetic resonance imaging ,Oxygen–haemoglobin dissociation curve ,Oxygenation ,Hypoxia (medical) ,Tumor Oxygenation ,Carbogen ,medicine ,Radiology, Nuclear Medicine and imaging ,Carbogen Breathing ,medicine.symptom ,Nuclear medicine ,business - Abstract
PURPOSE: To investigate the combined use of hyperoxia-induced ?R(2) * and ?R(1) as a noninvasive imaging biomarker of tumor hypoxia. MATERIALS AND METHODS: MRI was performed on rat GH3 prolactinomas (n = 6) and human PC3 prostate xenografts (n = 6) propagated in nude mice. multiple gradient echo and inversion recovery truefisp images were acquired from identical transverse slices to quantify tumor R(2) * and R(1) before and during carbogen (95% O(2) /5% CO(2) ) challenge, and correlates of ?R(2) * and ?R(1) assessed. RESULTS: Mean baseline R(2) * and R(1) were 119 � 7 s(-1) and 0.6 � 0.03 s(-1) for GH3 prolactinomas and 77 � 12 s(-1) and 0.7 � 0.02 s(-1) for PC3 xenografts, respectively. During carbogen breathing, mean ?R(2) * and ?R(1) were -20 � 8 s(-1) and 0.08 � 0.03 s(-1) for GH3 and -0.5 � 1 s(-1) and 0.2 � 0.08 s(-1) for the PC3 tumors, respectively. A pronounced relationship between ?R(2) * and ?R(1) was revealed. CONCLUSION: Considering the blood oxygen-hemoglobin dissociation curve, fast R(2) * suggested that GH3 prolactinomas were more hypoxic at baseline, and their carbogen response dominated by increased hemoglobin oxygenation, evidenced by highly negative ?R(2) *. PC3 tumors were less hypoxic at baseline, and their response to carbogen dominated by increased dissolved oxygen, evidenced by highly positive ?R(1) . Because the two biomarkers are sensitive to different oxygenation ranges, the combination of ?R(2) * and ?R(1) may better characterize tumor hypoxia than each alone. J. Magn. Reson. Imaging 2013;. � 2013 Wiley Periodicals, Inc.
- Published
- 2013
139. Why Do People Choose Not to Have Screening for Hemochromatosis?
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Jane Halliday, Amy Nisselle, Michelle Wolthuizen, Katie Allen, MaryAnne Aitken, Sylvia A Metcalfe, and Martin B. Delatycki
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Male ,medicine.medical_specialty ,Iron ,MEDLINE ,Blood Donors ,Session (web analytics) ,Surveys and Questionnaires ,Epidemiology ,medicine ,Humans ,Mass Screening ,Genetic Testing ,Workplace ,Genetics (clinical) ,Hemochromatosis ,Genetic testing ,medicine.diagnostic_test ,business.industry ,Iron levels ,General Medicine ,Iron blood ,medicine.disease ,Early Diagnosis ,Blood donor ,Family medicine ,Physical therapy ,Female ,business - Abstract
Hemochromatosis is a common disorder of iron overload most commonly due to homozogosity for the HFE C282Y substitution. A workplace-screening program was conducted in which over 11,000 individuals were screened for this mutation. A substudy of this project was to ascertain why people chose not to attend information and screening sessions offered in their workplace.Staff were recruited by email, questionnaires in common areas, and direct approach. A purpose-designed questionnaire sought the reasons for not attending information and screening sessions.The nonattender questionnaire was distributed at 24 workplaces and completed by 872 individuals. The most common reason for not attending sessions, accounting for 70.1%, was practical (e.g., unaware of session, too busy, or unavailable). Other relatively common reasons were that the individual had low iron levels or were a blood donor (14.9%), or that hemochromatosis was considered unimportant (12.2%). Insurance concerns were very rarely cited as the reason for nonattendance (1.0%).The nonattender data presented here indicate that concerns about insurance, anxiety, and use of genetic information are not major factors for why people did not attend workplace information and screening sessions for hereditary hemochromatosis. Practical barriers were the major reasons identified. This highlights that when implementing screening programs, as many practical barriers as possible need to be overcome, so that a maximum number of people who would like to be informed about screening are given the opportunity to do so.
- Published
- 2013
140. MRI measurements of vessel calibre in tumour xenografts: Comparison with vascular corrosion casting
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Yann Jamin, Robert S. Bradley, Simon Walker-Samuel, Jessica K.R. Boult, Jake S. Burrell, John C. Waterton, Lauren C.J. Baker, Jane Halliday, Philip J. Withers, and Simon P. Robinson
- Subjects
Pathology ,medicine.medical_specialty ,Time Factors ,X-ray microtomography ,Imaging biomarker ,Vascular Disrupting Agent ZD6126 ,Mice, Nude ,Corrosion Casting ,Biochemistry ,Article ,030218 nuclear medicine & medical imaging ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Organophosphorus Compounds ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,ZD6126 ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,X-Ray Microtomography ,Cell Biology ,Magnetic Resonance Imaging ,3. Good health ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Female ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Neoplasm Transplantation ,Blood vessel - Abstract
Vessel size index (Rv, μm) has been proposed as a quantitative magnetic resonance imaging (MRI) derived imaging biomarker in oncology, for the non-invasive assessment of tumour blood vessel architecture and vascular targeted therapies. Appropriate pre-clinical evaluation of Rv in animal tumour models will improve the interpretation and guide the introduction of the biomarker into clinical studies. The objective of this study was to compare Rv measured in vivo with vessel size measurements from high-resolution X-ray computed tomography (μCT) of vascular corrosion casts measured post mortem from the same tumours, with and without vascular targeted therapy. MRI measurements were first acquired from subcutaneous SW1222 colorectal xenografts in mice following treatment with 0 (n = 6), 30 (n = 6) or 200 mg/kg (n = 3) of the vascular disrupting agent ZD6126. The mice were then immediately infused with a low viscosity resin and, following polymerisation and maceration of surrounding tissues, the resulting tumour vascular casts were dissected and subsequently imaged using an optimised μCT imaging approach. Vessel diameters were not measurable by μCT in the 200 mg/kg group as the high dose of ZD6126 precluded delivery of the resin to the tumour vascular bed. The mean Rv for the three treatment groups was 24, 23 and 23.5 μm respectively; the corresponding μCT measurements from corrosion casts from the 0 and 30 mg/kg cohorts were 25 and 28 μm. The strong association between the in vivo MRI and post mortem μCT values supports the use of Rv as an imaging biomarker in clinical trials of investigational vascular targeted therapies., Highlights ► Non-invasive quantitation of vessel calibre in tumour xenografts in vivo ► Assessment of tumour vessel calibre response to a vascular disrupting agent ► Generation of vascular corrosion casts from the same tumours imaged by MRI ► Quantitation of vessel calibre from corrosion casts by microCT ► Excellent agreement between the in vivo MRI and post mortem microCT vessel calibres
- Published
- 2012
141. Psychosocial and behavioral impact of breast cancer risk assessed by testing for common risk variants: protocol of a prospective study
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Jane Halliday, Tatiane Yanes, Tony Roscioli, Bettina Meiser, Mary-Anne Young, Rajneesh Kaur, Gillian Mitchell, Paul A. James, and Kristine Barlow-Stewart
- Subjects
0301 basic medicine ,Adult ,Cancer Research ,medicine.medical_specialty ,Genetic counseling ,Translational research ,Breast Neoplasms ,Genetic Counseling ,030105 genetics & heredity ,lcsh:RC254-282 ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Study Protocol ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Single nucleotide polymorphism (SNP) ,Surveys and Questionnaires ,Behavioral outcomes ,Genetics ,medicine ,Humans ,Prospective Studies ,Family history ,Prospective cohort study ,Genomic testing ,Aged ,Genetic counselling ,business.industry ,Polygenic risk ,Australia ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Clinical trial ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,Physical therapy ,Female ,Personalized medicine ,business ,Psychosocial ,New Zealand - Abstract
Background The ‘common variant, common disease’ model predicts that a significant component of hereditary breast cancer unexplained by pathogenic variants in moderate or high-penetrance genes is due to the cumulative effect of common risk variants in DNA (polygenic risk). Assessing a woman’s breast cancer risk by testing for common risk variants can provide useful information for women who would otherwise receive uninformative results by traditional monogenic testing. Despite increasing support for the utility of common risk variants in hereditary breast cancer, research findings have not yet been integrated into clinical practice. Translational research is therefore critical to ensure results are effectively communicated, and that women do not experience undue adverse psychological outcomes. Methods In this prospective study, 400 women with a personal and/or high risk family history of breast cancer will be recruited from six familial cancer centers (FCCs) in Australia. Eligible women will be invited to attend a FCC and receive their personal polygenic risk result for breast cancer. Genetic health professionals participating in the study will receive training on the return of polygenic risk information and a training manual and visual aids will be developed to facilitate patient communication. Participants will complete up to three self-administered questionnaires over a 12-months period to assess the short-and long-term psychological and behavioral outcomes of receiving or not receiving their personal polygenic risk result. Discussion This is the world’s first study to assess the psychological and behavioral impact of offering polygenic risk information to women from families at high risk of breast cancer. Findings from this research will provide the basis for the development of a new service model to provide polygenic risk information in familial cancer clinics. Trial registration The study was retrospectively registered on 27th April 2017 with the Australian and New Zealand Clinical Trials Group (Registration no: ACTRN12617000594325; clinical trial URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372743). Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3485-0) contains supplementary material, which is available to authorized users.
- Published
- 2016
142. Evaluation of novel combined carbogen USPIO (CUSPIO) imaging biomarkers in assessing the antiangiogenic effects of cediranib (AZD2171) in rat C6 gliomas
- Author
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Simon Walker-Samuel, Anderson J. Ryan, John C. Waterton, Simon P. Robinson, Jane Halliday, Jessica K.R. Boult, Lauren C.J. Baker, Yann Jamin, and Jake S. Burrell
- Subjects
Male ,Radiation-Sensitizing Agents ,Cancer Research ,Pathology ,medicine.medical_specialty ,Contrast Media ,Hemodynamics ,Angiogenesis Inhibitors ,Biology ,Cediranib ,Rats, Nude ,Carbogen ,Glioma ,Biomarkers, Tumor ,Tumor Cells, Cultured ,medicine ,Animals ,Magnetite Nanoparticles ,Fluorescent Dyes ,medicine.diagnostic_test ,Tumor hypoxia ,Dextrans ,Magnetic resonance imaging ,Hypoxia (medical) ,medicine.disease ,Magnetic Resonance Imaging ,Rats ,Oncology ,Nitroimidazoles ,Quinazolines ,Benzimidazoles ,medicine.symptom ,Perfusion ,medicine.drug - Abstract
The recently described combined carbogen USPIO (CUSPIO) magnetic resonance imaging (MRI) method uses spatial correlations in independent imaging biomarkers to assess specific components of tumor vascular structure and function. Our study aimed to evaluate CUSPIO biomarkers for the assessment of tumor response to antiangiogenic therapy. CUSPIO imaging was performed in subcutaneous rat C6 gliomas before and 2 days after treatment with the potent VEGF-signaling inhibitor cediranib (n = 12), or vehicle (n = 12). Histological validation of Hoechst 33342 uptake (perfusion), smooth muscle actin staining (maturation), pimonidazole adduct formation (hypoxia) and necrosis were sought. Following treatment, there was a significant decrease in fractional blood volume (-43%, p < 0.01) and a significant increase in hemodynamic vascular functionality (treatment alteredδ R 2* carbogen from 1.2 to -0.2 s -1, p < 0.05). CUSPIO imaging revealed an overall significant decrease in plasma perfusion (-27%, p < 0.05) following cediranib treatment, that was associated with selective effects on immature blood vessels. The CUSPIO responses were associated with a significant 15% reduction in Hoechst 33342 uptake (p < 0.05), but no significant difference in vascular maturation or necrosis. Additionally, treatment with cediranib resulted in a significant 40% increase in tumor hypoxia (p < 0.05). The CUSPIO imaging method provides novel and more specific biomarkers of tumor vessel maturity and vascular hemodynamics, and their response to VEGF-signaling inhibition, compared to current MR imaging biomarkers utilized in the clinic. Such biomarkers may prove effective in longitudinally monitoring tumor vascular remodeling and/or evasive resistance in response to antiangiogenic therapy. © 2011 UICC.
- Published
- 2016
143. Use of the Brainlab Disposable Stylet for endoscope and peel-away navigation
- Author
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Ian Kamaly and Jane Halliday
- Subjects
medicine.medical_specialty ,Neuronavigation ,Endoscope ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Child ,medicine.diagnostic_test ,business.industry ,Neuroendoscopes ,Endoscopy ,Surgical Instruments ,Spinal surgery ,Surgery ,Stylet ,030220 oncology & carcinogenesis ,Neurology (clinical) ,business ,Fenestration ,Software ,Biomedical engineering - Abstract
Neuronavigation, the ability to perform real-time intra-operative guidance during cranial and/or spinal surgery, has increased both accuracy and safety in neurosurgery [2]. Cranial navigation of existing surgical instruments using Brainlab requires the use of an instrument adapter and clamp, which in our experience renders an endoscope ‘top-heavy’, difficult to manipulate, and the process of registration of the adapter quite time-consuming. A Brainlab Disposable Stylet was used to navigate fenestration of an entrapped temporal horn in a pediatric case. Accuracy was determined by target visualization relative to neuronavigation targeting. Accuracy was also calculated using basic trigonometry to establish the maximum tool tip inaccuracy for the disposible stylet inserted into a peel-away (Codman) and endoscope. The Brainlab Disposable Stylet was easier to use, more versatile, and as accurate as use of an instrument adapter and clamp. The maximum tool-tip inaccuracy for the endoscope was 0.967 mm, and the Codman peel-away 0.489 mm. A literature review did not reveal any reports of use of the Brainlab Disposable Stylet in this way, and we are unaware of this being used in common neurosurgical practice. We would recommend this technique in endoscopic cases that require use of Brainlab navigation.
- Published
- 2016
144. Spatially dense morphometrics of craniofacial sexual dimorphism in 1-year-olds
- Author
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Ine Saey, Tony Penington, Jane Halliday, Evelyn Muggli, Harold Matthews, and Peter Claes
- Subjects
0301 basic medicine ,Male ,Histology ,Population ,Sexing ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Imaging, Three-Dimensional ,Image Interpretation, Computer-Assisted ,Humans ,Craniofacial ,Least-Squares Analysis ,education ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Morphometrics ,education.field_of_study ,Sex Characteristics ,Crania ,Skull ,Infant ,030206 dentistry ,Cell Biology ,Anatomy ,Original Articles ,biology.organism_classification ,Sexual dimorphism ,030104 developmental biology ,Evolutionary biology ,Face ,Female ,Allometry ,Algorithms ,Developmental Biology ,Sex characteristics - Abstract
Recent advances in the field of geometric morphometrics allow for powerful statistical hypothesis testing for effects of biological and environmental variables on anatomical shape. This study used partial least-squares regression (PLSR) and the recently developed bootstrapped response-based imputation modelling (BRIM) algorithm to test for sexual dimorphism in the craniofacial shape of 1-year-old humans. We observed a recession of the forehead in boys relative to girls, and differences in the nose, consistent with adult dimorphism. Results also suggest that the degree to which individuals express dimorphic traits is continuous throughout the population. This is also seen in adult dimorphism but in 1-year-olds the amount of overlap between groups is much higher, indicating the strength of dimorphism between sexes is lower. Our results demonstrate early sexual dimorphism that is not attributable to the influx of sex hormones at puberty. This highlights the need to look at very early ontogeny for the origins of sexual dimorphism. We suggest that future work look at potential mediating effects of this early dimorphism on the later impact of puberty. The subtle shape differences we have detected, may also be applied to sexing fossilised crania. A common artefact in 3D images of faces of young children is that they often have their mouths open to varying degrees, introducing variability in the data unrelated to anatomy. We describe two PLSR-based methods of correcting this. These methods may facilitate surgical planning and assessment of young children based on 3D images.
- Published
- 2016
145. Response of HT29 colorectal xenograft model to cediranib assessed with 18 F-fluoromisonidazole positron emission tomography, dynamic contrast-enhanced and diffusion-weighted MRI
- Author
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Sean Carlin, Louisa Bokacheva, Carl Le, Khushali Kotedia, Megan Reese, Sally-Ann Ricketts, Jane Halliday, and Jason A. Koutcher
- Subjects
CD31 ,medicine.diagnostic_test ,business.industry ,Gadolinium ,chemistry.chemical_element ,Cediranib ,chemistry ,Positron emission tomography ,Dynamic contrast-enhanced MRI ,medicine ,Molecular Medicine ,Effective diffusion coefficient ,Radiology, Nuclear Medicine and imaging ,Nuclear medicine ,business ,Perfusion ,Spectroscopy ,Diffusion MRI ,medicine.drug - Abstract
Cediranib (AZD2171, AstraZeneca, UK) is a small-molecule pan-VEGFR inhibitor. The tumor response to short-term cediranib treatment was studied using dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI at 7 T as well as 18F-fluoromisonidazle (18F-FMISO) PET and histological markers. Rats bearing subcutaneous HT29 human colorectal tumors were imaged at baseline, then received three doses of cediranib (3 mg/kg per dose daily) or vehicle (dosed daily), with follow up imaging performed 2 hours after the final cediranib or vehicle dose. Tumors were excised and evaluated for the perfusion marker Hoechst 33342, endothelial cell marker CD31, smooth muscle actin (SMA), intercapillary distance (ICD) and tumor necrosis. DCE-MRI-derived parameters decreased significantly in cediranib-treated tumors relative to pre-treatment values: the muscle-normalized initial area under the gadolinium concentration curve (nIAUC90) by 48% (p = 0.002), the enhancing fraction (EnF) by 43% (p = 0.003) and Ktrans by 57% (p = 0.003), but remained unchanged in controls. No change between pre- and post-treatment tumor apparent diffusion coefficient (ADC) in either cediranib- or vehicle-treated group was observed over the course of this study. 18F-FMISO SUVmean decreased by 33% (p = 0.008) in the cediranib group, but showed no significant change in the control group. Histological analysis showed that the number of CD31-positive vessels (59 per mm2), the fraction of SMA-positive vessels (80 to 87%) and ICD (0.17 mm) were similar in cediranib- and vehicle-treated groups. The fraction of perfused blood vessels in cediranib-treated tumors (81±7%) was lower than in vehicle controls (91±3%, p = 0.02). The necrotic fraction was slightly higher in cediranib-treated rats (34±12%) than in controls (26±10%, p = 0.23). These findings suggest that short-term treatment with cediranib causes a decrease of tumor perfusion/permeability across the tumor cross-section, but changes in vascular morphology, vessel density or tumor cellularity do not manifest at this early time point.
- Published
- 2012
146. Outcomes of singleton births after blastocyst versus nonblastocyst transfer in assisted reproductive technology
- Author
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David L. Healy, Dhanushi Thilakshana Fernando, Sue Breheny, and Jane Halliday
- Subjects
Adult ,medicine.medical_specialty ,Time Factors ,Reproductive Techniques, Assisted ,Victoria ,Cleavage Stage, Ovum ,medicine.medical_treatment ,Fertilization in Vitro ,Risk Assessment ,Intracytoplasmic sperm injection ,Embryo Culture Techniques ,Pregnancy ,Risk Factors ,Odds Ratio ,medicine ,Humans ,Sperm Injections, Intracytoplasmic ,reproductive and urinary physiology ,Retrospective Studies ,Gynecology ,Chi-Square Distribution ,Placental abruption ,Antepartum hemorrhage ,Obstetrics ,business.industry ,Infant, Newborn ,Obstetrics and Gynecology ,Gestational age ,Embryo Transfer ,medicine.disease ,Placenta previa ,Pregnancy Complications ,Logistic Models ,Treatment Outcome ,Reproductive Medicine ,Multivariate Analysis ,embryonic structures ,Small for gestational age ,Female ,business ,Live birth ,Live Birth - Abstract
Objective To compare obstetric and perinatal outcomes of singleton births after assisted reproductive technology (ART) with blastocyst transfer (days 5 to 6) versus nonblastocyst transfer (days 2 to 4). Design Retrospective cohort study. Setting Monash IVF. Patient(s) 4,202 women who conceived using in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) between 2004 and 2009. Intervention(s) Records analysis of fresh and frozen-thawed embryo transfers resulting in singleton births of at least 20 weeks' gestation. Main Outcome Measure(s) Perinatal outcomes: preterm birth, low birthweight, very low birthweight, small for gestational age, large for gestational age, preeclampsia, antepartum hemorrhage, placental abruption, placenta previa, and postpartum hemorrhage; and covariates: maternal age, year of birth of the baby, private health insurance status, maternal body mass index, smoking status, parity, gender of baby, and variations in treatment procedures. Result(s) Multivariate analysis found no statistically significant difference between transfers on days 5 and 6 and days 2 and 4 for all maternal and perinatal outcomes. There were modest increases in the adjusted odds ratios for preeclampsia (adjusted odds ratio 1.72, 99% confidence interval 0.93–3.20) and placenta previa (1.65, 0.92–2.98). Conclusion(s) Obstetric and perinatal outcomes after blastocyst transfer on days 5 to 6 are similar when compared with embryo cleavage-stage transfers on days 2 to 4.
- Published
- 2012
147. Comparisons of the Efficacy of a Jak1/2 Inhibitor (AZD1480) with a VEGF Signaling Inhibitor (Cediranib) and Sham Treatments in Mouse Tumors Using DCE-MRI, DW-MRI, and Histology
- Author
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Deborah Lawson, John C. Gore, Dennis Huszar, John C. Waterton, Thomas E. Yankeelov, Mary E. Loveless, Michael Collins, Jane Halliday, Murali V P Nadella, and Corinne Reimer
- Subjects
CD31 ,Cancer Research ,medicine.medical_specialty ,Pathology ,Imaging biomarker ,Angiogenesis ,Urology ,H&E stain ,Mice, Nude ,lcsh:RC254-282 ,Cediranib ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Enzyme Inhibitors ,030304 developmental biology ,0303 health sciences ,business.industry ,Histology ,Janus Kinase 1 ,Neoplasms, Experimental ,Janus Kinase 2 ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Magnetic Resonance Imaging ,Xenograft Model Antitumor Assays ,3. Good health ,Vascular endothelial growth factor ,Pyrimidines ,chemistry ,030220 oncology & carcinogenesis ,Quinazolines ,Pyrazoles ,Female ,Histopathology ,business ,Research Article ,medicine.drug - Abstract
Jak1/2 inhibition suppresses STAT3 phosphorylation that is characteristic of many cancers. Activated STAT3 promotes the transcription of factors that enhance tumor growth, survival, and angiogenesis. AZD1480 is a novel small molecule inhibitor of Jak1/2, which is a key mediator of STAT3 activation. This study examined the use of diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) biomarkers in assessing early tumor response to AZD1480. Cediranib (AZD2171), a vascular endothelial growth factor signaling inhibitor, was used as a comparator. Thirty mice were injected with Calu-6 lung cancer cells and randomized into the three treatment groups: AZD1480, cediranib, and sham. DW-MRI and DCE-MRI protocols were performed at baseline and at days 3 and 5 after treatment. The percent change from baseline measurements for K(trans), ADC, and v(e) were calculated and compared with hematoxylin and eosin (H&E), CD31, cParp, and Ki-67 histology data. Decreases in K(trans) of 29% (P < .05) and 53% (P < .05) were observed at days 3 and 5, respectively, for the cediranib group. No significant changes in K(trans) occurred for the AZD1480 group, but a significant increase in ADC was demonstrated at days 3 (63%, P < .05) and 5 (49%, P < .05). CD31 staining indicated diminished vasculature in the cediranib group, whereas significantly increased cParp staining for apoptotic activity and extracellular space by image analysis of H&E were present in the AZD1480 group. These imaging biomarker changes, and corresponding histopathology, support the use of ADC, but not K(trans), as a pharmacodynamic biomarker of response to AZD1480 at these time points.
- Published
- 2012
148. The relationship between common patterns of prenatal alcohol exposure and neurodevelopment in two-year old children
- Author
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Jane Halliday, Peter J. Anderson, Jeffrey M. Craig, Sharon Lewis, Colleen O'Leary, Della Forster, Cate Nagle, Evi Muggli, Susan Donath, and Elizabeth J Elliott
- Subjects
Pediatrics ,medicine.medical_specialty ,Pregnancy ,animal structures ,business.industry ,media_common.quotation_subject ,Breastfeeding ,Cognition ,Abstinence ,medicine.disease ,Child development ,Prenatal alcohol exposure ,Pediatrics, Perinatology and Child Health ,Cohort ,medicine ,business ,Motor skill ,media_common ,Clinical psychology - Abstract
Background: Around 60% of women drink some alcohol while pregnant. There is conflicting evidence on the effect on the fetus of common patterns of prenatal alcohol exposure (PAE) e.g. low level or sporadic drinking. Guidelines recommend abstinence as the safest option, creating problems for those advising women who drink at these levels before pregnancy recognition or beyond. The Asking QUestions about Alcohol (AQUA) study aimed to accurately measure PAE and account for important cofactors, to reduce uncertainty about child outcomes. Method: Detailed data on PAE were prospectively collected in a pre-birth cohort of over 1500 mother/child dyads. There was also extensive data collection of predictors of child development at one and two-year's post-partum. A sub-group of children was followed up at two years of age with a neurodevelopmental assessment (Bayley III). Two-step multivariable regression analyses of an effect of PAE accounted for independent risk factors that related to 1) pregnancy, including sociodemographic, psychologic and lifestyle variables such as diet and supplement use, and 2) the postnatal care-giving environment, including breastfeeding and maternal psychological wellbeing. Results: Adjustment for independent risk factors ameliorated any putative associations between PAE and cognitive, language and motor development in 554 two year-old children spread evenly across six PAE groups. Conclusions: Assessing neurodevelopmental outcomes associated with PAE is strongly influenced by other modifiable and non-modifiable risk factors. Although we found no adverse neurodevelopmental outcomes at two years of age, follow-up will be necessary in these children when complex higher-level cognitive, language and motor skills are required.
- Published
- 2017
149. Acardia
- Author
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Zhu Li, John C. Carey, Leonora Luna Muñoz, Marcia L. Feldkamp, Lorenzo D. Botto, Emanuele Leoncini, Hermien E. K. de Walle, R. Brian Lowry, Pierpaolo Mastroiacovo, María Luisa Martínez-Frías, Maurizio Clementi, Lisa Marengo, Margery Morgan, Paul Merlob, Annukka Ritvanen, Emmanuelle Amar, Anke Rissmann, Eduardo E. Castilla, Guido Cocchi, Gioacchino Scarano, Jane Halliday, and Reproductive Origins of Adult Health and Disease (ROAHD)
- Subjects
Male ,Pediatrics ,TRISOMY-2 ,International Cooperation ,twin reversed-arterial perfusion sequence ,Epidemiology ,Prevalence ,Registries ,Genetics (clinical) ,High rate ,medicine.diagnostic_test ,Europe ,COTWIN ,Lifestyle factors ,PREGNANCY ,Population Surveillance ,Cohort ,Female ,epidemiology ,Pregnancy, Multiple ,Maternal Age ,Adult ,Heart Defects, Congenital ,China ,medicine.medical_specialty ,FETUS ,twinning ,MONOZYGOTIC TWINS ,acephalus ,TRAP sequence ,INDUCED OVULATION ,Congenital Abnormalities ,Young Adult ,Diseases in Twins ,Genetics ,medicine ,Humans ,Genetic testing ,Anencephaly ,Pregnancy ,business.industry ,CHORIONICITY ,Australia ,Infant, Newborn ,Twins, Monozygotic ,acardia ,medicine.disease ,Epidemiologic Studies ,malformation ,ARTERIAL PERFUSION SEQUENCE ,Etiology ,CLOMIPHENE ,Americas ,Epidemiologic data ,business - Abstract
Acardia is a severe, complex malformation of monozygotic twinning, but beyond clinical case series, very few epidemiologic data are available. The goals of this study were to assess the epidemiologic characteristics of acardia from birth defect registries in the International Clearinghouse for Birth Defects Surveillance and Research (Clearinghouse), and compare these findings to current literature. The study included 17 surveillance programs of the Clearinghouse representing 23 countries from North and South America, Europe, China, and Australia. Anonymized individual records with clinical and demographic data were reviewed centrally by clinical geneticists. A literature search was performed. A total of 164 cases of acardia were reported from an underlying cohort of 21.2 million births. Of these, 23% were elective pregnancy terminations. Rates did not vary significantly by maternal age. For many cases, information on pregnancy exposures and genetic testing was missing. However, these limited data did not suggest high rates of chronic illnesses (diabetes, seizure disorders) or lifestyle factors such as smoking. One case had trisomy 13. Major malformations were reported in 2.4% of co-twins. With some basic assumptions, the total prevalence of acardia was estimated at 1 in 50,000-70,000 births, and 1 in 200-280 monozygotic twins. In summary, acardia is a dramatic, probably underreported, and incompletely understood malformation. Studies on its epidemiology and etiology are challenging and still rare. An international collaboration of epidemiologists, clinicians, and geneticists is necessary to understand the etiology, pathogenesis, and occurrence of this severe malformation complex. (C) 2011 Wiley Periodicals, Inc.
- Published
- 2011
150. A quantitative comparison of the influence of individual versus population-derived vascular input functions on dynamic contrast enhanced-MRI in small animals
- Author
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Jane Halliday, Jennifer G. Whisenant, John C. Waterton, John C. Gore, Carsten Liess, Richard D. Dortch, Lei Xu, Mary E. Loveless, and Thomas E. Yankeelov
- Subjects
education.field_of_study ,medicine.diagnostic_test ,business.industry ,viruses ,media_common.quotation_subject ,Population ,Magnetic resonance imaging ,computer.software_genre ,Precontrast ,Concordance correlation coefficient ,Nuclear magnetic resonance ,Voxel ,Region of interest ,Dynamic contrast-enhanced MRI ,medicine ,Contrast (vision) ,Radiology, Nuclear Medicine and imaging ,Nuclear medicine ,business ,education ,computer ,media_common - Abstract
For quantitative analysis of dynamic contrast enhanced magnetic resonance imaging data, the time course of the concentration of the contrast agent in the blood plasma, or vascular input function (VIF), is required. We compared pharmacokinetic parameters derived using individual and population-based VIFs in mice for two different contrast agents, gadopentetate dimeglumine and P846. Eleven mice with subcutaneous 4T(1) breast cancer xenografts were imaged at 7 T. A precontrast T(1) map was acquired along with dynamic T(1) -weighted gradient echo images before, during, and after a bolus injection of contrast agent delivered via a syringe pump. Each animal's individual VIF and derived population-averaged VIF were used to extract parameters from the signal-time curves of tumor tissue at both the region of interest and voxel level. The results indicate that for both contrast agents, K(trans) values estimated using population-averaged VIF have a high correlation (concordance correlation coefficient > 0.85) with K(trans) values estimated using individual VIF on both a region of interest and voxel level. This work supports the validity of using of a population-based VIF with a stringent injection protocol in preclinical dynamic contrast enhanced magnetic resonance imaging studies.
- Published
- 2011
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