Obstetrics and Gynaecology - Research Publications

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    Sexual identity and mental health in young people: an opportunity to reduce health inequity
    Borschmann, R ; Marino, J (Elsevier, 2019)
    One in every 25 Britons aged 16–24 years identifies as lesbian, gay, or bisexual. 1 Cross-sectional studies consistently report that sexual-minority young people have poorer mental health profiles than their heterosexual peers, 2 including higher prevalence of self-harm and suicide attempts. 3 However, without longitudinal data to document changes over time, these findings are of little clinical utility.
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    Non-rhinovirus enteroviruses associated with respiratory infections in Peru (2005-2010)
    Huaman, JL ; Carrion, G ; Ampuero, JS ; Gomez, J ; Ocana, V ; Paz, I ; Gomez, E ; Chavez, E ; Sarmiento, F ; Pozo, E ; Laguna-Torres, VA ; Halsey, ES (BMC, 2014-09-22)
    BACKGROUND: Enteroviruses (EVs) are a common cause of respiratory tract infections and are classified into seven species (EVA-D and rhinoviruses [RHVs] A-C) with more than 200 different serotypes. Little is known about the role of non-RHV EVs in respiratory infections in South America. The aim of this study was to describe the epidemiology of non-RHV EVs detected in patients with influenza-like illness enrolled in a passive surveillance network in Peru. METHODS: Throat swabs and epidemiological data were collected from participants after obtaining verbal consent. Viral isolation was performed in cell culture and identified by immunofluorescence assay. Serotype identification of EV isolates was performed using commercial monoclonal antibodies. Identification of non-serotypeable isolations was carried out by reverse transcriptase-PCR, followed by sequencing. RESULTS: Between 2005 and 2010, 24,239 samples were analyzed, and 9,973 (41.1%) possessed at least one respiratory virus. EVs were found in 175 samples (0.7%). Our results revealed a clear predominance of EVB species, 90.9% (159/175). No EVDs were isolated. The mean and median ages of EV-positive subjects were 9.1 and 4.0 years, respectively, much younger than the population sampled, 17.6 and 12.0 years. Sixteen serotypes were identified, four EVA, 11 EVB, and one EVC species. The most common serotypes were coxsackievirus B1, coxsackievirus B2, coxsackievirus B5, and coxsackievirus B3. CONCLUSION: This study provides data about the serotypes of EVs circulating in Peru and sets the need for further studies.
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    Streamlined genetic education is effective in preparing women newly diagnosed with breast cancer for decision making about treatment-focused genetic testing: a randomized controlled noninferiority trial
    Quinn, VF ; Meiser, B ; Kirk, J ; Tucker, KM ; Watts, KJ ; Rahman, B ; Peate, M ; Saunders, C ; Geelhoed, E ; Gleeson, M ; Barlow-Stewart, K ; Field, M ; Harris, M ; Antill, YC ; Cicciarelli, L ; Crowe, K ; Bowen, MT ; Mitchell, G (NATURE PUBLISHING GROUP, 2017-04)
    PURPOSE: Increasingly, women newly diagnosed with breast cancer are being offered treatment-focused genetic testing (TFGT). As the demand for TFGT increases, streamlined methods of genetic education are needed. METHODS: In this noninferiority trial, women aged <50 years with either a strong family history (FH+) or other features suggestive of a germ-line mutation (FH-) were randomized before definitive breast cancer surgery to receive TFGT education either as brief written materials (intervention group (IG)) or during a genetic counseling session at a familial cancer clinic (usual-care group (UCG)). Women completed self-report questionnaires at four time points over 12 months. RESULTS: A total of 135 women were included in the analysis, all of whom opted for TFGT. Decisional conflict about TFGT choice (primary outcome) was not inferior in the IG compared with the UCG (noninferiority margin of -10; mean difference = 2.45; 95% confidence interval -2.87-7.76; P = 0.36). Costs per woman counseled in the IG were significantly lower (AUD$89) compared with the UCG (AUD$173; t(115) = 6.02; P < 0.001). CONCLUSION: A streamlined model of educating women newly diagnosed with breast cancer about TFGT seems to be a cost-effective way of delivering education while ensuring that women feel informed and supported in their decision making, thus freeing resources for other women to access TFGT.Genet Med 19 4, 448-456.
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    Pulmonary hemodynamic responses to in utero ventilation in very immature fetal sheep
    Allison, BJ ; Crossley, KJ ; Flecknoe, SJ ; Morley, CJ ; Polglase, GR ; Hooper, SB (BIOMED CENTRAL LTD, 2010-08-19)
    BACKGROUND: The onset of ventilation at birth decreases pulmonary vascular resistance (PVR) resulting in a large increase in pulmonary blood flow (PBF). As the large cross sectional area of the pulmonary vascular bed develops late in gestation, we have investigated whether the ventilation-induced increase in PBF is reduced in immature lungs. METHODS: Surgery was performed in fetal sheep at 105 d GA (n = 7; term ~147 d) to insert an endotracheal tube, which was connected to a neonatal ventilation circuit, and a transonic flow probe was placed around the left pulmonary artery. At 110 d GA, fetuses (n = 7) were ventilated in utero (IUV) for 12 hrs while continuous measurements of PBF were made, fetuses were allowed to develop in utero for a further 7 days following ventilation. RESULTS: PBF changes were highly variable between animals, increasing from 12.2 ± 6.6 mL/min to a maximum of 78.1 ± 23.1 mL/min in four fetuses after 10 minutes of ventilation. In the remaining three fetuses, little change in PBF was measured in response to IUV. The increases in PBF measured in responding fetuses were not sustained throughout the ventilation period and by 2 hrs of IUV had returned to pre-IUV control values. DISCUSSION AND CONCLUSION: Ventilation of very immature fetal sheep in utero increased PBF in 57% of fetuses but this increase was not sustained for more than 2 hrs, despite continuing ventilation. Immature lungs can increase PBF during ventilation, however, the present studies show these changes are transient and highly variable.
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    Prediction of hepatitis C virus interferon/ribavirin therapy outcome based on viral nucleotide attributes using machine learning algorithms.
    KayvanJoo, AH ; Ebrahimi, M ; Haqshenas, G (Springer Science and Business Media LLC, 2014-08-23)
    BACKGROUND: Hepatitis C virus (HCV) causes chronic hepatitis C in 2-3% of world population and remains one of the health threatening human viruses, worldwide. In the absence of an effective vaccine, therapeutic approach is the only option to combat hepatitis C. Interferon-alpha (IFN-alpha) and ribavirin (RBV) combination alone or in combination with recently introduced new direct-acting antivirals (DAA) is used to treat patients infected with HCV. The present study utilized feature selection methods (Gini Index, Chi Squared and machine learning algorithms) and other bioinformatics tools to identify genetic determinants of therapy outcome within the entire HCV nucleotide sequence. RESULTS: Using combination of several algorithms, the present study performed a comprehensive bioinformatics analysis and identified several nucleotide attributes within the full-length nucleotide sequences of HCV subtypes 1a and 1b that correlated with treatment outcome. Feature selection algorithms identified several nucleotide features (e.g. count of hydrogen and CG). Combination of algorithms utilized the selected nucleotide attributes and predicted HCV subtypes 1a and 1b therapy responders from non-responders with an accuracy of 75.00% and 85.00%, respectively. In addition, therapy responders and relapsers were categorized with an accuracy of 82.50% and 84.17%, respectively. Based on the identified attributes, decision trees were induced to differentiate different therapy response groups. CONCLUSIONS: The present study identified new genetic markers that potentially impact the outcome of hepatitis C treatment. In addition, the results suggest new viral genomic attributes that might influence the outcome of IFN-mediated immune response to HCV infection.
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    Subverting Host Cell P21-Activated Kinase: A Case of Convergent Evolution across Pathogens.
    John Von Freyend, S ; Kwok-Schuelein, T ; Netter, HJ ; Haqshenas, G ; Semblat, J-P ; Doerig, C (MDPI AG, 2017-04-21)
    Intracellular pathogens have evolved a wide range of strategies to not only escape from the immune systems of their hosts, but also to directly exploit a variety of host factors to facilitate the infection process. One such strategy is to subvert host cell signalling pathways to the advantage of the pathogen. Recent research has highlighted that the human serine/threonine kinase PAK, or p21-activated kinase, is a central component of host-pathogen interactions in many infection systems involving viruses, bacteria, and eukaryotic pathogens. PAK paralogues are found in most mammalian tissues, where they play vital roles in a wide range of functions. The role of PAKs in cell proliferation and survival, and their involvement in a number of cancers, is of great interest in the context of drug discovery. In this review we discuss the latest insights into the surprisingly central role human PAK1 plays for the infection by such different infectious disease agents as viruses, bacteria, and parasitic protists. It is our intention to open serious discussion on the applicability of PAK inhibitors for the treatment, not only of neoplastic diseases, which is currently the primary objective of drug discovery research targeting these enzymes, but also of a wide range of infectious diseases.
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    Breast milk donation after neonatal death in Australia: a report.
    Carroll, KE ; Lenne, BS ; McEgan, K ; Opie, G ; Amir, LH ; Bredemeyer, S ; Hartmann, B ; Jones, R ; Koorts, P ; McConachy, H ; Mumford, P ; Polverino, J (Springer Science and Business Media LLC, 2014)
    Lactation and breast milk can hold great value and meaning for grieving mothers who have experienced a recent death of an infant. Donation to a human milk bank (HMB) as an alternative to discarding breast milk is one means of respecting the value of breast milk. There is little research, national policy discussion, or organizational representation in Australia on the subject of breast milk donation after infant death. On 29 November 2013 the Mercy Hospital for Women in Melbourne, Australia hosted Australia's first National Stakeholder Meeting (NSM) on the topic of milk donation after neonatal death. The NSM drew together representatives from Australian HMBs, neonatal intensive care units (NICUs) currently using donor human milk, and Australia's chief NICU parent support organization. The NSM was video-recorded and transcribed, and analyzed thematically by researchers. This article reports the seven dominant themes discussed by stakeholders during the NSM: the spectrum of women's lactation and donation experiences after infant death; the roles of the HMB and NICU in meeting the needs of the bereaved donor; how bereaved mothers' lactation autonomy may interface with a HMB's donation guidelines; how milk donation may be discussed with bereaved mothers; the variation between four categories of milk donation after neonatal death; the impact of limited resources and few HMBs on providing donation programs for bereaved mothers in Australia. This article provides evidence from researchers and practitioners that can assist HMB staff in refining their bank's policy on milk donation after infant death, and provides national policy makers with key considerations to support lactation, human milk banking, and bereavement services nation-wide.
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    Prenatal alcohol exposure and infant gross motor development: a prospective cohort study (vol 19, 149, 2019)
    Hutchinson, D ; Youssef, GJ ; McCormack, C ; Wilson, J ; Allsop, S ; Najman, J ; Elliott, E ; Burns, L ; Jacobs, S ; Honan, I ; Rossen, L ; Fiedler, H ; Teague, S ; Ryan, J ; Olsson, CA ; Mattick, RP (BMC, 2019-07-04)
    Following publication of the original article [1], the authors opted to revise the first paragraph of the section "Characteristics associated with maternal drinking in pregnancy". Below is the updated version.
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    Perinatal Maternal Mental Health, Fetal Programming and Child Development
    Lewis, AJ ; Austin, E ; Knapp, R ; Vaiano, T ; Galbally, M (MDPI, 2015-12)
    Maternal mental disorders over pregnancy show a clear influence on child development. This review is focused on the possible mechanisms by which maternal mental disorders influence fetal development via programming effects. This field is complex since mental health symptoms during pregnancy vary in type, timing and severity and maternal psychological distress is often accompanied by higher rates of smoking, alcohol use, poor diet and lifestyle. Studies are now beginning to examine fetal programming mechanisms, originally identified within the DOHaD framework, to examine how maternal mental disorders impact fetal development. Such mechanisms include hormonal priming effects such as elevated maternal glucocorticoids, alteration of placental function and perfusion, and epigenetic mechanisms. To date, mostly high prevalence mental disorders such as depression and anxiety have been investigated, but few studies employ diagnostic measures, and there is very little research examining the impact of maternal mental disorders such as schizophrenia, bipolar disorder, eating disorders and personality disorders on fetal development. The next wave of longitudinal studies need to focus on specific hypotheses driven by plausible biological mechanisms for fetal programming and follow children for a sufficient period in order to examine the early manifestations of developmental vulnerability. Intervention studies can then be targeted to altering these mechanisms of intergenerational transmission once identified.