Disparities in integrating non-invasive prenatal testing into antenatal healthcare in Australia: a survey of healthcare professionals.

BACKGROUND: Non-invasive prenatal testing (NIPT) has been clinically available in Australia on a user-pays basis since 2012. There are numerous providers, with available tests ranging from targeted NIPT (only trisomies 21, 18, and 13 +/- sex chromosome aneuploidy) to genome-wide NIPT. While NIPT is being implemented in the public health care systems of other countries, in Australia, the implementation of NIPT has proceeded without public funding. The aim of this study was to investigate how NIPT has been integrated into antenatal care across Australia and reveal the successes and challenges in its implementation in this context. METHODS: An anonymous online survey was conducted from September to October 2022. Invitations to participate were sent to healthcare professionals (HCPs) involved in the provision of NIPT in Australia through professional society mailing lists and networks. Participants were asked questions on their knowledge of NIPT, delivery of NIPT, and post-test management of results. RESULTS: A total of 475 HCPs responded, comprising 232 (48.8%) obstetricians, 167 (35.2%) general practitioners, 32 (6.7%) midwives, and 44 (9.3%) genetic specialists. NIPT was most commonly offered as a first-tier test, with most HCPs (n = 279; 60.3%) offering it to patients as a choice between NIPT and combined first-trimester screening. Fifty-three percent (n = 245) of respondents always offered patients a choice between NIPT for the common autosomal trisomies and expanded (including genome-wide) NIPT. This choice was understood as supporting patient autonomy and informed consent. Cost was seen as a major barrier to access to NIPT, for both targeted and expanded tests. Equitable access, increasing time demands on HCPs, and staying up to date with advances were frequently reported as major challenges in delivering NIPT. CONCLUSIONS: Our findings demonstrate substantial variation in the clinical implementation of NIPT in Australia, including in the offers of expanded screening options. After a decade of clinical use, Australian clinicians still report ongoing challenges in the clinical and equitable provision of NIPT.

Regulating non-invasive prenatal testing (NIPT) for fetal sex determination.

Non-invasive prenatal testing (NIPT) can be used to determine the chromosomal sex of the fetus at an early stage in a pregnancy. The use of NIPT for fetal sex determination raises concerns about potential selective termination of pregnancy by prospective parents who desire a child of a particular sex. Although sex selection for medical reasons is generally accepted, non-medical sex selection (NMSS) has been the subject of considerable controversy. In this article, we explore the current regulatory landscape around reproductive genetic testing techniques that may lead to NMSS, both internationally and within Australia. Specifically, we contrast the approach to regulating preimplantation genetic testing (PGT) with the minimal regulation of NIPT in Australia as a case study for reform. We examine ethical concerns raised in relation to NMSS, which form the basis of the current moratorium on the use of PGT for NMSS. We then highlight some key differences between using PGT for NMSS and NIPT for fetal sex determination to determine whether access to the latter should be regulated and, if so, how. We conclude that there is insufficient evidence to restrict access to NIPT for fetal sex determination and, based on our Australian case study, recommend a facilitative approach to regulating NIPT that would support individuals to make informed reproductive decisions.

Parent-Implemented Telepractice Autism Intervention: A Case Study of Maintenance and Generalization.

The extent to which people maintain new skills and generalize those skills to new contexts without support are two aspects of intervention research that can be difficult to examine, especially over a sustained period of time and across a variety of contexts. In past research, we have explored teaching parents and caregivers to implement evidence-based communication strategies with their young children with autism who are minimally verbal. When a former research participant contacted us with a request to participate in our project again, four years later and with a different son, we used this as an opportunity to ask questions about her maintenance of the skills in using the targeted strategies, and her generalization of those skills to a different child. Using the data collected with her older son, Ali, and new data collected four years later with her younger son, Rami, we present a case study of this mother. We discuss the implications of the findings on interpreting the efficacy of the telepractice intervention's programming for generalization, identifying opportunities for refining the intervention, and insights useful for other intervention research.

Ethical issues associated with prenatal screening using non-invasive prenatal testing for sex chromosome aneuploidy.

Prenatal screening for sex chromosome aneuploidies (SCAs) is increasingly available through expanded non-invasive prenatal testing (NIPT). NIPT for SCAs raises complex ethical issues for clinical providers, prospective parents and future children. This paper discusses the ethical issues that arise around NIPT for SCAs and current guidelines and protocols for management. The first section outlines current practice and the limitations of NIPT for SCAs. It then outlines key guidelines before discussing the ethical issues raised by this use of NIPT. We conclude that while screening for SCAs should be made available for people seeking to use NIPT, its implementation requires careful consideration of what, when and how information is provided to users.

Judicial Discomfort over 'Innovative' Treatment for Adolescents with Gender Dysphoria.

Medical treatment for adolescents with gender dysphoria has attracted considerable attention in recent years, with continuing court involvement in Australia and recent judicial review proceedings in the UK. In Re Imogen [No 6], the Family Court of Australia held that an application to the Family Court is mandatory if a parent or a medical practitioner of an adolescent diagnosed with gender dysphoria disputes the diagnosis, the adolescent's capacity to consent, or the proposed treatment. In this article, we examine the Family Court's rationale for preserving its welfare jurisdiction in gender dysphoria cases. We analyse case law developments in Australia and more recently in the UK and identify a thread of judicial discomfort in gender dysphoria jurisprudence about adolescents consenting to medical treatment that the court perceives to be 'innovative', 'experimental', 'unique', or 'controversial'. We explore whether treatment for gender dysphoria can be characterised as 'innovative' and identify four factors that appear to be influencing courts in Australia and the UK. We also consider how such a characterisation might impact (if at all) on an adolescent's capacity to consent to gender dysphoria treatment. We critique the ongoing role of courts in these cases and recommend a robust decision-making framework for gender dysphoria treatment to minimise court involvement in the future.

A Successful Kindergarten Transition for Children with Disabilities: Collaboration Throughout the Process.

The transition to kindergarten can be a memorable, yet stressful time for children and families. For children with disabilities and their caregivers, the transition to kindergarten can be especially difficult due to changes in environment, supports, and services that occur as part of the transition. The purpose of this article is to highlight specific practices and strategies that can enhance collaboration throughout the transition to kindergarten. Fictional vignettes are used to describe the perspectives of, and also the practices and strategies used by, members of an education team as they support a child with a disability and her caregiver. Readers are provided with examples of practices and planning tools that can be used to support children with disabilities throughout the transition to kindergarten process. High-intensity transition practices and strategies that can be used before, during, and after kindergarten transition are specifically highlighted. Additionally, the need for both preschool and kindergarten collaboration and support is emphasized. Supplementary Information: The online version contains supplementary material available at 10.1007/s10643-021-01246-6.

Fetal information as shared information: using NIPT to test for adult-onset conditions.

The possibilities of non-invasive prenatal testing (NIPT) are expanding, and the use of NIPT for adult-onset conditions may become widely available in the near future. If parents use NIPT to test for these conditions, and the pregnancy is continued, they will have information about the child's genetic predisposition from birth. In this paper, we argue that prospective parents should be able to access NIPT for an adult-onset condition, even when they have no intention to terminate the pregnancy. We begin by outlining the arguments against testing in such a situation, which generally apply the same considerations that apply in the predictive testing of a minor to the fetus in utero. We then contend, firstly, that there are important practical considerations that support availability of testing for prospective parents regardless of their stated intentions. Secondly, we object to the ethical equation of a fetus in utero with a minor. We base our analysis on a view of pregnancy that conceptualises the fetus as a part of the gestational parent, as opposed to the more common 'container' model of pregnancy. We suggest that fetal information is best conceptualised as shared information between the gestational parent and future child. Thus, it should be approached in similar ways as other kinds of shared information (such as genetic information with implications for family members), where a person has a claim over their own information, but should be encouraged to consider the interests of other relevant parties.

Re Imogen: the role of the Family Court of Australia in disputes over gender dysphoria treatment.

This article examines Re Imogen (No 6) (2020) 61 Fam LR 344, a decision of the Family Court of Australia, which held that an application to the Family Court is mandatory if a parent or a medical practitioner of a child or adolescent diagnosed with gender dysphoria disputes the diagnosis, the capacity to consent, or the proposed treatment. First, we explain the regulatory framework for the medical treatment of gender dysphoria in children and adolescents, including the development of the welfare jurisdiction under Section 67ZC of the Family Law Act 1975 (Cth). We then provide an overview of the Re Imogen decision, and discuss the balancing exercise involved in determining a child's best interests in the medical treatment context. We challenge the Family Court's conclusion that, in relation to a dispute about diagnosis or treatment, a finding that the child or adolescent is Gillick competent to consent to treatment is not determinative, and the Family Court must determine the dispute. We argue that this conclusion represents an unjustified incursion into the right of Gillick competent transgender children and adolescents to make decisions about their own bodies and identities, and that the protective role of parents and the Family Court cannot justify interfering with their bodily autonomy in this context. Finally, we propose an alternative regulatory framework that removes the Family Court from the medical treatment process for gender dysphoria in circumstances of dispute between a parent and their Gillick competent child.

The role of the Mental Health Tribunal in setting duration of compulsory treatment in Victoria.

This article explores the role of the Mental Health Tribunal (the Tribunal) in setting duration of compulsory treatment orders under the Mental Health Act 2014 (Vic) (the MH Act) using qualitative analysis of data obtained by a Tribunal working group. It explores the extent to which there is a difference between the duration of treatment orders requested by treating teams and those made by the Tribunal, as well as the factors the Tribunal takes into account in setting a different duration. Results reveal the Tribunal made a treatment order of different (mostly shorter) duration in one out of five hearings. In these cases, two out of four factors identified by the working group were dominant influences: (1) ensuring congruence with the principles of the MH Act; and (2) information presented by one or more participants at the hearing. There were also high levels of attendance from either the patient, their support person or their legal representative when the Tribunal made a treatment order of different duration. This suggests participation by patients and support people at hearings provides the Tribunal with the information it needs to consider the principles under the MH Act meaningfully when exercising its discretion to determine the duration of compulsory treatment orders.

Development and validation of a real-time microelectrochemical sensor for clinical monitoring of tissue oxygenation/perfusion.

Oxygen is of critical importance to tissue viability and there is increasing demand for its reliable real-time clinical monitoring in order to prevent, diagnose, and treat several pathological disorders, including hypoxia, stroke and reperfusion injury. Herein we report the development and characterisation of a prototype clinical O2 sensor, and its validation in vivo, including proof-of-concept monitoring in patients undergoing surgery for carpal tunnel release. An integrated platinum-based microelectrochemical device was custom designed and controlled using a miniaturised telemetry-operated single channel clinical potentiostat. The in vitro performance of different sensor configurations is presented, with the best sensor design (S2) displaying appropriate linearity (R2 = 0.994) and sensitivity (0.569 ± 0.022 nA µM-1). Pre-clinical validation of S2 was performed in the hind limb muscle of anaesthetised rats; tourniquet application resulted in a significant rapid decrease in signal (90 ± 27%, [ΔO2] ca. 140 ± 18 µM), with a return to baseline within a period of ca. 3 min following tourniquet release. Similar trends were observed in the clinical study; an immediate decrease in signal (39 ± 3%, [ΔO2] ca. 30 ± 20 µM), with basal levels re-established within 2 min of tourniquet release. These results confirm that continuous real-time monitoring of dynamic changes in tissue O2 can serve as an indicator of reperfusion status in patients undergoing carpal tunnel surgery, and suggests the potential usefulness of the developed microelectrochemical sensor for other medical conditions where clinical monitoring of O2 and perfusion is important.

Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKCß/Mitochondrial Oxidant Signaling.

Pulmonary vasoconstriction resulting from intermittent hypoxia (IH) contributes to pulmonary hypertension (pHTN) in patients with sleep apnea (SA), although the mechanisms involved remain poorly understood. Based on prior studies in patients with SA and animal models of SA, the objective of this study was to evaluate the role of PKCß and mitochondrial reactive oxygen species (mitoROS) in mediating enhanced pulmonary vasoconstrictor reactivity after IH. We hypothesized that PKCß mediates vasoconstriction through interaction with the scaffolding protein PICK1 (protein interacting with C kinase 1), activation of mitochondrial ATP-sensitive potassium channels (mitoKATP), and stimulated production of mitoROS. We further hypothesized that this signaling axis mediates enhanced vasoconstriction and pHTN after IH. Rats were exposed to IH or sham conditions (7 h/d, 4 wk). Chronic oral administration of the antioxidant Tempol or the PKCß inhibitor LY-333531 abolished IH-induced increases in right ventricular systolic pressure and right ventricular hypertrophy. Furthermore, scavengers of O2- or mitoROS prevented enhanced PKCß-dependent vasoconstrictor reactivity to endothelin-1 in pulmonary arteries from IH rats. In addition, this PKCß/mitoROS signaling pathway could be stimulated by the PKC activator PMA in pulmonary arteries from control rats, and in both rat and human pulmonary arterial smooth muscle cells. These responses to PMA were attenuated by inhibition of mitoKATP or PICK1. Subcellular fractionation and proximity ligation assays further demonstrated that PKCß acutely translocates to mitochondria upon stimulation and associates with PICK1. We conclude that a PKCß/mitoROS signaling axis contributes to enhanced vasoconstriction and pHTN after IH. Furthermore, PKCß mediates pulmonary vasoconstriction through interaction with PICK1, activation of mitoKATP, and subsequent mitoROS generation.

The Discriminatory Legal Barrier of Partner Consent in Victorian ART Law: EHT18 v Melbourne IVF.

In September 2018, the Federal Court of Australia found that a Victorian woman did not need her estranged husband's consent to undergo in vitro fertilisation treatment (IVF) using donor sperm. The woman, who was 45 years of age, made an urgent application to the Court for permission to undergo IVF using donor sperm. In a single judge ruling, Griffiths J held that the requirement in the Assisted Reproductive Treatment Act 2008 (Vic) ('ART Act') for a married woman to obtain the consent of her husband discriminated against the woman in question on the basis of her marital status in contravention of the Commonwealth Sex Discrimination Act 1984 (Cth) ('SD Act'). His Honour declared the Victorian law in this instance 'invalid and inoperable' by operation of section 109 of the Commonwealth Constitution to the extent it was inconsistent with the Commonwealth law. Although the declarations by the Federal Court were limited in their terms to the circumstances of the case, the judgment raises broader issues about equity of access to assisted reproductive treatment (ART) in Victoria. The issue of partner consent as a barrier to access to ART was specifically raised by an independent review of the ART Act in Victoria. The Victorian Government released an interim report late last year as a first stage of the review, which canvasses some options for reform. This raises a broader question as to whether prescriptive legislation imposing detailed access requirements for ART is necessary or even helpful.

Legality of Embryonic Gene Editing in Australia.

The CRISPR-cas9 genome editing system (CRISPR) has been used to make precise and heritable changes to a diverse range of animals. The use of CRISPR to edit embryonic cells initially raised widespread criticism and calls for an international ban. However, the rapid development of genome editing has prompted governments around the world to review the regulatory frameworks that oversee genetic technologies. In Australia, the Prohibition of Human Cloning for Reproduction Act 2002 (Cth) and the Research Involving Human Embryos Act 2002 (Cth) expressly regulate the use of genome editing in early human embryos. This article analyses how these two Acts regulate research involving CRISPR and the implications of this for research practices in Australia. We argue that, given the current regulatory uncertainty around the legality of genome editing research in Australia, legislative reform is needed and propose reforms to provide greater clarity in this area.

Comparing Non-Medical Sex Selection and Saviour Sibling Selection in the Case of JS and LS v Patient Review Panel: Beyond the Welfare of the Child?

The national ethical guidelines relevant to assisted reproductive technology (ART) have recently been reviewed by the National Health and Medical Research Council (NHMRC). The review process paid particular attention to the issue of non-medical sex selection, although ultimately, the updated ethical guidelines maintain the pre-consultation position of a prohibition on non-medical sex selection. Whilst this recent review process provided a public forum for debate and discussion of this ethically contentious issue, the Victorian case of JS and LS v Patient Review Panel (Health and Privacy) [2011] VCAT 856 provides a rare instance where the prohibition on non-medical sex selection has been explored by a court or tribunal in Australia. This paper analyses the reasoning in that decision, focusing specifically on how the Victorian Civil and Administrative Tribunal applied the statutory framework relevant to ART and its comparison to other uses of embryo selection technologies. The Tribunal relied heavily upon the welfare-of-the-child principle under the Assisted Reproductive Treatment Act 2008 (Vic). The Tribunal also compared non-medical sex selection with saviour sibling selection (that is, where a child is purposely conceived as a matched tissue donor for an existing child of the family). Our analysis leads us to conclude that the Tribunal's reasoning fails to adequately justify the denial of the applicants' request to utilize ART services to select the sex of their prospective child.

Actin polymerization contributes to enhanced pulmonary vasoconstrictor reactivity after chronic hypoxia.

Chronic hypoxia (CH) augments basal and endothelin-1 (ET-1)-induced pulmonary vasoconstrictor reactivity through reactive oxygen species (ROS) generation and RhoA/Rho kinase (ROCK)-dependent myofilament Ca2+ sensitization. Because ROCK promotes actin polymerization and the actin cytoskeleton regulates smooth muscle tension, we hypothesized that actin polymerization is required for enhanced basal and ET-1-dependent vasoconstriction after CH. To test this hypothesis, both end points were monitored in pressurized, endothelium-disrupted pulmonary arteries (fourth-fifth order) from control and CH (4 wk at 0.5 atm) rats. The actin polymerization inhibitors cytochalasin and latrunculin attenuated both basal and ET-1-induced vasoconstriction only in CH vessels. To test whether CH directly alters the arterial actin profile, we measured filamentous actin (F-actin)-to-globular actin (G-actin) ratios by fluorescent labeling of F-actin and G-actin in fixed pulmonary arteries and actin sedimentation assays using homogenized pulmonary artery lysates. We observed no difference in actin polymerization between groups under baseline conditions, but ET-1 enhanced actin polymerization in pulmonary arteries from CH rats. This response was blunted by the ROS scavenger tiron, the ROCK inhibitor fasudil, and the mDia (RhoA effector) inhibitor small-molecule inhibitor of formin homology domain 2. Immunoblot analysis revealed an effect of CH to increase both phosphorylated (inactive) and total levels of the actin disassembly factor cofilin but not phosphorylated cofilin-to-total cofilin ratios. We conclude that actin polymerization contributes to increased basal pulmonary arterial constriction and ET-1-induced vasoconstrictor reactivity after CH in a ROS- and ROCK-dependent manner. Our results further suggest that enhanced ET-1-mediated actin polymerization after CH is dependent on mDia but independent of changes in the phosphorylated cofilin-to-total cofilin ratio. NEW & NOTEWORTHY This research is the first to demonstrate a role for actin polymerization in chronic hypoxia-induced basal pulmonary arterial constriction and enhanced agonist-induced vasoconstrictor activity. These results suggest that a reactive oxygen species-Rho kinase-actin polymerization signaling pathway mediates this response and may provide a mechanistic basis for the vasoconstrictor component of pulmonary hypertension.

Comparison of methods for individualized astronaut organ dosimetry: Morphometry-based phantom library versus body contour autoscaling of a reference phantom.

One of the hazards faced by space crew members in low-Earth orbit or in deep space is exposure to ionizing radiation. It has been shown previously that while differences in organ-specific and whole-body risk estimates due to body size variations are small for highly-penetrating galactic cosmic rays, large differences in these quantities can result from exposure to shorter-range trapped proton or solar particle event radiations. For this reason, it is desirable to use morphometrically accurate computational phantoms representing each astronaut for a risk analysis, especially in the case of a solar particle event. An algorithm was developed to automatically sculpt and scale the UF adult male and adult female hybrid reference phantom to the individual outer body contour of a given astronaut. This process begins with the creation of a laser-measured polygon mesh model of the astronaut's body contour. Using the auto-scaling program and selecting several anatomical landmarks, the UF adult male or female phantom is adjusted to match the laser-measured outer body contour of the astronaut. A dosimetry comparison study was conducted to compare the organ dose accuracy of both the autoscaled phantom and that based upon a height-weight matched phantom from the UF/NCI Computational Phantom Library. Monte Carlo methods were used to simulate the environment of the August 1972 and February 1956 solar particle events. Using a series of individual-specific voxel phantoms as a local benchmark standard, autoscaled phantom organ dose estimates were shown to provide a 1% and 10% improvement in organ dose accuracy for a population of females and males, respectively, as compared to organ doses derived from height-weight matched phantoms from the UF/NCI Computational Phantom Library. In addition, this slight improvement in organ dose accuracy from the autoscaled phantoms is accompanied by reduced computer storage requirements and a more rapid method for individualized phantom generation when compared to the UF/NCI Computational Phantom Library.

Response to 'A relational approach to Saviour Siblings?' by Selgelid.

In his concise argument, 'A relational approach to saviour siblings?', Selgelid reiterates some of the arguments raised in the author meets critics discussion of my book, Saviour Siblings In this response, I highlight an important misunderstanding in one of the arguments put forward by Selgelid, which forms the basis of a large portion of his analysis. Contrary to what Selgelid contends, I do not use the deafness case in my discussion of the non-identity problem to contend that the case of selecting for deafness is ethically different from the case of saviour siblings. As I state in my reply, I use the case of deafness not as a comparator for saviour siblings but rather to illustrate the different categories of risk that apply in selection cases Given this confusion, I restate my objection to relying on the non-identity problem in evaluating risk of harm associated with the embryo biopsy process for preimplantation genetic diagnosis. Finally, I reiterate that the individual interests of saviour siblings remain important in the decision-making matrix and emphasise that Saviour Siblings offers a more contextualised approach to the welfare of the child in selective reproduction, which includes both individual and collective interests.