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Stem cell-derived embryo models (SCEMs) are model embryos used in scientific research to gain a better understanding of early embryonic development. The way humans develop from a single-cell zygote to a complex multicellular organism remains poorly understood. However, research looking at embryo development is difficult because of restrictions on the use of human embryos in research. Stem cell embryo models could reduce the need for human embryos, allowing us to both understand early development and improve assisted reproductive technologies. There have been several rapid advances in creating SCEMs in recent years. These advances potentially provide a new avenue to study early human development. The benefits of SCEMs are predicated on the claim that they are different from embryos and should, therefore, be exempt from existing regulations that apply to embryos (such as the 14-day rule). SCEMs are proposed as offering a model that can capture the inner workings of the embryo but lack its moral sensitivities. However, the ethical basis for making this distinction has not been clearly explained. In this current controversy, we focus on the ethical justification for treating SCEMs differently to embryos, based on considerations of moral status.

Purpose Next generation sequencing has led to the creation of large pools of genomic data with analysis rather than data generation now the limiting factor. Artificial intelligence (AI) may be required to optimize the benefits of these data, but little is known about how the public feels about the use of AI in genomics. Methods We conducted focus groups with members of the Australian public. Participants were recruited via social media advertisements. We explored potential uses of AI in genomic medicine, the benefits, risks, and the possible social implications of its use. Results Participants ( n  = 34) largely felt comfortable with AI analysing their own genomic data and generally agreed about its benefits. Concerns were raised over data security, the potential for misdiagnosis, and bias AI may perpetuate. Many participants wanted checking mechanisms for when results were generated using AI. Conclusions The insights gained from these discussions help to understand public concerns around the use of AI in genomic medicine. Our findings can help to inform both policies around genomic AI and how to educate the public on its use. Graphical abstract

IntroductionNewborn bloodspot screening (NBS) is a highly successful public health programme that uses biochemical and other assays to screen for severe but treatable childhood-onset conditions. Introducing genomic sequencing into NBS programmes increases the range of detectable conditions but raises practical and ethical issues. Evidence from prospectively ascertained cohorts is required to guide policy and future implementation. This study aims to develop, implement and evaluate a genomic NBS (gNBS) pilot programme.Methods and analysisThe BabyScreen+ study will pilot gNBS in three phases. In the preimplementation phase, study materials, including education resources, decision support and data collection tools, will be designed. Focus groups and key informant interviews will also be undertaken to inform delivery of the study and future gNBS programmes. During the implementation phase, we will prospectively recruit birth parents in Victoria, Australia, to screen 1000 newborns for over 600 severe, treatable, childhood-onset conditions. Clinically accredited whole genome sequencing will be performed following standard NBS using the same sample. High chance results will be returned by genetic healthcare professionals, with follow-on genetic and other confirmatory testing and referral to specialist services as required. The postimplementation phase will evaluate the feasibility of gNBS as the primary aim, and assess ethical, implementation, psychosocial and health economic factors to inform future service delivery.Ethics and disseminationThis project received ethics approval from the Royal Children’s Hospital Melbourne Research Ethics Committee: HREC/91500/RCHM-2023, HREC/90929/RCHM-2022 and HREC/91392/RCHM-2022. Findings will be disseminated to policy-makers, and through peer-reviewed journals and conferences.

Recent dramatic reductions in the timeframe in which genomic sequencing can deliver results means its application in time-sensitive screening programs such as newborn screening (NBS) is becoming a reality. As genomic NBS (gNBS) programs are developed around the world, there is an increasing need to address the ethical and social issues that such initiatives raise. This study therefore aimed to explore the Australian public’s perspectives and values regarding key gNBS characteristics and preferences for service delivery. We recruited English-speaking members of the Australian public over 18 years of age via social media; 75 people aged 23–72 participated in 1 of 15 focus groups. Participants were generally supportive of introducing genomic sequencing into newborn screening, with several stating that the adoption of such revolutionary and beneficial technology was a moral obligation. Participants consistently highlighted receiving an early diagnosis as the leading benefit, which was frequently linked to the potential for early treatment and intervention, or access to other forms of assistance, such as peer support. Informing parents about the test during pregnancy was considered important. This study provides insights into the Australian public’s views and preferences to inform the delivery of a gNBS program in the Australian context.

Background Implementing genomic sequencing into newborn screening programs allows for significant expansion in the number and scope of conditions detected. We sought to explore public preferences and perspectives on which conditions to include in genomic newborn screening (gNBS). Methods We recruited English-speaking members of the Australian public over 18 years of age, using social media, and invited them to participate in online focus groups. Results Seventy-five members of the public aged 23–72 participated in one of fifteen focus groups. Participants agreed that if prioritisation of conditions was necessary, childhood-onset conditions were more important to include than later-onset conditions. Despite the purpose of the focus groups being to elicit public preferences, participants wanted to defer to others, such as health professionals or those with a lived experience of each condition, to make decisions about which conditions to include. Many participants saw benefit in including conditions with no available treatment. Participants agreed that gNBS should be fully publicly funded. Conclusion How many and which conditions are included in a gNBS program will be a complex decision requiring detailed assessment of benefits and costs alongside public and professional engagement. Our study provides support for implementing gNBS for treatable childhood-onset conditions.

Individuals with ADHD and comorbid hoarding disorder are vulnerable to severe consequences from hoarding symptoms. Despite this, and the early onset of hoarding disorder, the nature of hoarding symptoms in children with comorbid ADHD is unknown. We therefore explored the phenomenology of hoarding symptoms among ten 8–12year olds with ADHD and clinically significant hoarding symptoms through parental perceptions. Parents completed in-depth semi-structured interviews. The data was analyzed using Interpretative Phenomenological Analysis. Six superordinate themes were identified: emotional distress; parental avoidance and accommodating behaviors; family impacts of hoarding; excessive acquisition and saving; executive functioning; parental insight and intervention. In contrast to previous suggestions that emotional distress was not associated with hoarding in ADHD, these findings highlight that emotional distress appeared to be core to the hoarding disorder profile of the present sample of children with ADHD. This has important implications for health practitioners who may consider conceptualizing, assessing, and treating hoarding symptoms in children with comorbid ADHD using a cognitive behavioral model of hoarding disorder.

IntroductionAs routine genomic testing expands, so too does the opportunity to look for additional health information unrelated to the original reason for testing, termed additional findings (AF). Analysis for many different types of AF may be available, particularly to families undergoing trio genomic testing. The optimal model for service delivery remains to be determined, especially when the original test occurs in the acute care setting.Methods and analysisFamilies enrolled in a national study providing ultrarapid genomic testing to critically ill children will be offered analysis for three types of AF on their stored genomic data: paediatric-onset conditions in the child, adult-onset conditions in each parent and reproductive carrier screening for the parents as a couple. The offer will be made 3–6 months after diagnostic testing. Parents will have access to a modified version of the Genetics Adviser web-based decision support tool before attending a genetic counselling appointment to discuss consent for AF. Parental experiences will be evaluated using qualitative and quantitative methods on data collected through surveys, appointment recordings and interviews at multiple time points. Evaluation will focus on parental preferences, uptake, decision support use and understanding of AF. Genetic health professionals’ perspectives on acceptability and feasibility of AF will also be captured through surveys and interviews.Ethics and disseminationThis project received ethics approval from the Melbourne Health Human Research Ethics Committee as part of the Australian Genomics Health Alliance protocol: HREC/16/MH/251. Findings will be disseminated through peer-review journal articles and at conferences nationally and internationally.

Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

Voriconazole has been associated with cutaneous squamous cell carcinoma (cSCC) in transplant patients but less is known about the risk in less severely immunosuppressed patients. Our aim was to estimate the incidence of cSCC after voriconazole exposure in patients with chronic pulmonary aspergillosis on a background of chronic lung disease. The notes of patients seen at a tertiary referral centre from 2009 to 2019 with chronic pulmonary aspergillosis were reviewed for the diagnosis of cSCC and voriconazole use documented. Among 1111 patients, 668 (60.1%) received voriconazole for longer than 28 days. Twelve patients received a diagnosis of cSCC; nine had used voriconazole. Mean duration of voriconazole use was 36.7 months. The crude incidence rate was 4.88 in 1000 person/years in those who had voriconazole and 2.79 in 1000 patient/years in those who did not receive voriconazole for longer than 28 days. On Cox regression, age (HR 1.09, 95% CI 1.02–1.16, p = 0.01) and male gender (HR 3.97, 95% CI 0.84–18.90, p = 0.082) were associated with cSCC. Voriconazole use was associated with a slightly increased risk, which was not significant (HR 1.35, 95% CI 0.35–5.20, p = 0.659). Voriconazole use beyond 28 days did not lead to a significantly increased risk of cSCC in a large cohort of patients with chronic pulmonary aspergillosis.

Immunotherapies and targeted therapies have revolutionised treatment of metastatic melanoma and improved survival rates. However, survivors treated with novel therapies are vulnerable to high levels of fear of cancer recurrence or progression (FCR). Existing FCR interventions have rarely been trialled in people with advanced cancer. The current study aimed to evaluate the acceptability and feasibility of Fear-Less: a stepped-care model to treat FCR in people with metastatic melanoma treated with immunotherapy or targeted therapy. Sixty-one outpatients with metastatic melanoma were screened using the Fear of Cancer Recurrence Inventory Short Form (FCRI-SF) and Fear of Progression Questionnaire Short Form (FoP-Q-SF). Survivors with subthreshold FCR were stratified to a self-management intervention while those with clinical levels of FCR were provided with an individual therapy, Conquer Fear. Survivor experience surveys and rescreening were administered post-intervention completion. Results indicated that Fear-Less was an acceptable and feasible FCR intervention. Results provided preliminary support for the potential impact of Fear-Less in reducing FCR. Fear-Less is a promising first step in providing an acceptable and feasible stepped-care model to treat FCR in survivors with metastatic disease.