Consumer attitudes and preferences toward psychiatric genetic counselling and educational resources: A scoping review.

INTRODUCTION: The etiology of psychiatric disorders is multifactorial including genomic and environmental risk factors. Psychiatric genetic counseling is an emerging field that may promote processes of adaptation to, and the management of, psychiatric disorders. Many countries lack dedicated services leading to a gap in care. This scoping review will inform the development of psychiatric genetics-based educational resources. OBJECTIVES: To explore individuals with a psychiatric disorder and their relatives' attitudes and beliefs toward psychiatric genetics, genetic counseling, and genetics-based education. To evaluate how best to convey education to consumers. METHOD: Database literature searches occurred on May 2nd, 2023, using PubMed, Medline, and PsycINFO. Reviews, letters to the editor, case reports, and publications before 2003 were excluded. RESULTS: Twenty-four papers met the inclusion criteria. Results suggest individuals with a psychiatric disorder and their relatives tended to overestimate risk, and express concern about reproductive decision- making. Genetic counseling and educational resources were perceived to be useful and empowering. CONCLUSION: Affected individuals and relatives are interested in gaining greater insight into their own and/or their relative's psychiatric disorder, management strategies, and understanding familial risks. PRACTICE IMPLICATIONS: The evidence from this review may inform the development of genetics-based educational resources or guide future research.

Exploring Consumers' Motivations and Experiences of Engaging as Partners in Cancer Research.

BACKGROUND AND OBJECTIVE: Consumer engagement improves research quality and relevance but can be difficult to implement. This study aimed to explore the motivations and understand the barriers, if any, experienced by consumers before and when partnering with cancer research teams. METHODS: Semi-structured interviews were conducted with consumers and the results analysed thematically. Two groups were recruited: consumers who were members of the consumer registry and patients who did not have previous experience of being a consumer in a researcher partnership. RESULTS: Twenty-one interviews were conducted with a total of 22 participants aged between 26 and 74 years. Consumers motivation was driven by altruism to help others and personal benefits. Barriers to beginning and maintaining consumer engagement included consumers' perceptions of being appreciated by researchers and meaningful communication between researchers and consumers. CONCLUSIONS: Australian policy has made important steps towards consumer engagement in research. This study showed that demonstrating an appreciation for consumers and effective communication are key areas to consider when designing implementation strategies of these policies in the cancer research space in the future.

Personalising genetic counselling (POETIC) trial: Protocol for a hybrid type II effectiveness-implementation randomised clinical trial of a patient screening tool to improve patient empowerment after cancer genetic counselling.

BACKGROUND: Genetic counselling aims to identify, and address, patient needs while facilitating informed decision-making about genetic testing and promoting empowerment and adaptation to genetic information. Increasing demand for cancer genetic testing and genetic counsellor workforce capacity limitations may impact the quality of genetic counselling provided. The use of a validated genetic-specific screening tool, the Genetic Psychosocial Risk Instrument (GPRI), may facilitate patient-centred genetic counselling. The aim of this study is to assess the effectiveness and implementation of using the GPRI in improving patient outcomes after genetic counselling and testing for an inherited cancer predisposition. METHODS: The PersOnalising gEneTIc Counselling (POETIC) trial is a hybrid type 2 effectiveness-implementation trial using a randomised control trial to assess the effectiveness of the GPRI in improving patient empowerment (primary outcome), while also assessing implementation from the perspective of clinicians and the healthcare service. Patients referred for a cancer risk assessment to the conjoint clinical genetics service of two metropolitan hospitals in Victoria, Australia, who meet the eligibility criteria and consent to POETIC will be randomised to the usual care or intervention group. Those in the intervention group will complete the GPRI prior to their appointment with the screening results available for the clinicians' use during the appointment. Appointment audio recordings, clinician-reported information about the appointment, patient-reported outcome measures, and clinical data will be used to examine the effectiveness of using the GPRI. Appointment audio recordings, health economic information, and structured interviews will be used to examine the implementation of the GPRI. DISCUSSION: The POETIC trial takes a pragmatic approach by deploying the GPRI as an intervention in the routine clinical practice of a cancer-specific clinical genetics service that is staffed by a multidisciplinary team of genetics and oncology clinicians. Therefore, the effectiveness and implementation evidence generated from this real-world health service setting aims to optimise the relevance of the outcomes of this trial to the practice of genetic counselling while enhancing the operationalisation of the screening tool in routine practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry registration number 12621001582842p. Date of registration: 19th November 2021.

Comprehensive phylogenomic time tree of bryophytes reveals deep relationships and uncovers gene incongruences in the last 500 million years of diversification.

PREMISE: Bryophytes form a major component of terrestrial plant biomass, structuring ecological communities in all biomes. Our understanding of the evolutionary history of hornworts, liverworts, and mosses has been significantly reshaped by inferences from molecular data, which have highlighted extensive homoplasy in various traits and repeated bursts of diversification. However, the timing of key events in the phylogeny, patterns, and processes of diversification across bryophytes remain unclear. METHODS: Using the GoFlag probe set, we sequenced 405 exons representing 228 nuclear genes for 531 species from 52 of the 54 orders of bryophytes. We inferred the species phylogeny from gene tree analyses using concatenated and coalescence approaches, assessed gene conflict, and estimated the timing of divergences based on 29 fossil calibrations. RESULTS: The phylogeny resolves many relationships across the bryophytes, enabling us to resurrect five liverwort orders and recognize three more and propose 10 new orders of mosses. Most orders originated in the Jurassic and diversified in the Cretaceous or later. The phylogenomic data also highlight topological conflict in parts of the tree, suggesting complex processes of diversification that cannot be adequately captured in a single gene-tree topology. CONCLUSIONS: We sampled hundreds of loci across a broad phylogenetic spectrum spanning at least 450 Ma of evolution; these data resolved many of the critical nodes of the diversification of bryophytes. The data also highlight the need to explore the mechanisms underlying the phylogenetic ambiguity at specific nodes. The phylogenomic data provide an expandable framework toward reconstructing a comprehensive phylogeny of this important group of plants.

Target capture and genome skimming for plant diversity studies.

Recent technological advances in long-read high-throughput sequencing and assembly methods have facilitated the generation of annotated chromosome-scale whole-genome sequence data for evolutionary studies; however, generating such data can still be difficult for many plant species. For example, obtaining high-molecular-weight DNA is typically impossible for samples in historical herbarium collections, which often have degraded DNA. The need to fast-freeze newly collected living samples to conserve high-quality DNA can be complicated when plants are only found in remote areas. Therefore, short-read reduced-genome representations, such as target capture and genome skimming, remain important for evolutionary studies. Here, we review the pros and cons of each technique for non-model plant taxa. We provide guidance related to logistics, budget, the genomic resources previously available for the target clade, and the nature of the study. Furthermore, we assess the available bioinformatic analyses, detailing best practices and pitfalls, and suggest pathways to combine newly generated data with legacy data. Finally, we explore the possible downstream analyses allowed by the type of data generated using each technique. We provide a practical guide to help researchers make the best-informed choice regarding reduced genome representation for evolutionary studies of non-model plants in cases where whole-genome sequencing remains impractical.

Impact of a risk based breast screening decision aid on understanding, acceptance and decision making.

Internationally, population breast cancer screening is moving towards a risk-stratified approach and requires engagement and acceptance from current and future screening clients. A decision aid ( www.defineau.org ) was developed based on women's views, values, and knowledge regarding risk-stratified breast cancer screening. This study aims to evaluate the impact of the decision aid on women's knowledge, risk perception, acceptance of risk assessment and change of screening frequency, and decision-making. Here we report the results of a pre and post-survey in which women who are clients of BreastScreen Victoria were invited to complete an online questionnaire before and after viewing the decision aid. 3200 potential participants were invited, 242 responded with 127 participants completing both surveys. After reviewing the decision aid there was a significant change in knowledge, acceptance of risk-stratified breast cancer screening and of decreased frequency screening for lower risk. High levels of acceptance of risk stratification, genetic testing and broad support for tailored screening persisted pre and post review. The DEFINE decision aid has a positive impact on acceptance of lower frequency screening, a major barrier to the success of a risk-stratified program and may contribute to facilitating change to the population breast screening program in Australia.

Development and evaluation of a novel educational program for providers on the use of polygenic risk scores.

PURPOSE: This study aimed to develop an online educational program for using polygenic risk score (PRS) for breast and ovarian cancer risk assessments and to evaluate the impact on the attitudes, confidence, knowledge, and preparedness of genetic health care providers (GHPs). METHODS: The educational program comprises an online module that covers the theoretical aspects of PRS and a facilitated virtual workshop with prerecorded role-plays and case discussions. Data were collected in pre- and posteducation surveys. Eligible participants were GHPs working in Australian familial cancer clinics registered to recruit patients for a breast and ovarian cancer PRS clinical trial (n = 12). RESULTS: A total of 124 GHPs completed the PRS education, of whom 80 (64%) and 67 (41%) completed the pre- and posteducation surveys, respectively. Before education, GHPs reported limited experience, confidence, and preparedness using PRS, but they recognized its potential benefits. After education, GHPs indicated improved attitudes (P ≤ .001), confidence (P ≤ .001), knowledge (P ≤ .001), and preparedness (P ≤ .001) to use PRS. Most GHPs thought that the program entirely met their learning needs (73%) and was completely relevant to their clinical practice (88%). GHPs identified PRS implementation barriers, including limited funding models, diversity issues, and need for clinical guidelines. CONCLUSION: Our education program improved GHP attitudes, confidence, knowledge, and preparedness for using PRS/personalized risk and provides a framework for the development of future programs.

Genetic factors predict hybrid formation in the British flora.

Natural hybridization can have a profound evolutionary impact, with consequences ranging from the extinction of rare taxa to the origin of new species. Natural hybridization is particularly common in plants; however, our understanding of the general factors that promote or prevent hybridization is hampered by the highly variable outcomes in different lineages. Here, we quantify the influence of different predictors on hybrid formation across species from an entire flora. We combine estimates of hybridization with ecological attributes and a new species-level phylogeny for over 1,100 UK flowering plant species. Our results show that genetic factors, particularly parental genetic distance, as well as phylogenetic position and ploidy, are key determinants of hybrid formation, whereas many other factors such as range overlap and genus size explain much less variation in hybrid formation. Overall, intrinsic genetic factors shape the evolutionary and ecological consequences of natural hybridization across species in a flora.

A high quality, high molecular weight DNA extraction method for PacBio HiFi genome sequencing of recalcitrant plants.

BACKGROUND: PacBio HiFi sequencing provides highly accurate long-read sequencing datasets which are of great advantage for whole genome sequencing projects. One limitation of the method is the requirement for high quality, high molecular weight input DNA. This can be particularly challenging for plants that frequently contain common and species-specific secondary metabolites, which often interfere with downstream processes. Cape Primroses (genus Streptocarpus), are some of these recalcitrant plants and are selected here as material to develop a high quality, high molecular weight DNA extraction protocol for long read genome sequencing. RESULTS: We developed a DNA extraction method for PacBio HiFi sequencing for Streptocarpus grandis and Streptocarpus kentaniensis. A CTAB lysis buffer was employed to avoid guanidine, and the traditional chloroform and phenol purification steps were replaced with pre-lysis sample washes. Best cells/nucleus lysis was achieved with 4 h at 58 °C. The obtained high quality and high molecular weight DNAs were tested in PacBio SMRTBell™ library preparations, which resulted in circular consensus sequencing (CCS) reads from 17 to 27 Gb per cell, and a read length N50 from 14 to 17 kbp. To evaluate the quality of the reads for whole genome sequencing, they were assembled with HiFiasm into draft genomes, with N50 = 49 Mb and 23 Mb, and L50 = 10 and 11. The longest contigs were 95 Mb and 57 Mb respectively, showing good contiguity as these are longer than the theoretical chromosome length (genome size/chromosome number) of 78 Mb and 55 Mb, for S. grandis and S. kentaniensis respectively. CONCLUSIONS: DNA extraction is a critical step towards obtaining a complete genome assembly. Our DNA extraction method here provided the required high quality, high molecular weight DNA for successful standard-input PacBio HiFi library preparation. The contigs from those reads showed a high contiguity, providing a good starting draft assembly towards obtaining a complete genome. The results obtained here were highly promising, and demonstrated that the DNA extraction method developed here is compatible with PacBio HiFi sequencing and suitable for de novo whole genome sequencing projects of plants.

Proband-mediated interventions to increase disclosure of genetic risk in families with a BRCA or Lynch syndrome condition: a systematic review.

Interventions to assist family communication about inherited cancer risk have the potential to improve family cancer outcomes. This review aimed to evaluate the efficacy of proband-mediated interventions employed within genetics clinics to increase disclosure of genetic risk to at-risk relatives. MEDLINE, Embase, CINAHL, PubMed and PsycINFO were searched for publications between 1990-2020. The quality of studies was assessed. From 5605 records reviewed, 9 studies (4 randomised control trials and 5 cohort studies) were included involving families with BRCA1, BRCA2 and Lynch syndrome. Intervention delivery modes included genetic counselling with additional telephone or in-person follow-up, letters, videos, and decision aids. The percentages of at-risk relatives informed by the proband about their risk ranged from 54.0% to 95.5% in the intervention or family-mediated comparison group. Of those who were informed, 24.4-60.0% contacted a genetics clinic and 22.8-76.2% had genetic testing after they were counselled at a genetics clinic. Significant differences between intervention and control group were reported on all three outcomes by one study, and with relatives contacting a genetics clinic by another study. The studies suggest but do not conclusively show, that tailored genetic counselling with additional follow-up can increase both the proportion of informed relatives and relatives who contact the genetics clinic. With the increase in germline testing, interventions are required to consider the family communication process and address post-disclosure variables (e.g., relative's perceptions, emotional reactions) through engagement with probands and relatives to maximise the public health benefit of identifying inherited cancer risk in families.

Becoming and being a parent with an inherited predisposition to diffuse gastric cancer: A qualitative study of young adults with a CDH1 pathogenic variant.

PURPOSE: This study explored the experiences of young people with hereditary diffuse gastric cancer (HDGC), an inherited cancer predisposition syndrome, as they navigate becoming and being a parent. DESIGN: We used interpretive description and conducted semi-structured interviews with 13 young Australians (18-39 years) with a CDH1 pathogenic variant (PV). Data were analyzed using team-based, reflexive thematic analysis. FINDINGS: Participants' reproductive decisions centered on the perceived manageability of HDGC, namely via gastrectomy, and timing of their genetic testing. Participants yet to have children and those with challenging gastrectomy experiences favored using reproductive technologies to prevent passing on their PV. Parents who had children before genetic testing described complicated decisions about having more children. Gastrectomy was considered a parental responsibility but recovery diminished parenting abilities. CONCLUSION: Young people with HDGC face unique challenges navigating reproductive decision-making and parenting with gastrectomy. Findings lend credence to calls for longitudinal, developmentally sensitive genetic counseling services.

Psychiatric genetic counseling: A survey of Australian genetic counselors' practice and attitudes.

Genetic counseling plays a critical role in supporting individuals and their families' adaption to psychiatric conditions, addressing the multifactorial nature of these conditions in a personally meaningful and empowering way. Yet data related to the practice and attitudes of Australian genetic counselors about psychiatric genetic counseling (PGC) is limited. This survey investigated the practice of Australian genetic counselors, and their attitudes toward PGC. Genetic counselors (N = 393) were invited to participate in an anonymous online survey between March and May 2022. Forty-four genetic counselors (response rate = 11%) from Australia and New Zealand responded. No respondents practice in psychiatric genetics as their speciality area; most respondents do not see any patients where the primary indication is a personal and/or family history of psychiatric disorders (91%). Greater than half of respondents (56%) believed there was sufficient evidence to support PGC, and 64% enquire about personal and/or family history of psychiatric disorders, but only 25% provide genetic counseling on this topic. Most respondents do not feel confident providing risk assessments for psychiatric disorders (72%), while the majority expressed interest in attending specialist training (95%), and in incorporating PGC into future practice (77%). Australian genetic counselors would benefit from psychiatric genetic education and training, and establishment of specialized PGC services would address this gap in patient care, while providing opportunities for genetic counselors to gain skills and experience in PGC.

The Clinical and Psychosocial Outcomes for Women Who Received Unexpected Clinically Actionable Germline Information Identified through Research: An Exploratory Sequential Mixed-Methods Comparative Study.

Background Research identifying and returning clinically actionable germline variants offer a new avenue of access to genetic information. The psychosocial and clinical outcomes for women who have received this 'genome-first care' delivering hereditary breast and ovarian cancer risk information outside of clinical genetics services are unknown. Methods: An exploratory sequential mixed-methods case-control study compared outcomes between women who did (cases; group 1) and did not (controls; group 2) receive clinically actionable genetic information from a research cohort in Victoria, Australia. Participants completed an online survey examining cancer risk perception and worry, and group 1 also completed distress and adaptation measures. Group 1 participants subsequently completed a semi structured interview. Results: Forty-five participants (group 1) and 96 (group 2) completed the online survey, and 31 group 1 participants were interviewed. There were no demographic differences between groups 1 and 2, although more of group 1 participants had children (p = 0.03). Group 1 reported significantly higher breast cancer risk perception (p < 0.001) compared to group 2, and higher cancer worry than group 2 (p < 0.001). Some group 1 participants described how receiving their genetic information heightened their cancer risk perception and exacerbated their cancer worry while waiting for risk-reducing surgery. Group 1 participants reported a MICRA mean score of 27.4 (SD 11.8, range 9−56; possible range 0−95), and an adaptation score of 2.9 (SD = 1.1). Conclusion: There were no adverse psychological outcomes amongst women who received clinically actionable germline information through a model of 'genome-first' care compared to those who did not. These findings support the return of clinically actionable research results to research participants.

Teachers' Perceptions and Experiences of Menstrual Cycle Education and Support in UK Schools.

The purpose of this study was 2-fold, to (1) explore current education provision in UK schools including barriers to menstrual cycle education and (2) assess the perceived support teachers received to deliver menstrual cycle education. Seven hundred eighty-nine teachers (91% female) from all stages of school education in England (48%), Scotland (24%), Wales (22%) and Northern Ireland (6%) completed an online survey. The survey captured information on menstrual education in schools, teacher's knowledge and confidence of the menstrual cycle, support provided to teachers, provision of menstrual products in school and perceived impact of the menstrual cycle on young people in school. Four hundred ninety-eight teachers reported lessons were provided on the menstrual cycle (63%), predominantly delivered within personal, social, health and economic or science subjects, with over half of the lessons focusing on the biology (56%) or provision of menstrual products (40%) rather than lived experiences (14%). Teachers perceived the menstrual cycle affected participation in PE (88%), pupil confidence (88%), school attendance (82%) and attitude and behavior (82%). Overall, 80% of teachers felt receiving training would be beneficial to improve menstrual education. The results highlight education is scientifically focused, with less education on management of symptoms or lived experiences. Teachers also perceive the menstrual cycle to influence multiple aspects of school attendance and personal performance. There is a need to address menstrual education provided in schools across the UK to help empower girls to manage their menstrual cycle, preventing a negative impact on health and school performance.

Assessing the acceptability, feasibility, and usefulness of a psychosocial screening tool to patients and clinicians in a clinical genetics service in Australia.

Increasing demand for clinical genetic services may impact the resources and quality of genetic counseling, potentially impacting patient outcomes. Using a psychosocial screening tool may aid the provision of genetic counseling by reliably identifying patients' psychosocial needs. The Genetic Psychosocial Risk Instrument (GPRI) is a validated genetic-specific screening tool designed to identify psychological risk factors that predict distress in patients having genetic testing. This questionnaire-based study investigated the perceived acceptability, feasibility, and usefulness of the GPRI in patients and clinicians in routine clinical genetic practice. From December 2018 to January 2019, 154 patients attending an Australian clinical genetic service were invited to complete a paper-based survey that included the GPRI. The GPRI was scored and provided to the clinician for use in the appointment. In February 2019, clinicians completed an anonymous online survey regarding acceptability, feasibility, and usefulness of the GPRI. Descriptive statistics, chi-squared, t tests, and regression analyses were used to analyze the patient data, and descriptive statistics were employed for clinician surveys. A total of 145 patients participated (94% response rate). The average GPRI score was 46.3 (95% CI 43.6-49.0) with 41% of patients meeting the 50-point threshold indicating high risk for psychological distress. The GPRI was highly acceptable to patients, regardless of their level of psychosocial risk. Fourteen clinicians participated (54% response rate): 85% found the GPRI not too time consuming, and 86% believed it improved patient care by identifying patient needs. All were willing to use the GPRI routinely. The use of the GPRI is highly acceptable to patients and clinicians in this setting, assisting in identifying patients at risk for distress, prompting clinicians to address concerns, provide psychosocial support, and consider ongoing referral. As 41% of patients' scores indicated a high risk of distress, the GPRI is an important tool for potentially enhancing overall patient outcomes.

Reproduction and Genetic Responsibility: An Interpretive Description of Reproductive Decision-Making for Young People With Li-Fraumeni Syndrome.

The reproductive decision-making of young people (aged 15-39 years) with Li-Fraumeni syndrome (LFS), an early onset inherited cancer syndrome, has not been studied in depth. Using interpretive description methodology, we conducted semi-structured interviews with 30 young Australians (mean age 25.5 years) diagnosed with LFS or at 50% genetic risk. With reflexive thematic analysis, we show how young people's reproductive decision-making and ideals for family formation were shaped by a sense of genetic responsibility to ensure the health of future biological kin. Reproductive technology provided choices for family formation in the context of LFS and also complicated reproductive decisions, as these choices were difficult to understand, make, or carry out. We uphold that reproductive decision-making when living with LFS is a profoundly moral practice that may pose significant challenges for young people navigating their formative years. We offer genetic counseling practice recommendations to support individuals with LFS when making reproductive decisions.

Multispectral label-free Raman spectroscopy can detect ovarian and endometrial cancer with high accuracy.

Up to 70% of ovarian cancer patients are diagnosed with advanced-stage disease and the degree of cytoreduction is an important survival prognostic factor. The aim of this study was to evaluate if Raman spectroscopy could detect cancer from different organs within the abdominopelvic region, including the ovaries. A Raman spectroscopy probe was used to interrogate specimens from a cohort of nine patients undergoing cytoreductive surgery, including four ovarian cancer patients and three patients with endometrial cancer. A feature-selection algorithm was developed to determine which spectral bands contributed to cancer detection and a machine-learning model was trained. The model could detect cancer using only eight spectral bands. The receiver-operating-characteristic curve had an area-under-the-curve of 0.96, corresponding to an accuracy, a sensitivity and a specificity of 90%, 93% and 88%, respectively. These results provide evidence multispectral Raman spectroscopy could be developed to detect ovarian cancer intraoperatively.

Young people's experiences of a CDH1 pathogenic variant: Decision-making about gastric cancer risk management.

The most effective option for gastric cancer risk management in individuals with a CDH1 germline pathogenic or likely pathogenic variant (PV) in Australia is prophylactic total gastrectomy (PTG). There is, however, increasing confidence in endoscopic surveillance as a risk management strategy thus affording individuals with a CDH1 PV with challenging decisions regarding their gastric cancer risk management. For young people, this decision-making comes at a complex development stage of emerging and young adulthood. This study aims to explore the factors that influence young people's decision-making about their gastric cancer risk management due to a CDH1 PV. Potential participants were identified and approached through the Parkville Familial Cancer Centre in Melbourne, Australia. Thematic analysis was used to interpret and analyze the data. Qualitative interviews were conducted with 13 people with a CDH1 PV aged 18 to 39 years, inclusive. The interviews found that participants' familial and shared experiences of cancer and risk management, perceived tolerance of uncertainty, and desire for control over their cancer risk were fundamental in their decision-making about their gastric cancer risk management. The participants' young adult life stage was also deemed particularly important in decisions about the timing of PTG. The findings of this study are vital to inform decisional counseling discussions with this unique population.