The ethical challenges of diversifying genomic data: A qualitative evidence synthesis.

This article aims to explore the ethical issues arising from attempts to diversify genomic data and include individuals from underserved groups in studies exploring the relationship between genomics and health. We employed a qualitative synthesis design, combining data from three sources: 1) a rapid review of empirical articles published between 2000 and 2022 with a primary or secondary focus on diversifying genomic data, or the inclusion of underserved groups and ethical issues arising from this, 2) an expert workshop and 3) a narrative review. Using these three sources we found that ethical issues are interconnected across structural factors and research practices. Structural issues include failing to engage with the politics of knowledge production, existing inequities, and their effects on how harms and benefits of genomics are distributed. Issues related to research practices include a lack of reflexivity, exploitative dynamics and the failure to prioritise meaningful co-production. Ethical issues arise from both the structure and the practice of research, which can inhibit researcher and participant opportunities to diversify data in an ethical way. Diverse data are not ethical in and of themselves, and without being attentive to the social, historical and political contexts that shape the lives of potential participants, endeavours to diversify genomic data run the risk of worsening existing inequities. Efforts to construct more representative genomic datasets need to develop ethical approaches that are situated within wider attempts to make the enterprise of genomics more equitable.

Interventions to support patients with sharing genetic test results with at-risk relatives: a synthesis without meta-analysis (SWiM).

Whilst the finding of heritable susceptibility to disease was once relatively rare, mainstreaming of genetic testing has resulted in a steady increase. Patients are often encouraged to share their genetic test results with relevant relatives, but relatives may not receive this information, leaving them without knowledge of their own risk. Therefore, strategies to help communicate such information are important. This review aimed to explore the efficacy of existing interventions to improve the sharing of genetic test results. A synthesis without meta-analysis design was used. A systematic search of Medline, CINAHL, PsychINFO, and AMED was conducted, and five studies were identified worldwide. Data were extracted for each study regarding study aim, participant characteristics, condition, intervention details, comparison, study duration, outcome measures, theory and behaviour change techniques used. Limited efficacy and application of theory was found. Knowledge, motivation and self-efficacy were not increased in any intervention. No gender differences in communication behaviour were encountered in interventions that recruited men and women. Two studies reported an evaluation of acceptability, which showed that the interventions were well received by patients and health professionals. No study reported the involvement of the target population in any phase of intervention development. Given the lack of health psychology-informed interventions in this area of clinical genetics, we recommend genetic health professionals, health psychologists and patients collaborate on all stages of future interventions that involve the cascading of genetic health information within families. We also provide guidance regarding use of theory and intervention elements for future intervention development.

Distinct and shared therapeutic neural mechanisms of mindfulness-based and social support stress reduction groups in adults with autism spectrum disorder.

BACKGROUND: Mindfulness-based stress reduction (MBSR) alleviates depression and anxiety in adults with autism spectrum disorder (ASD); however, underlying therapeutic neural mechanisms and mindfulness-specific effects have yet to be elucidated. METHODS: We randomly assigned adults with ASD to MBSR or social support/education (SE). They completed questionnaires that assessed depression, anxiety, mindfulness traits, autistic traits and executive functioning abilities as well as a self-reflection functional MRI task. We used repeated-measures analysis of covariance (ANCOVA) to evaluate behavioural changes. To identify task-specific connectivity changes, we performed a generalized psychophysiological interactions (gPPI) functional connectivity (FC) analysis on regions of interest (ROIs; insula, amygdala, cingulum and prefrontal cortex [PFC]). We used Pearson correlations to explore brain-behaviour relationships. RESULTS: Our final sample included 78 adults with ASD - 39 who received MBSR and 39 who received SE. Mindfulness-based stress reduction uniquely improved executive functioning abilities and increased mindfulness traits, whereas both MBSR and SE groups showed reductions in depression, anxiety and autistic traits. Decreases specific to MBSR in insula-thalamus FC were associated with anxiety reduction and increased mindfulness traits, including the trait "nonjudgment;" MBSR-specific decreases in PFC-posterior cingulate connectivity correlated with improved working memory. Both groups showed decreased amygdala-sensorimotor and medial-lateral PFC connectivity, which corresponded with reduced depression. LIMITATIONS: Larger sample sizes and neuropsychological evaluations are needed to replicate and extend these findings. CONCLUSION: Together, our findings suggest that MBSR and SE are similarly efficacious for depression, anxiety and autistic traits, whereas MBSR produced additional salutary effects related to executive functioning and mindfulness traits. Findings from gPPI identified shared and distinct therapeutic neural mechanisms, implicating the default mode and salience networks. Our results mark an early step toward the development of personalized medicine for psychiatric symptoms in ASD and offer novel neural targets for future neurostimulation research. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04017793.

Interventions to promote physical distancing behaviour during infectious disease pandemics or epidemics: A systematic review.

OBJECTIVES: Physical distancing, defined as keeping 1-2m apart when co-located, can prevent cases of droplet or aerosol transmitted infectious diseases such as SARS-CoV2. During the COVID-19 pandemic, distancing was a recommendation or a requirement in many countries. This systematic review aimed to determine which interventions and behavior change techniques (BCTs) are effective in promoting adherence to distancing and through which potential mechanisms of action (MOAs). METHODS: Six databases were searched. The review included studies that were (a) conducted on humans, (b) reported physical distancing interventions, (c) included any comparator (e.g., pre-intervention versus post-intervention; randomized controlled trial), and (d) reported actual distancing or predictors of distancing behavior. Risk of bias was assessed using the Mixed Methods Appraisal Tool. BCTs and potential MoAs were identified in each intervention. RESULTS: Six articles (with seven studies and 19 comparisons) indicated that distancing interventions could successfully change MoAs and behavior. Successful BCTs (MoAs) included feedback on behavior (e.g., motivation); information about health consequences, salience of health consequences (e.g., beliefs about consequences), demonstration (e.g., beliefs about capabilities), and restructuring the physical environment (e.g., environmental context and resources). The most promising interventions were proximity buzzers, directional systems, and posters with loss-framed messages that demonstrated the behaviors. CONCLUSIONS: The evidence indicates several BCTs and potential MoAs that should be targeted in interventions and highlights gaps that should be the focus of future research.

Genetic testing and family entanglements.

The development of the 'new genetics' in the early 1990's opened up a new space which required some patients and families to understand and navigate genetic testing. The social science literature that has grown alongside the 'new genetics', now spanning more than thirty years, has continued to explore and question assumptions about attitudes and responses towards genetic technologies. In this article we highlight how individual experience of genetic disease and personal responses towards genetic technologies can only be understood by considering their context. We focus on the rich literature on family within sociology, science and technology studies, anthropology, and family studies, to explore the myriad ways in which family is implicated in the patient experience of genetic testing. We explore these connections by drawing on a set of interviews held with individuals who have undergone a predictive test for a genetic condition, including Huntington's Disease and breast cancer. Five themes were developed: family disclosure, family gatekeeping, going for testing, individual and collective communication practices, and receiving a negative test result. To conclude, we highlight how these connections might be considered through the lens of entanglement, explaining the complex mechanisms through which family and genetics are intimately entwined.

Quality of life in adults with autism spectrum disorder: influence of age, sex, and a controlled, randomized mindfulness-based stress reduction pilot intervention.

PURPOSE: Adults with autism spectrum disorder (ASD) consistently report worse functional health and well-being, compared to neurotypical (NT) peers. In a series of studies, we aimed to elucidated the effects of sex, age, and their interaction on health-related quality of life (HRQoL) and evaluated the effectiveness of mindfulness-based stress reduction (MBSR) for improving health-, disability-, and autism-related QoL, with possible sex and age outcome moderators, in adults with ASD. METHODS: Study 1 used the 36-Item Short Form Survey to compare mental and physical HRQoL composite scores in adults with ASD (n = 67) and matched NT adults (n = 66). Study 2 was a randomized pilot evaluation of the effect of MBSR, compared to an active control intervention with social support and relaxation education (support/education; n = 56), on the World Health Organization QoL BREF, Disability, and Autism-Specific scales in adults with ASD. RESULTS: In Study 1, we replicated findings that mental HRQoL is worse in both men and women with ASD, compared to NT counterparts, but physical HRQoL is only worse in women with ASD. We present novel findings that older age is associated with better mental HRQoL in women with ASD only. In Study 2, MBSR improved disability-related QoL in adults with ASD over and above the support/education intervention, but both interventions improved mental HRQoL. Lastly, both interventions were more effective for HRQoL improvements in women with ASD. CONCLUSION: Findings encourage precision medicine approaches tailored to age and sex groups for best HRQoL outcomes in adults with ASD. CLINICALTRIALS: gov Identifier: NCT04017793.

Experiences of adolescents living with Silver-Russell syndrome.

OBJECTIVE: The psychosocial impact of growing up with Silver-Russell syndrome (SRS), characterised by growth failure and short stature in adulthood, has been explored in adults; however, there are no accounts of contemporary lived experience in adolescents. Such data could inform current healthcare guidance and transition to adult services. We aimed to explore the lived experience of adolescents with SRS. DESIGN/SETTING/PATIENTS: In-depth, semi-structured interviews were conducted between January 2015 and October 2016 with a sample of eight adolescents aged 13-18 (five girls) with genetically confirmed SRS from the UK. Qualitative interviews were transcribed and coded to identify similarities and differences using thematic analysis; codes were then grouped to form overarching themes. RESULTS: We identified four themes from the interview data: (1) the psychosocial challenges of feeling and looking different; (2) pain, disability and fatigue; (3) anticipated stigma; and (4) building resilience and acceptance. Despite adolescents accepting SRS in their lives, they described ongoing psychosocial challenges and anticipated greater problems to come, such as stigma from prospective employers. CONCLUSIONS: Adolescents with SRS may experience psychosocial difficulties from as young as 10 years old related to feeling and looking different; pain, disability and fatigue; anticipated stigma; and future challenges around employment. We discuss these findings in relation to recommendations for the care of adolescents with SRS to prepare them for adult life.

Phenotype of genetically confirmed Silver-Russell syndrome beyond childhood.

BACKGROUND: Silver-Russell syndrome is an imprinting disorder that restricts growth, resulting in short adult stature that may be ameliorated by treatment. Approximately 50% of patients have loss of methylation of the imprinting control region (H19/IGF2:IG-DMR) on 11p15.5 and 5%-10% have maternal uniparental disomy of chromosome 7. Most published research focuses on the childhood phenotype. Our aim was to describe the phenotypic characteristics of older patients with SRS. METHODS: A retrospective cohort of 33 individuals with a confirmed molecular diagnosis of SRS aged 13 years or above were carefully phenotyped. RESULTS: The median age of the cohort was 29.6 years; 60.6% had a height SD score (SDS) ≤-2 SDS despite 70% having received growth hormone treatment. Relative macrocephaly, feeding difficulties and a facial appearance typical of children with SRS were no longer discriminatory diagnostic features. In those aged ≥18 years, impaired glucose tolerance in 25%, hypertension in 33% and hypercholesterolaemia in 52% were noted. While 9/33 accessed special education support, university degrees were completed in 40.0% (>21 years). There was no significant correlation between quality of life and height SDS. 9/25 were parents and none of the 17 offsprings had SRS. CONCLUSION: Historical treatment regimens for SRS were not sufficient for normal adult growth and further research to optimise treatment is justified. Clinical childhood diagnostic scoring systems are not applicable to patients presenting in adulthood and SRS diagnosis requires molecular confirmation. Metabolic ill-health warrants further investigation but SRS is compatible with a normal quality of life including normal fertility in many cases.

Exploring broad consent in the context of the 100,000 Genomes Project: a mixed methods study.

The 100,000 Genomes Project (100kGP)-a hybrid clinical-research initiative-was set up to analyse whole-genome sequences (WGS) from patients living with a rare disease or cancer. The project positioned participant consent as being of central importance, but consent in the context of genomic testing raises challenging issues. In this mixed method study, we surveyed 1337 100kGP participants regarding their experiences of taking part in the project and conducted in-depth interviews with 24 survey respondents to explore these findings further. Survey responses were analysed using descriptive statistics and interview data were analysed thematically. The consent approach of the 100kGP resulted in a proportion of our study's participants not understanding the complexities of the project and what types of results they might receive; for example, 20% of participants who we surveyed from the cancer arm did not recall what decisions they had made regarding additional findings. It is not surprising that a project such as this, with such diverse aims and participant groups, would throw up at least some challenges. However, participants reported being satisfied with their experience of the project to date. Our study highlights that in the context of consent for more complex endeavours, such as the 100kGP, it is important to assess (and document) an agreement to take part, but complicated decisions about what and when to communicate may need revisiting over time in response to changing contexts. We discuss the implications of our findings with reference to participants of the 100kGP and the newly formed NHS Genomic Medicine Service.

Genome sequencing in healthcare: understanding the UK general public's views and implications for clinical practice.

Technological advances have seen the offer of genome sequencing becoming part of mainstream medical practice. Research has elicited patient and health professional views on the ethical issues genome sequencing raises, however, we know little about the general public's views. These views offer an insight into people's faith in such technologies, informing discussion regarding the approach to consent in clinic. We aimed to garner public views regarding genome sequencing, incidental findings (IFs), and sharing genetic information with relatives. Participants (n = 1954) from the British general public completed a survey, distributed via email. Overall, the public had a positive view of genomic sequencing, choosing 'informative' as the most popular word (52%) and 'family legacy' as the most popular analogy (33%) representing genomic sequencing for them. Fifty-three percent  agree that their relative had the right to be told about genetic information relevant to them. Fifty-four percent would expect to be told about IFs whether they had asked for them or not. Clinical practice needs to acknowledge these perspectives and expectations in order to facilitate meaningful discussion during the consent process for genomic tests. We suggest that: (a) optimistic perspectives on the usefulness of genomic tests need to be tempered by discussion in clinic about the likelihood that genomic results might be uninformative, uncertain or unexpected; (b) discussions regarding the familial nature of results are needed before testing: the majority of patients will welcome this and any concerns can be explored further; and (c) a wider discussion is required regarding the consent approach for genomic testing.

Lived experience of Silver-Russell syndrome: implications for management during childhood and into adulthood.

OBJECTIVE: There is limited information on the psychosocial impact of growing up with Silver-Russell syndrome (SRS), characterised by slow growth in utero leading to short stature in adulthood. Such information could aid families in making difficult treatment decisions and guide management strategies for health professionals. We aimed to explore the lived experience of people with SRS across the lifespan. DESIGN/SETTING/PATIENTS: In-depth, semi-structured interviews were conducted between January 2015 and October 2016 with a sample of 15 adults (six women) with genetically confirmed SRS from the UK. Qualitative interviews were transcribed and coded to identify similarities and differences: codes were then grouped to form overarching themes. RESULTS: Four themes were identified from participant accounts: (1) appearance-related concerns extending beyond height; (2) strategies to deal with real and perceived threats; (3) women's experiences of pain, disability and feeling older than their years; and (4) feeling overlooked in romantic relationships. These themes show that other factors, beyond short stature, affect patient well-being and indicate a mismatch between patient need and healthcare provision. CONCLUSIONS: Challenges in SRS during childhood and adolescence were central to the psychosocial impact of SRS, and were not limited to height. These challenges, as well as symptoms such as pain and fatigue for women, have not previously been documented. To help individuals with SRS develop strategies to manage psychosocial issues, we recommend clinicians incorporate psychological services as an integral part of multidisciplinary teams managing individuals with SRS during childhood, adolescence and adulthood.

Climate controls prokaryotic community composition in desert soils of the southwestern United States.

Aridisols are the dominant soil type in drylands, which occupy one-third of Earth's terrestrial surface. We examined controls on biogeographical patterns of Aridisol prokaryotic (bacterial and archaeal) communities at a regional scale by comparing communities from 100 Aridisols throughout the southwestern United States using high-throughput sequencing of the 16S rRNA gene. We found that microbial communities differed among global biomes and deserts of the Southwest. Differences among biomes were driven by differences in taxonomic identities, whereas differences among deserts of the Southwest were driven by differences in relative sequence abundance. Desert communities were dominated by Actinobacteria, Proteobacteria and Crenarchaeota, supporting the notion of a core set of abundant taxa in desert soils. Our findings contrast with studies showing little taxonomic overlap at the OTU level (97% sequence similarity) across large spatial scales, as we found ∼90% of taxa in at least two of the three deserts. Geographic distance structured prokaryotic communities indirectly through the influence of climate and soil properties. Structural equation modeling suggests that climate exerts a stronger influence than soil properties in shaping the composition of Aridisol microbial communities, with annual heat moisture index (an aridity metric) being the strongest climate driver. Annual heat moisture index was associated with decreased microbial diversity and richness. If the Desert Southwest becomes hotter and drier as predicted, these findings suggest that prokaryotic diversity and richness in Aridisols will decline.