Gene targeting as a therapeutic avenue in diseases mediated by the complement alternative pathway.

The complement alternative pathway (AP) is implicated in numerous diseases affecting many organs, ranging from the rare hematological disease paroxysmal nocturnal hemoglobinuria (PNH), to the common blinding disease age-related macular degeneration (AMD). Critically, the AP amplifies any activating trigger driving a downstream inflammatory response; thus, components of the pathway have become targets for drugs of varying modality. Recent validation from clinical trials using drug modalities such as inhibitory antibodies has paved the path for gene targeting of the AP or downstream effectors. Gene targeting in the complement field currently focuses on supplementation or suppression of complement regulators in AMD and PNH, largely because the eye and liver are highly amenable to drug delivery through local (eye) or systemic (liver) routes. Targeting the liver could facilitate treatment of numerous diseases as this organ generates most of the systemic complement pool. This review explains key concepts of RNA and DNA targeting and discusses assets in clinical development for the treatment of diseases driven by the alternative pathway, including the RNA-targeting therapeutics ALN-CC5, ARO-C3, and IONIS-FB-LRX, and the gene therapies GT005 and HMR59. These therapies are but the spearhead of potential drug candidates that might revolutionize the field in coming years.

Relaxation of Natural Selection in the Evolution of the Giant Lungfish Genomes.

Nonadaptive hypotheses on the evolution of eukaryotic genome size predict an expansion when the process of purifying selection becomes weak. Accordingly, species with huge genomes, such as lungfish, are expected to show a genome-wide relaxation signature of selection compared with other organisms. However, few studies have empirically tested this prediction using genomic data in a comparative framework. Here, we show that 1) the newly assembled transcriptome of the Australian lungfish, Neoceratodus forsteri, is characterized by an excess of pervasive transcription, or transcriptional leakage, possibly due to suboptimal transcriptional control, and 2) a significant relaxation signature in coding genes in lungfish species compared with other vertebrates. Based on these observations, we propose that the largest known animal genomes evolved in a nearly neutral scenario where genome expansion is less efficiently constrained.

Unravelling the mystery of endemic versus translocated populations of the endangered Australian lungfish (Neoceratodus forsteri).

The Australian lungfish is a primitive and endangered representative of the subclass Dipnoi. The distribution of this species is limited to south-east Queensland, with some populations considered endemic and others possibly descending from translocations in the late nineteenth century shortly after European discovery. Attempts to resolve the historical distribution of this species have met with conflicting results based on descriptive genetic studies. Understanding if all populations are endemic or some are the result of, or influenced by, translocation events, has implications for conservation management. In this work, we analysed the genetic variation at three types of markers (mtDNA genomes, 11 STRs and 5196 nuclear SNPs) using the approximate Bayesian computation (ABC) algorithm to compare several demographic models. We postulated different contributions of Mary River and Burnett River gene pools into the Brisbane River and North Pine River populations, related to documented translocation events. We ran the analysis for each marker type separately, and we also estimated the posterior probabilities of the models combining the markers. Nuclear SNPs have the highest power to correctly identify the true model among the simulated datasets (where the model was known), but different marker types typically provided similar answers. The most supported demographic model able to explain the real dataset implies that an endemic gene pool is still present in the Brisbane and North Pine Rivers and coexists with the gene pools derived from past documented translocation events. These results support the view that ABC modelling can be useful to reconstruct complex historical translocation events with contemporary implications, and will inform ongoing conservation efforts for the endangered and iconic Australian lungfish.

A community engagement training program for basic and translational cancer researchers.

PURPOSE: There is an increasing awareness of the importance of patient engagement in cancer research, but many basic and translational researchers have never been trained to do so. To address this unmet need, a 1-year patient engagement training program for researchers was developed. METHODS: Eleven researchers and eleven paired research advocates participated. This program, designed for virtual delivery, included 3 didactic modules focused on (1) Community Outreach and Engagement principles and methods, (2) Communication skills, and (3) Team Science. This was followed by longitudinal projects to be completed by the researcher/advocate pairs, including learning about the research project, and co-authoring abstracts, manuscripts and grant proposals. Monthly group meetings allowed pairs to share their experiences. The program culminated in the pairs creating and presenting oral abstracts for the University of Kansas Cancer Center's Annual Research Symposium. RESULTS: All participants indicated that the modules had a positive impact on their ability to collaborate in research. Both researcher self-evaluations and patient advocate evaluations of their researcher partner showed an improvement in researcher communication competency. Results from the Patient Engagement in Research Scale showed that advocates were highly engaged. Within 1 year after program completion, participating pairs have completed four abstracts and 9 grant proposals. CONCLUSION: The program will be modified based on participant feedback, and can be adapted for future cohorts if an increased number of sessions per month and shortened program duration are desired. The program's virtual format allows scalability across institutions to potentially benefit large cohorts of researchers.

Acute, diel, and annual temperature variability and the thermal biology of ectotherms.

Global warming is increasing mean temperatures and altering temperature variability at multiple temporal scales. To better understand the consequences of changes in thermal variability for ectotherms it is necessary to consider thermal variation at different time scales (i.e., acute, diel, and annual) and the responses of organisms within and across generations. Thermodynamics constrain acute responses to temperature, but within these constraints and over longer time periods, organisms have the scope to adaptively acclimate or evolve. Yet, hypotheses and predictions about responses to future warming tend not to explicitly consider the temporal scale at which temperature varies. Here, focusing on multicellular ectothermic animals, we argue that consideration of multiple processes and constraints associated with various timescales is necessary to better understand how altered thermal variability because of climate change will affect ectotherms.

Dementia Early-Stage Cognitive Aids New Trial (DESCANT) of memory aids and guidance for people with dementia: randomised controlled trial.

BACKGROUND: Common memory aids for people with dementia at home are recommended. However, rigorous evaluation is lacking, particularly what guidance or support is valued. OBJECTIVE: To investigate effects of memory aids and guidance by dementia support practitioners (DSPs) for people in early-stage dementia through a pragmatic, randomised controlled trial. METHODS: Of 469 people with mild-to-moderate dementia and their informal carers, 468 were randomised to a DSP with memory aids or to usual care plus existing dementia guide. Allocation was stratified by Trust/Health Board; time since first attendance at memory service; gender; age; and living with primary carer or not. Primary outcome was Bristol Activities of Daily Living Scale (BADLS) Score at 3 and 6 months (primary end-point). Secondary outcomes for people with dementia: quality of life (CASP-19; DEMQOL); cognition and functioning (Clinical Dementia Rating Scale; S-MMSE); capability (ICECAP-O); social networks (LSNS-R); and instrumental daily living activities (R-IDDD). Secondary outcomes for carers: psychological health (GHQ-12); sense of competence (SSCQ). RESULTS: DSPs were successfully trained, compliance was good and welcomed by participants. Mean 6 months BADLS Score increased to 14.6 (SD: 10.4) in intervention and 12.6 (SD: 8.1) in comparator, indicative of greater dependence in the activities of daily living. Adjusted between-group difference was 0.38 (95% CI: -0.89 to 1.65, p=0.56). Though this suggests greater dependency in the intervention group the difference was not significant. No differences were found in secondary outcomes. CONCLUSIONS: This intervention did not maintain independence in the activities of daily living with no improvement in other outcomes for people with dementia or carers. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN12591717.

Implementing the Dementia Early Stage Cognitive Aids New Trial (DESCANT) intervention: mixed-method process evaluation alongside a pragmatic randomised trial.

OBJECTIVES: The DESCANT (Dementia Early Stage Cognitive Aids New Trial) intervention provided a personalised care package designed to improve the cognitive abilities, function and well-being of people with early-stage dementia and their carers, by providing a range of memory aids, together with appropriate training and support. This sub-study aimed to assess implementation and identify contextual factors potentially associated with participant outcomes. METHOD: A mixed-methods approach was adopted alongside the pragmatic randomised trial. Data were obtained from intervention records and interviews with five dementia support practitioners across seven National Health Service Trusts in England and Wales. A reporting framework was constructed from available literature and data assessed by descriptive statistics and thematic analysis. RESULTS: Participation and engagement was high with 126 out of 128 participants completing the intervention with packages tailored to individual participants. Misplacing items and poor orientation to date and time were common areas of need. Memory aids frequently supplied included orientation clocks (91%), whiteboards (60%), calendars (43%) and notebooks (32%), plus bespoke items. Intervention duration and timing were broadly consistent with expectations. Variation reflected participants' needs, circumstances and preferences. Qualitative findings suggested a potentially positive impact on the well-being of people with dementia and their carers. Issues associated with successful roll-out of the intervention are explored in the discussion. CONCLUSION: Successful implementation increased confidence in future findings of the randomised trial. Depending on these, DESCANT may prove a scalable intervention with potential to improve the function and quality of life of people with dementia and their carers.

Hospital admissions and place of death of residents of care homes receiving specialist healthcare services: A systematic review without meta-analysis.

AIM: To synthesize evidence on the ability of specialist care home support services to prevent hospital admission of older care home residents, including at end of life. DESIGN: Systematic review, without meta-analysis, with vote counting based on direction of effect. DATA SOURCES: Fourteen electronic databases were searched from January 2010 to January 2019. Reference lists of identified reviews, study protocols and included documents were scrutinized for further studies. REVIEW METHODS: Papers on the provision of specialist care home support that addressed older, long-term care home residents' physical health needs and provided comparative data on hospital admissions were included. Two reviewers undertook study selection and quality appraisal independently. Vote counting by direction of effect and binomial tests determined service effectiveness. RESULTS: Electronic searches identified 79 relevant references. Combined with 19 citations from an earlier review, this gave 98 individual references relating to 92 studies. Most were from the UK (22), USA (22) and Australia (19). Twenty studies were randomized controlled trials and six clinical controlled trials. The review suggested interventions addressing residents' general health needs (p < .001), assessment and management services (p < .0001) and non-training initiatives involving medical staff (p < .0001) can reduce hospital admissions, while there was also promising evidence for services targeting residents at imminent risk of hospital entry or post-hospital discharge and training-only initiatives. End-of-life care services may enable residents to remain in the home at end of life (p < .001), but the high number of weak-rated studies undermined confidence in this result. CONCLUSION: This review suggests specialist care home support services can reduce hospital admissions. More robust studies of services for residents at end of life are urgently needed. IMPACT: The review addressed the policy imperative to reduce the avoidable hospital admission of older care home residents and provides important evidence to inform service design. The findings are of relevance to commissioners, providers and residents.

Functional expression of complement factor I following AAV-mediated gene delivery in the retina of mice and human cells.

Dry age-related macular degeneration (AMD) is characterised by loss of central vision and currently has no approved medical treatment. Dysregulation of the complement system is thought to play an important role in disease pathology and supplementation of Complement Factor I (CFI), a key regulator of the complement system, has the potential to provide a treatment option for AMD. In this study, we demonstrate the generation of AAV constructs carrying the human CFI sequence and expression of CFI in cell lines and in the retina of C57BL/6 J mice. Four codon optimised constructs were compared to the most common human CFI sequence. All constructs expressed CFI protein; however, most codon optimised sequences resulted in significantly reduced CFI secretion compared to the non-optimised CFI sequence. In vivo expression analysis showed that CFI was predominantly expressed in the RPE and photoreceptors. Secreted protein in vitreous humour was demonstrated to be functionally active. The findings presented here have led to the formulation of an AAV-vectored gene therapy product currently being tested in a first-in-human clinical trial in subjects with geographic atrophy secondary to dry AMD (NCT03846193).

The Dementia Early Stage Cognitive Aids New Trial (DESCANT) intervention: A goal attainment scaling approach to promote self-management.

OBJECTIVES: This study investigated goals identified by people with dementia and their carers to promote the self-management of symptoms and abilities; measured achievement using goal attainment scaling (GAS); and explored the reflections of Dementia Support Practitioners (DSPs) facilitating it. METHODS AND DESIGN: Within this pragmatic randomised trial, DSPs gave memory aids, training and support to people with mild to moderate dementia and their carers at home. Data were collected across seven NHS Trusts in England and Wales (2016-2018) and abstracted from intervention records and semi-structured interviews with DSPs delivering the intervention, supplemented by a subset of the trial dataset. Measures were created to permit quantification and descriptive analysis and interview data thematically analysed. A GAS measure for this intervention in this client group was derived. RESULTS: Engagement was high across the 117 participants and 293 goals were identified. These reflected individual circumstances and needs and enabled classification and assessment of their attainment. Seventeen goal types were identified across six domains: self-care, household tasks, daily occupation, orientation, communication, and well-being and safety. On average participants achieved nominally significant improvement regarding the specified goals of 1.4 with standard deviation of 0.6. Five interviews suggested that DSPs' experiences of goal setting were also positive. CONCLUSIONS: GAS is useful for assessing psychosocial interventions for people with early-stage dementia. It has a utility in identifying goals, promoting self-management and providing a personalised outcome measure. There is a strong case for exploring whether these clear benefits translate to other interventions in other populations in other places.

Total-evidence analysis of an undescribed fauna: resolving the evolution and classification of Australia's golden trapdoor spiders (Idiopidae: Arbanitinae: Euoplini).

In the trapdoor spider genus Euoplos Rainbow & Pulleine (tribe Euoplini), it was discovered recently that two divergent lineages occur in sympatry in eastern Australia. This challenged the monogeneric classification of the tribe and, in combination with inadequate taxonomic descriptions of some species, precluded comprehensive taxonomic revision. To resolve these issues, we conducted a total-evidence cladistic analysis on a largely undescribed continental fauna-the first such analysis on a group of Australian Mygalomorphae. We combined multilocus molecular data and/or morphological and behavioural data from all known species from eastern Australia (described and undescribed), plus a subset of Western Australian species, to produce a phylogeny for the tribe. We mapped morphological/behavioural characters onto this to identify clade-specific diagnostic characters, and applied these data to a generic reclassification of the tribe. We recovered two sympatric lineages in the Euoplini (the "wafer-door" and "plug-door/palisade" lineages), and revealed the phylogenetic position of all known eastern Australian species within these. Character mapping revealed morphological and behavioural (burrow architecture) features that allow diagnosis of the lineages and clades within them. We erect a new genus, Cryptoforis gen.n., to represent the wafer-door lineage, describe the type species, Cryptoforis hughesae sp.n., and transfer two species from Euoplos to Cryptoforis: C. tasmanica (Hickman, 1928) and C. victoriensis (Main, 1995). This study resolves phylogenetic structure within the Euoplini, and characterizes clades within the tribe to facilitate future taxonomic revisions. It also demonstrates that, whereas male morphology is more informative, female morphological characters relating to genitalia and the scopulation/spination of the anterior legs display phylogenetic signal in the Euoplini, highlighting the subtle nature of informative female characters in mygalomorph spiders.

Commissioning social care for people with dementia living at home: Findings from a national survey.

OBJECTIVE: To explore the complexities, circumstances, and range of services commissioned for people with dementia living at home. METHODS: A national survey was used to collect data from English local authorities in 2015. Commissioners of services for older adults were invited to complete a questionnaire. An exploratory cluster analysis of nominal data was conducted using a TwoStep procedure to identify distinct groups. RESULTS: A total of 122 authorities (83%) responded to the request. Four approaches to commissioning were identified, reflecting commissioning practices at the organisational, strategic, and individual service user levels. Commissioning at the service user level was most apparent. Bivariate analysis found that these configurations were not associated with the types of dementia specific services provided but were related to the number available. Authorities delivered a greater range of specialist services when joint commissioning between social care and health partners was undertaken. However, the joint commissioning of services was less observed in services specifically for people with dementia than in generic services for all older people. There was limited evidence that local circumstances (population configuration and deprivation levels) were associated with this approach to commissioning. CONCLUSIONS: The significant role of health partners in the delivery of social care services to support older people living with dementia in their own homes is evident. As the population with dementia ages and physical health needs increase, how dementia specific services differ from and complement those services available to all older people warrants further investigation.

Heritability of plumage colour morph variation in a wild population of promiscuous, long-lived Australian magpies.

Colour polymorphisms have evolutionary significance for the generation and maintenance of species diversity. Demonstrating heritability of polymorphic traits can be challenging for wild populations of long-lived species because accurate information is required on trait expression and familial relationships. The Australian magpie Cracticus tibicen has a continent-wide distribution featuring several distinct plumage morphs, differing primarily in colour of back feathers. Black or white-backed morphs occur in eastern Australia, with intermediate morphs common in a narrow hybrid zone where the two morphs meet. This study investigated heritability of back colour phenotypes in a hybrid zone population (Seymour, Victoria) based on long-term observational data and DNA samples collected over an 18 year period (1993-2010). High extra-pair paternity (~ 36% offspring), necessitated verification of parent-offspring relationships by parentage analysis. A total of 538 birds (221 parents and 317 offspring) from 36 territories were analysed. Back colour was a continuous trait scored on a five-morph scale in the field (0-4). High and consistent estimates of back colour heritability (h2) were obtained via weighted mid-parent regression (h2 = 0.94) and by animal models (h2 = 0.92, C.I. 0.80-0.99). Single-parent heritability estimates indicated neither maternal nor paternal non-genetic effects (e.g., parent body condition) played a large role in determining offspring back colour, and environmental effects of territory group and cohort contributed little to trait heritability. Distinctive back colouration of the Australian magpie behaves as a quantitative trait that is likely polygenic, although mechanisms responsible for maintaining these geographically structured morphs and the hybrid zone where they meet are unknown.

Dissection by genomic and plumage variation of a geographically complex hybrid zone between two Australian non-sister parrot species, Platycercus adscitus and Platycercus eximius.

The study of hybrid zones advances understanding of the speciation process, and approaches incorporating genomic data are increasingly used to draw significant conclusions about the impact of hybridisation. Despite the progress made, the complex interplay of factors that can lead to substantially variable hybridisation outcomes are still not well understood, and many systems and/or groups remain comparatively poorly studied. Our study aims to broaden the literature on avian hybrid zones, investigating a potentially geographically and temporally complex putative hybrid zone between two native Australian non-sister parrot species, the pale-headed and eastern rosellas (Platycercus adscitus and Platycercus eximius, respectively). We analysed six plumage traits and >1400 RADseq loci and detected hybrid individuals and an unexpectedly complex geographic structure. The hybrid zone is larger than previously described due to either observer bias or its movement over recent decades. It comprises different subregions where genetic and plumage signals of admixture vary markedly in their concordance. Evidence of contemporary hybridisation (later generation and backcrossed individuals) both within and beyond the previously defined zone, when coupled with a lack of F1 hybrids and differential patterns of introgression among potentially diagnostic loci, indicates a lack of post-zygotic barriers to gene flow between species. Despite ongoing gene flow, species boundaries are likely maintained largely by strong pre-mating barriers. These findings are discussed in detail and future avenues for research into this system are proposed, which would be of benefit to the speciation and hybrid zone literature.

Applying a new concept of embedding qualitative research: an example from a quantitative study of carers of people in later stage dementia.

BACKGROUND: Qualitative methods are increasingly included in larger studies to provide a richer understanding of people's experience. This paper explores the potential of using a novel approach to embedded qualitative design as part of an observational study examining the effectiveness of home support for people in later stage dementia in England. The method involved collecting and analysing unsolicited conversational comments made by participants as they completed standardised measures. An evaluation of the method is presented using the voices of participants to illustrate its potential. METHODS: The conversations of 17 carers recruited to an observational study were audio recorded to gather commentary made while completing a structured interview. Data were interrogated using thematic analysis to investigate the feasibility of conducting an embedded qualitative study, the potential richness of the material and participants' reactions to formal questioning and participating in research. RESULTS: The findings revealed that qualitative data were available from this approach. Analysis generated three themes from carers: conflicting carer emotions; the importance of maintaining normality and agency within day-to-day life; and tensions between these desires and making use of formal services. Important issues for carers were revealed establishing the benefit of using the method. The advantages of exploiting unsolicited conversation included enhancing understanding of people's lived experience, reducing participant burden in research and easing the process of data collection. In addition, it provided an opportunity to evaluate individuals' experience of the research process. CONCLUSIONS: The findings demonstrate how unsolicited comments during structured interviews may appear incidental but can reveal important aspects of living with dementia. The method also emphasised methodological challenges for research in dementia, including the influence and impact of the research context. Further research is required to evaluate the method with other groups including people with dementia themselves.

Carer preferences for home support services in later stage dementia.

OBJECTIVES: To examine the relative importance of different home support attributes from the perspective of carers of people with later-stage dementia. METHOD: Preferences from 100 carers, recruited through carers' organisations, were assessed with a Discrete Choice Experiment (DCE) survey, administered online and by paper questionnaire. Attributes were informed by an evidence synthesis and lay consultations. A conditional logit model was used to estimate preference weights for the attributes within a home support 'package'. RESULTS: The most preferred attributes were 'respite care, available regularly to fit your needs' (coefficient 1.29, p = < 0.001) and 'home care provided regularly for as long as needed' (coefficient 0.93, p = < 0.001). Cost had a significant effect with lower cost packages preferred. Findings were similar regardless of the method of administration, with respite care considered to be the most important attribute for all carers. Carers reported that completing the DCE had been a positive experience; however, feedback was mixed overall. CONCLUSIONS: These carer preferences concur with emerging evidence on home support interventions for dementia. Respite care, home care and training on managing difficulties provided at home are important components. Carers' preferences revealed the daily challenges of caring for individuals with later stage dementia and the need for tailored and specialised home support.

Hospital admissions and place of death of residents of care homes receiving specialist healthcare services: Protocol for a systematic review.

AIM: To synthesize the evidence relating to the ability of specialist care home support services to prevent the hospital admission of older care home residents, including hospital admission at the end-of-life. DESIGN: Systematic review and narrative synthesis. METHODS: Ten electronic databases will be searched from 2010 - 31 December 2018 using predetermined search terms. All studies of specialist healthcare services to meet care home residents' physical healthcare needs which provide outcome data on hospital admission or place of death compared with usual care will be included. Two reviewers will independently assess studies' eligibility and methodological quality using the Effective Public Health Practice Project Quality Assessment Tool. Data will be extracted by one reviewer and checked by a second according to predetermined categories. Data will be synthesized in evidence tables and narrative. Funder: National Institute for Health Research School for Social Care Research, November 2016. DISCUSSION: Care of older people in care home settings is a key aspect of nursing nationally and internationally. This review will increase understanding of the extent to which different models of specialist healthcare support for care homes are associated with key resident outcomes. IMPACT: Standard healthcare support for care home residents is often inadequate, resulting in avoidable hospital admissions and lack of resident choice as to place of death. Although a range of specialist healthcare services are emerging, little is known about their relative effectiveness. This paper marshalls evidence of relevance to commissioners investing in healthcare provision to care homes to meet NHS targets.

Monitoring age-related trends in genomic diversity of Australian lungfish.

An important challenge for conservation science is to detect declines in intraspecific diversity so that management action can be guided towards populations or species at risk. The lifespan of Australian lungfish (Neoceratodus forsteri) exceeds 80 years, and human impacts on breeding habitat over the last half century may have impeded recruitment, leaving populations dominated by old postreproductive individuals, potentially resulting in a small and declining breeding population. Here, we conduct a "single-sample" evaluation of genetic erosion within contemporary populations of the Australian lungfish. Genetic erosion is a temporal decline in intraspecific diversity due to factors such as reduced population size and inbreeding. We examined whether young individuals showed signs of reduced genetic diversity and/or inbreeding using a novel bomb radiocarbon dating method to age lungfish nonlethally, based on 14 C ratios of scales. A total of 15,201 single nucleotide polymorphic (SNP) loci were genotyped in 92 individuals ranging in age from 2 to 77 years old. Standardized individual heterozygosity and individual inbreeding coefficients varied widely within and between riverine populations, but neither was associated with age, so perceived problems with recruitment have not translated into genetic erosion that could be considered a proximate threat to lungfish populations. Conservation concern has surrounded Australian lungfish for over a century. However, our results suggest that long-lived threatened species can maintain stable levels of intraspecific variability when sufficient reproductive opportunities exist over the course of a long lifespan.

Spiny trapdoor spiders (Euoplos) of eastern Australia: Broadly sympatric clades are differentiated by burrow architecture and male morphology.

Spiders of the infraorder Mygalomorphae are fast becoming model organisms for the study of biogeography and speciation. However, these spiders can be difficult to study in the absence of fundamental life history information. In particular, their cryptic nature hinders comprehensive sampling, and linking males with conspecific females can be challenging. Recently discovered differences in burrow entrance architecture and male morphology indicated that these challenges may have impeded our understanding of the trapdoor spider genus Euoplos in Australia's eastern mesic zone. We investigated the evolutionary significance of these discoveries using a multi-locus phylogenetic approach. Our results revealed the existence of a second, previously undocumented, lineage of Euoplos in the eastern mesic zone. This new lineage occurs in sympatry with a lineage previously known from the region, and the two are consistently divergent in their burrow entrance architecture and male morphology, revealing the suitability of these characters for use in phylogenetic studies. Divergent burrow entrance architecture and observed differences in microhabitat preferences are suggested to facilitate sympatry and syntopy between the lineages. Finally, by investigating male morphology and plotting it onto the phylogeny, we revealed that the majority of Euoplos species remain undescribed, and that males of an unnamed species from the newly discovered lineage had historically been linked, erroneously, to a described species from the opposite lineage. This paper clarifies the evolutionary relationships underlying life history diversity in the Euoplos of eastern Australia, and provides a foundation for urgently needed taxonomic revision of this genus.

Preserving fertility in women with cancer (PreFer): Decision-making and patient-reported outcomes in women offered egg and embryo freezing prior to cancer treatment.

OBJECTIVE: Women of childbearing age with new cancer diagnoses have to make rapid decisions about fertility preservation (FP) before starting cancer treatment (CT). The aim of the PreFer study was to explore this FP decision-making process and its impact on patient-reported outcomes (PROMs) and health-related quality of life (HRQoL). METHODS: A prospective, mixed-methods design was used (questionnaires, in-depth interviews). Interviews were analysed using thematic analysis. Fifty-eight women with new cancer diagnoses were recruited. Comparisons were made between women who declined FP referral in oncology (Group1) and women who chose referral (Group2). Group 2 was further split into those who had some FP (2A) and those who did not (2B). Questionnaires and PROMs were administered prior to and after the fertility consultation, before the start of CT and 3 months post CT. Interviews were conducted with one participant from Group 2. RESULTS: HRQoL was negatively affected, particularly depression. Women's lack of understanding about the relationship between CT and fertility were evident. Five themes emerged from the interviews as barriers and facilitators to the FP decision-making process. CONCLUSION: The results indicate that better information and support resources aimed at women to support their decision making are needed, such as patient decision-aids. Women from Group 1 were found to suffer significantly worse depression compared with the general UK population, highlighting the need for psychological support in the FP care-pathway and for research exploring the contributions of depression and hopelessness to the decision-making process.