The potential of genomics for restoring ecosystems and biodiversity.

Billions of hectares of natural ecosystems have been degraded through human actions. The global community has agreed on targets to halt and reverse these declines, and the restoration sector faces the important but arduous task of implementing programmes to meet these objectives. Existing and emerging genomics tools offer the potential to improve the odds of achieving these targets. These tools include population genomics that can improve seed sourcing, meta-omics that can improve assessment and monitoring of restoration outcomes, and genome editing that can generate novel genotypes for restoring challenging environments. We identify barriers to adopting these tools in a restoration context and emphasize that regulatory and ethical frameworks are required to guide their use.

Genomic determinants, architecture, and constraints in drought-related traits in Corymbia calophylla.

BACKGROUND: Drought adaptation is critical to many tree species persisting under climate change, however our knowledge of the genetic basis for trees to adapt to drought is limited. This knowledge gap impedes our fundamental understanding of drought response and application to forest production and conservation. To improve our understanding of the genomic determinants, architecture, and trait constraints, we assembled a reference genome and detected ~ 6.5 M variants in 432 phenotyped individuals for the foundational tree Corymbia calophylla. RESULTS: We found 273 genomic variants determining traits with moderate heritability (h2SNP = 0.26-0.64). Significant variants were predominantly in gene regulatory elements distributed among several haplotype blocks across all chromosomes. Furthermore, traits were constrained by frequent epistatic and pleiotropic interactions. CONCLUSIONS: Our results on the genetic basis for drought traits in Corymbia calophylla have several implications for the ability to adapt to climate change: (1) drought related traits are controlled by complex genomic architectures with large haplotypes, epistatic, and pleiotropic interactions; (2) the most significant variants determining drought related traits occurred in regulatory regions; and (3) models incorporating epistatic interactions increase trait predictions. Our findings indicate that despite moderate heritability drought traits are likely constrained by complex genomic architecture potentially limiting trees response to climate change.

Mapping Online Community Spaces Through Online Focus Group Discussions Among Gay, Bisexual, and Other Men Who Have Sex With Men in Guangdong, China: Implications for Human Immunodeficiency Virus/Sexually Transmitted Disease Prevention Services.

BACKGROUND: Chinese gay, bisexual, and other men who have sex with men (GBMSM) face discrimination in many facility-based health services, thus increasing the importance of online engagement. The purpose of this study was to examine online GBMSM community spaces and implications for HIV/sexually transmitted disease prevention services. METHODS: We conducted a total of 6 online focus group discussions with Chinese GBMSM from Guangdong province on the chat-based platform WeChat in 2021. Focus group discussions were asynchronous, and participants were able to provide and map out online spaces that they had participated in and share their perspectives on online engagement. Data were analyzed through framework analysis. RESULTS: Overall, 48 participants participated. Most were mainly sexually attracted to men (n = 43; 90.0%) and never participated in in-person LGBTQ-related events (n = 29; 60.4%). Participants articulated a typology of online spaces along the axes of whether such spaces were Chinese platforms (vs. non-Chinese) or whether they were GBMSM-specific (vs. non-GBMSM-specific). Participants articulated several advantages of online spaces, including greater anonymity, opportunities for community building, sharing of sexual health information, and being able to meet other GBMSM more efficiently. Drawbacks included the lack of personal connection, lack of safety measures for youth, encountering deception and the use of fake profile pictures, and needing a virtual proxy network to access some websites. Participants provided suggestions to further improve their experiences of online spaces. CONCLUSIONS: Although broad-based, GBMSM-specific messaging can be implemented in Chinese, GBMSM-specific spaces, sexual health messaging may also reach niche GBMSM communities in a variety of non-GBMSM spaces.

Genetic mixing in conservation translocations increases diversity of a keystone threatened species, Bettongia lesueur.

Translocation programmes are increasingly being informed by genetic data to monitor and enhance conservation outcomes for both natural and established populations. These data provide a window into contemporary patterns of genetic diversity, structure and relatedness that can guide managers in how to best source animals for their translocation programmes. The inclusion of historical samples, where possible, strengthens monitoring by allowing assessment of changes in genetic diversity over time and by providing a benchmark for future improvements in diversity via management practices. Here, we used reduced representation sequencing (ddRADseq) data to report on the current genetic health of three remnant and seven translocated boodie (Bettongia lesueur) populations, now extinct on the Australian mainland. In addition, we used exon capture data from seven historical mainland specimens and a subset of contemporary samples to compare pre-decline and current diversity. Both data sets showed the significant impact of population founder source (whether multiple or single) on the genetic diversity of translocated populations. Populations founded by animals from multiple sources showed significantly higher genetic diversity than the natural remnant and single-source translocation populations, and we show that by mixing the most divergent populations, exon capture heterozygosity was restored to levels close to that observed in pre-decline mainland samples. Relatedness estimates were surprisingly low across all contemporary populations and there was limited evidence of inbreeding. Our results show that a strategy of genetic mixing has led to successful conservation outcomes for the species in terms of increasing genetic diversity and provides strong rationale for mixing as a management strategy.

Population genomic diversity and structure in the golden bandicoot: a history of isolation, extirpation, and conservation.

Using genetic information to develop and implement conservation programs is vital for maintaining biodiversity and ecosystem resilience. Evaluation of the genetic variability within and among remnant populations can inform management of both natural and translocated populations to maximise species' adaptive potential, mitigate negative impacts of inbreeding, and subsequently minimise risk of extinction. Here we use reduced representation sequencing to undertake a genetic assessment of the golden bandicoot (Isoodon auratus), a threatened marsupial endemic to Australia. The currently recognised taxon consists of three subspecies distributed among multiple natural and translocated populations. After confirming the genetic distinctiveness of I. auratus from two closely related taxa, I. fusciventer and I. macrourus, we identified four genetic clusters within I. auratus. These clusters exhibited substantial genetic differentiation (pairwise FST values ranging from 0.18 to 0.65, pairwise DXY ranging from 0.1 to 0.168), reflecting long-term isolation of some populations on offshore islands and the influence of genetic drift. Mainland natural populations in the Kimberley region had the highest genetic diversity and the largest contribution to overall allelic and gene diversity compared to both natural and translocated island populations. A population translocated to Guluwuru Island in the Northern Territory had the lowest genetic diversity. Our data suggest that island populations can appear genetically unique due to genetic drift and this needs to be taken into account when considering genetic diversity in conservation efforts to maintain overall genetic diversity of the species. We effectively demonstrate how genomic information can guide practical conservation planning, especially when declining species are represented by multiple isolated populations.

Linking life history to landscape for threatened species conservation in a multiuse region.

Landscape-scale conservation that considers metapopulation dynamics will be essential for preventing declines of species facing multiple threats to their survival. Toward this end, we developed a novel approach that combines occurrence records, spatial-environmental data, and genetic information to model habitat, connectivity, and patterns of genetic structure and link spatial attributes to underlying ecological mechanisms. Using the threatened northern quoll (Dasyurus hallucatus) as a case study, we applied this approach to address the need for conservation decision-making tools that promote resilient metapopulations of this threatened species in the Pilbara, Western Australia, a multiuse landscape that is a hotspot for biodiversity and mining. Habitat and connectivity were predicted by different landscape characteristics. Whereas habitat suitability was overwhelmingly driven by terrain ruggedness, dispersal was facilitated by proximity to watercourses. Although there is limited evidence for major physical barriers in the Pilbara, areas with high silt and clay content (i.e., alluvial and hardpan plains) showed high resistance to dispersal. Climate subtlety shaped distributions and patterns of genetic turnover, suggesting the potential for local adaptation. By understanding these spatial-environmental associations and linking them to life-history and metapopulation dynamics, we highlight opportunities to provide targeted species management. To support this, we have created habitat, connectivity, and genetic uniqueness maps for conservation decision-making in the region. These tools have the potential to provide a more holistic approach to conservation in multiuse landscapes globally.

La conservación a nivel del paisaje que incluye las dinámicas metapoblacionales será esencial para prevenir la declinación de especies con múltiples amenazas a su supervivencia. Enfocados en este fin, desarrollamos una estrategia novedosa que combina los registros presenciales, datos espacio-ambientales e información genética para modelar la conectividad de hábitat y los patrones de estructura genética y conectar los atributos espaciales con los mecanismos ecológicos subyacentes. Usamos al cuol del norte (Dasyurus hallucatus) como estudio de caso para aplicar esta estrategia y abordar la necesidad de herramientas de decisión en la conservación que promuevan metapoblaciones resilientes de esta especie en la Pilbara de Australia Occidental, un paisaje multiusos que es un punto caliente para la biodiversidad y la minería. Diferentes características del paisaje pronosticaron la conectividad y el hábitat. Mientras que la escabrosidad del terreno causó enormemente la idoneidad del hábitat, la dispersión estuvo propiciada por la proximidad a los cauces. Aunque hay evidencias limitadas de barreras físicas importantes en la Pilbara, las áreas con un contenido elevado de limo y arcilla (es decir, planicies aluviales y de alio) mostraron una gran resistencia a la dispersión. La matización climática determinó la distribución y los patrones del recambio genético, lo que sugiere un potencial para la adaptación local. Si entendemos estas asociaciones espacio-ambientales y las conectamos con las dinámicas metapoblacionales y de historia de vida, podemos resaltar las oportunidades para proporcionar un manejo focalizado de la especie. Para respaldar esto hemos creado mapas de hábitat, conectividad y singularidad genética para las decisiones de conservación en la región. Estas herramientas tienen el potencial de proporcionar una estrategia más holística para la conservación en los paisajes multiusos de todo el mundo.

Self-help smoking cessation intervention for Spanish-speaking Hispanics/Latinxs in the United States: A randomized controlled trial.

BACKGROUND: Hispanic/Latinx smokers living in the United States face unique challenges in quitting smoking. This study evaluated the efficacy of a culturally relevant, Spanish-language, extended self-help smoking cessation intervention among Hispanic smokers. METHODS: A 2-arm parallel randomized controlled trial was conducted with Hispanic/Latinx smokers living in the United States who preferred health information in Spanish and smoked 5 or more cigarettes per week. Participants were randomly allocated to receive Libre del Cigarrillo (LDC), which consisted of 11 booklets and 9 pamphlets mailed monthly over 18 months, or the usual care (UC), which was a single Spanish-language self-help booklet from the National Cancer Institute. The primary outcome was self-reported 7-day point prevalence smoking abstinence assessed 6, 12, 18, and 24 months after the baseline. Eight prespecified moderators of the intervention were evaluated. Cost-effectiveness was also evaluated. All statistical tests were 2-sided. RESULTS: Data from all participants randomized to LDC (n = 714) or UC (n = 703) were used for analyses after multiple imputation to manage missing data. Generalized estimating equation analyses indicated that LDC abstinence rates were higher (P < .001) across all assessments. Logistic regression analyses revealed that at 24 months, the abstinence rate was greater for LDC (33.1%) than UC (24.3%; odds ratio, 1.54; 95% confidence interval, 1.18-2.02; P = .002). Men exhibited a strong intervention effect at all assessments (P values < .001), whereas the intervention effect for women was observed only at 6 and 12 months (P values < .018). In comparison with UC, the incremental cost per quitter in the LDC arm was $648.43 at 18 months and $683.93 at 24 months. CONCLUSIONS: A culturally relevant, Spanish-language intervention was efficacious and cost-effective for smoking cessation. LAY SUMMARY: Research is needed to develop interventions for ethnic minority smokers. The aim of the current study was to test a Spanish-language adaptation of a validated and easily implemented self-help smoking cessation intervention in a nationwide randomized controlled trial. The findings demonstrated that the intervention produced greater smoking abstinence in comparison with a standard self-help booklet. Participants also were more satisfied with the intervention, and it was cost-effective. Efforts aimed at promoting tobacco abstinence in this underserved population could have significant public health implications, including potential reductions in cancer health disparities associated with tobacco smoking.

Signatures of natural selection in a foundation tree along Mediterranean climatic gradients.

Temperature and precipitation regimes are rapidly changing, resulting in forest dieback and extinction events, particularly in Mediterranean-type climates (MTC). Forest management that enhance forests' resilience is urgently required, however adaptation to climates in heterogeneous landscapes with multiple selection pressures is complex. For widespread trees in MTC we hypothesized that: patterns of local adaptation are associated with climate; precipitation is a stronger factor of adaptation than temperature; functionally related genes show similar signatures of adaptation; and adaptive variants are independently sorting across the landscape. We sampled 28 populations across the geographic distribution of Eucalyptus marginata (jarrah), in South-west Western Australia, and obtained 13,534 independent single nucleotide polymorphic (SNP) markers across the genome. Three genotype-association analyses that employ different ways of correcting population structure were used to identify putatively adapted SNPs associated with independent climate variables. While overall levels of population differentiation were low (FST  = 0.04), environmental association analyses found a total of 2336 unique SNPs associated with temperature and precipitation variables, with 1440 SNPs annotated to genic regions. Considerable allelic turnover was identified for SNPs associated with temperature seasonality and mean precipitation of the warmest quarter, suggesting that both temperature and precipitation are important factors in adaptation. SNPs with similar gene functions had analogous allelic turnover along climate gradients, while SNPs among temperature and precipitation variables had uncorrelated patterns of adaptation. These contrasting patterns provide evidence that there may be standing genomic variation adapted to current climate gradients, providing the basis for adaptive management strategies to bolster forest resilience in the future.

The nuanced nature of mesic refugia in arid landscapes: a tale of two peas.

BACKGROUND AND AIMS: Understanding how genetic diversity is distributed and maintained within species is a central tenet of evolutionary and conservation biology, yet is understudied in arid regions of the globe. In temperate, glaciated environments, high genetic diversity in plant species is frequently found in refugial areas, which are often associated with southern non-glaciated landscapes. In arid, unglaciated environments, landscape features providing mesic conditions are likely to be refugia, although our understanding needs more refinement in these biomes. We test whether refugia and nuclear diversity hotspots occur in high-elevation, topographically complex areas for co-distributed shrubs (Petalostylis labicheoides and Indigofera monophylla; Fabaceae) in the ancient, arid Pilbara bioregion of north-western Australia. METHODS: We conducted extensive sampling of the Pilbara (>1400 individuals from 62 widespread populations) to detect patterns in nuclear diversity and structure based on 13-16 microsatellite loci. Evidence of historical refugia was investigated based on patterns of diversity in three non-coding chloroplast (cp) sequence regions for approx. 240 individuals per species. Haplotype relationships were defined with median-joining networks and maximum likelihood phylogenetic trees. KEY RESULTS: We found cpDNA evidence for a high-elevation refugium in P. labicheoides but not for I. monophylla that instead exhibited extraordinary haplotype diversity and evidence for persistence across a widespread area. Nuclear diversity hotspots occurred in, but were not exclusive to, high-elevation locations and extended to adjacent, low-elevation riparian areas in both species. CONCLUSIONS: Phylogeographic refugia in arid environments may occur in high-elevation areas for some species but not all, and may be influenced by species-specific traits: a mesic montane refugium in P. labicheoides could be related to its preference for growth in water-gaining areas, while a lack of such evidence in I. monophylla could be related to maintenance of cpDNA diversity in a large soil seed bank and dynamic evolutionary history. Mesic environments created by the intersection of topographically complex landscapes with riparian zones can be contemporary reservoirs of genetic diversity in arid landscapes.

Hispanic/Latinx Ethnic Subgroup Differences in Sociodemographic, Sociocultural, and Smoking Characteristics in a Cessation Trial: An Exploratory Study.

INTRODUCTION: Hispanic/Latinx smokers in the United States are often treated as a homogeneous group. However, population-based studies suggest that cigarette use differs among Hispanic/Latinx subgroups by sociodemographic or sociocultural characteristics. This secondary analysis aimed to advance the limited literature by examining differences in smoking-related variables. AIMS AND METHODS: We used baseline data from a randomized controlled trial testing a self-help Spanish-language smoking cessation intervention. Puerto Rican (PR), Mexican, and Cuban, the three largest Hispanic/Latinx subgroups in the sample (N = 1028), were first compared on sociodemographic and sociocultural variables (acculturation and familism). Primary analyses assessed subgroup differences in cigarette use variables (eg, cigarettes per day [CPD], nicotine dependence [Fagerström Test for Nicotine Dependence], and daily smoking) and smoking-related cognitive constructs (motivation to quit, smoking outcome expectancies, and abstinence self-efficacy) controlling for sociodemographic and sociocultural variables. Additional analyses explored differences between men and women within subgroups. RESULTS: Mexicans exhibited the lowest levels of daily smoking (90% vs. 95% Cubans and 96% PR; p = .001), CPD (M = 13.5, SD = 9.5 vs. M = 20.1, SD = 9.9 Cubans and M = 16.7, SD = 10.1 PR; p = .016), and nicotine dependence (M = 4.2, SD = 2.3 vs. M = 6.0, SD = 2.1 Cubans and M = 5.7, SD = 2.2 PR; p < .001), with no differences between PRs and Cubans. Within-subgroup comparisons between men and women showed the most differences among PRs (eg, men were more nicotine dependent [M = 6.0, SD = 1.9] than women [M = 5.4, SD = 2.3; p = .041]) and Cubans (eg, men smoked more CPD [M = 22.2, SD = 12.2] than women [M = 19.3, SD = 12.0; p = .042]), and the fewest among Mexicans. CONCLUSIONS: Findings support heterogeneity within Hispanic/Latinx smokers and highlight the potential utility of examining sociodemographic, sociocultural, and smoking characteristics important for developing salient cessation interventions. IMPLICATIONS: Findings demonstrate that treatment-seeking Hispanic/Latinx smokers in the United States differ in sociodemographic, sociocultural, and smoking-related variables (cigarette use and smoking-related cognitive constructs) by subgroup (ie, PR, Mexican, and Cuban) and within subgroups by sex. These differences suggest that heterogeneity among subgroups should be considered when developing cessation interventions for Hispanics/Latinxs. Future research should examine how differences in sociodemographic and smoking-related variables impact intervention outcomes and explore the role of sociocultural factors (eg, acculturation and familism) as determinants of cessation.

Addressing a critical need for caregiver support in neuro-oncology: development of a caregiver navigation intervention using eSNAP social resource visualization.

Informal caregivers are key to oncology care, but often have unmet needs, leading to poor psychological and physical health outcomes. Comprehensive, proactive caregiver support programs are needed. We describe the development of a support intervention for caregivers of persons with brain tumors. The intervention uses a caregiver navigator to help participants identify and capitalize on existing social support resources captured using a web-based tool (eSNAP) and connects participants to existing formal services. We describe the iterative development process of the manualized intervention with particular focus on the caregiver navigator sessions. The process included review of the literature and published patient navigation programs, expert and stakeholder review, and study team member review. Quantitative and qualitative data were captured from the first 15 participants randomized to receive the intervention, enrolled from February 2020 to December 2020. Four participants dropped from the study, 9 completed at least 7 modules, and 8 participants completed all 8. Quantitative and qualitative data were collected primarily from those who completed the intervention; data suggest caregivers were satisfied with the intervention and found it helpful. Our intervention is one of the first theory-based caregiver support interventions to include caregiver navigation in neuro-oncology. We use best-practice guidelines for design, including extensive stakeholder feedback. COVID-19 may have impacted recruitment and participation, but some preliminary data suggest that those able to engage with the intervention find it helpful. Data collection is ongoing in a larger trial. If effective, caregiver navigation could be a model for future interventions to ensure caregiver support.

Training cancer caregiver navigators: experiences from implementing the eSNAP and caregiver navigator intervention.

Patient navigation is increasingly common in cancer care. While navigation programs often involve informal family caregivers, few navigation interventions specifically target the family caregiver. We developed the eSNAP and Caregiver Navigator Intervention to help cancer family caregivers identify and capitalize on informal and formal social support resources. While the skill set for patient navigators may be adequate for supporting caregivers, other skills and areas of knowledge expertise are needed. In addition, sparse documentation of navigator training best practices creates further challenges for dissemination and implementation. Our goal is to describe the education and training of cancer caregiver navigators within key competencies used to prepare and support navigators to deliver our manualized intervention. Nationally recognized navigation competencies, related to developing a sensitivity to ethical, cultural, and professional issues, knowledge development, skills development, and practice-based learning, were identified and adapted. Performance goals were identified within each competency. Training activities were selected to support competency development. Based on adult learning theories, we emphasize multiple learning strategies, including experiential learning and critical reflection. Two caregiver navigators engaged in initial training between December, 2019 and February, 2020. Initial training was supervised by study leadership, who coordinated with experts and stakeholders. Navigators completed initial training. We describe lessons learned. To ensure that navigators are well-equipped to provide effective services, evidence-based training programs that include navigation and protocol-specific competencies are needed. Given the lack of detailed training programs in the literature, we created a flexible, multimodal learning approach that other teams may adopt.

A Quantitative Analysis of Facial Asymmetry in Torticollis Using 3-Dimensional Photogrammetry.

OBJECTIVE: To assess whether children with torticollis have quantifiably greater facial asymmetry than their age-matched controls using 3-dimensional (3D) photogrammetry. DESIGN: We retrospectively analyzed patients diagnosed with torticollis and age-matched volunteers who underwent 3D photogrammetry of their faces. We calculated the root mean square deviation (RMSD) between native and reflected facial images, as a measure of asymmetry. Two observers independently measured RMSD values for all study participants. The Spearman correlation coefficient evaluated interobserver reliability. The Wilcoxon rank-sum test with Bonferroni adjusted P values for multiple comparisons. SETTING: Institutional. PARTICIPANTS: Twenty patients diagnosed with torticollis and 12 age-matched volunteers. Patients were analyzed on a computer database and volunteers were selected and consented in the hospital. We excluded patients with a history of facial trauma, facial operations, or other craniofacial diagnoses. INTERVENTIONS: Facial surface scans were obtained using the Canfield Vectra stereophotogrammetry system. The technology captures surface anatomy without radiation. MAIN OUTCOME MEASURES: RMSD comparisons between patients with torticollis and age-matched controls. RESULTS: Compared to controls, patients with torticollis had statistically significant greater full face, upper third, and middle third facial asymmetry. There was a trend toward greater asymmetry of the lower facial third. CONCLUSIONS: We used 3D photogrammetry to quantitate facial asymmetry from torticollis. We found greater asymmetry in patients with torticollis than in their unaffected peers. All areas of the face appeared to be affected, though the asymmetry in the lower facial third just failed to reach significance.

Tailored Messages About Research Participation: Using an Interactive Information Aid to Improve Study Recruitment.

After a diagnosis of cancer (or other serious disease), patients may be asked to consider joining a clinical trial. Because most people are unfamiliar with the scientific concepts that are necessary to the provision of meaningful informed consent, patient education is necessary. Increasing knowledge alone is not sufficient; understanding how clinical trial participation aligns with personal circumstances and knowledge is central to the decision-making process. In this study, 302 cancer patients and survivors evaluated an interactive information aid (IA) designed to inform their decision to join a research study or clinical trial by providing tailored information to patients' responses to questions pertaining to seven key barriers or facilitators of clinical trial participation. The development of the IA was done with input from the authors' Clinical Translational Science Institute; linked components of the IA were vetted by members and leaders of the institution's NCI-designated comprehensive cancer center. Results of the study indicated that the information aid was successful in significantly reducing fears and increasing knowledge, attitudes, perceived behavioral control, and behavioral intentions about research participation relative to a control condition. Thus, an interactive information aid that provides information that is responsive to patients' values, knowledge, and personal circumstances can help patients to be better prepared to consider a decision about research participation.

Repeated extreme heatwaves result in higher leaf thermal tolerances and greater safety margins.

The frequency and severity of heatwave events are increasing, exposing species to conditions beyond their physiological limits. Species respond to heatwaves in different ways, however it remains unclear if plants have the adaptive capacity to successfully respond to hotter and more frequent heatwaves. We exposed eight tree populations from two climate regions grown under cool and warm temperatures to repeated heatwave events of moderate (40°C) and extreme (46°C) severity to assess adaptive capacity to heatwaves. Leaf damage and maximum quantum efficiency of photosystem II (Fv /Fm ) were significantly impacted by heatwave severity and growth temperatures, respectively; populations from a warm-origin avoided damage under moderate heatwaves compared to those from a cool-origin, indicating a degree of local adaptation. We found that plasticity to heatwave severity and repeated heatwaves contributed to enhanced thermal tolerance and lower leaf temperatures, leading to greater thermal safety margins (thermal tolerance minus leaf temperature) in a second heatwave. Notably, while we show that adaptation and physiological plasticity are important factors affecting plant adaptive capacity to thermal stress, plasticity of thermal tolerances and thermal safety margins provides the opportunity for trees to persist among fluctuating heatwave exposures.

Immune-related adverse events in cancer patients being treated with immune checkpoint inhibitors.

INTRODUCTION: With the increased use of immune checkpoint inhibitors (ICI), it is essential to improve our understanding of immune-related adverse events (irAE). To date, most studies describing irAE have been performed in clinical trial populations, which may not be an accurate description of irAE in real-world populations. Also, identification of patients at increased risk of irAE is needed as early recognition may improve irAE outcomes. METHODS: We performed a retrospective analysis of patients who received an ICI between January 2014 and October 2018 at a single institution (Tufts Medical Center). Each patient was followed for up to 12 months for the outcome of a physician-reported irAE. Kaplan-Meier curves were created for the time to development and resolution of initial irAE. A Cox proportional hazards model was created to evaluate whether the following variables were independent predictors of an initial irAE: age ≥65 years, female sex, non-Caucasian race, radiation in previous 6 months, current smoking status, melanoma, and combination ICI (ipilimumab and nivolumab). RESULTS: Of 131 patients followed, 57 patients (43.5%) developed at least one irAE at a median of 250 days (95% confidence interval (CI) 132 days-not estimable). The most common irAE included dermatitis, thyroid dysfunction, and pneumonitis. Nearly two-thirds of patients with an irAE had ICI therapy withdrawn, and nearly 60% had immunosuppression initiated. In multivariable analysis, we found a significant association between irAE development and age ≥65 years hazard ratio (HR) 1.80, 95% CI (1.03-3.14) and current smoking status (HR 2.26, 95% CI 1.06-4.82). DISCUSSION: We detected a high rate of irAE and that irAE and subsequent management can be clinically burdensome in this patient population. While further studies are needed to validate these findings, this study provides insights into the magnitude, time course, management of, and possible predictors of irAE in a real-world setting.

A randomized wait-list controlled trial of a social support intervention for caregivers of patients with primary malignant brain tumor.

BACKGROUND: Informal family caregivers constitute an important and increasingly demanding role in the cancer healthcare system. This is especially true for caregivers of patients with primary malignant brain tumors based on the rapid progression of disease, including physical and cognitive debilitation. Informal social network resources such as friends and family can provide social support to caregivers, which lowers caregiver burden and improves overall quality of life. However, barriers to obtaining needed social support exist for caregivers. To address this need, our team developed and is assessing a multi-component caregiver support intervention that uses a blend of technology and personal contact to improve caregiver social support. METHODS: We are currently conducting a prospective, longitudinal 2-group randomized controlled trial which compares caregivers who receive the intervention to a wait-list control group. Only caregivers directly receive the intervention, but the patient-caregiver dyads are enrolled so we can assess outcomes in both. The 8-week intervention consists of two components: (1) The electronic Social Network Assessment Program, a web-based tool to visualize existing social support resources and provide a tailored list of additional resources; and (2) Caregiver Navigation, including weekly phone sessions with a Caregiver Navigator to address caregiver social support needs. Outcomes are assessed by questionnaires completed by the caregiver (baseline, 4-week, 8-week) and the cancer patient (baseline, and 8-week). At 8 weeks, caregivers in the wait-list condition may opt into the intervention. Our primary outcome is caregiver well-being; we also explore patient well-being and caregiver and patient health care utilization. DISCUSSION: This protocol describes a study testing a novel social support intervention that pairs a web-based social network visualization tool and resource list (eSNAP) with personalized caregiver navigation. This intervention is responsive to a family-centered model of care and calls for clinical and research priorities focused on informal caregiving research. TRIAL REGISTRATION: clinicaltrials.gov , Registration number: NCT04268979 ; Date of registration: February 10, 2020, retrospectively registered.

What Motivates You to Share? The Effect of Interactive Tailored Information Aids on Information Sharing about Clinical Trials.

Cancer patients learn about research studies outside of the clinical environment, including websites, print and online advertisements, and interpersonal interactions. When cancer patients share credible information about clinical trials, they also frequently help clarify misunderstandings that may exist in their social networks. The present study investigated how an interactive tailored information aid on clinical trial participation motivated patients' information sharing behaviors. In this study of 312 cancer patients and survivors, an interactive tailored information aid improved patients' likelihood of sharing online and offline information more than a non-interactive tool. Information sharing was directly predicted by cognitive absorption and perceived visual informativeness. In addition, perceived utility and ease of use indirectly impact information sharing positively through the antecedent factors of user engagement and design esthetics. Education level further moderated this effect; information sharing was higher among patients with more education. The implications of these findings are discussed and recommendations for future research are provided.

Contrasting patterns of local adaptation along climatic gradients between a sympatric parasitic and autotrophic tree species.

Sympatric tree species are subject to similar climatic drivers, posing a question as to whether they display comparable adaptive responses. However, no study has explicitly examined local adaptation of co-occurring parasitic and autotrophic plant species to the abiotic environment. Here we test the hypotheses that a generalist parasitic tree would display a weaker signal of selection and that genomic variation would associate with fewer climatic variables (particularly precipitation) but have similar spatial patterns to a sympatric autotrophic tree species. To test these hypotheses, we collected samples from 17 sites across the range of two tree species, the hemiparasite Nuytsia floribunda (n = 264) and sympatric autotroph Melaleuca rhaphiophylla (n = 272). We obtained 5,531 high-quality genome-wide single nucleotide polymorphisms (SNPs) for M. rhaphiophylla and 6,727 SNPs for N. floribunda using DArTseq genome scan technology. Population differentiation and environmental association approaches were used to identify signals of selection. Generalized dissimilarly modelling was used to detect climatic and spatial patterns of local adaptation across climatic gradients. Overall, 322 SNPs were identified as putatively adaptive for the autotroph, while only 57 SNPs were identified for the parasitic species. We found genomic variation to associate with different sets of bioclimatic variables for each species, with precipitation relatively less important for the parasite. Spatial patterns of predicted adaptive variability were different and indicate that co-occurring species with disparate life history traits may not respond equally to selective pressures (i.e., temperature and precipitation). Together, these findings provide insight into local adaptation of sympatric parasitic and autotrophic tree species to abiotic environments.

Pollen adaptation to ant pollination: a case study from the Proteaceae.

BACKGROUND AND AIMS: Ant-plant associations are widely diverse and distributed throughout the world, leading to antagonistic and/or mutualistic interactions. Ant pollination is a rare mutualistic association and reports of ants as effective pollinators are limited to a few studies. Conospermum (Proteaceae) is an insect-pollinated genus well represented in the south-western Australia biodiversity hotspot, and here we aimed to evaluate the role of ants as pollinators of C. undulatum. METHODS: Pollen germination after contact with several species of ants and bees was tested for C. undulatum and five co-flowering species for comparison. We then sampled the pollen load of floral visitors of C. undulatum to assess whether ants carried a pollen load sufficient to enable pollination. Lastly, we performed exclusion treatments to assess the relative effect of flying- and non-flying-invertebrate floral visitors on the reproduction of C. undulatum. For this, we measured the seed set under different conditions: ants exclusion, flying-insects exclusion and control. KEY RESULTS: Pollen of C. undulatum, along with the other Conospermum species, had a germination rate after contact with ants of ~80 % which did not differ from the effect of bees; in contrast, the other plant species tested showed a drop in the germination rate to ~10 % following ant treatments. Although ants were generalist visitors, they carried a pollen load with 68-86 % of suitable grains. Moreover, ants significantly contributed to the seed set of C. undulatum. CONCLUSIONS: Our study highlights the complexity of ant-flower interactions and suggests that generalizations neglecting the importance of ants as pollinators cannot be made. Conospermum undulatum has evolved pollen with resistance to the negative effect of ant secretions on pollen grains, with ants providing effective pollination services to this threatened species.