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Echinoids are key components of modern marine ecosystems. Despite a remarkable fossil record, the emergence of their crown group is documented by few specimens of unclear affinities, rendering much of their early history uncertain. The origin of sand dollars, one of its most distinctive clades, is also unclear due to an unstable phylogenetic context and discrepancies between molecular divergence times and fossil evidence. We employ seventeen novel genomes and transcriptomes to build a phylogenomic dataset with a near-complete sampling of major lineages. With it, we revise the phylogeny and divergence times of echinoids, and place their history within the broader context of echinoderm evolution. We also introduce the concept of a chronospace—a multidimensional representation of node ages—and use it to explore the effects of using alternative gene samples, models of molecular evolution, and clock priors. We find the choice of clock model to have the strongest impact on divergence times, while the use of site-heterogeneous models shows little effects. The choice of loci shows an intermediate impact, affecting mostly deep Paleozoic nodes, for which clock-like genes recover dates more congruent with fossil evidence. Our results reveal that crown group echinoids originated in the Permian and diversified rapidly in the Triassic, despite the relative lack of fossil evidence for this early diversification. We also clarify the relationships among sand dollars and their close relatives, showing that the genus Apatopygus represents a relict lineage with a deep Jurassic origin. Surprisingly, the origin of sand dollars is confidently dated to the Cretaceous, implying ghost ranges spanning approximately 50 million years, a remarkable discrepancy with their rich fossil record.

Background: There are limited data on real-world treatment patterns and outcomes for follicular lymphoma (FL) in the relapsed/refractory (r/r) setting, with shorter response durations reported after each relapse (Link et al, 2019; Rivas-Delgado et al, 2019 and Batlevi et al, 2020). We examined treatment patterns for patients with FL initiating third line (3L) therapy at a single institution by time period in the post-rituximab era (2004-2010 and 2011-2020), and clinical outcomes for the overall cohort receiving therapy between 2004 and 2020. Methods: This is a retrospective, observational study of patients with FL who initiated 3L therapy between 2004 and 2020 in routine clinical practice at The Christie NHS Foundation Trust, UK. We selected patients aged ≥18 years at 3L initiation, with histologically documented FL Grade 1−3a treated with two prior lines of systemic therapy including an anti-CD20 monoclonal antibody and an alkylating agent, and at least one year of follow-up after initiating 3L therapy; follow-up ended June 2021. We excluded patients with grade 3b FL or transformation to high grade lymphoma any time before 3L treatment. Overall response rate (ORR) and complete response (CR) to 3L therapy was calculated, and overall survival (OS), progression free survival (PFS) and time to next treatment (TTNT) were estimated using the Kaplan-Meier (KM) method with 3L therapy initiation date as the index date. Results: Overall, 41 patients met all eligibility criteria; 11 and 30 patients received 3L therapy between 2004-2010 and 2011-2020, respectively. Median age at index date was 59 years and 53.7% were male; 73.2% had grade 1 or 2 FL; 78.1% had advanced stage (III/IV) FL at diagnosis. Median follow-up was 33.9 (IQR: 14.5, 63.0) months, and median time from diagnosis to 3L treatment was 60.2 (IQR: 29.4, 89.1) months. The most common regimen in 3L was rituximab plus bendamustine (R-benda) followed by rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab used as a single agent (R-mono). Treatment patterns differed by time period (Table 1). R-benda was more commonly used between 2011 and 2020. The most common sequence was rituximab plus cyclophosphamide, vincristine and prednisone (R-CVP) followed by R-CHOP and R-benda (Figure 1). ORR to 3L treatment was 61.0%, CR 29.3%. Median OS, PFS and TTNT with 95% confidence interval (CI) were 70.0 (30.2-NR), 19.2 (9.5-34.7) and 11.8 (9.0-27.6) months after 3L initiation, respectively. Two- and five-year OS rates were 79% and 50%, and two-year PFS rate was 37%. Conclusions: Patients with r/r FL treated in the routine 3L setting have highly variable treatment patterns and unfavorable outcomes, representing a continued unmet medical need. This study is limited by its small size and evolving treatments, warranting a larger study of more recently treated 3L patients to evaluate the impact of modern treatment pathways and novel therapies on clinical outcomes for r/r FL. Figure 1 Figure 1. Disclosures Linton: University of Manchester: Current Employment; BeiGene: Research Funding; Hartley Taylor: Honoraria; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Aptitude Health: Honoraria; Celgene: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Julian: Genentech, Inc.: Current Employment, Current holder of stock options in a privately-held company. Gibb: The Christie NHS Foundation Trust: Current Employment; Takeda: Honoraria, Research Funding, Speakers Bureau. Li: Genesis Research: Current Employment. Liu: Genesis Research: Current Employment. Shewade: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Radford: BMS: Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Honoraria, Speakers Bureau; AstraZeneca: Current holder of individual stocks in a privately-held company.

Polyembryony, or the production of multiple offspring from a single zygote, is a widespread phenomenon in the animal kingdom. Various types of polyembryony have been described in arthropods, bryozoans, chordates, cnidarians, echinoderms, and platyhelminthes. We describe the induction of polyembryony in embryos of the sand dollar Echinarachnius parma and the pencil urchin Eucidaris tribuloides in response to elevated temperature and reduced salinity. Data on the environmental variation in temperature and salinity that normally occurs during the spawning season, combined with the range of laboratory conditions over which polyembryony was induced, suggest that polyembryony may occur frequently in these species under natural conditions. We tested an additional two species of echinoids for similar responses, but found little evidence for polyembryony in the green urchin Strongylocentrotus droebachiensis or the variegated urchin Lytechinus variegatus, suggesting that polyembryony is not a universal response of echinoids to fluctuations in temperature and salinity. The unexpected developmental changes that we observed in response to present-day fluctuations in temperature and salinity suggest that ongoing and future environmental shifts may drive substantial changes in marine invertebrate developmental patterns, and that these changes will be different across taxa.

Life history characteristics play a pervasive role in the ecology and evolution of species. Transitions between feeding and non-feeding larval development have occurred many times in both terrestrial and marine phyla, however we lack a comprehensive understanding of how such shifts occur. The sea biscuits Clypeaster rosaceus and Clypeaster subdepressus employ different life history strategies (facultatively feeding larvae and obligately feeding larvae, respectively) but can hybridize. In this study, we examined the development of hybrid larvae between these two species in order to investigate the inheritance of larval developmental mode. Our results show that both reciprocal hybrid crosses developed via the feeding mode of their maternal species. However, as feeding larvae can obtain both energy and hormones from algal food, we tested how hormones alone affected development by setting up a treatment where we added exogenous thyroid hormone, but no food. In this treatment the offspring of all four crosses (two homospecific and two heterospecific crosses) were able to metamorphose without algal food. Therefore we hypothesize that although hybrid developmental mode was inherited from the maternal species, this result was not solely due to energetic constraints of egg size.

Hatching plasticity occurs in response to a wide range of stimuli across many animal taxa, including annelids, arthropods, mollusks, and chordates. Despite the prominence of echinoderms in developmental biology and more than 100 years of detailed examination of their development under a variety of conditions, environmentally cued hatching plasticity has never been reported in the phylum Echinodermata. Here we report plasticity in the timing and stage of hatching of embryos of the sand dollar Echinarachnius parma in response to reductions in salinity. Embryos of E. parma increased their time to hatching more than twofold in response to ecologically relevant salinity reductions, while maintaining an otherwise normal developmental schedule. Embryos that experienced the greatest delay in hatching time emerged from the fertilization envelope as four-arm pluteus larvae rather than hatching as blastulae or early gastrulae. Salinity manipulations across multiple male-female pairs indicated high variability in hatching time both within and among clutches, suggesting significant intraspecific variation in developmental responses to salinity.