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A current challenge in the fields of evolutionary, ecological, and conservation genomics is balancing production of large-scale datasets with additional training often required to handle such datasets. Thus, there is an increasing need for conservation geneticists to continually learn and train to stay up-to-date through avenues such as symposia, meetings, and workshops. The ConGen meeting is a near-annual workshop that strives to guide participants in understanding population genetics principles, study design, data processing, analysis, interpretation, and applications to real-world conservation issues. Each year of ConGen gathers a diverse set of instructors, students, and resulting lectures, hands-on sessions, and discussions. Here, we summarize key lessons learned from the 2019 meeting and more recent updates to the field with a focus on big data in conservation genomics. First, we highlight classical and contemporary issues in study design that are especially relevant to working with big datasets, including the intricacies of data filtering. We next emphasize the importance of building analytical skills and simulating data, and how these skills have applications within and outside of conservation genetics careers. We also highlight recent technological advances and novel applications to conservation of wild populations. Finally, we provide data and recommendations to support ongoing efforts by ConGen organizers and instructors-and beyond-to increase participation of underrepresented minorities in conservation and eco-evolutionary sciences. The future success of conservation genetics requires both continual training in handling big data and a diverse group of people and approaches to tackle key issues, including the global biodiversity-loss crisis., (© The American Genetic Association. 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Environmental factors can promote phenotypic variation through alterations in the epigenome and facilitate adaptation of an organism to the environment. Although hydrogen sulfide is toxic to most organisms, the fish Poecilia mexicana has adapted to survive in environments with high levels that exceed toxicity thresholds by orders of magnitude. Epigenetic changes in response to this environmental stressor were examined by assessing DNA methylation alterations in red blood cells, which are nucleated in fish. Males and females were sampled from sulfidic and nonsulfidic natural environments; individuals were also propagated for two generations in a nonsulfidic laboratory environment. We compared epimutations between the sexes as well as field and laboratory populations. For both the wild-caught (F0) and the laboratory-reared (F2) fish, comparing the sulfidic and nonsulfidic populations revealed evidence for significant differential DNA methylation regions (DMRs). More importantly, there was over 80% overlap in DMRs across generations, suggesting that the DMRs have stable generational inheritance in the absence of the sulfidic environment. This is an example of epigenetic generational stability after the removal of an environmental stressor. The DMR-associated genes were related to sulfur toxicity and metabolic processes. These findings suggest that adaptation of P. mexicana to sulfidic environments in southern Mexico may, in part, be promoted through epigenetic DNA methylation alterations that become stable and are inherited by subsequent generations independent of the environment., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Hibernation is characterized by depression of many physiological processes. To determine if this state is reversible in a non-food caching species, we fed hibernating grizzly bears (Ursus arctos horribilis) dextrose for 10 days to replace 53% or 100% of the estimated minimum daily energetic cost of hibernation. Feeding caused serum concentrations of glycerol and ketones (β-hydroxybutyrate) to return to active season levels irrespective of the amount of glucose fed. By contrast, free fatty acids (FFAs) and indices of metabolic rate, such as general activity, heart rate, strength of heart rate circadian rhythm, and insulin sensitivity were restored to approximately 50% of active season levels. Body temperature was unaffected by feeding. To determine the contribution of adipose to the metabolic effects observed after glucose feeding, we cultured bear adipocytes collected at the beginning and end of the feeding and performed metabolic flux analysis. We found a ∼33% increase in energy metabolism after feeding. Moreover, basal metabolism before feeding was 40% lower in hibernation cells compared with fed cells or active cells cultured at 37°C, thereby confirming the temperature independence of metabolic rate. The partial depression of circulating FFAs with feeding likely explains the incomplete restoration of insulin sensitivity and other metabolic parameters in hibernating bears. Further depression of metabolic function is likely to be an active process. Together, the results provide a highly controlled model to examine the relationship between nutrient availability and metabolism on the hibernation phenotype in bears., Competing Interests: Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2021. Published by The Company of Biologists Ltd.)

microRNAs (miRNAs) are post-transcriptional regulators of gene expression and can play an important role in modulating organismal development and physiology in response to environmental stress. However, the role of miRNAs in mediating adaptation to diverse environments in natural study systems remains largely unexplored. Here, we characterized miRNAs and their expression in Poecilia mexicana, a species of small fish that inhabits both normal streams and extreme environments in the form of springs rich in toxic hydrogen sulphide (H 2 S). We found that P. mexicana has a similar number of miRNA genes as other teleosts. In addition, we identified a large population of mature miRNAs that were differentially expressed between locally adapted populations in contrasting habitats, indicating that miRNAs may contribute to P. mexicana adaptation to sulphidic environments. In silico identification of differentially expressed miRNA-mRNA pairs revealed, in the sulphidic environment, the downregulation of miRNAs predicted to target mRNAs involved in sulphide detoxification and cellular homeostasis, which are pathways essential for life in H 2 S-rich springs. In addition, we found that predicted targets of upregulated miRNAs act in the mitochondria (16.6% of predicted annotated targets), which is the main site of H 2 S toxicity and detoxification, possibly modulating mitochondrial function. Together, the differential regulation of miRNAs between these natural populations suggests that miRNAs may be involved in H 2 S adaptation by promoting functions needed for survival and reducing functions affected by H 2 S. This study lays the groundwork for further research to directly demonstrate the role of miRNAs in adaptation to H 2 S. Overall, this study provides a critical stepping-stone towards a comprehensive understanding of the regulatory mechanisms underlying the adaptive variation in gene expression in a natural system., (© 2020 European Society For Evolutionary Biology.)

Objectives: Poor communication is a major contributor to sentinel events in hospitals. Suboptimal communication between physicians and nurses may be due to poor understanding of team members' roles. We sought to evaluate the impact of a shadowing experience on nurse-resident interprofessional collaboration, bidirectional communication, and role perceptions., Methods: This mixed-methods study took place at 2 large academic children's hospitals with pediatric residency programs during the 2018-2019 academic year. First-year residents and nurses participated in a reciprocal, structured 4-hour shadowing experience. Participants were surveyed before, immediately after, and 6 months after their shadowing experience by using an anonymous web-based platform containing the 20-item Interprofessional Collaborative Competency Attainment Survey, as well as open-ended qualitative questions. Quantitative data were analyzed via linear mixed models. Qualitative data were thematically analyzed., Results: Participants included 33 nurses and 53 residents from the 2 study sites. The immediate postshadowing survey results revealed statistically significant improvements in 12 Interprofessional Collaborative Competency Attainment Survey question responses for nurses and 19 for residents ( P ≤ .01). Subsequently, 6 questions for nurses and 17 for residents revealed sustained improvements 6 months after the intervention. Qualitative analysis identified 5 major themes related to optimal nurse-resident engagement: effective communication, collaboration, role understanding, team process, and patient-centered., Conclusions: The reciprocal shadowing experience was associated with an increase in participant understanding of contributions from all interprofessional team members. This improved awareness may improve patient care. Future work may be conducted to assess the impact of spread to different clinical areas and elucidate patient outcomes that may be associated with this intervention., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: To examine the association between (GWG) and epithelial ovarian cancer (EOC)., Methods: We compared GWG between 670 incident EOC cases and 1,551 community controls from a population-based, case-control study conducted in Pennsylvania, Ohio, and New York from 2003 to 2008. Multivariable unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) associated with GWG adjusting for potential confounders. To explore the potential effect of maternal long-term weight retention after childbearing, we restricted analyses to women who began their childbearing years as normal/underweight and examined differences in EOC risk between those who were normal/underweight versus those who were overweight/obese at study baseline reference date., Results: Average GWG per full-term pregnancy did not differ between cases and controls. Among women who were normal/underweight at study baseline, greater average GWG was not associated with EOC (OR = 0.9, 0.8, 0.7 for quartiles 2, 3 and 4 of GWG gain, respectively, compared to quartile 1). In contrast, among women who were overweight/obese at study baseline, greater average GWG was positively associated with EOC (OR = 1.4, 1.8, 1.2, for quartiles 2, 3, and 4 compared to quartile 1; interaction p = 0.04)., Conclusion: We posit that maternal post-partum weight retention and not gestational weight gain itself among normal/underweight women may impact subsequent risk of EOC. If our hypothesis is supported in other studies designed to assess this question directly, then counseling women on the importance of healthy weight management after a pregnancy could provide another means to help women reduce their risk of this often-fatal malignancy.

The purpose of the study was to determine the effect of suture pattern and repair length on the load to failure in an ex vivo canine gingival model. Healthy mandibular gingiva and mucosa were harvested from fresh cadavers euthanized for purposes unrelated to the study. Samples were randomly assigned by length and pattern. Lingual and buccal free gingival margins were apposed using a simple interrupted (SI), cruciate (XT), simple continuous (SC), or unidirectional knotless continuous barbed suture (SF) closure technique with USP 4-0 poliglecaprone 25 i, ii applied over 2 lengths (3 cm and 6 cm). A custom template was used to ensure uniform suture bite application. Surgical time was recorded. Using a soft tissue mechanical testing frame, samples were tensioned to failure. Testing was video recorded and reviewed in conjunction with the tension trace data for tension at initial failure (T fail ) and maximum tension sustained (T max ). Two factor ANOVA by length and pattern was performed followed by individual one way T-tests. Statistically significant findings were XT-SC-SF patterns were quicker to perform than SI. SF was more likely to fail by suture breakage than tissue tearing, and SF withstood less tension at the 3 cm length than SI-XT-SC. No significant difference was detected in T max or T fail between SI and SC or XT. The study demonstrates that SC and XT are comparable to SI in tension resistance and faster to perform suggesting that SC and XT could replace SI for extraction site closure although further in vivo testing is required.

Aims: There are limited data in endometrial cancer for nodal control and appropriate treatment volume for non-surgically resected nodes treated with chemoradiotherapy (CRT) for patients who are not candidates for upfront extrafascial hysterectomy., Materials and Methods: Patients (n = 105) with clinical stage ≥ II endometrial cancer who were not candidates for upfront extrafascial hysterectomy treated with preoperative CRT were retrospectively reviewed. CRT included pelvic nodes to the common iliac for node-negative disease and para-aortic nodes to the renal vessel for any node-positive disease. Involved nodes most commonly received a boost of 55 Gy in 25 fractions ± additional 4-6 Gy sequential boost for nodes >2 cm., Results: Of the included 95 patients, 55 patients were node positive, with a total of 300 positive nodes. At a median follow-up of 25 months (interquartile range 9-46), the 3-year regional control was 91%. The 3-year involved nodal control rate was 96%. Involved nodal control was significantly higher in type I histology, nodes <2 cm and by radiation dose (75% for <55 Gy, 98% for 55 Gy in 25 fractions and 89% for >55 Gy, P = 0.03). The 3-year para-aortic failure rate for node negative patients treated with pelvis-only CRT was significantly higher with positron emission tomography/computed tomography (PET/CT) versus computed tomography (CT)-based staging (0% versus 20%)., Conclusion: This is the largest study examining regional control rates of involved lymph nodes with CRT for patients who were not candidates for upfront extrafascial hysterectomy. Nodal failure was low following CRT and dose ≥55 Gy in 25 fractions seems to be adequate for involved nodes., (Copyright © 2020. Published by Elsevier Ltd.)

Dam construction and longitudinal river habitat fragmentation disrupt important life histories and movement of aquatic species. This is especially true for Oncorhynchus mykiss that exhibits both migratory (steelhead) and non-migratory (resident rainbow) forms. While the negative effects of dams on salmonids have been extensively documented, few studies have had the opportunity to compare population genetic diversity and structure prior to and following dam removal. Here we examine the impacts of the removal of two dams on the Elwha River on the population genetics of O. mykiss. Genetic data were produced from >1200 samples collected prior to dam removal from both life history forms, and post-dam removal from steelhead. We identified three genetic clusters prior to dam removal primarily explained by isolation due to dams and natural barriers. Following dam removal, genetic structure decreased and admixture increased. Despite large O. mykiss population declines after dam construction, we did not detect shifts in population genetic diversity or allele frequencies of loci putatively involved in migratory phenotypic variation. Steelhead descendants from formerly below and above dammed populations recolonized the river rapidly after dam removal, suggesting that dam construction did not significantly reduce genetic diversity underlying O. mykiss life history strategies. These results have significant evolutionary implications for the conservation of migratory adaptive potential in O. mykiss populations above current anthropogenic barriers.

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers., Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data., Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers ( r G = 0.43, P = 2.66 × 10 -5 ). We found seven loci associated with risk for both cancers ( P Bonferroni < 2.4 × 10 -9 ). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified ( P < 5 × 10 -7 ). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation., Conclusions: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis., Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings., (©2020 American Association for Cancer Research.)

The now-dominant medical model of psychiatry has recently been challenged by the post-psychiatry movement. However, the former discounts the agential or subjective aspect of the human being; the latter misses the axiological aspect. A new model is proposed-the Transcendent Meaning Model (TMM)-that nests the individual person within the social (the interperson), and the social within the transcendent or ideological. The study concludes that TMM, with its integration of the personal, the social and the religious-ideological with the material, is a viable blueprint for a future psychiatry that can address some of the current model's vulnerabilities.

The results of a 3+1 sterile neutrino search using eight years of data from the IceCube Neutrino Observatory are presented. A total of 305 735 muon neutrino events are analyzed in reconstructed energy-zenith space to test for signatures of a matter-enhanced oscillation that would occur given a sterile neutrino state with a mass-squared differences between 0.01 and 100  eV^{2}. The best-fit point is found to be at sin^{2}(2θ&#95;{24})=0.10 and Δm&#95;{41}^{2}=4.5  eV^{2}, which is consistent with the no sterile neutrino hypothesis with a p value of 8.0%.

Rapid glacier recession is altering the physical conditions of headwater streams. Stream temperatures are predicted to rise and become increasingly variable, putting entire meltwater-associated biological communities at risk of extinction. Thus, there is a pressing need to understand how thermal stress affects mountain stream insects, particularly where glaciers are likely to vanish on contemporary timescales. In this study, we measured the critical thermal maximum (CT MAX ) of stonefly nymphs representing multiple species and a range of thermal regimes in the high Rocky Mountains, USA. We then collected RNA-sequencing data to assess how organismal thermal stress translated to the cellular level. Our focal species included the meltwater stonefly, Lednia tumana, which was recently listed under the U.S. Endangered Species Act due to climate-induced habitat loss. For all study species, critical thermal maxima (CT MAX  > 20°C) far exceeded the stream temperatures mountain stoneflies experience (<10°C). Moreover, while evidence for a cellular stress response was present, we also observed constitutive expression of genes encoding proteins known to underlie thermal stress (i.e., heat shock proteins) even at low temperatures that reflected natural conditions. We show that high-elevation aquatic insects may not be physiologically threatened by short-term exposure to warm temperatures and that longer-term physiological responses or biotic factors (e.g., competition) may better explain their extreme distributions., (© 2020 John Wiley & Sons Ltd.)

We report on the first measurement of the astrophysical neutrino flux using particle showers (cascades) in IceCube data from 2010-2015. Assuming standard oscillations, the astrophysical neutrinos in this dedicated cascade sample are dominated (∼90%) by electron and tau flavors. The flux, observed in the sensitive energy range from 16 TeV to 2.6 PeV, is consistent with a single power-law model as expected from Fermi-type acceleration of high energy particles at astrophysical sources. We find the flux spectral index to be γ=2.53±0.07 and a flux normalization for each neutrino flavor of ϕ&#95;{astro}=1.66&#95;{-0.27}^{+0.25} at E&#95;{0}=100  TeV, in agreement with IceCube's complementary muon neutrino results and with all-neutrino flavor fit results. In the measured energy range we reject spectral indices γ≤2.28 at ≥3σ significance level. Because of high neutrino energy resolution and low atmospheric neutrino backgrounds, this analysis provides the most detailed characterization of the neutrino flux at energies below ∼100  TeV compared to previous IceCube results. Results from fits assuming more complex neutrino flux models suggest a flux softening at high energies and a flux hardening at low energies (p value ≥0.06). The sizable and smooth flux measured below ∼100  TeV remains a puzzle. In order to not violate the isotropic diffuse gamma-ray background as measured by the Fermi Large Area Telescope, it suggests the existence of astrophysical neutrino sources characterized by dense environments which are opaque to gamma rays.

Changing climate and land-use practices have the potential to bring previously isolated populations of pest insects into new sympatry. This heightens the need to better understand how differing patterns of host-plant association, and unique endosymbionts, serve to promote genetic isolation or integration. We addressed these factors in populations of potato psyllid, Bactericera cockerelli (Šulc), a generalist herbivore that vectors a bacterial pathogen ( Candidatus Liberibacter solanacearum, causal pathogen of zebra chip disease) of potato ( Solanum tuberosum L.). Genome-wide SNP data revealed two major genetic clusters-psyllids collected from potato crops were genetically similar to psyllids found on a common weed, Lycium spp., but dissimilar from those found on another common non-crop host, Solanum dulcamara L. Most psyllids found on Lycium spp. and potato represented a single mitochondrial cytochrome oxidase I (COI) haplotype that has been suggested to not be native to the region, and whose arrival may have been concurrent with zebra chip disease first emerging. The putatively introduced COI haplotype usually co-occurred with endosymbiotic Wolbachia , while the putatively resident COI haplotype generally did not. Genetic intermediates between the two genetic populations of insects were rare, consistent with recent sympatry or reproductive isolation, although admixture patterns of apparent hybrids were consistent with introgression of genes from introduced into resident populations. Our results suggest that both host-plant associations and endosymbionts are shaping the population genetic structure of sympatric psyllid populations associated with different non-crop hosts. It is of future interest to explicitly examine vectorial capacity of the two populations and their potential hybrids, as population structure and hybridization might alter regional vector capacity and disease outbreaks., (© 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Aquatic insects comprise 10% of all insect diversity, can be found on every continent except Antarctica, and are key components of freshwater ecosystems. However, aquatic insect genome biology lags dramatically behind that of terrestrial insects. If genomic effort was spread evenly, one aquatic insect genome would be sequenced for every ~9 terrestrial insect genomes. Instead, ~24 terrestrial insect genomes have been sequenced for every aquatic insect genome. This discrepancy is even more dramatic if the quality of genomic resources is considered; for instance, while no aquatic insect genome has been assembled to the chromosome level, 29 terrestrial insect genomes spanning four orders have. We argue that a lack of aquatic insect genomes is not due to any underlying difficulty (e.g., small body sizes or unusually large genomes), yet it is severely hampering aquatic insect research at both fundamental and applied scales. By expanding the availability of aquatic insect genomes, we will gain key insight into insect diversification and empower future research for a globally important taxonomic group.

Extreme environments test the limits of life; yet, some organisms thrive in harsh conditions. Extremophile lineages inspire questions about how organisms can tolerate physiochemical stressors and whether the repeated colonization of extreme environments is facilitated by predictable and repeatable evolutionary innovations. We identified the mechanistic basis underlying convergent evolution of tolerance to hydrogen sulfide (H 2 S)-a toxicant that impairs mitochondrial function-across evolutionarily independent lineages of a fish ( Poecilia mexicana , Poeciliidae) from H 2 S-rich springs. Using comparative biochemical and physiological analyses, we found that mitochondrial function is maintained in the presence of H 2 S in sulfide spring P. mexicana but not ancestral lineages from nonsulfidic habitats due to convergent adaptations in the primary toxicity target and a major detoxification enzyme. Genome-wide local ancestry analyses indicated that convergent evolution of increased H 2 S tolerance in different populations is likely caused by a combination of selection on standing genetic variation and de novo mutations. On a macroevolutionary scale, H 2 S tolerance in 10 independent lineages of sulfide spring fishes across multiple genera of Poeciliidae is correlated with the convergent modification and expression changes in genes associated with H 2 S toxicity and detoxification. Our results demonstrate that the modification of highly conserved physiological pathways associated with essential mitochondrial processes mediates tolerance to physiochemical stress. In addition, the same pathways, genes, and-in some instances-codons are implicated in H 2 S adaptation in lineages that span 40 million years of evolution., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Landscape genomics studies focus on identifying candidate genes under selection via spatial variation in abiotic environmental variables, but rarely by biotic factors (i.e., disease). The Tasmanian devil (Sarcophilus harrisii) is found only on the environmentally heterogeneous island of Tasmania and is threatened with extinction by a transmissible cancer, devil facial tumor disease (DFTD). Devils persist in regions of long-term infection despite epidemiological model predictions of species' extinction, suggesting possible adaptation to DFTD. Here, we test the extent to which spatial variation and genetic diversity are associated with the abiotic environment (i.e., climatic variables, elevation, vegetation cover) and/or DFTD. We employ genetic-environment association analyses using 6886 SNPs from 3287 individuals sampled pre- and post-disease arrival across the devil's geographic range. Pre-disease, we find significant correlations of allele frequencies with environmental variables, including 365 unique loci linked to 71 genes, suggesting local adaptation to abiotic environment. The majority of candidate loci detected pre-DFTD are not detected post-DFTD arrival. Several post-DFTD candidate loci are associated with disease prevalence and were in linkage disequilibrium with genes involved in tumor suppression and immune response. Loss of apparent signal of abiotic local adaptation post-disease suggests swamping by strong selection resulting from the rapid onset of DFTD., (© 2020 The Authors. Evolution © 2020 The Society for the Study of Evolution.)

A three-dimensional body shape is problematic for camouflage because overhead lighting produces a luminance gradient across the body's surface. Countershading, a form of patterning where animals are darkest on their uppermost surface, is thought to counteract this luminance gradient and enhance concealment, but the mechanisms of protection remain unclear. Surprisingly, no study has examined how countershading alters prey contrast, or investigated how the presence of a dorsoventral luminance gradient affects detection under controlled viewing conditions. It has also been suggested that the direction of the dorsoventral luminance gradient (darkest or lightest on top) may interfere with predators' abilities to resolve prey's three-dimensional shape, yet this intriguing idea has never been tested. We used live fish predators (western rainbowfish, Melanotaenia australis ) and computer-generated prey images to compare the detectability of uniformly pigmented (i.e. non-countershaded) prey with that of optimally countershaded prey of varying contrasts against the background. Optimally countershaded prey were difficult for predators to detect, and the probability and speed of detection depended on prey luminance contrast with the background. In comparison, non-countershaded prey were always highly detectable, even though their average luminance closely matched the luminance of the background. Our findings suggest that uniformly pigmented three-dimensional prey are highly conspicuous to predators because overhead lighting increases luminance contrast between different body parts or between the body and the background. We found no evidence for the notion that countershading interferes with predator perception of three-dimensional form.

Ecological factors such as spatial habitat complexity and diet can explain variation in visual morphology, but few studies have sought to determine whether visual specialisation can occur among populations of the same species. We used a small Australian freshwater fish (the western rainbowfish, Melanotaenia australis ) to determine whether populations showed variation in eye size and eye position, and whether this variation could be explained by environmental (light availability, turbidity) and ecological (predation risk, habitat complexity, invertebrate abundance) variables. We investigated three aspects of eye morphology - (1) eye size relative to body size, (2) pupil size relative to eye size and (3) eye position in the head - for fish collected from 14 sites in a major river catchment in northwest Western Australia. We found significant variation among populations in all three measures of eye morphology, but no effect of sex on eye size or eye position. Variation in eye diameter and eye position was best explained by the level of habitat complexity. Specifically, fish occurring in habitats with low complexity (i.e. open water) tended to have smaller, more dorsally located eyes than those occurring in more complex habitats (i.e. vegetation present). The size of the pupil relative to the size of the eye was most influenced by the presence of surrounding rock formations; fish living in gorge habitats had significantly smaller pupils (relative to eye size) than those occupying semi-gorge sites or open habitats. Our findings reveal that different ecological and environmental factors contribute to habitat-specific visual specialisations within a species., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

This Letter presents the results from pointlike neutrino source searches using ten years of IceCube data collected between April 6, 2008 and July 10, 2018. We evaluate the significance of an astrophysical signal from a pointlike source looking for an excess of clustered neutrino events with energies typically above ∼1  TeV among the background of atmospheric muons and neutrinos. We perform a full-sky scan, a search within a selected source catalog, a catalog population study, and three stacked Galactic catalog searches. The most significant point in the northern hemisphere from scanning the sky is coincident with the Seyfert II galaxy NGC 1068, which was included in the source catalog search. The excess at the coordinates of NGC 1068 is inconsistent with background expectations at the level of 2.9σ after accounting for statistical trials from the entire catalog. The combination of this result along with excesses observed at the coordinates of three other sources, including TXS 0506+056, suggests that, collectively, correlations with sources in the northern catalog are inconsistent with background at 3.3σ significance. The southern catalog is consistent with background. These results, all based on searches for a cumulative neutrino signal integrated over the 10 years of available data, motivate further study of these and similar sources, including time-dependent analyses, multimessenger correlations, and the possibility of stronger evidence with coming upgrades to the detector.

Uterine carcinosarcoma is a rare and aggressive tumor with poor outcomes. Cancer antigen 125 is routinely used to track the disease course of ovarian cancer and has been suggested as a biomarker in other aggressive forms of uterine cancer. We sought to characterize cancer antigen 125 as a potential biomarker of disease status in uterine carcinosarcoma. Clinical and pathological data were abstracted for patients who had surgical staging for a pathologically confirmed uterine carcinosarcoma at our institution from January 2000 to March 2014. Non-parametric tests were used to compare changes in cancer antigen 125. Elevated cancer antigen 125 (>35 U/mL) as a predictor of survival was assessed via Kaplan-Meier curves. Among the 153 patients identified, 66 patients had at least one paired measure of cancer antigen 125 drawn preoperatively, post-treatment, or at the time of disease recurrence, and 19 patients had cancer antigen-125 levels at all three time points. Analysis of the 51 patients with both preoperative and post-treatment values found a significant drop in cancer antigen 125 ( p < 0.001). Among the 30 patients who had end-of-treatment and recurrence levels, a significant increase was noted ( p = 0.001). There was no significant difference in cancer antigen-125 levels preoperatively compared to at recurrence among the 23 patients with levels at both time-points ( p = 0.99). Elevated preoperative cancer antigen 125 was not associated with overall survival ( p = 0.12); elevated post-treatment cancer antigen 125 was associated with a worse overall survival ( p < 0.001). Based on this dataset, there seems to be utility in trending a cancer antigen-125 level in patients with uterine carcinosarcoma. A cancer antigen-125 level could predict recurrence and provide prognostic information regarding survival., Competing Interests: Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Eye regression occurs across cave-dwelling populations of many species and is often coupled with a decrease or loss in eye function. Teleost fishes are among the few vertebrates to undergo widespread colonization of caves and often exhibit eye regression with blindness. Cave populations of the poeciliid fish Poecilia mexicana (cave molly) exhibit reduced-albeit functional-eyes, offering the opportunity to investigate partial eye regression. We sequenced eye transcriptomes of cave and surface populations of P. mexicana to identify differentially expressed genes that potentially underlie eye regression in cave mollies. We identified 28 significantly differentially expressed genes, 20 of which were directly related to light sensitivity, eye structure and visual signaling. Twenty-six of these genes were downregulated in cave compared to surface populations. Functional enrichment analysis revealed eye-related gene ontologies that were under-represented in cave mollies. In addition, a set of co-expressed genes related to vision and circadian rhythm was correlated with habitat type (cave versus surface). Our study suggests that differential gene expression plays a key role in the beginning evolutionary stages of eye regression in P. mexicana , shedding further light on regressive evolution in cavefish.

In an era of unprecedented global change, exploring patterns of gene expression among wild populations across their geographic range is crucial for characterizing adaptive potential. RNA-sequencing studies have successfully characterized gene expression differences among populations experiencing divergent environmental conditions in a wide variety of taxa. However, few of these studies have identified transcriptomic signatures to multivariate, environmental stimuli among populations in their natural environments. Herein, we aim to identify environmental and sex-driven patterns of gene expression in the Tasmanian devil ( Sarcophilus harrisii ), a critically endangered species that occupies a heterogeneous environment. We performed RNA-sequencing on ear tissue biopsies from adult male and female devils from three populations at the extremes of their geographic range. There were no transcriptome-wide patterns of differential gene expression that would be suggestive of significant, environmentally-driven transcriptomic responses. The general lack of transcriptome-wide variation in gene expression levels across the devil's geographic range is consistent with previous studies that documented low levels of genetic variation in the species. However, genes previously implicated in local adaptation to abiotic environment in devils were enriched for differentially expressed genes. Additionally, three modules of co-expressed genes were significantly associated with either population of origin or sex.

Revealing the mechanisms underlying the reversible physiology of hibernation could have applications to both human and animal health as hibernation is often associated with disease-like states. The present study uses RNA-sequencing to reveal the tissue and seasonal transcriptional changes occurring in grizzly bears ( Ursus arctos horribilis ). Comparing hibernation to other seasons, bear adipose has a greater number of differentially expressed genes than liver and skeletal muscle. During hyperphagia, adipose has more than 900 differentially expressed genes compared to active season. Hibernation is characterized by reduced expression of genes associated with insulin signaling, muscle protein degradation, and urea production, and increased expression within muscle protein anabolic pathways. Across all three tissues we find a subset of shared differentially expressed genes, some of which are uncharacterized, that together may reflect a common regulatory mechanism. The identified gene families could be useful for developing novel therapeutics to treat human and animal diseases., Competing Interests: Competing interestsThe authors declare no competing interests.

The wings of butterflies and moths generate some of the most spectacular visual displays observed in nature [1-3]. Particularly striking effects are seen when light interferes with nanostructure materials in the wing scales, generating bright, directional colors that often serve as dynamic visual signals [4]. Structural coloration is not known in night-flying Lepidoptera, yet here we show a highly unusual form of wing coloration in a nocturnal, sexually dimorphic moth, Eudocima materna (Noctuidae). Males feature three dark wing patches on the dorsal forewings, and the apparent size of these patches strongly varies depending on the angle of the wing to the viewer. These optical special effects are generated using specialized wing scales that are tilted on the wing and behave like mirrors. At near-normal incidence of light, these "mirror scales" act as thin-film reflectors to produce a sparkly effect, but when light is incident at ∼20°-30° from normal, the reflectance spectrum is dominated by the diffuse scattering of the underlying, black melanin-containing scales, causing a shape-shifting effect. The strong sexual dimorphism in the arrangement and architecture of the scale nanostructures suggests that these patterns might function for sexual signaling. Flickering of the male's wings would yield a flashing, supernormal visual stimulus [5] to a viewer located 20°-30° away from the vertical, while being invisible to a viewer directly above the animal. Our findings reveal a novel use of structural coloration in nature that yields a dynamic, time-dependent achromatic optical signal that may be optimized for visual signaling in dim light., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

The molecular basis of convergent phenotypes is often unknown. However, convergence at a genomic level is predicted when there are large population sizes, gene flow among diverging lineages or strong genetic constraints. We used whole-genome resequencing to investigate genomic convergence in fishes ( Poecilia spp.) that have repeatedly colonized hydrogen sulfide (H 2 S)-rich environments in Mexico. We identified genomic similarities in both single nucleotide polymorphisms (SNPs) and structural variants (SVs) among independently derived sulfide spring populations, with approximately 1.2% of the genome being shared among sulfidic ecotypes. We compared these convergent genomic regions to candidate genes for H 2 S adaptation identified from transcriptomic analyses and found that a significant proportion of these candidate genes (8%) were also in regions where sulfidic individuals had similar SNPs, while only 1.7% were in regions where sulfidic individuals had similar SVs. Those candidate genes included genes involved in sulfide detoxification, the electron transport chain (the main toxicity target of H 2 S) and other processes putatively important for adaptation to sulfidic environments. Regional genomic similarity across independent populations exposed to the same source of selection is consistent with selection on standing variation or introgression of adaptive alleles across divergent lineages. However, combined with previous analyses, our data also support that adaptive changes in mitochondrially encoded subunits arose independently via selection on de novo mutations. Pressing questions remain on what conditions ultimately facilitate the independent rise of adaptive alleles at the same loci in separate populations, and thus, the degree to which evolution is repeatable or predictable. This article is part of the theme issue 'Convergent evolution in the genomics era: new insights and directions'.

Purpose: The role of neoadjuvant chemoradiation therapy in locally advanced type II endometrial cancer is controversial. We thus aimed to present our experience with the hypothesis that neoadjuvant chemoradiation therapy is associated with similarly high rates of downstaging and locoregional control for type II endometrial cancer and type I endometrial cancer., Methods and Materials: Thirty-four patients with type II endometrial cancer with clinical evidence of cervical ± parametrium involvement treated with neoadjuvant external beam radiation therapy (45-50.4 Gy in 25-28 fractions) and high-dose-rate brachytherapy with a median total dose of 20 Gy (range, 15-27.5) in 4 fractions (range, 3-5) and concurrent platinum chemotherapy ± adjuvant chemotherapy from 2008 to 2018 were retrospectively reviewed. Patients with type I pathologic diagnoses and those treated with definitive (rather than preoperative) intent were excluded., Results: Pathologic characteristics were as follows: 38% were carcinosarcoma, 18% serous, and 24% clear cell. Ninety-four percent of patients were downstaged to an extrafascial hysterectomy, and 94% had negative surgical margins. The 2-year local control, regional control, distant control, disease-free survival, and overall survival were 87.8%, 81.3%, 76.3%, 52.5%, and 63.7%, respectively. There was 1 subacute grade 3 and 1 late grade 3 small bowel obstruction, directly attributable to radiation therapy., Conclusions: Neoadjuvant chemoradiation therapy effectively downstages the majority of locally advanced type II endometrial cancers, thereby increasing the likelihood of achieving complete resection with negative margins., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Disentangling the contemporary and historical factors underlying the spatial distributions of species is a central goal of biogeography. For species with broad distributions but little capacity to actively disperse, disconnected geographical distributions highlight the potential influence of passive, long-distance dispersal (LDD) on their evolutionary histories. However, dispersal alone cannot completely account for the biogeography of any species, and other factors-e.g. habitat suitability, life history-must also be considered. North American ice worms ( Mesenchytraeus solifugus) are ice-obligate annelids that inhabit coastal glaciers from Oregon to Alaska. Previous studies identified a complex biogeographic history for ice worms, with evidence for genetic isolation, unexpectedly close relationships among geographically disjunct lineages, and contemporary migration across large (e.g. greater than 1500 km) areas of unsuitable habitat. In this study, we analysed genome-scale sequence data for individuals from most of the known ice worm range. We found clear support for divergence between populations along the Pacific Coast and the inland flanks of the Coast Mountains (mean F ST = 0.60), likely precipitated by episodic ice sheet expansion and contraction during the Pleistocene. We also found support for LDD of ice worms from Alaska to Vancouver Island, perhaps mediated by migrating birds. Our results highlight the power of genomic data for disentangling complex biogeographic patterns, including the presence of LDD.

Objective: To examine clinico-pathological characteristics and outcomes of uterine carcinosarcoma (UCS) in women aged ≥80 years., Methods: This is a secondary analysis of a previous multicenter retrospective study examining 906 women with stage I-IV UCS who underwent primary hysterectomy. Patient demographics, treatment types, tumor characteristics, and survival were examined across aged ≥80 (n = 82 [9.1%]), aged 60-79, (n = 526 [58.1%]), and aged <60 (n = 298 [32.9%])., Results: Women in the aged ≥80 group were more likely to be Caucasian, undergo simple hysterectomy without lymphadenectomy, and receive no postoperative therapy (all, P < 0.05). Tumors in the aged ≥80 group were more likely to have high-grade carcinoma, heterologous sarcoma, and sarcoma dominance but less likely to have lympho-vascular space invasion (all, P < 0.05). Lymphadenectomy did not improve survival in the aged ≥80 group (P > 0.05), whereas lymphadenectomy was protective for survival in the younger groups (both, P < 0.05). Postoperative chemotherapy was associated with improved progression-free survival (PFS) in the aged ≥80 group (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22-0.89, P = 0.021). With chemotherapy treatment, women in the aged ≥80 group had PFS similar to those in the aged 60-79 group (HR 0.97, 95%CI 0.51-1.83, P = 0.92). In contrast, without chemotherapy treatment, women in the aged ≥80 group had significantly decreased PFS compared to the aged 60-79 group (HR 1.62, 95%CI 1.09-2.40, P = 0.016). Similar associations were observed for postoperative radiotherapy., Conclusion: Nearly 10% of women with UCS are aged ≥80 that are characterized by aggressive tumor factors. Postoperative therapy but not extensive surgery may improve survival in this age group., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Recent Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology guidelines recommend that the dose to 90% (D90) of the high-risk clinical target volume (HRCTV) in cervical cancer be at least 85 Gy, with higher doses for poor response to radiation therapy., Methods and Materials: A retrospective review of brachytherapy delivered at a single institution was evaluated for dosimetry and outcomes. Significance of tumor parameters on local control was evaluated with Kaplan-Meier and univariable and multivariable Cox regression analysis. Correlations were determined with a linear regression model., Results: A total of 239 women underwent high-dose-rate brachytherapy for cervical cancer between 2007 and 2018 with evaluable dosimetry. Median follow-up was 28.6 months. The median prescribed dose was 27.5 Gy in 5 fractions, with a median HRCTV D90 of 83.9 Gy (range, 81.9-85.7 Gy), HRCTV volume of 31 cm 3 (range, 14.9-121.9 cm 3 ), and treatment time of 51 days (range, 36-83 days). Local control for the entire cohort at 5 years was 90.8%. Local control was worse with adenocarcinomas, HRCTV >40 cm 3 at brachytherapy, requirement for a higher brachytherapy dose, and treatment >51 days. On multivariable analysis, local control was worse with adenocarcinoma (hazard ratio, 4.141; 95% confidence interval, 1.498-11.444; P = .006) and HRCTV >40 cm 3 (hazard ratio, 3.640; 95% confidence interval, 1.316-10.069; P = .013). HRCTV EQD2 D90 > 85 Gy did not statistically improve outcomes for any subset. The 2-year progression-free survival for HRCTV >40 cm 3 was 66.2% versus 84.1% if ≤40 cm 3  (P < .001). Overall survival was predicted by HRCTV and overall treatment time in multivariable analysis. For women with HRCTV ≤40 cm 3 , overall survival at 2 years was 90.4% versus 68.5% if >40 cm 3  (P < .001)., Conclusion: Local control was excellent with magnetic resonance imaging-based planning in the entire cohort of patients. A poor response to external beam radiation (larger HRCTV) and adenocarcinoma histology predicted for worse local control despite association with higher brachytherapy prescription. Women with these risk factors face higher rates of extrapelvic progression and poorer overall survival., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Previous studies suggest that breastfeeding reduces epithelial ovarian cancer (EOC) risk. However, the effects of age, timing and episode details on the EOC-breastfeeding relationship have not been examined. The objective of this study was to examine the association between breastfeeding factors and epithelial ovarian cancer., Methods: We examined breastfeeding factors among parous women in a population-based, case-control study conducted in Pennsylvania, Ohio, and New York from 2003 to 2008. We compared 689 incident EOC cases to 1572 community controls. Multivariable unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) associated with breastfeeding patterns adjusting for potential confounders., Results: Compared to never breastfeeding, breastfeeding any offspring was associated with a 30% reduction in EOC risk (OR = 0.70; 95%CI = 0.58-0.85). That association lasted more than 30 years (OR = 0.69, 95%CI = 0.53-0.88). An average breastfeeding episode of 3 months was also associated with reduced risk (OR = 0.73, 95%CI = 0.58-0.80). A greater number of breastfeeding episodes was associated with greater risk reduction (OR = 0.78, 95%CI = 0.64-0.96 and OR = 0.49, 95%CI = 0.36-0.68 1-2 and 3+ episodes, respectively, compared to never breastfed, trend p = 0.01). Longer breastfeeding duration was also associated with reduced risk (OR = 0.75 and 0.62 for less than and greater than 1-year total duration, respectively, compared to never breastfed). An earlier age at first breastfeeding was further associated with increased protection (OR = 0.50-0.80, for first episode at age <25, 25-29, and 30+, respectively, trend p = 0.001)., Conclusions: Breastfeeding for as few as 3 months is associated with reduced EOC risk. Although this association decreases over time, it persists for more than 30 years. Longer cumulative duration, increasing number of breastfeeding episodes, and earlier age at first breastfeeding episode are each associated with increased benefit., (Copyright © 2019. Published by Elsevier Inc.)

Extreme environments typically require costly adaptations for survival, an attribute that often translates to an elevated influence of habitat conditions on biotic communities. Microbes, primarily bacteria, are successful colonizers of extreme environments worldwide, yet in many instances, the interplay between harsh conditions, dispersal, and microbial biogeography remains unclear. This lack of clarity is particularly true for habitats where extreme temperature is not the overarching stressor, highlighting a need for studies that focus on the role other primary stressors (e.g., toxicants) play in shaping biogeographic patterns. In this study, we leveraged a naturally paired stream system in southern Mexico to explore how elevated hydrogen sulfide (H 2 S) influences microbial diversity. We sequenced a portion of the 16S rRNA gene using bacterial primers for water sampled from three geographically proximate pairings of streams with high (> 20 μM) or low (~ 0 μM) H 2 S concentrations. After exploring bacterial diversity within and among sites, we compared our results to a previous study of macroinvertebrates and fish for the same sites. By spanning multiple organismal groups, we were able to illuminate how H 2 S may differentially affect biodiversity. The presence of elevated H 2 S had no effect on overall bacterial diversity (p = 0.21), a large effect on community composition (25.8% of variation explained, p < 0.0001), and variable influence depending upon the group-whether fish, macroinvertebrates, or bacteria-being considered. For bacterial diversity, we recovered nine abundant operational taxonomic units (OTUs) that comprised a core H 2 S-rich stream microbiome in the region. Many H 2 S-associated OTUs were members of the Epsilonproteobacteria and Gammaproteobacteria, which both have been implicated in endosymbiotic relationships between sulfur-oxidizing bacteria and eukaryotes, suggesting the potential for symbioses that remain to be discovered in these habitats.

High-energy neutrino emission has been predicted for several short-lived astrophysical transients including gamma-ray bursts (GRBs), core-collapse supernovae with choked jets, and neutron star mergers. IceCube's optical and x-ray follow-up program searches for such transient sources by looking for two or more muon neutrino candidates in directional coincidence and arriving within 100 s. The measured rate of neutrino alerts is consistent with the expected rate of chance coincidences of atmospheric background events and no likely electromagnetic counterparts have been identified in Swift follow-up observations. Here, we calculate generic bounds on the neutrino flux of short-lived transient sources. Assuming an E^{-2.5} neutrino spectrum, we find that the neutrino flux of rare sources, like long gamma-ray bursts, is constrained to <5% of the detected astrophysical flux and the energy released in neutrinos (100 GeV to 10 PeV) by a median bright GRB-like source is <10^{52.5}  erg. For a harder E^{-2.13} neutrino spectrum up to 30% of the flux could be produced by GRBs and the allowed median source energy is <10^{52}  erg. A hypothetical population of transient sources has to be more common than 10^{-5}  Mpc^{-3}  yr^{-1} (5×10^{-8}  Mpc^{-3}  yr^{-1} for the E^{-2.13} spectrum) to account for the complete astrophysical neutrino flux.

Purpose: Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus has been implicated as a causative factor for a subset of these patients. The purpose of this study was to evaluate whether p16-positivity (a human papillomavirus surrogate) predicts for better response rates in women who undergo surgery followed by adjuvant radiation therapy (RT)., Methods and Materials: We retrospectively analyzed data from women with VSCC who were treated with adjuvant RT. p16-Positivity was defined as diffuse strong immunoreactivity within the tumor. Time to event outcomes was performed with Kaplan-Meier and cumulative incidence methodologies., Results: Thirty-nine women were identified. Ten had positive results for p16 (p16+), and 29 had negative results (p16-). The median follow-up was 25.7 months. The median age at diagnosis was 59 years for women with p16+ tumors and 74 years for women with p16- tumors (P = .022). The distribution of stage did not differ by p16 status. The indications for adjuvant RT were close/positive margins in 19 women, positive nodes in 9 women, and both in 11 women. There were 21 recurrences: 15 vulvar, 3 isolated nodal, 2 synchronous vulvar/nodal, and 1 distant metastasis. In-field relapse rates at 3 years were lower in p16+ patients (32.5%) than in p16- patients (59.1%, P = .072). This trend was also observed in progression-free survival (P = .062). A p16+ status and a lower International Federation of Gynecology and Obstetrics stage were associated with fewer in-field relapses and improved progression-free survival in multivariable analyses. The p16 status was not a predictor of overall survival., Conclusions: p16-Positivity appears to be a prognostic factor for in-field relapse rates in patients with VSCC appropriately treated with adjuvant RT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance., Methods: This secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization., Results: Women in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01)., Conclusion: Characteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.

The colonization of novel environments often involves changes in gene expression, protein coding sequence, or both. Studies of how populations adapt to novel conditions, however, often focus on only one of these two processes, potentially missing out on the relative importance of different parts of the evolutionary process. In this study, our objectives were 1) to better understand the qualitative concordance between conclusions drawn from analyses of differential expression and changes in genic sequence and 2) to quantitatively test whether differentially expressed genes were enriched for sites putatively under positive selection within gene regions. To achieve this, we compared populations of fish (Poecilia mexicana) that have independently adapted to hydrogen-sulfide-rich environments in southern Mexico to adjacent populations residing in nonsulfidic waters. Specifically, we used RNA-sequencing data to compare both gene expression and DNA sequence differences between populations. Analyzing these two different data types led to similar conclusions about which biochemical pathways (sulfide detoxification and cellular respiration) were involved in adaptation to sulfidic environments. Additionally, we found a greater overlap between genes putatively under selection and differentially expressed genes than expected by chance. We conclude that considering both differential expression and changes in DNA sequence led to a more comprehensive understanding of how these populations adapted to extreme environmental conditions. Our results imply that changes in both gene expression and DNA sequence-sometimes at the same loci-may be involved in adaptation.

Clownfishes, with their showy coloration, are well known for their symbiosis with sea anemones and for their hierarchical reproductive system, but the function of their coloration is unclear. We used a phylogeny of 27 clownfish species to test whether fish coloration (i) serves a protective function that involves their anemone hosts, or (ii) signals species identity in species with overlapping host ranges that can potentially share the same host. We tested for an association between fish colour pattern traits, host morphology and host toxicity and examined coloration in relation to host sharing and geographic proximity. Fish with fewer stripes occupied fewer anemone species, and hosts with shorter tentacles, than fish with multiple stripes. There was a negative relationship between anemone toxicity and tentacle length and these protective traits together were correlated with the evolution of stripes. Host sharing or range overlap was not associated with coloration divergence. We propose that ancestral anemonefishes had multiple stripes that served for hiding/camouflage among the hosts' long tentacles, whereas increased specialization towards fewer and more toxic hosts (with shorter tentacles) led to the use of coloration as an aposematic signal. The intriguing notion that an aposematic signal could advertise the defence of another species may reflect the unique symbiotic relationship between anemonefishes and their hosts., (© 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.)

Purpose: Human papillomavirus (HPV) is implicated as a causative factor in vulvar squamous cell carcinoma (VSCC). This study evaluates if p16-positivity, a surrogate for HPV, predicts for better response rates to chemoradiation therapy and survival., Materials and Methods: We conducted a retrospective chart review of women treated with neoadjuvant or definitive chemoradiation (CRT) therapy from 2000 to 2016 for VSCC. p16 stain-positivity was defined as diffuse strong "block" immunoreactivity within invasive tumor., Results: Seventy-three women with median follow-up of 13.4 months were analyzed. Thirty-three (45.2%) had p16+ tumors. Median age was 73 years (range: 37-89); with p16+ tumors, the median age was 60 years vs 73 years for women with p16- tumors (p < 0.001). The distribution of tumor size and stage by p16-status were similar. The complete clinical response (cCR) rate for p16+ tumors was 63.6% vs 35.0% for p16- tumors (p = 0.014). The pathologic complete response (pCR) rate for women treated neoadjuvantly was 53.8% vs 31.4% for p16+ vs p16-, respectively (p = 0.067). The combined complete response (cCR orpCR [CCR]) rate was 63.6% for p16+ and 30.0% for p16- (p = 0.004). Two-year vulvar control (VC) for women with p16+ tumors was 75.5% vs. 49.5% for p16- (p = 0.008). In women with p16+ tumors who achieved CCR, 2-year VC was 92.3% vs 52.1% for CIR (p = 0.009). For p16- tumors, 2-year VC was 67.3% vs 41.1% for CCR and CIR (p = 0.072). No woman with a p16+ tumor developed distant metastases vs. 7 with p16- tumor (p = 0.013). OS was not statistically different between p16+ cohorts, but was improved for p16- patients with CR vs CIR, 72.9% vs 18.8% (p = 0.026)., Conclusions: p16-positive tumors appear to have better clinical and pathologic response rates and clinical outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS)., Methods: This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I-IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome., Results: Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36-2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39-2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08)., Conclusion: In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.

Super-utilizers account for many emergency department visits (EDV) and hospitalizations. Among Medicare/Medicaid patients, 5% to 10% account for >50% of spending. Little is known about super-utilization in gynecologic oncology. Charts of 64 gynecologic oncology patients with ≥3 EDV and/or admissions over 12 months were reviewed retrospectively. Cancer type distribution was 47% ovarian, 23% cervical, 23% endometrial, and 6% vulvar. Treatment at index visit was 61% chemotherapy, 16% no treatment, 8% recent surgery, and 6% radiation. Mean visits was 5.7 (SD 3.9, range 3-28). Most common presenting complaints were gastrointestinal and pain. Patients near end of life were more likely to be admitted. EDV frequently occurred outside standard work hours (63%). EDV/admissions resulted in total variable expenses of $1 462 581 ($982 933 direct expense, $479 648 service expense). Interventions to decrease super-utilization could target symptom management, off-hour support, patients on chemotherapy, and end of life. Approaches could include multidisciplinary resources, palliative care teams, extending office hours, and earlier initiation of hospice.

Aim: To explore inflammatory biomarkers secreted by adipose stem cells (ASCs) in omental, retroperitoneal and subcutaneous adipose tissues of women with endometrial cancer., Patients & Methods: ASCs were collected from 22 women, aged 35-83 years, undergoing hysterectomy for endometrial cancer. Angiopoietin-2, EGF, IL-8, leptin, VEGFA, VEGFC and VEFGD levels in the ASC-conditioned media were analyzed by Luminex., Results: We found a significant difference between the three depots for IL-8 (p < 0.0001), with the highest levels of IL-8 in the omental depot. VEGFA levels were highest in the retroperitoneal depot., Conclusion: This is one of the first studies to explore biomarker expression in ASC-conditioned media in adipose tissue. ASC characteristics may be important to evaluate in relation to cancer risk.