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Introduction: Takotsubo cardiomyopathy (TTCM) can occur in acute respiratory distress syndrome (ARDS) and a few cases in literature were reported to be associated with hemodynamic instability. All these patients were managed with venoarterial extracorporeal membrane oxygenation (VA-ECMO).Case presentation: We present two patients with ARDS-induced TTCM who were managed successfully with venovenous ECMO (VV-ECMO)., Conclusion: Ventricular function in both patients fully recovered three days after ECMO initiation, and they were subsequently weaned from ECMO once pulmonary function improved.

Competing Interests: AS reports research grants and lecture fees from CytoSorbents, lecture fees from AstraZeneca and Getinge, and travel support and consulting fees from ARTCLINE, all outside of the submitted work. All other authors declare no competing interests. This Comment developed from discussion with the ECMO Ethics Workgroup of the American Society for Bioethics and Humanities Clinical Ethics Consultation Affinity Group.

Many healthcare providers think withholding food and fluids from advance dementia patients, even if those patients requested that when competent, is immoral. This means such patients suffer unnecessarily long. Patients have the ethical right when capacitated to specify that they want assistance with food and drink stopped when they have advanced dementia. Physicians should implement these patient choices when advance dementia patients can no longer feed themselves. In some states there may be legal barriers to this practice. The perpetual placement of food and drink within reach of patients who are unable to feed themselves is futile, so there is no need for it. The best way for persons concerned about suffering in advanced dementia is to add a supplement to one's advance directive specifying under what circumstances one wants food and fluids assistance stopped., Competing Interests: I have no conflicts of interest of any kind, whether financial, professional, personal, or otherwise. Author disclosures are available in the supporting information., (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Colour is a critical property of many traps used to control or monitor insect pests, and applied entomologists continue to devote time and effort to improving colour for greater trapping efficiency. This work has often been guided by human colour perceptions, which differ greatly from those of the pests being studied. As a result, trap development can be a laborious process that is heavily reliant on trial and error. However, the responses of an insect's photoreceptors to a given trap colour can be calculated using well-established procedures. Photoreceptor responses represent sensory inputs that drive insect behaviour, and if their relationship to insect attraction can be determined or hypothesised, they provide metrics that can guide the rational optimisation of trap colour. This approach has recently been used successfully in separate studies of tsetse flies and thrips, but could be applied to a wide diversity of pest insects. Here we describe this approach to facilitate its use by applied entomologists. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Dispersal across biogeographic barriers is a key process determining global patterns of biodiversity as it allows lineages to colonize and diversify in new realms. Here we demonstrate that past biogeographic dispersal events often depended on species' traits, by analysing 7,009 tetrapod species in 56 clades. Biogeographic models incorporating body size or life history accrued more statistical support than trait-independent models in 91% of clades. In these clades, dispersal rates increased by 28-32% for lineages with traits favouring successful biogeographic dispersal. Differences between clades in the effect magnitude of life history on dispersal rates are linked to the strength and type of biogeographic barriers and intra-clade trait variability. In many cases, large body sizes and fast life histories facilitate dispersal success. However, species with small bodies and/or slow life histories, or those with average traits, have an advantage in a minority of clades. Body size-dispersal relationships were related to a clade's average body size and life history strategy. These results provide important new insight into how traits have shaped the historical biogeography of tetrapod lineages and may impact present-day and future biogeographic dispersal., (© 2023. The Author(s).)

Prey seldom rely on a single type of antipredator defence, often using multiple defences to avoid predation. In many cases, selection in different contexts may favour the evolution of multiple defences in a prey. However, a prey may use multiple defences to protect itself during a single predator encounter. Such "defence portfolios" that defend prey against a single instance of predation are distributed across and within successive stages of the predation sequence (encounter, detection, identification, approach (attack), subjugation and consumption). We contend that at present, our understanding of defence portfolio evolution is incomplete, and seen from the fragmentary perspective of specific sensory systems (e.g., visual) or specific types of defences (especially aposematism). In this review, we aim to build a comprehensive framework for conceptualizing the evolution of multiple prey defences, beginning with hypotheses for the evolution of multiple defences in general, and defence portfolios in particular. We then examine idealized models of resource trade-offs and functional interactions between traits, along with evidence supporting them. We find that defence portfolios are constrained by resource allocation to other aspects of life history, as well as functional incompatibilities between different defences. We also find that selection is likely to favour combinations of defences that have synergistic effects on predator behaviour and prey survival. Next, we examine specific aspects of prey ecology, genetics and development, and predator cognition that modify the predictions of current hypotheses or introduce competing hypotheses. We outline schema for gathering data on the distribution of prey defences across species and geography, determining how multiple defences are produced, and testing the proximate mechanisms by which multiple prey defences impact predator behaviour. Adopting these approaches will strengthen our understanding of multiple defensive strategies., (© 2023 The Authors. Journal of Evolutionary Biology published by John Wiley & Sons Ltd on behalf of European Society for Evolutionary Biology.)

Competing Interests: Declaration of competing interest Neither author has competing interests to declare.

Species' life histories determine population demographics and thus the probability that introduced populations establish and spread. Life histories also influence which species are most likely to be introduced, but how such 'introduction biases' arise remains unclear. Here, we investigate how life histories affect the probability of trade and introduction in phylogenetic comparative analyses across three vertebrate classes: mammals, reptiles and amphibians. We find that traded species have relatively high reproductive rates and long reproductive lifespans. Within traded species, introduced species have a more extreme version of this same life history profile. Species in the pet trade also have long reproductive lifespans but lack 'fast' traits, likely reflecting demand for rare species which tend to have slow life histories. We identify multiple species not yet traded or introduced but with life histories indicative of high risk of future trade, introduction and potentially invasion. Our findings suggest that species with high invasion potential are favoured in the wildlife trade and therefore that trade regulation is crucial for preventing future invasions., (© 2023. The Author(s).)

Deimatic behaviours, also referred to as startle behaviours, are used against predators and rivals. Although many are spectacular, their proximate and ultimate causes remain unclear. In this review we aim to synthesise what is known about deimatic behaviour and identify knowledge gaps. We propose a working hypothesis for deimatic behaviour, and discuss the available evidence for the evolution, ontogeny, causation, and survival value of deimatic behaviour using Tinbergen's Four Questions as a framework. Our overarching aim is to direct future research by suggesting ways to address the most pressing questions in this field., (© 2022 Cambridge Philosophical Society.)

Biological phenotypes are products of complex evolutionary processes in which selective forces influence multiple biological trait measurements in unknown ways. Phylogenetic comparative methods seek to disentangle these relationships across the evolutionary history of a group of organisms. Unfortunately, most existing methods fail to accommodate high-dimensional data with dozens or even thousands of observations per taxon. Phylogenetic factor analysis offers a solution to the challenge of dimensionality. However, scientists seeking to employ this modeling framework confront numerous modeling and implementation decisions, the details of which pose computational and replicability challenges.We develop new inference techniques that increase both the computational efficiency and modeling flexibility of phylogenetic factor analysis. To facilitate adoption of these new methods, we present a practical analysis plan that guides researchers through the web of complex modeling decisions. We codify this analysis plan in an automated pipeline that distills the potentially overwhelming array of decisions into a small handful of (typically binary) choices.We demonstrate the utility of these methods and analysis plan in four real-world problems of varying scales. Specifically, we study floral phenotype and pollination in columbines, domestication in industrial yeast, life history in mammals, and brain morphology in New World monkeys.General and impactful community employment of these methods requires a data scientific analysis plan that balances flexibility, speed and ease of use, while minimizing model and algorithm tuning. Even in the presence of non-trivial phylogenetic model constraints, we show that one may analytically address latent factor uncertainty in a way that (a) aids model flexibility, (b) accelerates computation (by as much as 500-fold) and (c) decreases required tuning. These efforts coalesce to create an accessible Bayesian approach to high-dimensional phylogenetic comparative methods on large trees., Competing Interests: Conflict of Interest statement The authors declare no conflicts of interest.

This special article is the first in a planned annual series for the Journal of Cardiothoracic and Vascular Anesthesia that will highlight significant literature from the world of graduate medical education (GME) that was published over the past year. The major themes selected for this inaugural review are the educational value of simulation and training workshops, the expanding role of social media and other information technologies in GME and recruitment, the state of residency and fellowship training before the COVID-19 pandemic, and the inevitable effects COVID-19 has had on graduate medical education. The authors would like to thank the editorial board for allowing us to shine a light on a small subset of the writing and research produced in this field, so that educators may understand how best to educate and train the next generation of anesthesiologists., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Comparative biologists are often interested in inferring covariation between multiple biological traits sampled across numerous related taxa. To properly study these relationships, we must control for the shared evolutionary history of the taxa to avoid spurious inference. An additional challenge arises as obtaining a full suite of measurements becomes increasingly difficult with increasing taxa. This generally necessitates data imputation or integration, and existing control techniques typically scale poorly as the number of taxa increases. We propose an inference technique that integrates out missing measurements analytically and scales linearly with the number of taxa by using a post-order traversal algorithm under a multivariate Brownian diffusion (MBD) model to characterize trait evolution. We further exploit this technique to extend the MBD model to account for sampling error or non-heritable residual variance. We test these methods to examine mammalian life history traits, prokaryotic genomic and phenotypic traits, and HIV infection traits. We find computational efficiency increases that top two orders-of-magnitude over current best practices. While we focus on the utility of this algorithm in phylogenetic comparative methods, our approach generalizes to solve long-standing challenges in computing the likelihood for matrix-normal and multivariate normal distributions with missing data at scale.

Background: Advance directives are legal documents that include living wills and durable health care power of attorney documents. They are critical components of care for seriously ill patients which are designed to be implemented when a patient is terminally ill and incapacitated. We sought to evaluate potential reasons for why advance directives were not appropriately implemented, by reviewing the electronic health record (EHR) in patients with terminal cancer., Methods: A retrospective analysis of the EHR of 500 cancer patients from 1/1/2013 to 12/31/2016 was performed. Data points were manually collected and entered in a central database., Results: Of the 500 patients, 160 (32%) had an advance directive (AD). The most common clinical terminology used by physicians indicating a terminal diagnosis was progressive (36.6%) and palliative (31%). The most common clinical terminology indicating incapacity was altered mental status (25.6%), and not oriented (14%). 34 (6.8%) patients met all criteria of having a terminal diagnosis, a documented AD, and were deemed incapacitated. Of these patients who met all of these data points, their ADs were implemented on average 1.7 days (SD: 4.4 days) after which they should have been. This resulted in a total of 58 days of additional care provided., Discussion: This study provided insight on to how ADs are managed in day to day practice in the hospital. From our analysis it appears that physicians are able to identify when a patient is terminal, however, it is typically later than it should have been recognized. Further studies should be performed focusing on harnessing the power of the EHR and providing physicians formative and evaluative feedback of practice patterns to ensure that ADs are honored when appropriate.

Caudal autotomy is a dramatic antipredator adaptation where prey shed their tail in order to escape capture by a predator. The mechanism underlying the effectiveness of caudal autotomy as a pre-capture defense has not been thoroughly investigated. We tested two nonexclusive hypotheses, that caudal autotomy works by providing the predator with a "consolation prize" that makes it break off the hunt to consume the shed tail, and the deflection hypothesis, where the autotomy event directs predator attacks to the autotomized tail enabling prey escape. Our experiment utilized domestic dogs Canis familiaris as model predator engaged to chase a snake-like stimulus with a detachable tail. The tail was manipulated to vary in length (long versus short) and conspicuousness (green versus blue), with the prediction that dog attacks on the tail should increase with length under the consolation-prize hypothesis and conspicuous color under the deflection hypothesis. The tail was attacked on 35% of trials, supporting the potential for pre-capture autotomy to offer antipredator benefits. Dogs were attracted to the tail when it was conspicuously colored, but not when it was longer. This supports the idea that deflection of predator attacks through visual effects is the prime antipredator mechanism underlying the effectiveness of caudal autotomy as opposed to provision of a consolation prize meal., Competing Interests: No conflicts of interest to declare., (© 2021 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Sexual selection produces extravagant male traits, such as colorful ornaments, via female mate choice. More rarely, in mating systems in which males allocate mating effort between multiple females, female ornaments may evolve via male mate choice. Females of many anthropoid primates exhibit ornaments that indicate intraindividual cyclical fertility, but which have also been proposed to function as interindividual quality signals. Rhesus macaque females are one such species, exhibiting cyclical facial color variation that indicates ovulatory status, but in which the function of interindividual variation is unknown. We collected digital images of the faces of 32 rhesus macaque adult females. We assessed mating rates, and consortship by males, according to female face coloration. We also assessed whether female coloration was linked to physical (skinfold fat, body mass index) or physiological (fecal glucocorticoid metabolite [fGCM], urinary C-peptide concentrations) condition. We found that redder-faced females were mated more frequently, and consorted for longer periods by top-ranked males. Redder females had higher fGCM concentrations, perhaps related to their increased mating activity and consequent energy mobilization, and blood flow. Prior analyses have shown that female facial redness is a heritable trait, and that redder-faced females have higher annual fecundity, while other evidence suggests that color expression is likely to be a signal rather than a cue. Collectively, the available evidence suggests that female coloration has evolved at least in part via male mate choice. Its evolution as a sexually selected ornament attractive to males is probably attributable to the high female reproductive synchrony found in this species., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Society for Behavioral Ecology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Extracorporeal circulation (ECC) support using intraoperative extracorporeal membrane oxygenation (ECMO) during lung transplantation (LTx) is now a routine practice for many high volume centers. Circuits that are dedicated to ECMO alone can be expensive and do not allow full cardiopulmonary bypass (CPB) to be performed. We describe our technique of instituting venoarterial ECMO during LTx using a less-expensive hybrid circuit that facilitates easy and immediate conversion to full CPB if needed, without interruption of ECC.

RAS mutant (MT) metastatic colorectal cancer (mCRC) is resistant to MEK1/2 inhibition and remains a difficult-to-treat group. Therefore, there is an unmet need for novel treatment options for RASMT mCRC. RALA and RALB GTPases function downstream of RAS and have been found to be key regulators of several cell functions implicated in KRAS-driven tumorigenesis. However, their role as regulators of the apoptotic machinery remains to be elucidated. Here, we found that inhibition of RALB expression, but not RALA, resulted in Caspase-8-dependent cell death in KRASMT CRC cells, which was not further increased following MEK1/2 inhibition. Proteomic analysis and mechanistic studies revealed that RALB depletion induced a marked upregulation of the pro-apoptotic cell surface TRAIL Death Receptor 5 (DR5) (also known as TRAIL-R2), primarily through modulating DR5 protein lysosomal degradation. Moreover, DR5 knockdown or knockout attenuated siRALB-induced apoptosis, confirming the role of the extrinsic apoptotic pathway as a regulator of siRALB-induced cell death. Importantly, TRAIL treatment resulted in the association of RALB with the death-inducing signalling complex (DISC) and targeting RALB using pharmacologic inhibition or RNAi approaches triggered a potent increase in TRAIL-induced cell death in KRASMT CRC cells. Significantly, high RALB mRNA levels were found in the poor prognostic Colorectal Cancer Intrinsic Subtypes (CRIS)-B CRC subgroup. Collectively, this study provides to our knowledge the first evidence for a role for RALB in apoptotic priming and suggests that RALB inhibition may be a promising strategy to improve response to TRAIL treatment in poor prognostic RASMT CRIS-B CRC.

Objective. To compare first-year student pharmacists and nursing students with respect to their spirituality and perceptions of the role of spirituality in professional education and practice. Methods. This was a five-year, cross-sectional study. All first-year student pharmacists and nursing students were invited to participate in the survey during the first week of the fall semester in 2012 through 2016. Descriptive and inferential statistics were used to analyze the data. Results. A total of 1,084 students participated, including 735 student pharmacists and 349 nursing students. Significant differences in baseline demographics were noted between the groups. Students in both groups reported having frequent spiritual experiences. A significantly larger percentage of nursing students reported these experiences compared to student pharmacists. Furthermore, compared with student pharmacists, nursing students were more likely to anticipate that spirituality would play a role in their academic course work (76% vs 58%) and professional practice (90% vs 74%). Conclusion. Student pharmacists and nursing students reported having frequent spiritual experiences, and both groups anticipated that spirituality would be incorporated into their education and professional practice., (© 2020 American Association of Colleges of Pharmacy.)

p53 is the most frequently mutated, well-studied tumor-suppressor gene, yet the molecular basis of the switch from p53-induced cell-cycle arrest to apoptosis remains poorly understood. Using a combination of transcriptomics and functional genomics, we unexpectedly identified a nodal role for the caspase-8 paralog and only human pseudo-caspase, FLIP(L), in regulating this switch. Moreover, we identify FLIP(L) as a direct p53 transcriptional target gene that is rapidly up-regulated in response to Nutlin-3A, an MDM2 inhibitor that potently activates p53. Genetically or pharmacologically inhibiting expression of FLIP(L) using siRNA or entinostat (a clinically relevant class-I HDAC inhibitor) efficiently promoted apoptosis in colorectal cancer cells in response to Nutlin-3A, which otherwise predominantly induced cell-cycle arrest. Enhanced apoptosis was also observed when entinostat was combined with clinically relevant, p53-activating chemotherapy in vitro, and this translated into enhanced in vivo efficacy. Mechanistically, FLIP(L) inhibited p53-induced apoptosis by blocking activation of caspase-8 by the TRAIL-R2/DR5 death receptor; notably, this activation was not dependent on receptor engagement by its ligand, TRAIL. In the absence of caspase-8, another of its paralogs, caspase-10 (also transcriptionally up-regulated by p53), induced apoptosis in Nutlin-3A-treated, FLIP(L)-depleted cells, albeit to a lesser extent than in caspase-8-proficient cells. FLIP(L) depletion also modulated transcription of canonical p53 target genes, suppressing p53-induced expression of the cell-cycle regulator p21 and enhancing p53-induced up-regulation of proapoptotic PUMA. Thus, even in the absence of caspase-8/10, FLIP(L) silencing promoted p53-induced apoptosis by enhancing PUMA expression. Thus, we report unexpected, therapeutically relevant roles for FLIP(L) in determining cell fate following p53 activation., Competing Interests: The authors declare no competing interest.

The dorsal surfaces of many taxonomic groups often feature repetitive pattern elements consisting of stripes, spots, or bands. Here, we investigate how distinct categories of camouflage pattern work by relating them to ecological and behavioral traits in 439 species of gecko. We use phylogenetic comparative methods to test outstanding hypotheses based on camouflage theory and research in other taxa. We found that bands are associated with nocturnal activity, suggesting bands provide effective camouflage for motionless geckos resting in refugia during the day. A predicted association between stripes and diurnal activity was not supported, suggesting that stripes do not work via dazzle camouflage mechanisms in geckos. This, along with a lack of support for our prediction that plain patterning should be associated with open habitats, suggests that similar camouflage patterns do not work in consistent ways across taxa. We also found that plain and striped lineages frequently switched between using open or closed habitats, whereas spotted lineages rarely transitioned. This suggests that pattern categories differ in how specialized or generalized their camouflage is. This result has ramifications for theory on how camouflage compromises to background heterogeneity and how camouflage pattern might influence evolutionary trajectories., (© 2019 The Authors. Evolution © 2019 The Society for the Study of Evolution.)

Discriminating conspecifics from heterospecifics can help avoid costly interactions between closely related sympatric species. The guenons, a recent primate radiation, exhibit high degrees of sympatry and form multi-species groups. Guenons have species-specific colorful face patterns hypothesized to function in species discrimination. Here, we use a machine learning approach to identify face regions most essential for species classification across fifteen guenon species. We validate these computational results using experiments with live guenons, showing that facial traits critical for accurate classification influence selective attention toward con- and heterospecific faces. Our results suggest variability among guenon species in reliance on single-trait-based versus holistic facial characteristics for species discrimination, with behavioral responses and computational results indicating variation from single-trait to whole-face patterns. Our study supports a role for guenon face patterns in species discrimination, and shows how complex signals can be informative about differences between species across a speciose and highly sympatric radiation., Competing Interests: SW, WA, JH No competing interests declared, (© 2020, Winters et al.)

Researchers increasingly use visualisation to make sense of their data and communicate findings more widely. But these are not necessarily straightforward processes. Theories of knowledge brokerage show how sociopolitical contexts and intermediary organisations that translate research for public audiences shape how users engage with evidence. Applying these ideas to data visualisation, I argue that several kinds of brokers (such as data collectors, designers and intermediaries) link researchers and audiences, contributing to the ways that people engage with visualisations. To do this, I draw on qualitative focus groups that elicited non-academic viewers' reactions to visualisations of data about UK migration. The results reveal two important features of engagement: perceptions of brokers' credibility and feelings of surprise arising from visualisations' content and design. I conclude by arguing that researchers, knowledge brokers and the public produce - as well as operate within - a complex visualisation space characterised by mutual, bi-directional connections.

Purpose: Transcriptomic profiling of colorectal cancer (CRC) has led to identification of four consensus molecular subtypes (CMS1-4), which have prognostic value in stage II/III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system has helped to define the biology specific to the epithelial component of colorectal tumors. However, the clinical value of these classifications in predicting response to standard-of-care adjuvant chemotherapy remains unknown., Patients and Methods: Using samples from 4 European sites, we assembled a novel stage II/III CRC patient cohort and performed transcriptomic profiling on 156 samples, targeted sequencing and generated a tissue microarray to enable integrated "multi-omics" analyses. We also accessed data from 2 published stage II/III CRC patient cohorts: GSE39582 and GSE14333 (479 and 185 samples respectively)., Results: The epithelial-rich CMS2 subtype of CRC benefitted significantly from adjuvant chemotherapy treatment in both stage II and III disease (p=0.02 and p<0.0001 respectively), while the CMS3 subtype significantly benefitted in stage III only (p=0.00073). Following CRIS sub-stratification of CMS2, we observed that only the CRIS-C subtype significantly benefitted from adjuvant chemotherapy in stage II and III disease (p=0.0081 and p<0.0001 respectively), while CRIS-D significantly benefitted in stage III only (p=0.0034). We also observed that CRIS-C patients with low levels of CD8+ tumor-infiltrating lymphocytes were most at risk of relapse in both stage II and III disease (p=0.0031)., Conclusion: Patient stratification using a combination of transcriptional subtyping and CD8 immunohistochemistry analyses is capable of identifying poor prognostic stage II/III patients who benefit from adjuvant standard-of-care chemotherapy. These findings are particularly relevant for stage II disease, where the overall benefit of adjuvant chemotherapy is marginal.

BRAF V600E mutations occur in ∼10% of colorectal cancer cases, are associated with poor survival, and have limited responses to BRAF/MEK inhibition with or without EGFR inhibition. There is an unmet need to understand the biology of poor prognostic BRAF MT colorectal cancer. We have used differential gene expression and pathway analyses of untreated stage II and stage III BRAF MT (discovery set: n = 31; validation set: n = 26) colorectal cancer, and an siRNA screen to characterize the biology underpinning the BRAF MT subgroup with poorest outcome. These analyses identified the unfolded protein response (UPR) as a novel and druggable pathway associated with the BRAF MT colorectal cancer subgroup with poorest outcome. We also found that oncogenic BRAF drives endoplasmic reticulum (ER) stress and UPR pathway activation through MEK/ERK. Furthermore, inhibition of GRP78, the master regulator of the UPR, using siRNA or small molecule inhibition, resulted in acute ER stress and apoptosis, in particular in BRAF MT colorectal cancer cells. In addition, dual targeting of protein degradation using combined Carfilzomib (proteasome inhibitor) and ACY-1215 (HDAC6-selective inhibitor) treatment resulted in marked accumulation of protein aggregates, acute ER stress, apoptosis, and therapeutic efficacy in BRAF MT in vitro and xenograft models. Mechanistically, we found that the apoptosis following combined Carfilzomib/ACY-1215 treatment is mediated through increased CHOP expression. Taken together, our findings indicate that oncogenic BRAF induces chronic ER stress and that inducers of acute ER stress could be a novel treatment strategy for poor prognostic BRAF MT colorectal cancer. Mol Cancer Ther; 17(6); 1280-90. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Coloration mediates the relationship between an organism and its environment in important ways, including social signaling, antipredator defenses, parasitic exploitation, thermoregulation, and protection from ultraviolet light, microbes, and abrasion. Methodological breakthroughs are accelerating knowledge of the processes underlying both the production of animal coloration and its perception, experiments are advancing understanding of mechanism and function, and measurements of color collected noninvasively and at a global scale are opening windows to evolutionary dynamics more generally. Here we provide a roadmap of these advances and identify hitherto unrecognized challenges for this multi- and interdisciplinary field., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Organisms frequently gain advantages when they engage in signalling with individuals of other species. Here, we provide a functionally structured framework of the great variety of interspecific visual signals seen in nature, and then describe the different signalling mechanisms that have evolved in response to each of these functional requirements. We propose that interspecific visual signalling can be divided into six major functional categories: anti-predator, food acquisition, anti-parasite, host acquisition, reproductive and agonistic signalling, with each function enabled by several distinct mechanisms. We support our classification by reviewing the ecological and behavioural drivers of interspecific signalling in animals and plants, principally focusing on comparative studies that address large-scale patterns of diversity. Collating diverse examples of interspecific signalling into an organized set of functional and mechanistic categories places anachronistic behavioural and morphological labels in fresh context, clarifies terminology and redirects research effort towards understanding environmental influences driving interspecific signalling in nature.This article is part of the themed issue 'Animal coloration: production, perception, function and application'., (© 2017 The Author(s).)

Primate trichromatic colour vision has been hypothesized to be well tuned for detecting variation in facial coloration, which could be due to selection on either signal wavelengths or the sensitivities of the photoreceptors themselves. We provide one of the first empirical tests of this idea by asking whether, when compared with other visual systems, the information obtained through primate trichromatic vision confers an improved ability to detect the changes in facial colour that female macaque monkeys exhibit when they are proceptive. We presented pairs of digital images of faces of the same monkey to human observers and asked them to select the proceptive face. We tested images that simulated what would be seen by common catarrhine trichromatic vision, two additional trichromatic conditions and three dichromatic conditions. Performance under conditions of common catarrhine trichromacy, and trichromacy with narrowly separated LM cone pigments (common in female platyrrhines), was better than for evenly spaced trichromacy or for any of the dichromatic conditions. These results suggest that primate trichromatic colour vision confers excellent ability to detect meaningful variation in primate face colour. This is consistent with the hypothesis that social information detection has acted on either primate signal spectral reflectance or photoreceptor spectral tuning, or both., (© 2017 The Authors.)

Competing theoretical models make different predictions on which life history strategies facilitate growth of small populations. While 'fast' strategies allow for rapid increase in population size and limit vulnerability to stochastic events, 'slow' strategies and bet-hedging may reduce variance in vital rates in response to stochasticity. We test these predictions using biological invasions since founder alien populations start small, compiling the largest dataset yet of global herpetological introductions and life history traits. Using state-of-the-art phylogenetic comparative methods, we show that successful invaders have fast traits, such as large and frequent clutches, at both establishment and spread stages. These results, together with recent findings in mammals and plants, support 'fast advantage' models and the importance of high potential population growth rate. Conversely, successful alien birds are bet-hedgers. We propose that transient population dynamics and differences in longevity and behavioural flexibility can help reconcile apparently contrasting results across terrestrial vertebrate classes., (© 2017 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.)

Purpose: A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled., Experimental Design: We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients., Results: We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed., Conclusions: Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and Kopetz, p. 3989., (©2016 American Association for Cancer Research.)

A recent phase II study of patients with metastatic colorectal carcinoma showed that mismatch repair gene status was predictive of clinical response to PD-1-targeting immune checkpoint blockade. Further examination revealed strong correlation between PD-L1 protein expression and microsatellite instability (MSI) in stage IV colorectal carcinoma, suggesting that the amount of PD-L1 protein expression could identify late-stage patients who might benefit from immunotherapy. To assess whether the clinical associations between PD-L1 gene expression and MSI identified in metastatic colorectal carcinoma are also present in stage II/III colorectal carcinoma, we used in silico analysis to elucidate the cell types expressing the PD-L1 gene. We found a statistically significant association of PD-L1 gene expression with MSI in early-stage colorectal carcinoma (P < 0.001) and show that, unlike in non-colorectal carcinoma tumors, PD-L1 is derived predominantly from the immune infiltrate. We demonstrate that PD-L1 gene expression has positive prognostic value in the adjuvant disease setting (PD-L1(low) vs. PD-L1(high) HR = 9.09; CI, 2.11-39.10). PD-L1 gene expression had predictive value, as patients with high PD-L1 expression appear to be harmed by standard-of-care treatment (HR = 4.95; CI, 1.10-22.35). Building on the promising results from the metastatic colorectal carcinoma PD-1-targeting trial, we provide compelling evidence that patients with PD-L1(high)/MSI/immune(high) stage II/III colorectal carcinoma should not receive standard chemotherapy. This conclusion supports the rationale to clinically evaluate this patient subgroup for PD-1 blockade treatment. Cancer Immunol Res; 4(7); 582-91. ©2016 AACR., (©2016 American Association for Cancer Research.)

The effects of intrasexual and intersexual selection on male trait evolution can be difficult to disentangle, especially based on observational data. Male-male competition can limit an observer's ability to identify the effect of female mate choice independently from sexual coercion. Here, we use an experimental approach to explore whether an ornament, the red facial skin exhibited by male rhesus macaques ( Macaca mulatta ), might be involved in both female mate choice and male-male competition. We used a noninvasive experimental approach based on the looking time paradigm in a free-ranging setting, showing images of differently colored male faces to both adult females ( N = 91) and males ( N = 77), as well as to juveniles ( N = 94) as a control. Results show that both adult females and males looked longer at dark red faces compared with pale pink ones. However, when considering the proportion of subjects that looked longer at dark red faces regardless of preference strength, only females showed a significant dark red bias. In contrast, juveniles did not show any preferences between stimuli, suggesting that the adult bias is not a consequence of the experimental design or related to a general sensory bias for red coloration among all age-sex classes. Collectively, these results support the role the ornament plays in female mate choice in this species and provide the first evidence that this ornament may play a role in male-male competition as well, despite a general lack of observational evidence for the latter effect to date.

Sexual selection typically produces ornaments in response to mate choice, and armaments in response to male-male competition. Unusually among mammals, many primates exhibit colour signals that may be related to one or both processes. Here, we document for the first time correlates of facial coloration in one of the more brightly coloured primates, the black-and-white snub-nosed monkey (Rhinopithecus bieti). Snub-nosed monkeys have a one-male unit (OMU) based social organization, but these units aggregate semi-permanently into larger bands. This form of mating system causes many males to become associated with bachelor groups. We quantified redness of the prominent lower lip in 15 males (eight bachelors, seven OMU holders) in a group at Xiangguqing, China. Using mixed models, our results show that lip redness increases with age. More interestingly, there is a significant effect of the interaction of group-holding status and mating season on redness; that is, lip colour of OMU males undergoes reddening in the mating season, whereas the lips of subadult and juvenile bachelor males become paler at that time of year. These results indicate that lip coloration is a badge of (group-holding) status during the mating season, with non-adults undergoing facial differentiation, perhaps to avoid the costs of reproductive competition. Future research should investigate whether lip coloration is a product of male-male competition, and/or female mate choice.

Why some organisms become invasive when introduced into novel regions while others fail to even establish is a fundamental question in ecology. Barriers to success are expected to filter species at each stage along the invasion pathway. No study to date, however, has investigated how species traits associate with success from introduction to spread at a large spatial scale in any group. Using the largest data set of mammalian introductions at the global scale and recently developed phylogenetic comparative methods, we show that human-mediated introductions considerably bias which species have the opportunity to become invasive, as highly productive mammals with longer reproductive lifespans are far more likely to be introduced. Subsequently, greater reproductive output and higher introduction effort are associated with success at both the establishment and spread stages. High productivity thus supports population growth and invasion success, with barriers at each invasion stage filtering species with progressively greater fecundity., (©2015 The Authors. Ecology Letters published by CNRS and John Wiley & Sons Ltd.)

Careful investigation of the form of animal signals can offer novel insights into their function. Here, we deconstruct the face patterns of a tribe of primates, the guenons (Cercopithecini), and examine the information that is potentially available in the perceptual dimensions of their multicomponent displays. Using standardized colour-calibrated images of guenon faces, we measure variation in appearance both within and between species. Overall face pattern was quantified using the computer vision 'eigenface' technique, and eyebrow and nose-spot focal traits were described using computational image segmentation and shape analysis. Discriminant function analyses established whether these perceptual dimensions could be used to reliably classify species identity, individual identity, age and sex, and, if so, identify the dimensions that carry this information. Across the 12 species studied, we found that both overall face pattern and focal trait differences could be used to categorize species and individuals reliably, whereas correct classification of age category and sex was not possible. This pattern makes sense, as guenons often form mixed-species groups in which familiar conspecifics develop complex differentiated social relationships but where the presence of heterospecifics creates hybridization risk. Our approach should be broadly applicable to the investigation of visual signal function across the animal kingdom., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

Humans find members of the opposite sex more attractive when their image is spatially associated with the color red. This effect even occurs when the red color is not on the skin or clothing (i.e. is extraneous). We hypothesize that this extraneous color effect could be at least partially explained by a low-level and biologically innate generalization process, and so similar extraneous color effects should be observed in non-humans. To test this possibility, we examined the influence of extraneous color in rhesus macaques ( Macaca mulatta ). Across two experiments, we determined the influence of extraneous red on viewing preferences (assessed by looking time) in free-ranging rhesus monkeys. We presented male and female monkeys with black and white photographs of the hindquarters of same and opposite sex conspecifics on either a red (experimental condition) or blue (control condition) background. As a secondary control, we also presented neutral stimuli (photographs of seashells) on red and blue backgrounds. We found that female monkeys looked longer at a picture of a male scrotum, but not a seashell, on a red background (Experiment 1), while males showed no bias. Neither male nor female monkeys showed an effect of color on looking time for female hindquarters or seashells (Experiment 2). The finding for females viewing males suggests that extraneous color affects preferences among rhesus macaques. Further, it raises the possibility that evolutionary processes gave rise to extraneous color effects during human evolution.

Sexual selection promotes the prevalence of heritable traits that increase an individual's reproductive rate. Despite theoretically strong directional selection, sexually selected traits can show inter-individual variation. Here, we investigate whether red skin ornamentation, a rare example of a male mammalian trait involved in mate attraction, influences fecundity and is heritable in rhesus macaques (Macaca mulatta), and explore the mechanisms that are involved in maintaining trait variation. Interestingly, the trait is expressed by and is attractive to both sexes. We collected facial images of 266 free-ranging individuals and modelled skin redness and darkness to rhesus macaque vision. We used 20 years of genetic parentage data to calculate selection gradients on the trait and perform heritability analyses. Results show that males who were both darkly coloured and high-ranking enjoyed higher fecundity. Female skin redness was positively linked to fecundity, although it remains unclear whether this influences male selectiveness. Heritability explained 10-15% of the variation in redness and darkness, and up to 30% for skin darkness when sexes are considered separately, suggesting sex-influenced inheritance. Our results suggest that inter-individual variation is maintained through condition-dependence, with an added effect of balancing selection on male skin darkness, providing rare evidence for a mammalian trait selected through inter-sexual selection., (© 2014 The Author(s) Published by the Royal Society. All rights reserved.)

Male sexually-selected traits can evolve through different mechanisms: conspicuous and colorful ornaments usually evolve through inter-sexual selection, while weapons usually evolve through intra-sexual selection. Male ornaments are rare among mammals in comparison to birds, leading to the notion that female mate choice generally plays little role in trait evolution in this taxon. Supporting this view, when ornaments are present in mammals they typically indicate social status and are products of male-male competition. This general mammalian pattern, however, may not apply to rhesus macaques ( Macaca mulatta ). Males of this species display conspicuous skin coloration, but this expression is not correlated to dominance rank, and is therefore unlikely to have evolved due to male-male competition. Here, we investigate whether male color expression influences female proceptivity towards males in the Cayo Santiago free-ranging rhesus macaque population. We collected face images of 24 adult males varying in dominance rank and age at the peak of the mating season, and modeled these to rhesus macaque visual perception. We also recorded female socio-sexual behaviors towards these males. Results show that dark red males received more sexual solicitations, by more females, than pale pink ones. Together with previous results, our study suggests that male color ornaments are more likely to be a product of inter- rather than intra-sexual selection. This may especially be the case in rhesus macaques due to the particular characteristics of male-male competition in this species.