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ABSTRACT Color varies in pattern and degree across the tree of life. In animals, genetic variation in color is hypothesized to have pleiotropic effects on a variety of behaviors due to shared dependence on underlying biochemical pathways. Such pleiotropy can constrain the independent evolution of color and behavior. Although associations between color and behavior have been reported, this relationship has not yet been addressed across a broad taxonomic scale with a formal meta‐analysis. We used a phylogenetic meta‐analytic approach to examine the relationship between individual variation in aggressive behavior and variation in multiple colors. Seventy‐four studies met our inclusion criteria (vertebrates = 70; invertebrates = 4). After accounting for phylogeny and correcting for publication bias, there was a positive association between measures of aggression and degree or area of coloration (mean = 0.248, 95% CI = (0.044, 0.477)). Because this positive association was not restricted to melanin‐based coloration, we conclude that this pattern does not strongly support the melanin pleiotropy hypothesis. Because the association was also not affected by moderators accounting for individual condition, social rank, or age, the results do not strongly support hypotheses that condition dependence accounts for relationships between color and aggressive behavior. The badge of status hypothesis predicts that arbitrary traits can evolve to signal aggression or social dominance. We propose that this is the most parsimonious explanation for the patterns we observe. Because of the lack of evidence for condition dependence in the association between color and aggression, we further propose that the genetic covariation between traits contributes to the evolution of the badges of status.

IntroductionMusculoskeletal pain affecting children is common. Rehabilitation and treatment effectiveness can be influenced by multiple individual and contextual factors. The need for more rigorous evaluation of physiotherapy treatment for children's pain, identification of the role of specific techniques, and exploration of the influence of the therapeutic alliance is needed. This scoping review of research aimed to examine: (1) What are the perceptions of children, parents, and physiotherapists about the importance of therapeutic alliance during musculoskeletal pain treatment? (2) What are the key characteristics of therapeutic alliance during a child's musculoskeletal pain treatment from the perspectives of children, parents, and physiotherapists? and (3) What are the perceived impacts of therapeutic alliance (positive and negative) during a child's physiotherapy treatment for musculoskeletal pain?MethodsThe scoping review, based on Arksey and O'Malley's framework and reporting was guided by PRISMA-ScR. The search strategy was based on three concept blocks: (1) Study population: Children (

Xishuangbanna, located in southern Yunnan, China, is a vital tropical rainforest reserve supporting rich biodiversity, including the endangered Asian elephant (Elephas maximus). Increasing human activities, such as urbanization and agricultural expansion, have degraded habitats and intensified human–elephant conflicts, adding to the challenges of conservation. This study integrates habitat quality assessment and conflict risk analysis using the InVEST model across 2128 villages, considering land use and habitat threats like cropland and roads. The model reveals significant overlap between high-conflict zones and low-quality habitats near key reserves, underscoring the need for targeted conservation strategies. We propose establishing Ecological Source Areas (ESAs) to protect high-quality habitats and Ecological Restoration Zones (ERZs) to improve ecological conditions in low-quality, high-conflict zones. ESAs are essential for providing continuous ecosystem services and ensuring ecological security, while ERZs focus resources on areas with high conflict risk that urgently need restoration. Additionally, we recommend creating ecological corridors to connect fragmented habitats, enhance connectivity, support herd interactions, and reduce conflicts by expanding elephants’ safe roaming range. This integrated framework emphasizes habitat protection, ecological restoration, and conflict mitigation while accounting for human dynamics to support sustainable conservation. Reducing overlap between human and elephant activities remains a key objective. Future research should refine these models with more detailed data and extend their application to other regions, focusing on adaptive management and monitoring to address evolving ecological and human dynamics.

Abstract Oncogenic KRAS mutations are well-described functionally and are known to drive tumorigenesis. Recent reports describe a significant prevalence of KRAS allelic imbalances or gene dosage changes in human cancers, including loss of the wild-type allele in KRAS mutant cancers. However, the role of wild-type KRAS in tumorigenesis and therapeutic response remains elusive. We report an in vivo murine model of colorectal cancer featuring deletion of wild-type Kras in the context of oncogenic Kras. Deletion of wild-type Kras exacerbates oncogenic KRAS signalling through MAPK and thus drives tumour initiation. Absence of wild-type Kras potentiates the oncogenic effect of KRASG12D, while incidentally inducing sensitivity to inhibition of MEK1/2. Importantly, loss of the wild-type allele in aggressive models of KRASG12D-driven CRC significantly alters tumour progression, and suppresses metastasis through modulation of the immune microenvironment. This study highlights the critical role for wild-type Kras upon tumour initiation, progression and therapeutic response in Kras mutant CRC.

It is estimated that disruptions to life caused by the COVID-19 pandemic have led to an increase in the number of children and young people suffering from mental health issues globally. In England one in four children experienced poor mental health in 2022. Social prescribing is gaining traction as a systems-based approach, which builds upon person-centered methods, to refer children and young people with non-clinical mental health issues to appropriate community assets. Recognition of social prescribing benefits for children's mental health is increasing, yet evidence is limited. Inconsistent terminology and variation of terms used to describe social prescribing practices across the literature hinders understanding and assessment of social prescribing's impact on children's mental health. This scoping review thus aims to systematically identify and analyse the various terms, concepts and language used to describe social prescribing with children and young people across the wider health and social care literature base. The scoping review will be undertaken using a six-stage framework which includes: identifying the research question, identifying relevant studies, study selection, charting the data, collating, summarising and reporting the results, and consultation. Electronic databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health, PsychInfo, Social Policy Practice, Scopus, Science Direct, Cochrane library and Joanna Briggs), alongside evidence from grey literature, hand search, citation tracking, and use of expert correspondence will be included in the review to ensure published and unpublished literature is captured. Data extraction will be carried out by two reviewers using a predefined form to capture study characteristics, intervention descriptions, outcomes, and key terms used to report social prescribing for children and young people. No formal quality appraisal or risk of bias evaluation will be performed, as this scoping review aims to map and describe the literature. Data will be stored and managed using the Rayaan.ai platform and a critical narrative of the common themes found will be included.

Klebsiella pneumoniae is a World Health Organization priority pathogen and a significant clinical concern for infections of the respiratory and urinary tracts due to widespread and increasing resistance to antimicrobials. In the absence of a vaccine, there is an urgent need to identify novel targets for therapeutic development. Bacterial pathogens, including K. pneumoniae, require the d-block metal ion zinc as an essential micronutrient, which serves as a cofactor for ~6% of the proteome. During infection, zinc acquisition necessitates the use of high affinity uptake systems to overcome niche-specific zinc limitation and host-mediated nutritional immunity. Here, we report the identification of ZnuCBA and ZniCBA, two ATP-binding cassette permeases that are highly conserved in Klebsiella species and contribute to K. pneumoniae AJ218 zinc homeostasis, and the high-resolution structure of the zinc-recruiting solute-binding protein ZniA. The Znu and Zni permeases appear functionally redundant with abrogation of both systems required to reduce K. pneumoniae zinc accumulation. Disruption of both systems also exerted pleiotropic effects on the homeostasis of other d-block elements. Zinc limitation perturbed K. pneumoniae cell morphology and compromised resistance to stressors, such as salt and oxidative stress. The mutant strain lacking both systems showed significantly impaired virulence in acute lung infection models, highlighting the necessity of zinc acquisition in the virulence and pathogenicity of K. pneumoniae.

Abstract Knowledge gaps regarding the potential role of pesticides in the loss of agricultural biodiversity worldwide and mixture-related issues hamper proper risk assessment of unintentional impacts of pesticides, rendering essential the monitoring of wildlife exposure to these compounds. Free-ranging mammal exposure to legacy (Banned and Restricted: BRPs) and currently used (CUPs) pesticides was investigated, testing the hypotheses of: (1) a background bioaccumulation for BRPs whereas a “hot-spot” pattern for CUPs, (2) different contamination profiles between carnivores and granivores/omnivores, and (3) the role of non-treated areas as refuges towards exposure to CUPs. Apodemus mice (omnivore) and Crocidura shrews (insectivore) were sampled over two French agricultural landscapes (n = 93). The concentrations of 140 parent chemicals and metabolites were screened in hair samples. A total of 112 compounds were detected, showing small mammal exposure to fungicides, herbicides and insecticides with 32 to 65 residues detected per individual (13–26 BRPs and 18–41 CUPs). Detection frequencies exceeded 75% of individuals for 13 BRPs and 25 CUPs. Concentrations above 10 ng/g were quantified for 7 BRPs and 29 CUPs (in 46% and 72% of individuals, respectively), and above 100 ng/g for 10 CUPs (in 22% of individuals). Contamination (number of compounds or concentrations) was overall higher in shrews than rodents and higher in animals captured in hedgerows and cereal crops than in grasslands, but did not differ significantly between conventional and organic farming. A general, ubiquitous contamination by legacy and current pesticides was shown, raising issues about exposure pathways and impacts on ecosystems. We propose a concept referred to as “biowidening”, depicting an increase of compound diversity at higher trophic levels. This work suggests that wildlife exposure to pesticide mixtures is a rule rather than an exception, highlighting the need for consideration of the exposome concept and questioning appropriateness of current risk assessment and mitigation processes.

Abstract When animals forage, they face complex multi-destination routing problems. Traplining behaviour—the repeated use of the same route—can be used to study how spatial memory might evolve to cope with complex routing problems in ecologically distinct taxa. We analyzed experimental data from multi-destination foraging arrays for five species, two cercopithecine monkeys (vervets, Chlorocebus pygerythrus, and Japanese macaques, Macaca fuscata) and three strepsirrhines (fat-tailed dwarf lemurs, Cheirogaleus medius, grey mouse lemurs, Microcebus murinus, and aye-ayes, Daubentonia madagascariensis). These species all developed relatively efficient route formations within the arrays but appeared to rely on variable cognitive mechanisms. We found a strong reliance on heuristics in cercopithecoid species, with initial routes that began near optimal and did not improve with experience. In strepsirrhines, we found greater support for reinforcement learning of location-based decisions, such that routes improved with experience. Further, we found evidence of repeated sequences of site visitation in all species, supporting previous suggestions that primates form traplines. However, the recursive use of routes was weak, differing from the strategies seen in well-known traplining animals. Differences between strepsirrhine and cercopithecine strategies may be the result of either ecological or phylogenetic trends, and we discuss future possibilities for disentangling the two.

COVID-19 necessitated the rapid transition to online learning, challenging the ability of Science, Technology, Engineering, and Math (STEM) professors to offer laboratory experiences to their students. As a result, many instructors sought online alternatives. In addition, recent literature supports the capacity of online curricula to empower students of historically underrepresented identities in STEM fields. Here, we present PARE-Seq, a virtual bioinformatics activity highlighting approaches to antimicrobial resistance (AMR) research. Following curricular development and assessment tool validation, pre- and post-assessments of 101 undergraduates from 4 institutions revealed that students experienced both significant learning gains and increases in STEM identity, but with small effect sizes. Learning gains were marginally modified by gender, race/ethnicity, and number of extracurricular work hours per week. Students with more extracurricular work hours had significantly lower increase in STEM identity score after course completion. Female-identifying students saw greater learning gains than male-identifying, and though not statistically significant, students identifying as an underrepresented minority reported larger increases in STEM identity score. These findings demonstrate that even short course-based interventions have potential to yield learning gains and improve STEM identity. Online curricula like PARE-Seq can equip STEM instructors to utilize research-driven resources that improve outcomes for all students, but support must be prioritized for students working outside of school.

ABSTRACT Metal ions are required by all organisms for the chemical processes that support life. However, in excess they can also exert toxicity within biological systems. During infection, bacterial pathogens such as Streptococcus pneumoniae are exposed to host-imposed metal intoxication, where the toxic properties of metals, such as copper, are exploited to aid in microbial clearance. However, previous studies investigating the antimicrobial efficacy of copper in vivo have reported variable findings. Here, we use a highly copper-sensitive strain of S. pneumoniae, lacking both copper efflux and intracellular copper buffering by glutathione, to investigate how copper stress is managed and where it is encountered during infection. We show that this strain exhibits highly dysregulated copper homeostasis, leading to the attenuation of growth and hyperaccumulation of copper in vitro. In a murine infection model, whole-tissue copper quantitation and elemental bioimaging of the murine lung revealed that infection with S. pneumoniae resulted in increased copper abundance in specific tissues, with the formation of spatially discrete copper hot spots throughout the lung. While the increased copper was able to reduce the viability of the highly copper-sensitive strain in a pneumonia model, copper levels in professional phagocytes and in a bacteremic model were insufficient to prosecute bacterial clearance. Collectively, this study reveals that host copper is redistributed to sites of infection and can impact bacterial viability in a hypersusceptible strain. However, in wild-type S. pneumoniae, the concerted actions of the copper homeostatic mechanisms are sufficient to facilitate continued viability and virulence of the pathogen. IMPORTANCE Streptococcus pneumoniae (the pneumococcus) is one of the world’s foremost bacterial pathogens. Treatment of both localized and systemic pneumococcal infection is becoming complicated by increasing rates of multidrug resistance globally. Copper is a potent antimicrobial agent used by the mammalian immune system in the defense against bacterial pathogens. However, unlike other bacterial species, this copper stress is unable to prosecute pneumococcal clearance. This study determines how the mammalian host inflicts copper stress on S. pneumoniae and the bacterial copper tolerance mechanisms that contribute to maintenance of viability and virulence in vitro and in vivo. This work has provided insight into the chemical biology of the host-pneumococcal interaction and identified a potential avenue for novel antimicrobial development.

BackgroundDepression is a common mental health condition that poses a significant public health burden. Effective treatments for depression exist; however, access to evidence-based care remains limited. Mobile health (mHealth) apps offer an avenue for improving access. However, few mHealth apps are informed by evidence-based treatments and even fewer are empirically evaluated before dissemination. To address this gap, we developed RuminAid, an mHealth app that uses evidence-based treatment components to reduce depression by targeting a single key depressogenic process—rumination. ObjectiveThe primary objective of this study was to collect qualitative and quantitative feedback that could be used to improve the design of RuminAid before the software development phase. MethodsWe reviewed empirically supported interventions for depression and rumination and used the key aspects of each to create a storyboard version of RuminAid. We distributed an audio-guided presentation of the RuminAid storyboard to 22 individuals for viewing and solicited user feedback on app content, design, and perceived functionality across 7 focus group sessions. ResultsThe consumer-rated quality of the storyboard version of RuminAid was in the acceptable to good range. Indeed, most participants reported that they thought RuminAid would be an engaging, functional, and informational app. Likewise, they endorsed overwhelming positive beliefs about the perceived impact of RuminAid; specifically, 96% (21/22) believed that RuminAid will help depressed ruminators with depression and rumination. Nevertheless, the results highlighted the need for improved app aesthetics (eg, a more appealing color scheme and modern design). ConclusionsFocus group members reported that the quality of information was quite good and had the potential to help adults who struggle with depression and rumination but expressed concern that poor aesthetics would interfere with users’ desire to continue using the app. To address these comments, we hired a graphic designer and redesigned each screen to improve visual appeal. We also removed time gating from the app based on participant feedback and findings from related research. These changes helped elevate RuminAid and informed its initial software build for a pilot trial that focused on evaluating its feasibility and acceptability.

The authors examine how we differentiate highly similar places from each other. They provide evidence for complementary neural mechanisms in the human hippocampus and prefrontal cortex involved in processing interfering and common elements important to remembering places that we have visited.

Children's social preferences are influenced by the relative status of other individuals, but also by their social identity and the degree to which those individuals are like them. Previous studies have investigated these aspects separately and showed that in some circumstances children prefer high-status individuals and own-gender individuals. Gender is a particularly interesting case to study because it is a strong dimension of social identity, but also one of the most prevalent forms of social hierarchy, with males conceptualised as superior to females, by adults and children alike. Here we directly asked how children's social preferences are influenced by status (winner or loser of a zero-sum conflict) and winner gender (female or male) in different scenarios (same or mixed-gender). In Experiment 1, children saw same-gender conflicts between two females or two males and they displayed an overall preference for winners. In Experiment 2, participants watched two mixed-gender conflicts, one where the female prevailed and one where the male prevailed. In this case, children chose the winner, but only when they had the same gender as themselves. Experiment 3 confirmed that children preferred own-gender individuals in the absence of conflict or status. Overall, children are sensitive to the relative status of other individuals and use this information to make social decisions. However, preschoolers do not prefer just any individual who wins access to a resource. They preferred dominant individuals, but only when they were of their own gender. This suggests that children's dominance evaluations are modulated by children's social identity.

Introduction Names are a reflection of identity and often have personal meaning. The chronic mispronunciation of names can undermine one's identity and be experienced as a microaggression. This workshop aims to provide historical context for names as well as resources for correct name pronunciation. Methods We developed a 60-minute interactive virtual workshop with didactics, small-group sharing of personal experiences, and case discussions. We used an anonymous postworkshop survey to evaluate workshop effectiveness. Results We presented the workshop at one local academic conference and two local educational conferences to learners of all levels from medical students to faculty. We collected postworkshop survey results from 78 participants of diverse racial and ethnic backgrounds. Participants reported learning historical context, ways to ask about correct name pronunciation, correcting name mispronunciation, documenting pronunciation, and sources for applications to practice. The main barriers to implementing workshop lessons included personal and structural factors. Discussion This workshop effectively fills an educational gap by addressing the importance of correct name pronunciation in order to provide a more inclusive environment for clinicians and patients alike.

Young people involved in climate justice activism engage in a range of tactics across entangled 'online' and 'offline' spaces. This article explores the affordances and ambivalences of humour in digital modes of contention for young people (aged 12-30) involved in climate justice activism. Four of the authors are 19-22 years old and involved in climate justice activist organising, and one author is a university-based researcher in her early 40s. Through a collaborative, intergenerational analysis of stories of hybrid digital climate activisms, we ask: what is the role of humour in young people's varied activist repertoires? Thinking with the conceptual resources of adrienne maree brown's "Pleasure Activism," we pose three analytic provocations: (i) humour can amplify generational tensions; (ii) humour is entwined with individual and collective identity-work; and (iii) sometimes humour is 'just a thing' (that can also help with burnout). We collaboratively analyse how young people use humour to dissent, through lampooning hierarchical power structures and profit-driven systems, drawing attention to intersectional injustices, and joyfully expressing affinity and solidarity. At the same time, humour may exclude, offend, and reinforce existing divisions and injustices. Humour is an underappreciated feature of organising towards a more just world, even as the pleasurable and just outcomes of humour are not guaranteed. We argue for further attention to young people's multimodal repertoires across hybrid spaces, and the multiplicity of feelings that accompany climate justice activisms.

Abstract An increasing number of studies have found that the implementation of feeding sites for wildlife-related tourism can affect animal health, behaviour and reproduction. Feeding sites can favour high densities, home range overlap, greater sedentary behaviour and increased interspecific contacts, all of which might promote parasite transmission. In the Yunnan snub-nosed monkey (Rhinopithecus bieti), human interventions via provisioning monkeys at specific feeding sites have led to the sub-structuring of a group into genetically differentiated sub-groups. The fed subgroup is located near human hamlets and interacts with domesticated animals. Using high-throughput sequencing, we investigated Entamoeba species diversity in a local host assemblage strongly influenced by provisioning for wildlife-related tourism. We identified 13 Entamoeba species or lineages in faeces of Yunnan snub-nosed monkeys, humans and domesticated animals (including pigs, cattle, and domestic chicken). In Yunnan snub-nosed monkeys, Entamoeba prevalence and OTU richness were higher in the fed than in the wild subgroup. Entamoeba polecki was found in monkeys, pigs and humans, suggesting that this parasite might circulates between the wild and domestic components of this local social–ecological system. The highest proportion of faeces positive for Entamoeba in monkeys geographically coincided with the presence of livestock and humans. These elements suggest that feeding sites might indirectly play a role on parasite transmission in the Yunnan snub-nosed monkey. The implementation of such sites should carefully consider the risk of creating hotspots of disease transmission, which should be prevented by maintaining a buffer zone between monkeys and livestock/humans. Regular screenings for pathogens in fed subgroup are necessary to monitor transmission risk in order to balance the economic development of human communities dependent on wildlife-related tourism, and the conservation of the endangered Yunnan snub-nosed monkey.

Abstract During the Spring Semester of 2020, an outbreak of a novel coronavirus (SARS‐CoV‐2) and the illnesses it caused (COVID‐19) led to widespread cancelling of on‐campus instruction at colleges and universities in the United States and other countries around the world. Response to the pandemic in university settings included a rapid and unexpected shift to online learning for faculty and students. The transition to teaching and learning online posed many challenges, and the experiences of students during this crisis may inform future planning for distance learning experiences during the ongoing pandemic and beyond. Herein, we discuss the experiences of first‐ and second‐year university students enrolled in a biology seminar course as their classes migrated to online environments. Drawing on reported student experiences and prior research and resources, we discuss the ways we will adjust our own teaching for future iterations of the course while offering recommendations for instructors tasked with teaching in online environments.

Poor eating habits often lead to health concerns. While mental health conditions such as stress and anxiety have been linked as predictors for eating behaviors, cognitive factors may also contribute to eating practices during the early stages of the mandatory COVID-19 lockdown. In the current study, participants responded to a survey that asked them to judge the passing of time (PoTJ) and to produce short intervals (via a time production task) as an index of the internal clock speed. Additionally, they responded to questions about snacking frequency and the tendency to overeat during lockdown. We observed that those who judged time to pass slowly also reported a greater tendency to snack and overeat during the pandemic. Additional analysis also revealed that the effect of PoTJ on snacking is moderated by the internal clock speed such that those who felt time was passing by slowly, and in combination with a faster internal clock (as indexed by shorter duration production), had a greater tendency to snack. The results suggest that different aspects of temporal cognition play potential roles in influencing different types of eating behaviors. Our findings therefore have implications for eating disorders, along with the potential of time-based intervention or behavioral modification approaches.

BackgroundThe RAND/UCLA Appropriateness Method (RAM), a variant of the Delphi Method, was developed to synthesize existing evidence and elicit the clinical judgement of medical experts on the appropriate treatment of specific clinical presentations. Technological advances now allow researchers to conduct expert panels on the internet, offering a cost-effective and convenient alternative to the traditional RAM. For example, the Department of Veterans Affairs recently used a web-based RAM to validate clinical recommendations for de-intensifying routine primary care services. A substantial literature describes and tests various aspects of the traditional RAM in health research; yet we know comparatively less about how researchers implement web-based expert panels. ObjectiveThe objectives of this study are twofold: (1) to understand how the web-based RAM process is currently used and reported in health research and (2) to provide preliminary reporting guidance for researchers to improve the transparency and reproducibility of reporting practices. MethodsThe PubMed database was searched to identify studies published between 2009 and 2019 that used a web-based RAM to measure the appropriateness of medical care. Methodological data from each article were abstracted. The following categories were assessed: composition and characteristics of the web-based expert panels, characteristics of panel procedures, results, and panel satisfaction and engagement. ResultsOf the 12 studies meeting the eligibility criteria and reviewed, only 42% (5/12) implemented the full RAM process with the remaining studies opting for a partial approach. Among those studies reporting, the median number of participants at first rating was 42. While 92% (11/12) of studies involved clinicians, 50% (6/12) involved multiple stakeholder types. Our review revealed that the studies failed to report on critical aspects of the RAM process. For example, no studies reported response rates with the denominator of previous rounds, 42% (5/12) did not provide panelists with feedback between rating periods, 50% (6/12) either did not have or did not report on the panel discussion period, and 25% (3/12) did not report on quality measures to assess aspects of the panel process (eg, satisfaction with the process). ConclusionsConducting web-based RAM panels will continue to be an appealing option for researchers seeking a safe, efficient, and democratic process of expert agreement. Our literature review uncovered inconsistent reporting frameworks and insufficient detail to evaluate study outcomes. We provide preliminary recommendations for reporting that are both timely and important for producing replicable, high-quality findings. The need for reporting standards is especially critical given that more people may prefer to participate in web-based rather than in-person panels due to the ongoing COVID-19 pandemic.

Abstract Background Transposable elements (TEs) are enriched in cytosine methylation, preventing their mobility within the genome. We previously identified a genome-wide repertoire of candidate intracisternal A particle (IAP) TEs in mice that exhibit inter-individual variability in this methylation (VM-IAPs) with implications for genome function. Results Here we validate these metastable epialleles and discover a novel class that exhibit tissue specificity (tsVM-IAPs) in addition to those with uniform methylation in all tissues (constitutive- or cVM-IAPs); both types have the potential to regulate genes in cis. Screening for variable methylation at other TEs shows that this phenomenon is largely limited to IAPs, which are amongst the youngest and most active endogenous retroviruses. We identify sequences enriched within cVM-IAPs, but determine that these are not sufficient to confer epigenetic variability. CTCF is enriched at VM-IAPs with binding inversely correlated with DNA methylation. We uncover dynamic physical interactions between cVM-IAPs with low methylation ranges and other genomic loci, suggesting that VM-IAPs have the potential for long-range regulation. Conclusion Our findings indicate that a recently evolved interplay between genetic sequence, CTCF binding, and DNA methylation at young TEs can result in inter-individual variability in transcriptional outcomes with implications for phenotypic variation.

Abstract Background Agenda setting is associated with more efficient care and better patient experience. This study develops a taxonomy of visit opening styles to assess use of agenda and non-agenda setting visit openings and their effects on participant experience. Methods This observational study analyzed 83 video recorded US primary care visits at a single academic medical center in California involving family medicine and internal medicine resident physicians (n = 49) and patients (n = 83) with chronic pain on opioids. Using conversation analysis, we developed a coding scheme that assessed the presence of agenda setting, distinct visit opening styles, and the number of total topics, major topics, surprise patient topics, and returns to prior topics discussed. Exploratory quantitative analyses were conducted to assess the relationship of agenda setting and visit opening styles with post-visit measures of both patient experience and physician perception of visit difficulty. Results We identified 2 visit opening styles representing agenda setting (agenda eliciting, agenda reframing) and 3 non-agenda setting opening styles (open-ended question, patient launch, physician launch). Agenda setting was only performed in 11% of visits and was associated with fewer surprise patient topics than visits without agenda setting (mean (SD) 2.67 (1.66) versus 4.28 (3.23), p = 0.03). Conclusions In this study of patients with chronic pain, resident physicians rarely performed agenda setting, whether defined in terms of “agenda eliciting” or “agenda re-framing.” Agenda setting was associated with fewer surprise topics. Understanding the communication context and outcomes of agenda setting may inform better use of this communication tool in primary care practice.

We demonstrate the ability of statistical data assimilation (SDA) to identify the measurements required for accurate state and parameter estimation in an epidemiological model for the novel coronavirus disease COVID-19. Our context is an effort to inform policy regarding social behavior, to mitigate strain on hospital capacity. The model unknowns are taken to be: the time-varying transmission rate, the fraction of exposed cases that require hospitalization, and the time-varying detection probabilities of new asymptomatic and symptomatic cases. In simulations, we obtain estimates of undetected (that is, unmeasured) infectious populations, by measuring the detected cases together with the recovered and dead - and without assumed knowledge of the detection rates. Given a noiseless measurement of the recovered population, excellent estimates of all quantities are obtained using a temporal baseline of 101 days, with the exception of the time-varying transmission rate at times prior to the implementation of social distancing. With low noise added to the recovered population, accurate state estimates require a lengthening of the temporal baseline of measurements. Estimates of all parameters are sensitive to the contamination, highlighting the need for accurate and uniform methods of reporting. The aim of this paper is to exemplify the power of SDA to determine what properties of measurements will yield estimates of unknown parameters to a desired precision, in a model with the complexity required to capture important features of the COVID-19 pandemic.

Abstract Voles can reach high densities with multiannual population fluctuations of large amplitude, and they are at the base of predator communities in Northern Eurasia and Northern America. This status places them at the heart of management conflicts wherein crop protection and health concerns are often raised against conservation issues. Here, a 20‐year survey describes the effects of large variations in grassland vole populations on the densities and the daily theoretical food intakes (TFI) of vole predators based on roadside counts. Our results show how the predator community responded to prey variations of large amplitude and how it reorganized with the increase in a dominant predator, here the red fox, which likely negatively impacted hare, European wildcat, and domestic cat populations. This population increase did not lead to an increase in the average number of predators present in the study area, suggesting compensations among resident species due to intraguild predation or competition. Large variations in vole predator number could be clearly attributed to the temporary increase in the populations of mobile birds of prey in response to grassland vole outbreaks. Our study provides empirical support for more timely and better focused actions in wildlife management and vole population control, and it supports an evidence‐based and constructive dialogue about management targets and options between all stakeholders of such socio‐ecosystems.

A crescente incorporação dos processos biofísicos pelo mercado verificado a partir do final dos anos 1980, em especial aqueles relacionados aos avanços das fronteiras agrícolas, foi interpretado por alguns autores em termos de "neoliberalização da natureza". Tal perspectiva foi bastante fértil nos estudos críticos das questões ambientais contemporâneas, mas foi colocada à prova ao sofrer sérias objeções desferidas a partir de diversos ângulos. Algumas dessas objeções questionam os fundamentos teóricos da tese da neoliberalização da natureza e apontam para um certo afrouxamento conceitual frente a diversidade das definições dos conceitos adotados. Outro tipo de objeção se volta para o seu limitado potencial de análise empírica, na medida em que, de tão amplo, não auxilia na compreensão de um conjunto de processos inevitavelmente incompletos e parciais. A presente contribuição propõe um balanço dos debates teóricos e empíricos sobre a neoliberalização da natureza passando por seus principais autores e tomando por referência pesquisas empíricas que temos realizado sobre o agronegócio no Brasil. Discutiremos em que medida os seus limites se devem às inconsistências apontadas pelos seus críticos ou, ao invés (e além) disso, à falta de precauções na mobilização de uma abordagem que merece, apesar de tudo, atenção e interesse.

Acquisition of the trace-element molybdenum via the high-affinity ATP-binding cassette permease ModABC is essential for Pseudomonas aeruginosa respiration in anaerobic and microaerophilic environments. This study determined the X-ray crystal structures of the molybdenum-recruiting solute-binding protein ModA from P. aeruginosa PAO1 in the metal-free state and bound to the group 6 metal oxyanions molybdate, tungstate, and chromate. Pseudomonas aeruginosa PAO1 ModA has a non-contiguous dual-hinged bilobal structure with a single metal-binding site positioned between the two domains. Metal binding results in a 22° relative rotation of the two lobes with the oxyanions coordinated by four residues, that contribute six hydrogen bonds, distinct from ModA orthologues that feature an additional oxyanion-binding residue. Analysis of 485 Pseudomonas ModA sequences revealed conservation of the metal-binding residues and β-sheet structural elements, highlighting their contribution to protein structure and function. Despite the capacity of ModA to bind chromate, deletion of modA did not affect P. aeruginosa PAO1 sensitivity to chromate toxicity nor impact cellular accumulation of chromate. Exposure to sub-inhibitory concentrations of chromate broadly perturbed P. aeruginosa metal homeostasis and, unexpectedly, was associated with an increase in ModA-mediated molybdenum uptake. Elemental analyses of the proteome from anaerobically grown P. aeruginosa revealed that, despite the increase in cellular molybdenum upon chromate exposure, distribution of the metal within the proteome was substantially perturbed. This suggested that molybdoprotein cofactor acquisition may be disrupted, consistent with the potent toxicity of chromate under anaerobic conditions. Collectively, these data reveal a complex relationship between chromate toxicity, molybdenum homeostasis and anaerobic respiration.

The electromagnetic emission resulting from neutron star mergers have been shown to encode properties of the ejected material in their light curves. The ejecta properties inferred from the kilonova emission has been in tension with those calculated based on the gravitational wave signal and numerical relativity models. Motivated by this tension, we construct a broad set of surrogate light curve models derived for kilonova ejecta. The four-parameter family of two-dimensional anisotropic simulations and its associated surrogate explore different assumptions about the wind outflow morphology and outflow composition, keeping the dynamical ejecta component consistent. We present the capabilities of these surrogate models in interpolating kilonova light curves across various ejecta parameters and perform parameter estimation for AT2017gfo both without any assumptions on the outflow and under the assumption that the outflow must be representative of solar r-process abundance patterns. Our parameter estimation for AT2017gfo shows these surrogate models help alleviate the ejecta property discrepancy while also illustrating the impact of systematic modeling uncertainties on these properties, urging further investigation.

Equity gaps exist for students with disabilities in educational contexts and these are exacerbated during disruptions to education, such as the COVID-19 pandemic. The pandemic forced swift changes in education with little guidance or time to prepare. Few researchers have explored the effectiveness and critical components of online learning for individuals with disabilities, and particularly for those students pursuing a diploma who are receiving special education services via small group instruction. This paper offers (a) a brief review of the literature regarding online education for students with disabilities, (b) a description of an online learning model employed with elementary, middle, and high school students with developmental disabilities receiving special education via small group instruction and (c) an exploratory examination of the online learning model's impact on student attendance and engagement using direct observation data collected across months and student and teacher social validity. The online learning model addresses technology, attendance, executive functioning, specialized instruction, social-emotional supports, communication and collaboration, and professional development. Student attendance and engagement were found to meet or approach pre-pandemic levels and student and teacher social validity data further validated the pilot online learning model.

Indigenous students often see higher education as a means by which they can meet their familial, community, and cultural responsibilities. Unfortunately, many collegiate institutions emphasize values and social protocols, a way of understanding, and a way of knowing that are unfamiliar and even hostile to Indigenous worldviews. To better understand the experience of Native and Indigenous STEM Students at our institution, we listened to students, alumni, faculty, and staff through a series of online forums modeled on the Indigenous tradition of Talking Circles. The discussion from participants in the Talking Circles resulted in 464 coded responses characterized as supports, barriers, and ideas in STEM. The results show how Indigenous students benefit from the integration of cultural wealth that resides in Indigenous knowledge, practices, and protocols. We have also gained insights into the importance of an Indigenized campus culture and have time-tested and effective programs that teach us how to promote such a culture. We review the major themes identified and provide recommendations to others interested in supporting Indigenous students in STEM.

There is a critical need to broaden access to engineering education in order to build a strong and diverse engineering workforce. However, four-year engineering programs are typically designed for students who are calculus-ready, so many students who wish to study engineering may need additional preparation and time to succeed. The NSF-funded Redshirt in Engineering Consortium was formed in 2016 to enhance the ability of academically talented but underprepared students from low-income backgrounds to successfully graduate with bachelor's degrees in engineering. The "redshirt" name is derived from the practice of giving some college athletes an extra year of eligibility to prepare for college-level competition. Implementation and evaluation of Redshirt programs across six universities participating in the Redshirt in Engineering Consortium revealed important lessons for schools considering a Redshirt program, including the importance of alignment with a college-wide commitment to increasing equity; sufficient funding for a full-time administrator; ability to fit shared curricular experiences within existing degree requirements; and attention to Redshirt's unique role in the landscape of existing equity programs. Over the course of the five-year grant, understanding of the Redshirt in Engineering Model also evolved to center on five key pillars: (1) a focus on supporting high-achieving students from low income or educationally disadvantaged backgrounds; (2) an expected five-year graduation timeline; (3) personal, professional, and study skills development; (4) intrusive advising; and (5) community-building and social support. This article defines the key elements of the Redshirt in Engineering Model, describes model adaptations and lessons learned through implementation and evaluation across the consortium, and suggests considerations for other institutions interested in implementing a Redshirt in Engineering program.

ABSTRACT Klebsiella pneumoniae is an opportunistic Gram-negative pathogen that is a leading cause of healthcare-associated infections, including pneumonia, urinary tract infections, and sepsis. Essential to the colonization and infection by K. pneumoniae is the acquisition of nutrients, such as the transition metal ion zinc. Zinc has crucial structural and catalytic roles in the proteome of all organisms. Nevertheless, in excess, it has the potential to mediate significant toxicity by dysregulating the homeostasis of other transition elements, disrupting enzymatic processes, and perturbing metalloprotein cofactor acquisition. Here, we sought to elucidate the zinc detoxification mechanisms of K. pneumoniae, which remain poorly defined. Using the representative K. pneumoniae AJ218 strain, we showed that the P-type ATPase, ZntA, which is upregulated in response to cellular zinc stress, was the primary zinc efflux pathway. Deletion of zntA rendered K. pneumoniae AJ218 highly susceptible to exogenous zinc stress and manifested as an impaired growth phenotype and increased cellular accumulation of the metal. Loss of zntA also increased sensitivity to cadmium stress, indicating a role for this efflux pathway in cadmium resistance. Disruption of zinc homeostasis in the K. pneumoniae AJ218 ΔzntA strain also impacted manganese and iron homeostasis and was associated with increased production of biofilm. Collectively, this work showed the critical role of ZntA in K. pneumoniae zinc tolerance and provided a foundation for further studies on zinc homeostasis and the future development of novel antimicrobials to target this pathway. IMPORTANCE Klebsiella pneumoniae is a leading cause of healthcare-associated infections, including pneumonia, urinary tract infections, and sepsis. Treatment of K. pneumoniae infections is becoming increasingly challenging due to high levels of antibiotic resistance and the rising prevalence of carbapenem-resistant, extended-spectrum β-lactamases producing strains. Zinc is essential to the colonization and infection by many bacterial pathogens but toxic in excess. This work described the first dissection of the pathways associated with resisting extracellular zinc stress in K. pneumoniae. This study revealed that the P-type ATPase ZntA was highly upregulated in response to exogenous zinc stress and played a major role in maintaining bacterial metal homeostasis. Knowledge of how this major bacterial pathogen resists zinc stress provided a foundation for antimicrobial development studies to target and abrogate their essential function.

Nonparametric estimation for a probability density function that describes multivariate data has typically been addressed by kernel density estimation (KDE). A novel density estimator recently developed by Farmer and Jacobs offers an alternative high-throughput automated approach to univariate nonparametric density estimation based on maximum entropy and order statistics, improving accuracy over univariate KDE. This article presents an extension of the single variable case to multiple variables. The univariate estimator is used to recursively calculate a product array of one-dimensional conditional probabilities. In combination with interpolation methods, a complete joint probability density estimate is generated for multiple variables. Good accuracy and speed performance in synthetic data are demonstrated by a numerical study using known distributions over a range of sample sizes from 100 to 106 for two to six variables. Performance in terms of speed and accuracy is compared to KDE. The multivariate density estimate developed here tends to perform better as the number of samples and/or variables increases. As an example application, measurements are analyzed over five filters of photometric data from the Sloan Digital Sky Survey Data Release 17. The multivariate estimation is used to form the basis for a binary classifier that distinguishes quasars from galaxies and stars with up to 94% accuracy.

The question of how education research can be 'useful' is an enduring and challenging one. In recent years, this question has been approached by universities through a widespread 'impact' agenda. In this article, we explore the tensions between usefulness and impact and present six stories that reflect on research use with communities. These stories engage issues of the risk of usefulness, the time that is needed to work collaboratively for research usefulness, whether theories developed in universities can be useful to communities for understanding the problems they face, who has the power to steer research to serve their purposes, and how community collective action can enhance the usefulness of research. The article concludes with a section that reflects on the importance of continuing to engage with the debates about research use in often highly commercially oriented university environments. This article brings together diverse voices that wrestle with the politics of research use beyond the neat, linear narratives of change that impact agendas tend to portray. These illustrations of the ethical dilemmas encountered through navigating research use with communities contribute to an ongoing conversation about refusing capitalist and colonialist logics of research extraction while working within institutions often driven by such logics.

Changes to the Welsh curriculum are becoming apparent. The Williams Report culminated in recommendations for schools and initial teacher education (ITE) on the inclusion and teaching of Black Asian and Minority Ethnic histories in Wales. The subsequent Welsh Government ITE action plan was designed to ensure the pro-active recruitment of trainee teachers from Black and racially minoritised backgrounds in Wales. As a result of this legislation, a team of ITE lecturers in a school of education in a Welsh university formed a research triad and larger research collective, the idea being that we needed to decolonise our own pedagogy and curriculum delivery and re-imagine ITE within an anti-racist paradigm. It was key to reflect on our ITE provision, ensuring that our curriculum delivery reflected the ambition of the new Curriculum for Wales, which encourages practitioners to think differently on what they teach, how they teach and what they want young people to learn. Using a patchwork methodology--which included 'deep thinking and deep listening'--we examined our current ITE delivery and work that has been done thus far and looked at the gains and areas for development. It became clear that staff within our 'ITE research collective' were becoming more knowledgeable and confident in working within a racial dynamic, and consequently felt more able to impart knowledge when engaging with other ITE colleagues and students. This paper charts our ongoing journey and makes recommendations gained from our experiences.

The aim of this study was to examine which topic- and learning-related knowledge and motivational beliefs predict the use of specific deep-level learning strategies during an independent learning task. Participants included 335 Estonian fourth- and sixth-grade students who were asked to read about light processes and seasonal changes. The study was completed electronically. Topic-related knowledge was assessed via an open question about seasonal changes, and learning-related knowledge was assessed via scenario-based tasks. Expectancies, interest, and utility values related to learning astronomy and using deep-level learning strategies were assessed via questions based on the Situated Expectancy-Value Theory. Deep-level learning strategies (using drawings in addition to reading and self-testing) were assessed while completing the reading task. Among topic-related variables, prior knowledge and utility value--but not interest or expectancy in learning astronomy--were related to using deep-level learning strategies. Among learning-related variables, interest and utility value of effective learning--but not metacognitive knowledge of learning strategies or expectancy in using deep-level learning strategies--were related to using deep-level learning strategies. This study confirms that it is not enough to examine students' knowledge and skills in using learning strategies with general or hypothetical questions, instead, it is of crucial importance to study students in real learning situations.

Many rodents, including most populations of arctic lemmings (genus Dicrostonyx and Lemmus), have cyclic population dynamics. Among the numerous hypotheses which have been proposed and tested to explain this typical characteristic of some terrestrial vertebrate communities, trophic interactions have often been presented as the most likely drivers of these periodic fluctuations. The possible role of parasites has, however, only seldom been assessed. In this study, we genetically measured the prevalence of two endoparasite taxa, eimerians and cestodes, in 372 faecal samples from collared lemmings, over a five year period and across three distant sites in Northeast Greenland. Prevalence of cestodes was low (2.7% over all sites and years) and this taxon was only found at one site (although in 4 out of 5 years) in adult hosts. By contrast, we found high prevalence for eimerians (77.7% over all sites and years), which occurred at all sites, in every year, for both age classes (at the Hochstetter Forland site where both adult and juvenile faeces were collected) and regardless of reproductive and social status inferred from the characteristics of the lemming nests where the samples had been collected. Prevalence of eimerians significantly varied among years (not among sites) and was higher for juvenile than for adult lemmings at the Hochstetter Forland site. However, higher prevalence of eimerians (Pt) was only associated with lower lemming density (Nt) at one of the three sites and we found no delayed density dependence between Nt and Pt+1 to support the parasite hypothesis. Our results show that there is no clear relation between lemming density and eimerian faecal prevalence in Northeast Greenland and hence no evidence that eimerians could be driving the cyclic population dynamics of collared lemmings in this region. Keywords: Eimerians, Cestodes, Population dynamics, Faecal prevalence, Greenland, Rodent-parasites interactions

Abstract Background A high rate of euthanized and spontaneously dead sows causes production losses and likely indicates underlying welfare problems. Identification of predisposing factors to on-farm deaths requires a thorough understanding of the causes. Post-mortem examination is needed for a proper diagnosis. The aims of this descriptive study were to determine causes of spontaneous deaths and euthanasia in sows in a convenience sample of Finnish herds and to describe pathological findings in the locomotor system and in teeth and gums. Results This study described post-mortem findings in 65 sows found dead or euthanized on 15 farms. All but one of the sows presented with two or more pathological findings. The majority of primary pathologic-anatomic diagnoses (PAD-1) were inflammatory. The most prevalent diagnoses were arthritis and peritonitis (9% of sows each). The locomotor system was the body part most commonly affected by lesions. Findings in the locomotor system unassociated with death were present in 85% of the animals, additionally 29% of PAD-1 s concerned the locomotor system. The prevalence for both degenerative joint disease and tooth wear was 71%. Farmers had noted clinical signs within 30 days of death in every euthanized sow and in half of the spontaneously dead ones. The farmer’s impression of the cause of death agreed at least partly with the PAD-1 in 44% of the cases. Conclusion Multiple pathologies were the norm in the present animals. This may indicate an extended course of illness and therefore also an unnecessary delay in medical treatment or euthanasia. The prevalence and clinical relevance of the most common disorders, including degenerative joint disease and tooth wear, need to be elucidated.

Background: New hypertension performance measures encourage more intensive treatment in older adults. Treatment intensification includes starting new medications and increasing the dose of old ones. Medication dose is particularly important to older adults, given their vulnerability to dose-related side effects. We previously validated a standardized measure of beneficial doses tested in hypertension trials, Hypertension Daily Dose (HDD). Aim of the study: To test whether changes in treatment intensity using HDD was associated with systolic blood pressure (SBP) and patient characteristics. Methods: Longitudinal study of all Veterans aged ≥65 years with a diagnosis of hypertension. We defined 3 groups of risk: 1) cardiovascular risk; 2) geriatric/frail; 3) low-risk (comparator). Using multinomial regression, we assessed the probability of deintensification, intensification, vs. stable treatment, according to SBP and group. Results: Among 1,331,111 Veterans, 19.9% had deintensification, and 29.6% intensification. Deintensification decreased, while intensification increased, with SBP. Compared to low-risk patients, cardiovascular risk patients had 1.11 (95% CI 1.10–1.13) times the odds of intensifying, and geriatric/frail patients 1.45 (95%CI 1.43–1.47) times the odds of deintensifying. Discussion: Patient-level HDD change was consistent with an expected association with cardiovascular risk and geriatric/frail conditions, suggesting that HDD can be used longitudinally to assess hypertension treatment modification in large health systems.