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A gaping wound of the foot and ankle can be difficult to close. In cases in which wound margin mobility is suitable, the use of a vessel loop, or loops, to provide sufficient tension for wound margin reapproximation can be a useful adjunct to the surgical management of wounds that would otherwise be very difficult to close without the use of a skin graft or flap coverage. In this report, we describe the use of a vessel loop, or loops, for reapproximation of the margins of gaping wounds of the foot or ankle. [ABSTRACT FROM AUTHOR]

Context/objectives: Establishing human connection is critical during serious illness conversations, however the sensory and relational environment of telehealth may require innovative communication practices for clinicians, patients, and families to do so effectively. We sought to explore if and how recommended in-person best practices for establishing human connection are adapted to the telehealth palliative care (telePC) setting, to enable discovery and description of practice innovations in this new care environment., Methods: We analyzed data from the Northern New England Palliative Care TeleConsult Research Study - a formative mixed-methods pilot study at two academic medical centers in rural US states with patients with serious illness (2019-2020). We used a qualitative descriptive approach paired with directed content analysis to analyze video-recorded telePC consultations., Results: Nine video-recorded telePC consultations were analyzed including 9 patients and 6 palliative care clinicians. Patient-participants had a mean age of 68 years, 56 % were women, and 38 % did not complete high school. Mean consultation duration was 52 min (standard deviation 10, range 40-70 min). Our qualitative analysis of visits resulted in three key themes describing clinician communication: 1) Practices for fostering human connection; 2) Practices for overcoming technical problems/difficulties; and 3) Practices for engaging in multi-participant tele-conversations., Conclusion: Our study findings help to provide proof-of-concept evidence that clinicians can use recommended in-person connection-building communication practices in telePC. As palliative care clinicians naturally adapt to telehealth environments, more empirical research is needed to understand which innovative approaches most effectively foster human connection., Innovation: TelePC represents an expanding, yet understudied, mode of palliative care delivery. This study is among the first to describe how the telePC context is catalyzing naturally-occurring communication innovations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025 The Authors.)

Identifying populations at highest risk from climate change is a critical component of conservation efforts. However, vulnerability assessments are usually applied at the species level, even though intraspecific variation in exposure, sensitivity and adaptive capacity play a crucial role in determining vulnerability. Genomic data can inform intraspecific vulnerability by identifying signatures of local adaptation that reflect population-level variation in sensitivity and adaptive capacity. Here, we address the question of local adaptation to temperature and the genetic basis of thermal tolerance in two stream frogs (Ascaphus truei and A. montanus). Building on previous physiological and temperature data, we used whole-genome resequencing of tadpoles from four sites spanning temperature gradients in each species to test for signatures of local adaptation. To support these analyses, we developed the first annotated reference genome for A. truei. We then expanded the geographic scope of our analysis using targeted capture at an additional 11 sites per species. We found evidence of local adaptation to temperature based on physiological and genomic data in A. montanus and genomic data in A. truei, suggesting similar levels of sensitivity (i.e., susceptibility) among populations regardless of stream temperature. However, invariant thermal tolerances across temperatures in A. truei suggest that populations occupying warmer streams may be most sensitive. We identified high levels of evolutionary potential in both species based on genomic and physiological data. While further integration of these data is needed to comprehensively evaluate spatial variation in vulnerability, this work illustrates the value of genomics in identifying spatial patterns of climate change vulnerability., (© 2025 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

While a best practice for evaluating the behaviour of genetic clustering algorithms on empirical data is to conduct parallel analyses on simulated data, these types of simulation techniques often involve sampling genetic data with replacement. In this paper we demonstrate that sampling with replacement, especially with large marker sets, inflates the perceived statistical power to correctly assign individuals (or the alleles that they carry) back to source populations-a phenomenon we refer to as resampling-induced, spurious power inflation (RISPI). To address this issue, we present gscramble, a simulation approach in R for creating biologically informed individual genotypes from empirical data that: (1) samples alleles from populations without replacement and (2) segregates alleles based on species-specific recombination rates. This framework makes it possible to simulate admixed individuals in a way that respects the physical linkage between markers on the same chromosome and which does not suffer from RISPI. This is achieved in gscramble by allowing users to specify pedigrees of varying complexity in order to simulate admixed genotypes, segregating and tracking haplotype blocks from different source populations through those pedigrees, and then sampling-using a variety of permutation schemes-alleles from empirical data into those haplotype blocks. We demonstrate the functionality of gscramble with both simulated and empirical data sets and highlight additional uses of the package that users may find valuable., (Published 2025. This article is a U.S. Government work and is in the public domain in the USA. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Maternal hyperglycemia during pregnancy adversely affects maternal and child outcomes. While mechanisms are not fully understood, maternal circulating miRNAs may play a role. We examined whether continuous glucose levels and hyperglycemia subtypes (gestational diabetes, type 2 diabetes, and glucose intolerance) were associated with circulating miRNAs during late pregnancy. Seven miRNAs (hsa-miR-107, hsa-let-7b-5p, hsa-miR-126-3p, hsa-miR-181a-5p, hsa-miR-374a-5p, hsa-miR-382-5p, and hsa-miR-337-5p) were associated ( p  < 0.05) with either hyperglycemia or continuous glucose levels prior to multiple testing correction. These miRNAs target genes involved in pathways relevant to maternal and child health, including insulin signaling, placental development, energy balance, and appetite regulation.

Background: Emerging cancer treatments are often most available to socially advantaged individuals. This study examines the relationship of patient educational attainment, income level, and rurality to the receipt of genome-matched treatment and overall survival., Methods: Survey and clinical data were collected from patients with cancer (n = 1258) enrolled in the Maine Cancer Genomics Initiative. Logistic regression models examined whether receipt of genome-matched treatment differed by patient education, income, and rurality. Kaplan-Meier curves and Cox regression were conducted to evaluate 12-month mortality. We completed additional exploratory analyses using Kaplan-Meier curves and Cox models stratified by receipt of genome-matched treatment. Logistic and Cox regression models were adjusted for age and gender., Results: Educational attainment, income level, and rurality were not associated with genome-matched treatment receipt. Of 1258 patients, 462 (36.7%) died within 365 days of consent. Mortality risk was associated with lower educational attainment (hazard ratio [HR] = 1.30, 95% confidence interval [CI] = 1.06 to 1.59; P = .013). No statistically significant differences in mortality risk were observed for income level or rurality. Exploratory models suggest that patients who did not receive genome-matched treatment with lower educational attainment had higher mortality risk (HR = 1.36, 95% CI = 1.09 to 1.69; P = .006). For patients who did receive genome-matched treatment, there was no difference in mortality risk between the education groups (HR = 1.01, 95% CI = 0.56 to 1.81; P > .9)., Conclusion: Although there were no disparities in who received genome-matched treatment, we found a disparity in mortality associated with education level, which was more pronounced for patients who did not receive genome-matched treatment. Future research is warranted to investigate the intersectionality of social disadvantage with clinical outcomes to address survival disparities., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Healthcare professionals (HCPs) can play an important role in encouraging patients and their caregivers to be vaccinated. The objective of this qualitative study was to investigate HCPs' perspectives on challenges in vaccine communication and unmet training needs in this domain., Methods: Semi-structured interviews were conducted with 41 HCPs (mainly nurses and physicians) with vaccination roles (23 in England; 18 in France), gathering information on: (1) HCPs' approach to vaccine conversations with patients; (2) Challenges of communicating about vaccines; (3) Vaccine-related training and learning resources available to HCPs, and; (4) HCPs' training needs around vaccine communication., Results: HCPs described a range of communication experiences that indicated insufficient time, information, and skills to confidently navigate difficult conversations with vaccine-hesitant patients. Communication skills were especially important to avoid conflict that could potentially damage the patient-provider relationship. Some HCPs interviewed had received communication training, but for most, this training was not specific to vaccination. Although general communication skills were transferable to vaccine conversations, most HCPs welcomed specific training and informational resources to support countering patients' misconceptions or misinformation about vaccines., Conclusions: HCPs would benefit from training tailored to address vaccine communication with patients, and this should be part of a systemic approach that also provides time and space to have effective vaccine conversations., (© 2024. The Author(s).)

Populations composed of individuals descended from multiple distinct genetic lineages often feature significant differences in phenotypic frequencies. We considered hatchery production of steelhead, the migratory anadromous form of the salmonid species Oncorhynchus mykiss, and investigated how differences among genetic lineages and environmental variation impacted life history traits. We genotyped 23,670 steelhead returning to the four California Central Valley hatcheries over 9 years from 2011 to 2019, confidently assigning parentage to 13,576 individuals to determine age and date of spawning and rates of iteroparity and repeat spawning within each year. We found steelhead from different genetic lineages showed significant differences in adult life history traits despite inhabiting similar environments. Differences between coastal and Central Valley steelhead lineages contributed to significant differences in age at return, timing of spawning, and rates of iteroparity among programs. In addition, adaptive genomic variation associated with life history development in this species varied among hatchery programs and was associated with the age of steelhead spawners only in the coastal lineage population. Environmental variation likely contributed to variations in phenotypic patterns observed over time, as our study period spanned both a marine heatwave and a serious drought in California. Our results highlight evidence of a strong genetic component underlying known phenotypic differences in life history traits between two steelhead lineages., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Genomic tumor testing (GTT) is an emerging technology aimed at identifying variants in tumors that can be targeted with genomically matched drugs. Due to limited resources, rural patients receiving care in community oncology settings may be less likely to benefit from GTT. We analyzed GTT results and observational clinical outcomes data from patients enrolled in the Maine Cancer Genomics Initiative (MCGI), which provided access to GTTs; clinician educational resources; and genomic tumor boards in community practices in a predominantly rural state. 1603 adult cancer patients completed enrollment; 1258 had at least one potentially actionable variant identified. 206 (16.4%) patients received a total of 240 genome matched treatments, of those treatments, 64% were FDA-approved in the tumor type, 27% FDA-approved in a different tumor type and 9% were given on a clinical trial. Using Inverse Probability of Treatment Weighting to adjust for baseline characteristics, a Cox proportional hazards model demonstrated that patients who received genome matched treatment were 31% less likely to die within 1 year compared to those who did not receive genome matched treatment (HR: 0.69; 95% CI: 0.52-0.90; p-value: 0.006). Overall, GTT through this initiative resulted in levels of genome matched treatment that were similar to other initiatives, however, clinical trials represented a smaller share of treatments than previously reported, and "off-label" treatments represented a greater share. Although this was an observational study, we found evidence for a potential 1-year survival benefit for patients who received genome matched treatments. These findings suggest that when disseminated and implemented with a supportive infrastructure, GTT may benefit cancer patients in rural community oncology settings, with further work remaining on providing genome-matched clinical trials., (© 2024. The Author(s).)

Life-history variation is the raw material of adaptation, and understanding its genetic and environmental underpinnings is key to designing effective conservation strategies. We used large-scale genetic pedigree reconstruction of anadromous steelhead trout (Oncorhynchus mykiss) from the Russian River, CA, USA, to elucidate sex-specific patterns of life-history traits and their heritability. SNP data from adults returning from sea over a 14-year period were used to identify 13,474 parent-offspring trios. These pedigrees were used to determine age structure, size distributions and family sizes for these fish, as well as to estimate the heritability of two key life-history traits, spawn date and age at maturity (first reproduction). Spawn date was highly heritable (h 2  = 0.73) and had a cross-sex genetic correlation near unity. We provide the first estimate of heritability for age at maturity in ocean-going fish from this species and found it to be highly heritable (h 2 from 0.29 to 0.62, depending on sex and method), with a much lower genetic correlation across sexes. We also evaluated genotypes at a migration-associated inversion polymorphism and found sex-specific correlations with age at maturity. The significant heritability of these two key reproductive traits in these imperiled fish, and their patterns of inheritance in the two sexes, is consistent with predictions of both natural and sexually antagonistic selection (sexes experience opposing selection pressures). This emphasizes the importance of anthropogenic factors, including hatchery practices and ecosystem modifications, in shaping the fitness of this species, thus providing important guidance for management and conservation efforts., (© 2023 The Authors. Molecular Ecology published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Vaccinations for seasonal influenza and pertussis have been recommended for pregnant women in England since 2010 and 2012, respectively. Uptake rates are suboptimal with large regional variations. To improve uptake, from 2016 onwards maternity trusts were commissioned to offer pertussis (and other) vaccinations in addition to these being available in primary care. Since 2021, Covid-19 vaccination has also been recommended for pregnant women. Overall maternal vaccination rates are routinely available, but not the relative provision by maternity trusts. We aimed to describe the national picture of maternity trust provision of maternal vaccinations, including how the maternity trust vaccination programme has progressed., Methods: Cross-sectional survey plus comparisons with 2017-18 figures for maternity trust provision of pertussis vaccination, and with UKHSA data for total pertussis vaccination., Results: Twelve NHS commissioners participated (from 13/06/22 to 31/03/23) providing data for 120 (of a total 124) maternity trusts across England. All 120 (100%) trusts were commissioned to deliver influenza, and 107 (89%) to deliver pertussis vaccinations, though not all actually administered the vaccines; 29% offered Covid-19 vaccinations. For 2021-22 we found a mean of 25% (range 0-81.3%) women were vaccinated for pertussis (a large increase compared with previous estimates for 2017-18); and 11% (range 0-74.2%) for influenza, via their maternity trust. Commissioners reported a negative impact of the pandemic on routine vaccination provision. There was indication of efficiency by vaccinating women attending for other appointments. There are diverse mechanisms for reporting pertussis and influenza vaccinations administered at maternity trusts back to primary care, which may be inefficient for maternity staff workload and accuracy of data transfer (especially for pertussis)., Conclusion: A high proportion of maternity trusts provide both pertussis and influenza vaccinations, despite a negative impact of the pandemic. Reasons for large between-trust variation in vaccination rates should be explored to improve uptake and equity., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Adam Finn reports a relationship with Joint Committee on Vaccination and Immunisation that includes: board membership. Adam Finn reports a relationship with WHO European Technical Advisory Group of Experts on Immunisation (until Dec 2022) that includes: board membership. Adam Finn reports a relationship with WHO Working Group on COVID19 vaccines that includes: board membership. Adam Finn reports a relationship with Bionet Asia, the Helmsley Charitable Trust, Hillevax, Imophoron, Janssen, RQ Bio and VB Vaccines. that includes: consulting or advisory. Adam Finn reports a relationship with AstraZeneca, Janssen, Valneva, Pfizer, Moderna, and Sanofi, and of other vaccines from these and other manufacturers, including GlaxoSmithKline that includes: funding grants and non-financial support. n/a., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Migration is driven by a combination of environmental and genetic factors, but many questions remain about those drivers. Potential interactions between genetic and environmental variants associated with different migratory phenotypes are rarely the focus of study. We pair low coverage whole genome resequencing with a de novo genome assembly to examine population structure, inbreeding, and the environmental factors associated with genetic differentiation between migratory and resident breeding phenotypes in a species of conservation concern, the western burrowing owl ( Athene cunicularia hypugaea ). Our analyses reveal a dichotomy in gene flow depending on whether the population is resident or migratory, with the former being genetically structured and the latter exhibiting no signs of structure. Among resident populations, we observed significantly higher genetic differentiation, significant isolation-by-distance, and significantly elevated inbreeding. Among migratory breeding groups, on the other hand, we observed lower genetic differentiation, no isolation-by-distance, and substantially lower inbreeding. Using genotype-environment association analysis, we find significant evidence for relationships between migratory phenotypes (i.e., migrant versus resident) and environmental variation associated with cold temperatures during the winter and barren, open habitats. In the regions of the genome most differentiated between migrants and residents, we find significant enrichment for genes associated with the metabolism of fats. This may be linked to the increased pressure on migrants to process and store fats more efficiently in preparation for and during migration. Our results provide a significant contribution toward understanding the evolution of migratory behavior and vital insight into ongoing conservation and management efforts for the western burrowing owl., (© 2023 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Context: Emotion regulation by the physician can influence the effectiveness of serious illness conversations. The feasibility of multimodal assessment of emotion regulation during these conversations is unknown., Objectives: To develop and assess an experimental framework for evaluating physician emotion regulation during serious illness conversations., Methods: We developed and then assessed a multimodal assessment framework for physician emotion regulation using a cross-sectional, pilot study on physicians trained in the Serious Illness Conversation Guide (SICG) in a simulated, telehealth encounter. Development of the assessment framework included a literature review and subject matter expert consultations. Our predefined feasibility endpoints included: an enrollment rate of ≥60% of approached physicians, >90% completion rate of survey items, and <20% missing data from wearable heart rate sensors. To describe physician emotion regulation, we performed a thematic analysis of the conversation, its documentation, and physician interviews., Results: Out of 12 physicians approached, 11 (92%) SICG-trained physicians enrolled in the study: five medical oncology and six palliative care physicians. All 11 completed the survey (100% completion rate). Two sensors (chest band, wrist sensor) had <20% missing data during study tasks. The forearm sensor had >20% missing data. The thematic analysis found that physicians': 1) overarching goal was to move beyond prognosis to reasonable hope; 2) tactically focused on establishing a trusting, supportive relationship; and 3) possessed incomplete awareness of their emotion regulation strategies., Conclusion: Our novel, multimodal assessment of physician emotion regulation was feasible in a simulated SICG encounter. Physicians exhibited an incomplete understanding of their emotion regulation strategies., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Understanding the geographic linkages among populations across the annual cycle is an essential component for understanding the ecology and evolution of migratory species and for facilitating their effective conservation. While genetic markers have been widely applied to describe migratory connections, the rapid development of new sequencing methods, such as low-coverage whole genome sequencing (lcWGS), provides new opportunities for improved estimates of migratory connectivity. Here, we use lcWGS to identify fine-scale population structure in a widespread songbird, the American Redstart (Setophaga ruticilla), and accurately assign individuals to genetically distinct breeding populations. Assignment of individuals from the nonbreeding range reveals population-specific patterns of varying migratory connectivity. By combining migratory connectivity results with demographic analysis of population abundance and trends, we consider full annual cycle conservation strategies for preserving numbers of individuals and genetic diversity. Notably, we highlight the importance of the Northern Temperate-Greater Antilles migratory population as containing the largest proportion of individuals in the species. Finally, we highlight valuable considerations for other population assignment studies aimed at using lcWGS. Our results have broad implications for improving our understanding of the ecology and evolution of migratory species through conservation genomics approaches., (© 2023 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Background: Neoadjuvant treatment with nab-paclitaxel and gemcitabine for potentially operable pancreatic adenocarcinoma has not been well studied in a prospective interventional trial and could down-stage tumors to achieve negative surgical margins., Methods: A single-arm, open-label phase 2 trial (NCT02427841) enrolled patients with pancreatic adenocarcinoma deemed to be borderline resectable or clinically node-positive from March 17, 2016 to October 5, 2019. Patients received preoperative gemcitabine 1000 mg/m 2 and nab-paclitaxel 125 mg/m 2 on Days 1, 8, 15, every 28 days for two cycles followed by chemoradiation with 50.4 Gy intensity-modulated radiation over 28 fractions with concurrent fluoropyrimidine chemotherapy. After definitive resection, patients received four additional cycles of gemcitabine and nab-paclitaxel. The primary endpoint was R0 resection rate. Other endpoints included treatment completion rate, resection rate, radiographic response rate, survival, and adverse events., Results: Nineteen patients were enrolled, with the majority having head of pancreas primary tumors, both arterial and venous vasculature involvement, and clinically positive nodes on imaging. Among them, 11 (58%) underwent definitive resection and eight of 19 (42%) achieved R0 resection. Disease progression and functional decline were primary reasons for deferring surgical resection after neoadjuvant treatment. Pathologic near-complete response was observed in two of 11 (18%) resection specimens. Among the 19 patients, the 12-month progression-free survival was 58%, and 12-month overall survival was 79%. Common adverse events were alopecia, nausea, vomiting, fatigue, myalgia, peripheral neuropathy, rash, and neutropenia., Conclusion: Gemcitabine and nab-paclitaxel followed by long-course chemoradiation represents a feasible neoadjuvant treatment strategy for borderline resectable or node-positive pancreatic cancer., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Hybridization between coastal cutthroat trout (Oncorhynchus clarkii clarkii) and steelhead (O. mykiss) was assessed in the Smith River, California. Individuals were categorized as pure or as 1 of 10 hybrid classes using 30 "diagnostic" single-nucleotide polymorphisms positioned on 26 separate chromosomes. Most of the individuals examined (n = 876), were pure coastal cutthroat trout (n = 634) or pure steelhead (n = 213), and 29 individuals were identified as having hybrid ancestry. Among hybrids, first generation hybrids (n = 15) and coastal cutthroat trout backcrosses (n = 12) were the most common. No individuals were identified as backcrosses to SH, suggesting the presence of genetic or behavioral mechanisms constraining such backcrosses, or the growth and survival of their progeny. Mitochondrial DNA of 14 of 15 F1 hybrids was of steelhead origin, suggesting that hybridization was driven primarily by sneak-mating of male coastal cutthroat trout with female steelhead. Evaluation of classical phenotypic characters for coastal cutthroat trout and steelhead (i.e. jaw slash, maxillary length, and hyoid teeth) were not reliable by themselves for identification of either pure parental fish or hybrids. In contrast, analysis with geometric morphometrics revealed distinctive body shapes for pure coastal cutthroat trout and steelhead, and the combination of classical traits and geometric morphology was mostly accurate in distinguishing them. However, first generation hybrids and backcrosses overlapped completely with parental types, highlighting challenges in hybrid identification using phenotypic traits., (© The Author(s) 2023. Published by Oxford University Press on behalf of The American Genetic Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The Maine Cancer Genomics Initiative (MCGI) aimed to overcome patient- and provider-level barriers to using genomic tumor testing (GTT) in rural practices by providing genomic tumor boards (GTBs), clinician education, and access to comprehensive large-panel next-generation sequencing to all patients with cancer in Maine. This paper describes the successful implementation of the initiative and three key services made operative between 2016 and 2020., Methods: A community-inclusive, hub-and-spoke approach was taken to implement the three program components: (1) a centralized GTB program; (2) a modular online education program, designed using an iterative approach with broad clinical stakeholders; and (3) GTT free of charge to clinicians and patients. Implementation timelines, participation metrics, and survey data were used to describe the rollout., Results: The MCGI was launched over an 18-month period at all 19 oncology practices in the State. Seventy-nine physicians (66 medical oncologists, 5 gynecologic oncologists, 1 neuro-oncologist, and 7 pediatric oncologists) enrolled on the study, representing 100% of all practicing oncologists in Maine. Between July 2017 and September 2020, 1610 patients were enrolled. A total of 515 cases were discussed by 47 (73%) clinicians in 196 GTBs. Clinicians who participated in the GTBs enrolled significantly more patients on the study, stayed in Maine, and reported less time spent in clinical patient care., Conclusion: The MCGI was able to engage geographically and culturally disparate cancer care practices in a precision oncology program using a hub-and-spoke model. By facilitating access to GTT, structured education, and GTBs, we narrowed the gap in the implementation of precision oncology in one of the most rural states in the country.

Background: Compared with normal cells, tumour cells contain elevated levels of reactive oxygen species (ROS). Increased levels of the antioxidant protein NAD(P)H:quinone oxidoreductase 1 (NQO1) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) correlate negatively with the survival of patients with pancreatic cancer. Napabucasin is an investigational, orally administered ROS generator bioactivated by NQO1., Methods: In the open-label, phase 3 CanStem111P study (NCT02993731), adults with previously untreated metastatic pancreatic adenocarcinoma (mPDAC) were randomised (1:1) to napabucasin plus nab-paclitaxel with gemcitabine or nab-paclitaxel with gemcitabine alone. The primary endpoint was overall survival (OS). In exploratory analyses, OS was evaluated in the subgroup of patients with tumours positive for pSTAT3 (biomarker-positive)., Findings: Between 30 January 2017 and 20 February 2019, a total of 1779 patients were screened across 165 study sites in Austria, Australia, Belgium, Canada, China, Czech Republic, France, Germany, Italy, Japan, Korea, Netherlands, Poland, Portugal, Russia, Singapore, Spain, Taiwan, Ukraine, and the US. Of the 565 and 569 patients randomised to the napabucasin and control treatment arms, respectively, 206 and 176 were biomarker-positive. Median (95% confidence interval [CI]) OS in the napabucasin and control treatment arms was 11.4 (10.5-12.2) and 11.7 (10.7-12.7) months, respectively (hazard ratio, 1.07; 95% CI, 0.93-1.23). Due to the lack of OS improvement in the napabucasin arm, CanStem111P was terminated due to futility. In the biomarker-positive subgroup, no difference between treatment arms was found for OS. Grade ≥3 adverse events were reported in 85.4% and 83.9% of napabucasin-treated and control-treated patients, respectively. The incidence of gastrointestinal-related grade ≥3 events was higher with napabucasin (diarrhoea: 11.6% vs 4.9%; abdominal pain: 10.0% vs 4.8%)., Interpretation: Our findings suggested that although the addition of napabucasin to nab-paclitaxel with gemcitabine did not improve efficacy in patients with previously untreated mPDAC, the safety profile of napabucasin was consistent with previous reports. CanStem111P represents the largest cohort of patients with mPDAC administered nab-paclitaxel with gemcitabine in the clinical trial setting. Our data reinforce the value of nab-paclitaxel plus gemcitabine as a platform for novel therapeutics approaches in mPDAC., Funding: The Sumitomo Pharma Oncology, Inc., Competing Interests: Tanios Bekaii-Saab has received research funding (paid to institution) from Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Amgen, Merck, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer, and Bristol Myers Squibb; served as a consultant (paid to institution) to Ipsen, Array, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte, and Merck; served as a consultant (paid to self) to AbbVie, Boehringer Ingelheim, Janssen, Eisai, Daichii Sankyo, Natera, TreosBio, Celularity, Exact Science, Sobi, Beigene, Xilis, AstraZeneca, and Foundation Medicine; served on independent data monitoring committees/data and safety monitoring boards (paid to self) for AstraZeneca, Exelixis, Lilly, PanCan, and 1Globe; participated in advisory boards for Imugene, Immuneering, and Sun Biopharma; and holds the following inventions/patents: WO/2018/183488 and WO/2019/055687. Takuji Okusaka has received research grants (paid to self and institution) from Eisai, Eli Lilly, Sumitomo Dainippon Pharma Oncology, AstraZeneca, Chugai, Bristol Myers Squibb, Merck Sharp & Dohme, Baxter, and Taiho; participates in advisory boards for Sumitomo Pharma Oncology, Bristol Myers Squibb, and Nihon Servier; and has been a member of speakers' bureaus at Eisai, Novartis, Eli Lilly, Sumitomo Pharma Oncology, AstraZeneca, Chugai, Bristol Myers Squibb, Merck Sharp & Dohme, Taiho, Nihon Servier, Ono, Yakult Honsha, Daiichi Sankyo, Nippon Shinyaku, Pfizer, and Mundipharma. Do-Youn Oh participates in advisory boards (paid to self) for AstraZeneca, Novartis, Genentech/Roche, 13 Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, Bristol Myers Squibb/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences and IQVIA and has received research grants (paid to institution) from AstraZeneca, Novartis, Array, Eli Lilly, 15 Servier, BeiGene, Merck Sharp & Dohme, and Handok. Makoto Ueno has been an invited speaker (paid to self) for Taiho, Yakult Honsha, AstraZeneca, Merck, Eisai, Merck Sharp & Dohme, Servier, and Chugai and has received research grants (paid to institution) from Astellas, Taiho, Eisai, AstraZeneca, Ono, Merck Sharp & Dohme, Merck, Incyte, and Chugai. Tatsuya Ioka is a member of speakers’ bureaus at and serves as an advisor to Taiho (paid to self), is on the advisory board (paid to self) at Incyte, and has received research grants (paid to institution) from AstraZeneca, Incyte, Eisai, and Astellas. Michele Reni has participated in advisory boards (paid to self) for Eli Lilly, Celgene, AstraZeneca, Shire, Baxter, Servier, SOTIO, Viatris, and Merck Sharp & Dohme. Hye Jin Choi has received consulting fees (paid to self) from AstraZeneca and Roche. Josep Tabernero has participated in advisory boards (paid to self) for Array, AstraZeneca, Avvinity, Bayer, Boehringer, Chugai, Daiichi Sankyo, F. Hoffman La Roche, Genentech, HalioDx, Hutinson, Ikena Oncology, IQVIA, Lily, Menarini, Merck Serono, Merus, Merck Sharp & Dohme, Mirati, Neophore, Novartis, Orion, Peptomyc, Pfizer, Pierre Fabre, Samsung Biologics, Sanofi, Seattle Genomics, Servier, Taiho, Tessa, and Theramyc. Jian Li is a salaried employee of Sumitomo Pharma Oncology. Emma Foos was a salaried employee of Sumitomo Pharma Oncology at the time that these analyses were undertaken. Cindy Oh was a salaried employee of Sumitomo Pharma Oncology at the time that these analyses were undertaken. Eric Van Cutsem has participated in advisory boards Abbvie, ALX, Amgen, Array, Astellas, Astrazeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks. His institution has also received research grants from Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. Weijia Fang, Eric C. Anderson, Jonathan S. Goldberg, Sang Cheul Oh, David Goldstein, Marcus Noel, and Chung-Pin Li have nothing to disclose., (© 2023 The Author(s).)

Purpose: Social determinants of health, such as rurality, income, and education, may widen health disparities by driving variation in patients' knowledge and perceptions of medical interventions. This effect may be greatest for medical technologies that are hard to understand and less accessible. This study explored whether knowledge and perceptions (expectations and attitudes) of patients with cancer toward large-panel genomic tumor testing (GTT), an emerging cancer technology, vary by patient rurality independent of other socioeconomic characteristics (education and income)., Methods: Patients with cancer enrolled in a large precision oncology initiative completed surveys measuring rurality, sociodemographic characteristics, and knowledge and perceptions of GTT. We used multivariable linear models to examine differences in GTT knowledge, expectations, and attitudes by patient rurality, education, and income level. Models controlled for age, sex and clinical cancer stage and type., Results: Rural patients had significantly lower knowledge of GTT than urban patients using bivariate models ( P = .025). However, this association disappeared when adjusting for education and income level: patients with lower educational attainment and lower income had lower knowledge and higher expectations ( P ≤ .002), whereas patients with higher income had more positive attitudes ( P = .005). Urban patients had higher expectations of GTT compared with patients living in large rural areas ( P = .011). Rurality was not associated with attitudes., Conclusion: Patients' education and income level are associated with knowledge, expectations, and attitudes toward GTT, whereas rurality is associated with patient expectations. These findings suggest that efforts to promote adoption of GTT should focus on improving knowledge and awareness among individuals with low education and income. These differences may lead to downstream disparities in GTT utilization, which should be explored in future research.

The ability to regulate the intake of unhealthy foods is critical in modern, calorie dense food environments. Frontal areas of the brain, such as the dorsolateral prefrontal cortex (DLPFC), are thought to play a central role in cognitive control and emotional regulation. Therefore, increasing activity in the DLPFC may enhance these functions which could improve the ability to reappraise and resist consuming highly palatable but unhealthy foods. One technique for modifying brain activity is transcranial direct current stimulation (tDCS), a non-invasive technique for modulating neuronal excitability that can influence performance on a range of cognitive tasks. We tested whether anodal tDCS targeting the right DLPFC would influence how people perceived highly palatable foods. In the present study, 98 participants were randomly assigned to receive a single session of active tDCS (2.0 mA) or sham stimulation. While receiving active or sham stimulation, participants viewed images of highly palatable foods and reported how pleasant it would be to eat each food (liking) and how strong their urge was to eat each food (wanting). We found that participants who received active versus sham tDCS stimulation perceived food as less pleasant, but there was no difference in how strong their urge was to eat the foods. Our findings suggest that modulating excitability in the DLPFC influences "liking" but not "wanting" of highly palatable foods. Non-invasive brain stimulation might be a useful technique for influencing the hedonic experience of eating but more work is needed to understand when and how it influences food cravings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Healthcare professionals (HCPs) play an important role in vaccination; those with low confidence in vaccines are less likely to recommend them to their patients and to be vaccinated themselves. The study's purpose was to adapt and validate long- and short-form versions of the International Professionals' Vaccine Confidence and Behaviors (I-Pro-VC-Be) questionnaire to measure psychosocial determinants of HCPs' vaccine confidence and their associations with vaccination behaviors in European countries., Research Design and Methods: After the original French-language Pro-VC-Be was culturally adapted and translated, HCPs involved in vaccination (mainly GPs and pediatricians) across Germany, Finland, France, and Portugal completed a cross-sectional online survey in 2022. A 10-factor multigroup confirmatory factor analysis (MG-CFA) of the long-form (10 factors comprising 34 items) tested for measurement invariance across countries. Modified multiple Poisson regressions tested the criterion validity of both versions., Results: 2,748 HCPs participated. The 10-factor structure fit was acceptable to good everywhere. The final MG-CFA model confirmed strong factorial invariance and showed very good fit. The long- and short-form I-Pro-VC-Be had good criterion validity with vaccination behaviors., Conclusion: This study validates the I-Pro-VC-Be among HCPs in four European countries; including long- and short-form tools for use in research and public health.

Adolescence is a key developmental period for the onset of social anxiety, as it is a time of social transitions and stressors. Therefore, it is important to identify protective factors within the environment that can prevent and/or reduce the effects of social anxiety in addition to existing evidence-based treatments. The presence of a supportive pet dog may be one way of reducing the effects of acute social stressors for youth, but these effects have not been tested robustly in real-world settings. This study aimed to assess the feasibility of using ecological momentary assessment (EMA) to assess physiological responses to pet interactions in real-life scenarios among adolescents with social anxiety ( n = 37). Results indicated that this protocol was perceived as feasible by youth participants and allowed for integration across different data streams. Participant use of a wearable sensor to collect electrodermal activity was generally successful, with an average of 12 h of data collected per participant. However, the use of a timestamp button on the sensor was not an effective strategy for data collection. These findings suggest that EMA using self-report activity diary data combined with continuous psychophysiological measurement using wearable sensors is generally a feasible person-centered approach for measuring adolescent-dog interactions in a way that maintains ecological validity., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to disclose.

Many ecological data sets are proportional, representing mixtures of constituent elements such as species, populations, or strains. Analyses of proportional data are challenged by categories with zero observations (zeros), all observations (ones), and overdispersion. In lieu of ad hoc data adjustments, we describe and evaluate a zero-and-one inflated Dirichlet regression model, with its corresponding R package (zoid), capable of handling observed data x $$ x $$ consisting of three possible categories: zeros, proportions, or ones. Instead of fitting the model to observations of single biological units (e.g., individual organisms) within a sample, we sum proportional contributions across units and estimate mixture proportions using one aggregated observation per sample. Optional estimation of overdispersion and covariate influences expand model applications. We evaluate model performance, as implemented in Stan, using simulations and two ecological case studies. We show that zoid successfully estimates mixture proportions using simulated data with varying sample sizes and is robust to overdispersion and covariate structure. In empirical case studies, we estimate the composition of a mixed-stock Chinook salmon (Oncorhynchus tshawytscha) fishery and analyze the stomach contents of Atlantic cod (Gadus morhua). Our implementation of the model as an R package facilitates its application to varied ecological data sets composed of proportional observations., (© 2022 The Ecological Society of America.)

Background: It is unknown whether telemedicine-delivered palliative care (tele-PC) supports emotionally responsive patient-clinician interactions. Objectives: We conducted a mixed-methods formative study at two academic medical centers in rural U.S. states to explore the acceptability, feasibility, and emotional responsiveness of tele-PC. Design: We assessed clinicians' emotional responsiveness through questionnaires, qualitative interviews, and video coding. Results: We completed 11 tele-PC consultations. Mean age was 71 years, 30% did not complete high school, 55% experienced at least moderate financial insecurity, and 2/3 rated their overall health poorly. All patients rated tele-PC as equal to, or better than, in-person PC at providing emotional support. There was a tendency toward higher positive and lower negative emotions following the consultation. Video coding identified 114 instances of patients expressing emotions, and clinicians detected and responded to 98% of these events. Conclusion: Tele-PC appears to support emotionally responsive patient-clinician interactions. A mixed-methods approach to evaluating tele-PC yields useful, complementary insights.

The increasing feasibility of assembling large genomic datasets for non-model species presents both opportunities and challenges for applied conservation and management. A popular theme in recent studies is the search for large-effect loci that explain substantial portions of phenotypic variance for a key trait(s). If such loci can be linked to adaptations, 2 important questions arise: 1) Should information from these loci be used to reconfigure conservation units (CUs), even if this conflicts with overall patterns of genetic differentiation? 2) How should this information be used in viability assessments of populations and larger CUs? In this review, we address these questions in the context of recent studies of Chinook salmon and steelhead (anadromous form of rainbow trout) that show strong associations between adult migration timing and specific alleles in one small genomic region. Based on the polygenic paradigm (most traits are controlled by many genes of small effect) and genetic data available at the time showing that early-migrating populations are most closely related to nearby late-migrating populations, adult migration differences in Pacific salmon and steelhead were considered to reflect diversity within CUs rather than separate CUs. Recent data, however, suggest that specific alleles are required for early migration, and that these alleles are lost in populations where conditions do not support early-migrating phenotypes. Contrasting determinations under the US Endangered Species Act and the State of California's equivalent legislation illustrate the complexities of incorporating genomics data into CU configuration decisions. Regardless how CUs are defined, viability assessments should consider that 1) early-migrating phenotypes experience disproportionate risks across large geographic areas, so it becomes important to identify early-migrating populations that can serve as reliable sources for these valuable genetic resources; and 2) genetic architecture, especially the existence of large-effect loci, can affect evolutionary potential and adaptability., (Published by Oxford University Press on behalf of The American Genetic Association 2022.)

In the last five years, interest in close-kin mark-recapture (CKMR), a variant of mark-recapture that uses genetically inferred kin as 'recaptures', has grown dramatically. However, understanding the basis of CKMR, and properly implementing it, remains challenging. This paper describes an R package, CKMRpop, for simulating age-structured populations with user-specified demography, overdispersed variance in reproductive success (allowing for different ratios of effective to census size) and random sampling of individuals. Using compiled code for the simulation makes it feasible to simulate populations of millions of individuals. From the simulation output, pairs of sampled individuals related within a user-specified number of generations are found. Such pairs form the foundation for CKMR inference, and simulating them provides insight for understanding the statistical basis for CKMR and for assessing the feasibility of CKMR in different scenarios. We predict that CKMRpop will serve as an important tool for researchers contemplating CKMR estimation of population size. Furthermore, the methods presented here for identifying and categorizing relationships beyond half-siblings allow a more complete picture of the wide variety of kin pairs encountered in populations. This identifies the fraction of kin pairs that may not be the target of a CKMR experiment, but may be inadvertently mistaken for a more closely related 'target' kin pair. Additionally, as more distant kin categories will likely be accurately inferred from increasingly available and inexpensive whole genome resequencing, understanding the distributions of more distant relationships in populations is a first step towards broadening the scope of CKMR to include them., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA.)

Global fisheries kill millions of seabirds annually through bycatch, but little is known about population-level impacts, particularly in species that form metapopulations. U.S. North Pacific groundfish fisheries catch thousands of Northern Fulmars ( Fulmarus glacialis rodgersii ) each year, making fulmars the most frequently caught seabird in federally managed U.S. fisheries. Here, we used genetic stock identification to assign 1,536 fulmars sampled as bycatch to one of four Alaska breeding colonies and quantified the similarity of bycatch locations at sea among colonies. We found disproportionately high bycatch from the Pribilof Islands (6% of metapopulation, 23% of bycatch), and disproportionately low bycatch from Chagulak Island (34% of metapopulation, 14% of bycatch). Overlap between fisheries and colony-specific foraging areas diverge more during the summer breeding season, leading to greater differences in bycatch susceptibility. Contemporary and historical gene flow likely contributes to low genetic differentiation among colonies (F ST  = 0.003-0.01), yet these values may not represent present connectivity. Our findings illustrate how genetic stock identification can link at-sea threats to colonies and inform management to reduce bycatch from impacted colonies., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Genomic Tumour Testing (GTT) is an emerging site of "experimental care" in oncology [Cambrosio, Alberto, Peter Keating, Etienne Vignola-Gagné, Sylvain Besle, and Pascale Bourret. 2018a. "Extending Experimentation: Oncology's Fading Boundary Bbetween Research and Care." New Genetics and Society 37 (3): 207-226. doi: 10.1080/14636778.2018.1487281]. Few efforts to implement GTT have reached community oncology practices or patients living in rural communities within the US. Drawing on interdisciplinary research on a state-wide cancer genomics initiative in the rural US state of Maine, this paper explores the valuation practices within community oncologist and cancer stakeholders accounts of "doing good" within genomic science and care. We contribute to STS literatures on the bio-economy by highlighting the affective dimensions of strategies for managing economic and non-economic values. Clinician and stakeholders negotiated de-economizing and capitalizing modes of doing good as they built local genomic platforms "for Maine." These situated modes of doing good and feeling good via cancer genomics shaped how they navigated the ethical ambiguities of US biomedical markets across the boundaries of research and care., Competing Interests: Disclosure statement No potential conflict of interest was reported by the author(s).

Distal radius fractures are common. Volar plating is a valuable approach for many fractures. There are also difficult fractures that require careful attention to the exposure and technique for successful volar plating. Classic approaches, such as external fixation with additional percutaneous reduction and pinning or bone graft and fragment-specific fixation, remain valuable especially when volar plating is not applicable. The main objectives are to review the intricacies of volar plating and the use of external fixation with distal radius fractures. This also includes an understanding of the associated injuries that are present with these fractures and the expected outcome of these injuries relative to the distal radius fracture. First, the challenges with volar locked plating as well as many tips and tricks to help with reduction and stabilization of these fractures are reviewed. Second, the benefits and tips and tricks of external fixation are discussed. Finally, the management of common combined injuries with distal radius fractures is reviewed.

Respiratory tract infections (RTIs) are ubiquitous among children in the community. A prospective observational study was performed to evaluate the diagnostic performance and quality of at-home parent-collected (PC) nasal and saliva swab samples, compared to nurse-collected (NC) swab samples, from children with RTI symptoms. Children with RTI symptoms were swabbed at home on the same day by a parent and a nurse. We compared the performance of PC swab samples as the test with NC swab samples as the reference for the detection of respiratory pathogen gene targets by reverse transcriptase PCR, with quality assessment using a human gene. PC and NC paired nasal and saliva swab samples were collected from 91 and 92 children, respectively. Performance and interrater agreement (Cohen's κ) of PC versus NC nasal swab samples for viruses combined showed sensitivity of 91.6% (95% confidence interval [CI], 85.47 to 95.73%) and κ of 0.84 (95% CI, 0.79 to 0.88), respectively; the respective values for bacteria combined were 91.4% (95% CI, 86.85 to 94.87%) and κ of 0.85 (95% CI, 0.80 to 0.89). In saliva samples, viral and bacterial sensitivities were lower at 69.0% (95% CI, 57.47 to 79.76%) and 78.1% (95% CI, 71.60 to 83.76%), as were κ values at 0.64 (95% CI, 0.53 to 0.72) and 0.70 (95% CI, 0.65 to 0.76), respectively. Quality assessment for human biological material (18S rRNA) indicated perfect interrater agreement. At-home PC nasal swab samples performed comparably to NC swab samples, whereas PC saliva swab samples lacked sensitivity for the detection of respiratory microbes. IMPORTANCE RTIs are ubiquitous among children. Diagnosis involves a swab sample being taken by a health professional, which places a considerable burden on community health care systems, given the number of cases involved. The coronavirus disease 2019 (COVID-19) pandemic has seen an increase in the at-home self-collection of upper respiratory tract swab samples without the involvement of health professionals. It is advised that parents conduct or supervise swabbing of children. Surprisingly, few studies have addressed the quality of PC swab samples for subsequent identification of respiratory pathogens. We compared NC and PC nasal and saliva swab samples taken from the same child with RTI symptoms, for detection of respiratory pathogens. The PC nasal swab samples performed comparably to NC samples, whereas saliva swab samples lacked sensitivity for the detection of respiratory microbes. Collection of swab samples by parents would greatly reduce the burden on community nurses without reducing the effectiveness of diagnoses.

Genetic changes underlying adaptation vary greatly in terms of complexity and, within the same species, genetic responses to similar selective pressures may or may not be the same. We examine both complex (supergene) and simple (SNP) genetic variants occurring in populations of rainbow trout (Oncorhynchus mykiss) independently isolated from ocean access and compared them to each other and to an anadromous below-barrier population representing their ancestral source to search for signatures of both parallel and nonparallel adaptation. All landlocked populations displayed an increased frequency of a large inversion on chromosome Omy05, while 3 of the 4 populations exhibited elevated frequencies of another inversion located on chromosome Omy20. In addition, we identified numerous regions outside these 2 inversions that also show significant shifts in allele frequencies consistent with adaptive evolution. However, there was little concordance among above-barrier populations in these specific genomic regions under selection. In part, the lack of concordance appears to arise from ancestral autopolyploidy in rainbow trout that provides duplicate genomic regions of similar functional composition for selection to act upon. Thus, while selection acting on landlocked populations universally favors the resident ecotype, outside of the major chromosomal inversions, the resulting genetic changes are largely distinct among populations. Our results indicate that selection on standing genetic variation is likely the primary mode of rapid adaptation, and that both supergene complexes and individual loci contribute to adaptive evolution, further highlighting the diversity of adaptive genomic variation involved in complex phenotypic evolution., (Published by Oxford University Press on behalf of The American Genetic Association 2021.)

Purpose: Large-panel genomic tumor testing (GTT) is an emerging technology with great promise but uncertain clinical value. Previous research has documented variability in academic oncologists' perceptions and use of GTT, but little is known about community oncologists' perceptions of GTT and how perceptions relate to clinicians' intentions to use GTT., Methods: Community oncology physicians (N = 58) participating in a statewide initiative aimed at improving access to large-panel GTT completed surveys assessing their confidence in using GTT, attitudes regarding the value of GTT, perceptions of barriers to GTT implementation, and future intentions to use GTTs. Descriptive and multivariable regression analyses were conducted to characterize these perceptions and to explore the relationships between them., Results: There was substantial variability in clinicians' perceptions of GTT. Clinicians generally had moderate confidence in their ability to use GTT, but lower confidence in patients' ability to understand test results and access targeted treatment. Clinicians had positive attitudes regarding the value of GTT. Clinicians' future intentions to use GTT were associated with greater confidence in using GTT and greater perceived barriers to implementing GTT, but not with attitudes about the value of GTT., Conclusions: Community oncologists' perceptions of large-panel genomic tumor testing are variable, and their future intentions to use GTT are associated with both their confidence in and perceived barriers to its use, but not with their attitudes towards GTT. More research is needed to understand other factors that determine how oncologists perceive and use GTT in clinical practice., (© 2021. The Author(s).)

Command-line software plays a critical role in biology research. However, processes for installing and executing software differ widely. The Common Workflow Language (CWL) is a community standard that addresses this problem. Using CWL, tool developers can formally describe a tool's inputs, outputs, and other execution details. CWL documents can include instructions for executing tools inside software containers. Accordingly, CWL tools are portable-they can be executed on diverse computers-including personal workstations, high-performance clusters, or the cloud. CWL also supports workflows, which describe dependencies among tools and using outputs from one tool as inputs to others. To date, CWL has been used primarily for batch processing of large datasets, especially in genomics. But it can also be used for analytical steps of a study. This article explains key concepts about CWL and software containers and provides examples for using CWL in biology research. CWL documents are text-based, so they can be created manually, without computer programming. However, ensuring that these documents conform to the CWL specification may prevent some users from adopting it. To address this gap, we created ToolJig, a Web application that enables researchers to create CWL documents interactively. ToolJig validates information provided by the user to ensure it is complete and valid. After creating a CWL tool or workflow, the user can create 'input-object' files, which store values for a particular invocation of a tool or workflow. In addition, ToolJig provides examples of how to execute the tool or workflow via a workflow engine. ToolJig and our examples are available at https://github.com/srp33/ToolJig., Competing Interests: SP, ZE, EA, JC, AB No competing interests declared, (© 2021, Piccolo et al.)

Large-panel genomic tumor testing (GTT) is an emerging technology that promises to make cancer treatment more precise. Because GTT is novel and complex, patients may have unrealistic expectations and limited knowledge of its benefits. These problems may limit the clinical value of GTT, but their prevalence and associated factors have not been explored., Methods: Patients with cancer enrolled in a large initiative to disseminate GTT in community oncology practices completed surveys assessing their expectations, knowledge, and attitudes about GTT. The study sample (N = 1,139) consisted of patients with a range of cancer types (22% gynecologic, 14% lung, 10% colon, 10% breast, and 46% other malignancies) and cancer stages (4% stage I, 3% stage II, 15% stage III, and 74% stage IV). Mean age was 64 years (standard deviation = 11); 668 (59%) were women; 71% had no college degree; 57% came from households with less than $50,000 US dollars household income; and 73% lived in a rural area., Results: Generally, patients had high expectations that they would benefit from GTT (M = 2.81 on 0-4 scale) and positive attitudes toward it (M = 2.98 on 0-4 scale). Patients also had relatively poor knowledge about GTT (48% correct answers on an objective test of GTT knowledge). Greater expectations for GTT were associated with lower knowledge (b = -0.46; P < .001), more positive attitudes (b = 0.40; P < .001), and lower education (b = -0.53; P < .001)., Conclusion: This research suggests patients have high expectations that they will benefit from GTT, which is associated with low knowledge, positive attitudes, and low education. More research is needed to understand the concordance between expectations and actual clinical outcomes., Competing Interests: Jens Rueter Travel, Accommodations, Expenses: Philips Healthcare No other potential conflicts of interest were reported. Jens Rueter Travel, Accommodations, Expenses: Philips Healthcare No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)

Novel medical technologies, like large-panel genomic tumor testing (GTT), offer great promise but also substantial uncertainty regarding their clinical value and appropriate use. The goal of this study was to understand how clinicians' perceived uncertainty about GTT, and uncertainty tolerance (UT), a construct that describes trait-level differences in individuals' responses to uncertainty, influence attitudes and self-efficacy regarding GTT. Community-based oncologists participating in a study of large-panel GTT completed surveys assessing their perceptions of uncertainty about GTT, and their attitudes and self-efficacy regarding GTT. Multivariable regression analyses examined the relationship between oncologists' perceived uncertainty of GTT and their GTT-related attitudes and self-efficacy, and the potential moderating effect of individual differences in UT. Fifty-seven oncologists completed surveys. Greater perceived uncertainty about GTT was associated with more negative attitudes towards it. This association was moderated by UT, such that lower UT was associated with a stronger negative relationship between perceived uncertainty and attitudes. That is, oncologists who perceive GTT as uncertain, tended to have more negative attitudes, particularly if they were low in the trait of uncertainty tolerance. More research is warranted to understand how uncertainty and uncertainty tolerance influence clinicians' responses to GTT and other novel medical interventions.

Global loss of biodiversity has placed new urgency on the need to understand factors regulating species response to rapid environmental change. While specialists are often less resilient to rapid environmental change than generalists, species-level analyses may obscure the extent of specialization when locally adapted populations vary in climate tolerances. Until recently, quantification of the degree of climate specialization in migratory birds below the species level was hindered by a lack of genomic and tracking information, but recent technological advances have helped to overcome these barriers. Here we take a genome-wide genetic approach to mapping population-specific migratory routes and quantifying niche breadth within genetically distinct populations of a migratory bird, the willow flycatcher (Empidonax traillii), which exhibits variation in the severity of population declines across its breeding range. While our sample size is restricted to the number of genetically distinct populations within the species, our results support the idea that locally adapted populations of the willow flycatcher with narrow climatic niches across seasons are already federally listed as endangered or in steep decline, while populations with broader climatic niches have remained stable in recent decades. Overall, this work highlights the value of quantifying niche breadth within genetically distinct groups across time and space when attempting to understand the factors that facilitate or constrain the response of locally adapted populations to rapid environmental change., (© 2021 John Wiley & Sons Ltd.)

Background and Objectives: Animal-assisted interventions (AAIs) are increasingly popular as treatments to reduce anxiety. However, there is little empirical evidence testing the mechanisms of action in AAIs, especially among adolescents. We examined whether two possible mechanisms, social interaction and/or physical contact with a therapy dog, might reduce anxiety during a social stressor., Design and Methods: To test these mechanisms, we randomly assigned 75 adolescents with low, middle, and high levels of social anxiety to complete a laboratory-based social evaluative stressor in one of three conditions: social interaction with a therapy dog (no physical interaction), social plus physical interaction with a therapy dog, or no interaction with a therapy dog. We measured self-reported anxiety and autonomic reactivity during the social stressor to assess the effects of contact with a therapy dog., Results and Conclusions: We found no evidence that the presence of a real dog, with or without the opportunity to touch it, reduced anxiety or autonomic reactivity or improved cognitive performance relative to the presence of a stuffed dog in the control condition, regardless of levels of preexisting social anxiety. Trial registration: ClinicalTrials.gov identifier: NCT03249116.

Urban greening increases vegetation and can restore ecological functions to urban systems. It has ties to restoration ecology, which aims to return degraded land to diverse, functional ecosystems. Both practices can be applied to maximizing ecosystem services and habitat in vacant lots, which are abundant in post-industrial cities, including Chicago, Illinois (USA), where our study took place. We tested four methods for increasing native plant diversity in vacant lots, ranging from low input to resource-intensive: seed bombing, broadcast seeding, planting plugs, and gardening. After three growing seasons, we assessed the growth of eight target native species and all non-target species. We expected that intensive treatments would have more target species stems and flowers and fewer non-target species, but we found that less-intensive options often produce equal or better results. From this, we recommend broadcast seeding as a viable, low-cost method for improving habitat and biodiversity in vacant lots.

Objective: To compare clinicians' and patients' preferences for disclosure of genomic tumor testing (GTT) results; to determine the sensitivity of these disclosure preferences to uncertainty about the actionability of results; and to explore factors associated with disclosure preferences., Methods: Community-based oncology clinicians (n = 94) and patients (n = 1121) were surveyed about their preferences for disclosing GTT results with varying levels of uncertainty (Tiers 1, 2, 3). Descriptive and multivariable regression analyses were used to compare clinicians' and patients' disclosure preferences and their sensitivity to uncertainty, and to explore associations between disclosure preferences and sociodemographic, clinical, and psychological factors., Results: Relatively more patients than clinicians preferred disclosure, and their preferences were less sensitive to the uncertainty of GTT results. For patients and clinicians, lower uncertainty sensitivity was associated with positive GTT attitudes; for patients it was also associated with greater uncertainty tolerance and knowledge of uncertainty in GTT., Conclusion: Relatively more cancer patients than clinicians prefer disclosure of GTT results, and their preferences are less sensitive to result uncertainty. Uncertainty sensitivity in disclosure preferences is associated with GTT-related attitudes and uncertainty tolerance., Practice Implications: Differences in cancer patients' and clinicians' preferences for disclosure of uncertain GTT results warrant greater attention in cancer care., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest in the authoring of this manuscript., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Differentiation between ecotypes is usually presumed to be complex and polygenic. Seasonal patterns of life history in salmon are used to categorize them into ecotypes, which are often considered "distinct" animals. Using whole-genome sequencing and tribal fishery sampling of Chinook salmon, we show that a single, small genomic region is nearly perfectly associated with spawning migration timing but not with adiposity or sexual maturity, traits long perceived as central to salmon ecotypes. Distinct migration timing does not prevent interbreeding between ecotypes, which are the result of a simple, ancient polymorphism segregating within a diverse population. Our finding that a complex migratory phenotype results from a single gene region will facilitate conservation and restoration of this iconic fish., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Competing Interests: The authors have declared that no competing interests exist.

We report the fabrication and characterization of metal-insulator-metal diodes incorporating vertically aligned carbon nanotube (VACNT) arrays encased in polymer for applications in high frequency optoelectronics. Polydimethylsiloxane (PDMS) and epoxy infiltrating media are used in this study. VACNT forests are embedded with polymer to form a planarized surface over which an array of tunneling diodes is fabricated. Diodes comprising Al 2 O 3 and HfO 2 dielectric multilayers achieve highly nonlinear and asymmetric current-voltage characteristics. Results show that asymmetry in excess of 92 can be achieved with multi-insulator barrier tuning, though there is a strong correlation between asymmetry, resistance, and device longevity. With our best performing and most stable device structure (PDMS-VACNT/Al 2 O 3 -HfO 2 -Al 2 O 3 -HfO 2 /PEDOT:PSS), we provide a demonstration of optical-to-d.c. rectification at 638 nm, realizing a current responsivity of 0.65 µA W -1 . Our approach to fabricating these VACNT diode arrays is facile and highly scalable. It is capable of being integrated with solution-processed materials and soft lithography techniques to create flexible devices for optical and infrared detection.

Inferring the evolutionary dynamics at play during the process of speciation by analyzing the genomic landscape of divergence is a major pursuit in population genomics. However, empirical assessments of genomic landscapes under varying evolutionary scenarios that are known a priori are few, thereby limiting our ability to achieve this goal. Here we combine RAD-sequencing and individual-based simulations to evaluate the genomic landscape of divergence in the silvereye ( Zosterops lateralis ). Using pairwise comparisons that differ in divergence timeframe and the presence or absence of gene flow, we document how genomic patterns accumulate along the speciation continuum. In contrast to previous predictions, our results provide limited support for the idea that divergence accumulates around loci under divergent selection or that genomic islands widen with time. While a small number of genomic islands were found in populations diverging with and without gene flow, in few cases were SNPs putatively under selection tightly associated with genomic islands. The transition from localized to genome-wide levels of divergence was captured using individual-based simulations that considered only neutral processes. Our results challenge the ubiquity of existing verbal models that explain the accumulation of genomic differences across the speciation continuum and instead support the idea that divergence both within and outside of genomic islands is important during the speciation process., (Copyright © 2020 Sendell-Price et al.)

Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explore mechanisms controlling genome compartment organization in Caenorhabditis elegans and investigate roles for compartments in regulating gene expression. Distal arms of C. elegans chromosomes, which are enriched for heterochromatic histone modifications H3K9me1/me2/me3, interact with each other both in cis and in trans, while interacting less frequently with central regions, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genes met-2 and set-25 significantly impaired formation of inactive Arm and active Center compartments. cec-4 mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: Perinuclear anchoring of chromosome arms via CEC-4 to promote their cis association, and an anchoring-independent mechanism that compacts individual chromosome arms. In both met-2 set-25 and cec-4 mutants, no dramatic changes in gene expression were found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene-expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X established by the dosage compensation condensin complex. Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels., Competing Interests: The authors declare no competing interest.

Connectivity of social-ecological systems promotes resilience across urban landscapes. Community gardens are social-ecological systems that support food production, social interactions, and biodiversity conservation. We investigate how these hubs of ecosystem services facilitate socio-ecological connectivity and service flows as a network across complex urban landscapes. In three US cities (Baltimore, Chicago, New York City), we use community garden networks as a model system to demonstrate how biophysical and social features of urban landscapes control the pattern and magnitude of ecosystem service flows through these systems. We show that community gardens within a city are connected through biological and social mechanisms, and connectivity levels and spatial arrangement differ across cities. We found that biophysical connectivity was higher than social connectivity in one case study, while they were nearly equal in the other two. This higher social connectivity can be attributed to clustered distributions of gardens within neighborhoods (network modularity), which promotes neighborhood-scale connectivity hotspots, but produces landscape-scale connectivity coldspots. The particular patterns illustrate how urban form and social amenities largely shape ecosystem service flows among garden networks. Such socio-ecological analyses can be applied to enhance and stabilize landscape connectedness to improve life and resilience in cities.