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Introduction: Most patients with advanced gallbladder cancer are treated with multiagent chemotherapy. Immune checkpoint inhibitors offer the possibility of a durable response with less toxicity. This prospective, multicenter, open-label study was designed to evaluate the anticancer activity of nivolumab plus ipilimumab in patients with advanced gallbladder cancer., Methods: Nineteen patients with advanced gallbladder cancer refractory to ≥1 previous therapy received nivolumab 240 mg intravenously every 2 weeks and ipilimumab 1 mg/kg intravenously every 6 weeks until disease progression or unacceptable toxicity. The primary end point was confirmed radiographic overall response rate (ORR) (complete response [CR] + partial response [PR] confirmed on subsequent scan); secondary end points included unconfirmed overall response, clinical benefit rate (confirmed and unconfirmed responses + stable disease >6 months), progression-free survival, overall survival, and toxicity., Results: The confirmed ORR was 16% (CR, n = 1 [5%]; PR, n = 2 [11%]); all were microsatellite stable, and the confirmed CR had undetectable programmed death-ligand 1 by immunohistochemistry. The unconfirmed ORR and clinical benefit rates were both 32%. The median duration of response was 14.8 months (range, 4-35.1+ months). The 6-month progression-free survival was 26% (95% CI, 12-55). The median overall survival was 7.0 months (95% CI, 3.9-19.1). The most common toxicities were fatigue (32%), anemia (26%), and anorexia (26%). Aspartate aminotransferase elevation was the most common grade 3/4 toxicity (11%). There was 1 possibly related death (sepsis with attendant hepatic failure)., Conclusions: Ipilimumab plus nivolumab was well tolerated and showed modest efficacy with durable responses in previously treated patients with advanced gallbladder cancer., Clinical Trial Registration: NCT02834013 (ClincialTrials.gov)., Plain Language Summary: This prospective study assessed the efficacy and safety of nivolumab plus ipilimumab in 19 patients with advanced gallbladder cancer refractory to previous therapy. The combination demonstrated modest efficacy with a 16% confirmed overall response rate, durable responses, and manageable toxicities, suggesting potential benefits for this challenging patient population., (© 2024 American Cancer Society.)

Background: Many people with opioid use disorder who stand to benefit from buprenorphine treatment are unwilling to initiate it due to experience with or fear of both spontaneous and buprenorphine-precipitated opioid withdrawal (BPOW). An effective means of minimizing withdrawal symptoms would reduce patient apprehensiveness, lowering the barrier to buprenorphine initiation. Ketamine, approved by the FDA as a dissociative anesthetic, completely resolved BPOW in case reports when infused at a sub-anesthetic dose range in which dissociative symptoms are common. However, most patients attempt buprenorphine initiation in the outpatient setting where altered mental status is undesirable. We explored the potential of short-term use of ketamine, self-administered sublingually at a lower, sub-dissociative dose to assist ambulatory patients undergoing transition to buprenorphine from fentanyl and methadone., Methods: Patients prescribed ketamine were either (1) seeking transition to buprenorphine from illicit fentanyl and highly apprehensive of BPOW or (2) undergoing transition to buprenorphine from illicit fentanyl or methadone and experiencing BPOW. We prescribed 4-8 doses of sublingual ketamine 16 mg (each dose bioequivalent to 3-6% of an anesthetic dose), monitored patients daily or near-daily, and adjusted buprenorphine and ketamine dosing based on patient response and prescriber experience., Results: Over a period of 14 months, 37 patients were prescribed ketamine. Buprenorphine initiation was completed by 16 patients, representing 43% of the 37 patients prescribed ketamine, and 67% of the 24 who reported trying it. Of the last 12 patients who completed buprenorphine initiation, 11 (92%) achieved 30-day retention in treatment. Most of the patients who tried ketamine reported reduction or elimination of spontaneous opioid withdrawal symptoms. Some patients reported avoidance of severe BPOW when used prophylactically or as treatment of established BPOW. We developed a ketamine protocol that allowed four of the last patients to complete buprenorphine initiation over four days reporting only mild withdrawal symptoms. Two patients described cognitive changes from ketamine at a dose that exceeded the effective dose range for the other patients., Conclusions: Ketamine at a sub-dissociative dose allowed completion of buprenorphine initiation in the outpatient setting in the majority of patients who reported trying it. Further research is warranted to confirm these results and develop reliable protocols for a range of treatment settings., (© 2024. The Author(s).)

Background: Mycophenolate is an immunomodulating agent successfully used for the treatment of moderate-to-severe atopic dermatitis (AD) in people. Mycophenolate is an effective steroid-sparing treatment option for use in dogs with inflammatory skin diseases., Objective: To evaluate whether once-daily modified-release mycophenolate (OKV-1001) is safe and effective for treating moderate-to-severe canine AD., Animals: Client-owned atopic dogs (n = 9) were enrolled., Materials and Methods: In an open-label multicentre pilot study, OKV-1001 (30 mg/kg every 24 h) was given orally for ≤84 days. Concomitant tapering doses of glucocorticoids were administered up to Day (D)28. Clinicians assessed Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) on D0, D14, D28, D56 and D84. Body weight and clinical pathological parameters were measured at baseline and at the end of the study., Results: Treatment with OKV-1001 combined with glucocorticoids significantly reduced the severity of AD within two weeks in seven of nine (77.8%) dogs. The mean percentage change from baseline in the CADESI-04 score was 29% (p = 0.009) at D14 (n = 9), 39% (p = 0.008) at D28 (n = 9) and 49% (p = 0.03) at D56 (n = 7) at which point glucocorticoids had been withdrawn. In two dogs the improvement in CADESI-04 was 62% and 23% (respectively) on D84. No significant adverse events including clinical pathological findings were reported., Conclusions and Clinical Relevance: Modified-release mycophenolate (OKV-1001) may represent a promising alternative treatment option for dogs with moderate-to-severe AD. The safety and efficacy profile of OKV-1001 will need to be established in larger, placebo-controlled clinical trials., (© 2024 The Author(s). Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

Conical intersections (CIs) are pivotal in many photochemical processes. Traditional quantum chemistry methods, such as the state-average multiconfigurational methods, face computational hurdles in solving the electronic Schrödinger equation within the active space on classical computers. While quantum computing offers a potential solution, its feasibility in studying CIs, particularly on real quantum hardware, remains largely unexplored. Here, we present the first successful realization of a hybrid quantum-classical state-average complete active space self-consistent field method based on the variational quantum eigensolver (VQE-SA-CASSCF) on a superconducting quantum processor. This approach is applied to investigate CIs in two prototypical systems─ethylene (C 2 H 4 ) and triatomic hydrogen (H 3 ). We illustrate that VQE-SA-CASSCF, coupled with ongoing hardware and algorithmic enhancements, can lead to a correct description of CIs on existing quantum devices. These results lay the groundwork for exploring the potential of quantum computing to study CIs in more complex systems in the future.

Alternatives assessment is a methodology used to identify, evaluate, and compare potential chemical and nonchemical solutions with a substance of concern. It is required in several chemicals management regulatory frameworks, with the objective of supporting the transition to safer chemistry and avoiding regrettable substitutions. Using expert input from symposium presentations and a discussion group hosted by the Association for the Advancement of Alternatives Assessment, four case examples of the use of alternatives assessment in regulatory frameworks were evaluated and compared: (1) the US Environmental Protection Agency Significant New Alternatives Policy (USEPA SNAP), (2) authorization provisions in the EU REACH (Registration, Evaluation, Authorisation, and Restriction of Chemicals) regulation, (3) the California (CA) Safer Consumer Products (SCP) Program, and (4) the Safer Products for Washington (WA) Program. Factors such as the purpose of the alternatives assessment, the timeline of actions, who completes the assessment, the role of stakeholder engagement, and the regulatory response options for each policy are outlined. Through these presentations and expert discussions, four lessons learned about the use of alternatives assessments in regulatory policy emerged: (1) the goal and purpose of the regulatory framework significantly affects its ability to result in safer substitution, (2) existing frameworks struggle with data access and insufficient stakeholder engagement, (3) some frameworks lack clear decision rules regarding what is a safer and feasible alternative, and (4) regulatory response options provide limited authority for enforcement and do not adequately address options where alternatives are unavailable or limited. Five recommendations address these lessons as well as how the application of alternatives assessment in regulatory settings could have greater impact in the future. This synthesis is not meant to be a comprehensive policy analysis, but rather an assessment based on the perspectives from experts in the field, which should be supplemented by formal policy analysis as policies are implemented over time. Integr Environ Assess Manag 2024;20:1035-1045. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

Libcint is a library designed for the evaluation of analytical integrals for Gaussian type orbitals. It prioritizes simplicity, ease of use, and efficiency for the development of quantum chemistry programs. In the release of version 6.0, Libcint supports the computation of integrals for various operators, such as overlap, Coulomb, Gaunt, Breit, attenuated Coulomb, Slater-type geminals, and Yukawa potential, as well as arbitrary orders of derivatives for these operators. To enhance the usability of the library, Libcint provides a uniform function signature for all integral functions. A code generator is included to automate the implementation of new integrals. To achieve better performance on modern central processing unit architectures, the library employs explicit single instruction multiple data parallelization in the code implementation., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Humans are exposed to hazardous chemicals found in consumer products. In 2019, the Pollution Prevention for Healthy People and Puget Sound Act was passed in Washington State. This law is meant to reduce hazardous chemicals in consumer products and protect human health and the environment. The law directs the Washington State Department of Ecology to assess chemicals and chemical classes found in products, determine whether there are safer alternatives, and make regulatory determinations., Objectives: To implement the law, the Department of Ecology developed a hazard-based framework for identifying safer alternatives to classes of chemicals., Methods: We developed a hazard-based framework, termed the "Criteria for Safer," to set a transparent bar for determining whether new chemical alternatives are safer than existing classes of chemicals. Our "Criteria for Safer" is a framework that builds on existing hazard assessment methodologies and published approaches for assessing chemicals and chemical classes., Discussion: We describe implementation of our criteria using a case study on the phthalates chemical class in two categories of consumer products: vinyl flooring and fragrances used in personal care and beauty products. Additional context and considerations that guided our decision-making process are also discussed, as well as benefits and limitations of our approach. This paper gives insight into our development and implementation of a hazard-based framework to address classes of chemicals in consumer products and will aid others working to build and employ similar approaches. https://doi.org/10.1289/EHP13549.

Purpose: The purpose of this study was to determine the prevalence of symptoms of a voice problem in college students and to assess if general health factors and vocal hygiene habits serve as risk factors for symptoms of a voice problem in this population., Methods: Participants (n = 289) from a university in the United States completed an online survey that included demographic and general health questions, the Screen6 questionnaire, and a list of 23 vocal hygiene habits. Four participants were excluded due to receiving voice therapy and the remaining 285 participants were divided into two groups based on the results of the Screen6 questionnaire: those with two or more symptoms of a voice problem daily or weekly (n = 84) and those with fewer symptoms (n = 201)., Results: 29.5% of the college students in this study experienced two or more symptoms weekly or daily. Throat clearing was the most commonly reported symptom. Risk factors included having a postnasal drip, experiencing severe seasonal allergies, and taking medication for depression or anxiety. The following vocal hygiene habits were reported to occur more frequently in those with symptoms of a voice problem: use your voice until it hurts, use extra muscular effort while talking, use extra respiratory effort while talking, use a pitch that you think is too high, and use a pitch that you think is too low. Nonuse behaviors, such as water and caffeine consumption, did not vary significantly between groups., Conclusions: People with two or more symptoms of a voice problem daily or weekly report using their voice in a way that may contribute to experiencing these symptoms. Vocal hygiene education for this demographic may be more impactful if it is catered to how the voice is used rather than nonuse voice care., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 The Voice Foundation. All rights reserved.)

Soils are a precious resource consistently placed under several threats and urgently in need of protection within a regulatory framework at the European level. Soils are central to the provision of environmental services as well as human existence on earth. The need to protect soil has been identified by several recent European strategies and fortunately, a specific European regulation for soil protection is on the way-the European Soil Monitoring Law (formerly: Soil Health Law). However, efforts need to ensure that the upcoming Soil Monitoring Law closes gaps between existing regulations for chemicals and acknowledges current European strategies for environmental protection and sustainability. This brief communication started from a fruitful discussion among SETAC Global Soils Interest Group members on a recent public consultation on the newly proposed Soil Monitoring Law of the European Commission and highlights critical points focusing on the chemical pollution of soils. We emphasize urgent needs such as the essential definition of a "healthy state" of soils; the implementation of a suitable set of indicators and quality standards for the description of physical, chemical, and biological states of soils; the enforcement of the "polluter-pays" principle; and the establishment of a Europe-wide monitoring program. Results from monitoring need to be fed back into regulatory frameworks, including the regulation of chemicals. Guidance documents for the risk assessment of chemicals are outdated and need to be updated. Finally, actions need to be taken to foster healthy soils, stop biodiversity decline, and ensure the functioning of ecosystem services for future generations. Integr Environ Assess Manag 2024;20:316-321. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

Separating the Coulomb potential into short-range and long-range components enables the use of different electron repulsion integral algorithms for each component. The short-range part can be efficiently computed using the analytical algorithm due to the locality in both the Gaussian-type orbital basis and the short-range Coulomb potentials. The integrals for the long-range Coulomb potential can be approximated with the density fitting method. A very small auxiliary basis is sufficient for the density fitting method to accurately approximate the long-range integrals. This feature significantly reduces the computational efforts associated with the N4 scaling in density fitting algorithms. For large molecules, the range separation and long-range density fitting method outperforms the conventional analytical integral evaluation scheme employed in Hartree-Fock calculations and provides more than twice the overall performance. In addition, this method offers a higher accuracy compared to conventional density fitting methods. The error in the Hartree-Fock energy can be easily reduced to 0.1 μEh per atom or smaller., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

The expensive cost of computing exact exchange in periodic systems limits the application range of density functional theory with hybrid functionals. To reduce the computational cost of exact change, we present a range-separated algorithm to compute electron repulsion integrals for Gaussian-type crystal basis. The algorithm splits the full-range Coulomb interactions into short-range and long-range parts, which are, respectively, computed in real and reciprocal space. This approach significantly reduces the overall computational cost, as integrals can be efficiently computed in both regions. The algorithm can efficiently handle large numbers of k points with limited central processing unit (CPU) and memory resources. As a demonstration, we performed an all-electron k-point Hartree-Fock calculation for LiH crystal with one million Gaussian basis functions, which was completed on a desktop computer in 1400 CPU hours., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Objectives/hypothesis: To determine if the Vocal Priorities Questionnaire (VPQ) could be used in people who were not seeking treatment for a voice problem. To determine if the VPQ could be used to compare groups based on self-reported voice problems. To determine if vocal priorities (loudness, clarity, pitch, pitch range) vary based on self-reported voice problems., Study Design: Prospective cross-sectional study., Methods: An online survey that contained demographic questions, questions about self-reported voice problems, and the VPQ was distributed to undergraduate university students. Confirmatory factor analyses (CFA) and exploratory factor analysis (EFA) were completed to determine if the VPQ was appropriate for use in this population. Invariance testing determined if the VPQ could be used to compare groups. Cronbach's alpha determined internal consistency. An analysis of variance was conducted to compare the scores for each vocal priority across three self-reported voice problem categories: never, current, and past., Results: Responses from 285 participants were analyzed. An initial CFA found that the four-priority VPQ originally proposed did not have adequate fit indices. An EFA and modified CFA revealed that four priorities were still present, but "not having a gravelly voice" fit better with the priority of pitch, not clarity. With this model, invariance was verified and Cronbach's alpha indicated internal consistency. Loudness was the top vocal priority for 34.8%. In those with a past voice problem, clarity was scored higher compared to those with a current voice problem, F(2, 284) = 5.298, P = 0.006, and pitch range was scored higher compared to those who had never experienced a voice problem, F(2, 284) = 5.431, P = 0.005., Conclusions: A modified four-priority version of the VPQ presented with acceptable dimensionality and invariance for college students with and without self-reported voice problems. Scores for clarity and pitch range were influenced by experiences with voice problems., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Voice Foundation. All rights reserved.)

The species-area relationship (SAR) has over a 150-year-long history in ecology, but how its shape and origins vary across scales and organisms remains incompletely understood. This is the first subcontinental freshwater study to examine both these properties of the SAR in a spatially explicit way across major organismal groups (diatoms, insects, and fish) that differ in body size and dispersal capacity. First, to describe the SAR shape, we evaluated the fit of three commonly used models, logarithmic, power, and Michaelis-Menten. Second, we proposed a hierarchical framework to explain the variability in the SAR shape, captured by the parameters of the SAR model. According to this framework, scale and species group were the top predictors of the SAR shape, climatic factors (heterogeneity and median conditions) represented the second predictor level, and metacommunity properties (intraspecific spatial aggregation, γ-diversity, and species abundance distribution) the third predictor level. We calculated the SAR as a sample-based rarefaction curve using 60 streams within landscape windows (scales) in the United States, ranging from 160,000 to 6,760,000 km 2 . First, we found that all models provided good fits (R 2  ≥ 0.93), but the frequency of the best-fitting model was strongly dependent on organism, scale, and metacommunity properties. The Michaelis-Menten model was most common in fish, at the largest scales, and at the highest levels of intraspecific spatial aggregation. The power model was most frequent in diatoms and insects, at smaller scales, and in metacommunities with the lowest evenness. The logarithmic model fit best exclusively at the smallest scales and in species-poor metacommunities, primarily fish. Second, we tested our framework with the parameters of the most broadly used SAR model, the log-log form of the power model, using a structural equation model. This model supported our framework and revealed that the SAR slope was best predicted by scale- and organism-dependent metacommunity properties, particularly spatial aggregation, whereas the intercept responded most strongly to species group and γ-diversity. Future research should investigate from the perspective of our framework how shifts in metacommunity properties due to climate change may alter the SAR., (© 2022 The Ecological Society of America.)

Leaf litter inputs can influence the structure and function of both terrestrial and adjacent aquatic ecosystems. Dioecy and herbivory are two factors that together have received little attention, yet have the potential to affect the quantity, quality, and timing of riparian litterfall, litter chemistry, and litter decomposition processes. Here, we explore litter chemistry differences for the dioecious Sitka willow ( Salix sitchensis Sanson ex. Bong), which is establishing on primary successional habitats at Mount St. Helens (WA, USA) and is heavily infested with a stem-boring weevil ( Cryptorhynchus lapathi ). Weevil-attacked branches produced summer senesced litter that had significantly higher %N, lower C:N ratios, and lower condensed tannins than litter from branches that were unattacked by the weevil and senesced naturally in the autumn. Weevils more often attack female willows; however, these common litter chemicals did not significantly differ between males and females within the weevil-attacked and -unattacked groups. High-resolution mass spectrometry was used to isolate compounds in litter from 10 Sitka willow individuals with approximately 1500-1600 individual compounds isolated from each sample. There were differences between weevil-attacked litter and green leaf samples, but at this level, there was no clustering of male and female samples. However, further exploration of the isolated compounds determined a suite of compounds present only in either males or females. These findings suggest some variation in more complex litter chemistry between the sexes, and that significant differences in weevil-attacked litter chemistry, coupled with the shift in seasonality of litter inputs to streams, could significantly affect in-stream ecological processes, such as decomposition and detritivore activity., Competing Interests: The authors do not have any conflicts of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

In Washington state, planned community births are attended by direct entry licensed midwives (LMs) and certified nurse-midwives (CNMs). The most recently published vital statistics data from 2018 reported that 3.6% of the 84,648 births in Washington occurred at home or in freestanding birthing centers. Approximately 16.2% of planned home birth and birth center clients experience intrapartum or early postpartum transfer to the hospital, while 1.8% of their newborns do. The safety of and satisfaction with these types of referrals depends on multisystem processes performed by a variety of health care professionals. Smooth Transitions is a quality improvement (QI) initiative in Washington state that was developed to enhance interprofessional collaboration between community-based midwives, emergency medical services (EMS), and hospital personnel to improve the quality of hospital transfers from planned community settings. Key interventions to date have included (1) information sharing to dispel misconceptions and provide context regarding community births and midwives; (2) co-creation of transfer guidelines; (3) regularly held interprofessional meetings to review transfers and build relationships; and (4) ongoing review of qualitative feedback that captures the perspectives of all involved. Responses on questionnaires and audits indicate that Smooth Transitions has had a positive impact on provider, staff, and patient experiences with hospital transfers. Future endeavors will include strengthening quantitative data collection processes to measure safety indicators, expanding relationships with EMS, and building a case review process that is legally protected. By engaging representatives of all stakeholder groups and addressing community-to-hospital transfers as a multisystems issue, replication of the Smooth Transitions QI Program nationally could promote increased community midwifery integration by enhancing the referral experience for both patients and caregivers., (© 2022 by the American College of Nurse-Midwives.)

We compared the sensitivity of closely related Pacific salmon and steelhead ( Oncorhynchus spp.) to untreated urban stormwater runoff across three storm events. Juvenile coho, sockeye, steelhead, and Chinook were exposed for 24 h to untreated urban runoff and then transferred to clean water for 48 h. As anticipated from previous studies, coho were highly susceptible to runoff toxicity, with cumulative mortality rates ranging from 92%-100% across the three storms. By contrast, juvenile sockeye were unaffected (100% survival), and cumulative mortality rates were intermediate for steelhead (4%-42%) and Chinook (0%-13%). Furthermore, coho died rapidly following the onset of stormwater exposure (generally <4 h), whereas mortality in Chinook and steelhead was delayed by 1-2 days. Similar to previous findings for coho, steelhead and Chinook did not recover when transferred to clean water. Lastly, significant mortality occurred in coho even when roadway runoff was diluted by 95% in clean water. Our findings extend the urban runoff mortality syndrome in salmonids and point to a near-term need for sublethal studies in steelhead and Chinook to more precisely understand stormwater risks to threatened species recovery efforts in the western United States., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Acoustic disturbance is a growing conservation concern for wildlife populations because it can elicit physiological and behavioral responses that can have cascading impacts on population dynamics. State-dependent behavioral and life history models implemented via Stochastic Dynamic Programming (SDP) provide a natural framework for quantifying biologically meaningful population changes resulting from disturbance by linking environment, physiology, and metrics of fitness. We developed an SDP model using the endangered western gray whale (Eschrichtius robustus) as a case study because they experience acoustic disturbance on their summer foraging grounds. We modeled the behavior and physiological dynamics of pregnant females as they arrived on the feeding grounds and predicted the probability of female and offspring survival, with and without acoustic disturbance and in the presence/absence of high prey availability. Upon arrival in mid-May, pregnant females initially exhibited relatively random behavior before they transitioned to intensive feeding that resulted in continual fat mass gain until departure. This shift in behavior co-occurred with a change in spatial distribution; early in the season, whales were more equally distributed among foraging areas with moderate to high energy availability, whereas by mid-July whales transitioned to predominate use of the location that had the highest energy availability. Exclusion from energy-rich offshore areas led to reproductive failure and in extreme cases, mortality of adult females that had lasting impacts on population dynamics. Simulated disturbances in nearshore foraging areas had little to no impact on female survival or reproductive success at the population level. At the individual level, the impact of disturbance was unequally distributed across females of different lengths, both with respect to the number of times an individual was disturbed and the impact of disturbance on vital rates. Our results highlight the susceptibility of large capital breeders to reductions in prey availability, and indicate that who, where, and when individuals are disturbed are likely to be important considerations when assessing the impacts of acoustic activities. This model provides a framework to inform planned acoustic disturbances and assess the effectiveness of mitigation strategies for large capital breeders., (© 2021 by the Ecological Society of America.)

Tire tread wear particles (TWP) are increasingly recognized as a global pollutant of surface waters, but their impact on biota in receiving waters is rarely addressed. In the developed U.S. Pacific Northwest, acute mortality of adult coho salmon ( Oncorhynchus kisutch ) follows rain events and is correlated with roadway density. Roadway runoff experimentally triggers behavioral symptoms and associated changes in blood indicative of cardiorespiratory distress prior to death. Closely related chum salmon ( O. keta ) lack an equivalent response. Acute mortality of juvenile coho was recently experimentally linked to a transformation product of a tire-derived chemical. We evaluated whether TWP leachate is sufficient to trigger the acute mortality syndrome in adult coho salmon. We characterized the acute response of adult coho and chum salmon to TWP leachate (survival, behavior, blood physiology) and compared it with that caused by roadway runoff. TWP leachate was acutely lethal to coho at concentrations similar to roadway runoff, with the same behaviors and blood parameters impacted. As with runoff, chum salmon appeared insensitive to TWP leachate at concentrations lethal to coho. Our results confirm that environmentally relevant TWP exposures cause acute mortalities of a keystone aquatic species.