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Background: Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors., Methods: Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from Analysis of Pre-treatment Tumor biopsies (PREDAPT), conducted across 17 US healthcare systems. PREDAPT aimed to validate OncoPrism-HNSCC, a clinical biomarker assay predictive of disease control in patients with recurrent or metastatic HNSCC treated with anti-PD-1 immune checkpoint inhibitors as a single agent (monotherapy) and in combination with chemotherapy (chemo-immunotherapy). The test used RNA-sequencing data and machine learning models to score each patient and place them into groups of low, medium, or high., Results: The OncoPrism-HNSCC prediction significantly correlated with disease control in both the monotherapy cohort (n=62, p=0.004) and the chemo-immunotherapy cohort (n=50, p=0.01). OncoPrism-HNSCC also significantly predicted progression-free survival in both cohorts (p=0.015 and p=0.037, respectively). OncoPrism-HNSCC had more than threefold higher specificity than programmed death-ligand 1 combined positive score and nearly fourfold higher sensitivity than tumor mutational burden for predicting disease control., Conclusions: Here, we demonstrate the clinical validity of the OncoPrism-HNSCC assay in identifying patients with disease control in response to anti-PD-1 immune checkpoint inhibitors., Trial Registration Number: NCT04510129., Competing Interests: Competing interests: KCF, JE, JH, RLW, MMP, DNM, JIG, and EJD are employed, have stock interests, and/or a financial relationship with Cofactor Genomics, maker of the OncoPrism-HNSCC test., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Nearshore seagrass, kelp, and other macroalgae beds (submerged aquatic vegetation [SAV]) are productive and important ecosystems. Mitigating anthropogenic impacts on these habitats requires tools to quantify their ecological value and the debits and credits of impact and mitigation. To summarize and clarify the state of SAV habitat quantification and available tools, we searched peer-reviewed literature and other agency documents for methods that either assigned ecological value to or calculated equivalencies between impact and mitigation in SAV. Out of 47 tools, there were 11 equivalency methods, 7 of which included a valuation component. The remaining valuation methods were most commonly designed for seagrasses and rocky intertidal macroalgae rather than canopy-forming kelps. Tools were often designed to address specific resource policies and associated habitat evaluation. Frequent categories of tools and methods included those associated with habitat equivalency analyses and those that scored habitats relative to reference or ideal conditions, including models designed for habitat suitability indices and the European Union's Water and Marine Framework Directives. Over 29 tool input metrics spanned 3 spatial scales of SAV: individual shoots or stipes, bed or site, and landscape or region. The most common metric used for both seagrasses and macroalgae was cover. Seagrass tools also often employed density measures, and some categories used measures of tissue content (e.g., carbon, nitrogen). Macroalgal tools for rocky intertidal habitats frequently included species richness or incorporated indicator species to assess habitat. We provide a flowchart for decision-makers to identify representative tools that may apply to their specific management needs., (© 2024 The Author(s). Conservation Biology published by Wiley Periodicals LLC on behalf of Society for Conservation Biology.)

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: 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.)

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).)

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.

Parents who choose to carry a pregnancy complicated by a life-limiting congenital anomaly such as anencephaly may give birth to a live neonate and be discharged home. Very little guidance is available to health care professionals providing palliative care in the home setting to this population. This article is a secondary analysis that discusses the concerns and complications that parents experienced after bringing home a neonate with anencephaly. Each parental experience is a qualitative descriptive summary extracted from a larger study on the impact of anencephaly on parents. Parents reported feeling alone in their grief and struggled with their partners' differing style of grief. Parents' primary concerns after hospital discharge included transporting their neonate home, feeding their neonate, changing cranial defect dressings, managing pain and seizures, addressing uncertainty, and facilitating a good death. All parents received hospice services from health care professionals without perinatal bereavement training or experience. Only 1 woman received follow-up care after the death of her son. Preparing and educating health care professionals providing hospice and palliative services with perinatal bereavement training may be beneficial. Identifying and allocating local and online perinatal bereavement resources may provide parents with the tools and support necessary to facilitate healing after perinatal loss., Competing Interests: The author has no conflicts of interest to disclose., (Copyright © 2021 by The Hospice and Palliative Nurses Association. All rights reserved.)

The industrial waterway in Portland Harbor, Oregon, is a migration corridor for a distinct population segment of Chinook Salmon (Upper Willamette River) currently protected by the U.S. Endangered Species Act. Juveniles are exposed to a suite of contaminants during outmigration including polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethanes. We collected natural origin subyearling Chinook salmon from sites in and around the industrial harbor to evaluate growth (otolith microstructural analysis) in relation to measured chemical concentrations in tissue. A reduced growth rate was associated with higher tissue contaminant concentrations, particularly mixtures represented by PAHs and certain PCBs, which were elevated in juvenile Chinook collected throughout sites within Portland Harbor relative to those captured upstream. First-year growth is an established predictor of individual survival and eventual reproductive success in Chinook salmon. Therefore, our results indicate that legacy pollution may be limiting the population abundance of threatened Willamette River Chinook salmon, and future habitat remediation or restoration actions may benefit ongoing species recovery efforts.

Pacific lamprey (Entosphenus tridentatus) are important anadromous fish throughout their range in western North America. As conservation programs for lamprey expand, disease surveillance is becoming more prevalent. During routine surveillance, Yersinia ruckeri biotype II was isolated from Pacific lamprey. This is the first documented Y. ruckeri detection in Pacific lamprey., (© Wildlife Disease Association 2021.)

Liquid-cell scanning/transmission electron microscopy (S/TEM) has impacted our understanding of multiple areas of science, most notably nanostructure nucleation and growth and electrochemistry and corrosion. In the case of electrochemistry, the incorporation of electrodes requires the use of silicon nitride membranes to confine the liquid. The combined thickness of the liquid layer and the confining membranes prevents routine atomic-resolution characterization. Here, we show that by performing electrochemical water splitting in situ to generate a gas bubble, we can reduce the thickness of the liquid to a film approximately 30 nm thick that remains covering the sample. The reduced thickness of the liquid allows the acquisition of atomic-scale S/TEM images with chemical and valence analysis through electron energy loss spectroscopy (EELS) and structural analysis through selected area electron diffraction (SAED). This contrasts with a specimen cell entirely filled with liquid, where the broad plasmon peak from the liquid obscures the EELS signal from the sample and induces beam incoherence that impedes SAED analysis. The gas bubble generation is fully reversible, which allows alternating between a full cell and thin-film condition to obtain optimal experimental and analytical conditions, respectively. The methodology developed here can be applied to other scientific techniques, such as X-ray scattering, Raman spectroscopy, and X-ray photoelectron spectroscopy, allowing for a multi-modal, nanoscale understanding of solid-state samples in liquid media.

Before 2001, all serosurveys for morbilliviruses in sea otters (Enhydra lutris) in California, Washington, and Alaska, US, documented a 0% seroprevalence. The first published serologic detections of morbillivirus in sea otters occurred in 2001-02 in live-captured Washington sea otters, with a documented 80% seroprevalence. We conducted a retrospective study of sea otter cases from 1989 to 2010 compiled at the US Geological Survey, National Wildlife Health Center to identify cases of morbilliviral disease in Washington sea otters and to characterize the disease using immunohistochemistry, reverse transcription (RT)-PCR, genetic sequencing, virus isolation, and serology. We identified six cases of morbilliviral disease and 12 cases of morbilliviral infection in this population of sea otters during 2000-10. Significant histologic findings included inflammation in the white and gray matter of the brain characterized by lymphoplasmacytic perivascular cuffing, neuronal necrosis, and satellitosis in gray matter and by spongiosis, myelin degeneration, spheroids, and gemistocytes in white matter. Intranuclear and intracytoplasmic viral inclusion bodies were found in neurons, Purkinje cells, and glia. Immunohistochemistry for canine distemper virus (CDV) showed positive staining in neurons, glial cells, and cell processes. A pan-morbillivirus RT-PCR with subsequent restriction endonuclease digestion or sequencing identified CDV. Virus isolation was not successful. Two sea otters with morbilliviral encephalitis showed greater antibody titers to CDV than phocine distemper virus. Histologic changes were confined to the central nervous system and resembled neurologic canine distemper in domestic dogs. Cases of sea otters with morbilliviral infection without histologic changes could represent early infections or incompletely cleared sublethal infections. We found that morbillivirus was present in the Washington sea otter population as early as 2000, and we provide a description of the pathology of canine distemper in sea otters., (© Wildlife Disease Association 2020.)

We diagnosed leptospirosis in six northern sea otters ( Enhydra lutris kenyoni ) that stranded on beaches in Washington State, US in 2002. Significant gross findings included cyanotic oral mucous membranes, renal swelling, congestion or pale streaks on the cut surface of renal lobules, hematuria, dehydration, lymphadenopathy, pulmonary congestion, and rarely adrenal hemorrhage and congestion. Histopathology showed lymphoplasmacytic tubulointerstitial nephritis with intraluminal spirochetes and immunoreactivity to leptospiral antigens in the renal tubules and interstitium. A quantitative polymerase chain reaction (qPCR) using kidney or urine for the leptospiral lipL32 gene was positive with cycle threshold values indicative of abundant or moderate amounts of nucleic acid. A microscopic agglutination test showed the highest serum antibody titer to serovar Pomona and positive titers to serovars Autumnalis, Bratislava, Hebdomadis, Grippotyphosa, Icterohaemorrhagiae, Pyrogenes, Ballum, Canicola, and Hardjo. Although antibodies to Leptospira interrogans have been previously detected in sea otters, this report describes the pathology of leptospirosis in diseased free-ranging sea otters.

The growth of Ge nanowires in water inside a liquid transmission electron microscope (TEM) holder has been demonstrated at room temperature. Each nanowire growth event was stimulated by the incident electron beam on otherwise unsupported liquid Ga or liquid In nanodroplets. A variety of conditions were explored, including liquid metal nanodroplet surface condition, liquid metal nanodroplet size and density, formal concentration of dissolved GeO 2 , and electron beam intensity. The cumulative observations from a series of videos recorded during growth events suggested the following points. First, the conditions necessary for initiating nanowire growth at uncontacted liquid metal nanodroplets in a liquid TEM cell indicate the process was governed by solvated electrons generated from secondary electrons scattered by the liquid metal nanodroplets. The attained current densities were comparable to those achieved in conventional electrochemical liquid-liquid-solid (ec-LLS) growths outside of a TEM. Second, the surface condition of the liquid metal nanodroplets was quite influential on whether nanowire growth occurred and surface diffusion of Ge adatoms contributed to the rate of crystallization. Third, the Ge nanowire growth rates were limited by the feed rate of Ge to the crystal growth front rather than the rate of crystallization at the liquid metal/solid Ge interface. Estimates of an electrochemical current for the reduction of dissolved GeO 2 were nominally in line with currents used for Ge nanowire growth by ec-LLS outside of the TEM. Fourth, the Ge nanowire growths in the liquid TEM cell occurred far from thermodynamic equilibrium, with supersaturation values of 10 4 prior to nucleation. These collective points provide insight on how to further control and improve Ge nanowire morphology and crystallographic quality by the ec-LLS method.

Behaviors of dynamic polymers such as microtubules and actin are frequently assessed at one or both of the following scales: (a) net assembly or disassembly of bulk polymer, (b) growth and shortening of individual filaments. Previous work has derived various forms of an equation to relate the rate of change in bulk polymer mass (i.e., flux of subunits into and out of polymer, often abbreviated as "J") to individual filament behaviors. However, these versions of the "J equation" differ in the variables used to quantify individual filament behavior, which correspond to different experimental approaches. For example, some variants of the J equation use dynamic instability parameters, obtained by following particular individual filaments for long periods of time. Another form of the equation uses measurements from many individuals followed over short time steps. We use a combination of derivations and computer simulations that mimic experiments to (a) relate the various forms of the J equation to each other, (b) determine conditions under which these J equation forms are and are not equivalent, and (c) identify aspects of the measurements that can affect the accuracy of each form of the J equation. Improved understanding of the J equation and its connections to experimentally measurable quantities will contribute to efforts to build a multiscale understanding of steady-state polymer behavior., (© 2019 Wiley Periodicals, Inc.)

We developed a framework for the hierarchical pathways of bottom-up (niche dimensionality) and top-down control (herbivory) on biomass of stream algae via changes in guild composition (relative abundance of low profile, high profile, and motile guilds), species richness, and evenness. We further tested (1) the contrasting predictions of resource competition theory vs. the benthic model of coexistence on how the number of added nutrients constrains species richness, (2) the relationship between species richness and evenness, and (3) the biodiversity-ecosystem-function paradigm. Implementing a combination of field and lab experiments that manipulated for the first time in benthic algae herbivory and/or niche dimensionality, i.e., the number of added nutrients (NAN), including nitrogen, phosphorus, iron, and manganese, we made the following discoveries. First, important predictors of guild composition were herbivory (field) and NAN (lab); of richness, NAN (field) and NAN and guild composition (lab); of evenness, guild composition (field and lab) and herbivory (field); and of biomass, guild composition, NAN, and richness + evenness (field and lab). Herbivory increased the proportions of the low profile and motile guilds but decreased the proportion of the high profile guild. In the absence of grazing, greater proportions of the high profile guild resulted in elevated richness and biomass but diminished evenness, whereas in the presence of grazing, these relationships generally disappeared. Second, both experiments confirmed the prediction of the benthic model that species richness increases with NAN, a pattern inconsistent with resource competition theory. Third, supplementation with manganese and/or iron increased algal richness, indicating that micronutrients, which have generally been overlooked in stream ecology, added dimensions to the algal niche. Fourth, the richness-evenness relationship, observed only in the absence of herbivory, depended on the size of the species pool. It was positive at richness lower than 49 species (lab), implying complementarity and facilitation, while at higher richness (field and lab), this relationship was negative, consistent with negative interspecific interactions. Finally, the greater dependence of biomass production on guild composition and NAN than on richness and evenness suggests that more comprehensive, environmentally explicit, and trait-based approaches are necessary for the study of the biodiversity-ecosystem-function paradigm., (© 2019 by the Ecological Society of America.)

Alternatives assessment has emerged as a science policy field that supports the evaluation and adoption of safer chemistries in manufacturing processes and consumer products. The recent surge in the development and practice of alternatives assessment has revealed notable methodological challenges. Spurred by this need, we convened an informal community of practice comprising industry experts, academics, and scientists within government and nongovernmental organizations to prioritize a research and practice agenda for the next 5 years that, if implemented, would significantly advance the field of alternatives assessment. With input from over 40 experts, the agenda outlines specific needs to advance methods, tools, and guidance in 5 critical areas: hazard assessment, comparative exposure characterization, life cycle considerations, decision making, and professional practice. Fifteen research and practice needs were identified, ranging from relatively simple efforts to define a minimum hazard data set to the development of more complex performance and decision-analytic methods and data integration tools. Some research needs involve adapting existing approaches to the alternatives assessment context, while others will require the development of entirely new methods and tools. The proposed research and practice agenda is ambitious. Implementing it will require expanding the current network of researchers from academia, government, and industry, as well as increased funding for methodological, application, and evaluation research. Integr Environ Assess Manag 2018;00:000-000. © 2018 SETAC., (© 2018 SETAC.)

Background: Few studies have clearly provided evidence evaluating the effectiveness of family-written journals in reducing stress after critical illness., Objective: Study whether critical care unit (CCU) patients and their families who participated in journaling compared to those who did not, experience lower stress manifestations after discharge., Methods: Non-randomized controlled trial conducted with CCU patients who required mechanical ventilation for more than 24 hours and a CCU stay more than 72 hours, along with one of their family members., Results: At 1 and 4 months following CCU discharge, patients with family members who journaled reported fewer stress symptoms when compared to patients who did not have journals (mean Posttraumatic Stress Syndrome 14 [PTSS-14] scores 31.8 vs. 38.1 and 32.2 vs. 34.7, respectively). Family members who journaled, compared to those who did not, reported fewer stress manifestations at 1 month however not at 4 months (mean PTSS-14 scores 26.9 vs. 43.7 and 28.0 vs. 24.4, respectively). There was no significant difference in CCU memories between patient groups at 1 and 4 months., Conclusion and Implications for Nursing: Research is needed with larger samples however this study supports journaling as a low-cost, nurse-driven, stress reduction intervention for both patients recovering from critical illness and their family members who visit them., (© Copyright 2019 Springer Publishing Company, LLC.)

The synthesis, characterization, and incorporation of phenyl-C 61 -butyric acid methyl ester (PC 61 BM)-like derivatives as electron transporting materials (ETMs) in inverted perovskite solar cells (PSCs) are reported. These compounds have the same structure except for the ester substituent, which was varied from methyl to phenyl to thienyl and to pyridyl. The three latter derivatives performed better than PC 61 BM in PSCs, mainly attributed to the specific interactions of the fullerenes with the perovskite layer, as evidenced by X-ray photoelectron spectroscopy (XPS) and steady-state and time-resolved photoluminescence (SS- and TRPL) measurements. The experimental results were fully supported by density functional theory (DFT) calculations, which showed that the strongest interactions were exhibited by the compound possessing the pyridyl substituent.

Discovering genetic markers associated with phenotypic or ecological characteristics can improve our understanding of adaptation and guide conservation of key evolutionary traits. The Lahontan cutthroat trout (Oncorhynchus clarkii henshawi) of the northern Great Basin Desert, USA, demonstrated exceptional tolerance to high temperatures in the desert lakes where it resided historically. This trait is central to a conservation hatchery effort to protect the genetic legacy of the nearly extinct lake ecotype. We genotyped full-sibling families from this conservation broodstock and samples from the only two remaining, thermally distinct, native lake populations at 4,644 new single nucleotide polymorphisms (SNPs). Family-based genome-wide association testing of the broodstock identified nine and 26 SNPs associated with thermal tolerance (p < 0.05 and p < 0.1), measured in a previous thermal challenge experiment. Genes near the associated SNPs had complex functions related to immunity, growth, metabolism and ion homeostasis. Principal component analysis using the thermotolerance-related SNPs showed unexpected divergence between the conservation broodstock and the native lake populations at these loci. F ST outlier tests on the native lake populations identified 18 loci shared between two or more of the tests, with two SNPs identified by all three tests (p < 0.01); none overlapped with loci identified by association testing in the broodstock. A recent history of isolation and the complex genetic and demographic backgrounds of Lahontan cutthroat trout probably limited our ability to find shared thermal tolerance loci. Our study extends the still relatively rare application of genomic tools testing for markers associated with important phenotypic or environmental characteristics in species of conservation concern., (© 2019 John Wiley & Sons Ltd.)

Objectives: Several companies offer saliva and/or hair tests for food and environmental allergies in companion animals, but provide no validation of test accuracy. We examined one such hair and saliva allergy test to determine whether it could reliably differentiate between a normal dog and an allergic dog, and to examine test repeatability., Materials and Methods: Ten fur and saliva samples were submitted from a known allergic dog and a normal, non-allergic dog. Five fake fur samples and water were also submitted to determine whether the test could differentiate between a real dog and toy animal. The company performed testing for 128 food and environmental allergens. Statistical analyses were performed to determine whether the response distribution differed significantly between dogs, using the Pearson chi-square coefficient, as well as to determine test-retest reliability by calculating Cohen's kappa for each allergen., Results: The distribution of test results from samples obtained from allergic, non-allergic or fake dogs was not different from that expected due to random chance. Test-retest reproducibility was poor to slight., Clinical Significance: Hair and saliva testing should not be used to diagnose allergies and is not a substitute for veterinary-directed allergy evaluation and diagnostics., (© 2018 British Small Animal Veterinary Association.)

An estimated 30.2 million Americans have diabetes, and this number is expected to increase based on trends over recent decades and compounded by an aging U.S., Population: As reviewed in this article, type 2 diabetes mellitus (T2DM) is associated with impaired health-related quality of life (HRQoL) and with a substantial socioeconomic burden. Compared with individuals without T2DM, those with T2DM have worse HRQoL, greater decrements in HRQoL over time, and possibly greater depressive symptomology. Diabetes-related complications and comorbidities (e.g., obesity and cardiovascular disease) are associated with worse HRQoL. Hypoglycemic episodes are associated with reduced HRQoL and greater levels of depression; they can also interfere with social and occupational activities. In turn, low HRQoL can be a driver for poor glycemic control. In 2012, the total estimated cost associated with diagnosed diabetes in the United States was $245 billion. Factors contributing to increased health care resource utilization and costs in patients with T2DM include medical comorbidities, diabetes-related complications, inadequate glycemic control, and hypoglycemic episodes. Readmission is a key driver of hospital-related costs and is more common among elderly patients with T2DM. Elderly patients with T2DM represent a particularly vulnerable population given that these patients may have varying degrees of physical and mental comorbidities that can increase their risk of hypoglycemia, falls, and depression. This review demonstrates that T2DM imposes a considerable burden on both the individual and society. Treatment strategies should consider the effects of treatment on HRQoL and on outcomes (e.g., complications and hypoglycemia) that affect both HRQoL and costs. Management strategies that maximize HRQoL while minimizing the risk of hypoglycemia and other treatment-related complications are particularly critical in the elderly., Disclosures: This supplement was funded by Novo Nordisk. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance.

This article provides an overview of the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic GLP-1 receptors, which increases insulin secretion, delays gastric emptying, and increases satiety. As a class, GLP-1 RAs lower A1c levels and have been associated with reductions in weight and blood pressure and reduced fluctuations in glucose levels, and they have a low risk of hypoglycemia. Exenatide extended release (ER) and dulaglutide monotherapy have shown similar or superior reductions in A1c and weight compared with various oral antidiabetic drugs (OADs). Semaglutide has been shown to reduce both A1c and body weight compared with placebo and, in head-to-head studies versus both exenatide ER and dulaglutide, showed greater reductions in A1c and body weight. Once-weekly GLP-1 RAs have also been evaluated as add-on therapy in the continuum of care for the treatment of T2DM in combination with a variety of background medications, including 1 or more OADs (metformin, sulfonylureas, and/or thiazolidinediones), basal insulin, and prandial insulin. Gastrointestinal adverse events (e.g., nausea, vomiting, and diarrhea) are the most common side effects with once-weekly GLP-1 RAs. Rates of hypoglycemia, and especially major/severe hypoglycemia, are low with once-weekly GLP-1 RAs but, as expected, are higher when used in combination with sulfonylureas or insulin. These once-weekly GLP-1 RAs provide a safe and effective treatment option for patients with T2DM and may offer improved convenience and possibly greater adherence compared with daily GLP-1 RAs., Disclosures: This supplement was funded by Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Schneider reports advisory board fees from Intarcia, Lilly, and Novo Nordisk. Wyne has nothing to disclose.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular (ASCVD) disease, which is the largest contributor to the economic burden of diabetes. Minimization of disease morbidity through comprehensive management of ASCVD risk factors, including but not limited to hyperglycemia, is a key goal of T2DM therapy. Emerging evidence with some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) points to beneficial effects across a range of atherosclerotic risk factors and possible improvement of some cardiovascular outcomes independent of these effects. Given these benefits, there has been substantial interest in evaluating the cardiovascular safety of GLP-1 RAs as well as their potential to reduce the risk of major adverse cardiac events (MACE). Following the superior clinical outcome with the once-daily GLP-1 RA liraglutide (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results [LEADER]), this review examines and summarizes the effects of once-weekly GLP-1 RAs, including exenatide extended release (ER), dulaglutide, and semaglutide, on reducing cardiovascular events in patients with T2DM. A phase 3 cardiovascular outcomes trial (EXSCEL) of exenatide ER found no significant difference between exenatide ER and placebo in reducing MACE in patients with T2DM. In a phase 3 premarketing trial in T2DM patients at high risk of cardiovascular disease (SUSTAIN-6), semaglutide significantly reduced the risks of MACE and non-fatal stroke compared with placebo. A phase 3 study (REWIND) is underway to evaluate the effects of dulaglutide on MACE. Considering the substantial costs of cardiovascular disease in patients with T2DM, it will be of interest to assess the impact of treatment with once-weekly GLP-1 RAs on cardiovascular disease-related costs among patients with T2DM., Disclosures: This supplement was funded by Novo Nordisk. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Wyne has nothing to disclose.

During 2002-15 we examined the causes of mortality in a population of northern sea otters ( Enhydra lutris kenyoni). Beachcast sea otters were collected primarily from the US coast of Washington. Although there are no permanent sea otter residents in Oregon, several beachcast otters were collected from the Oregon coast. Infectious diseases were the primary cause of death (56%) for otters we examined. Sarcocystosis was the leading infectious cause of death (54%) and was observed throughout the study period. Some infectious diseases, such as morbilliviral encephalitis and leptospirosis, were documented for a limited number of years and then not detected again despite continued testing for these pathogens in necropsied animals. Trauma was the second most common cause of death (14%) during the study period. The continued stable growth of the Washington population of otters suggests they are able to tolerate current mortality rates.

Urbanization poses a global challenge to species conservation. This is primarily understood in terms of physical habitat loss, as agricultural and forested lands are replaced with urban infrastructure. However, aquatic habitats are also chemically degraded by urban development, often in the form of toxic stormwater runoff. Here we assess threats of urbanization to coho salmon throughout developed areas of the Puget Sound Basin in Washington, USA. Puget Sound coho are a sentinel species for freshwater communities and also a species of concern under the U.S. Endangered Species Act. Previous studies have demonstrated that stormwater runoff is unusually lethal to adult coho that return to spawn each year in urban watersheds. To further explore the relationship between land use and recurrent coho die-offs, we measured mortality rates in field surveys of 51 spawning sites across an urban gradient. We then used spatial analyses to measure landscape attributes (land use and land cover, human population density, roadways, traffic intensity, etc.) and climatic variables (annual summer and fall precipitation) associated with each site. Structural equation modeling revealed a latent urbanization gradient that was associated with road density and traffic intensity, among other variables, and positively related to coho mortality. Across years within sites, mortality increased with summer and fall precipitation, but the effect of rainfall was strongest in the least developed areas and was essentially neutral in the most urbanized streams. We used the best-supported structural equation model to generate a predictive mortality risk map for the entire Puget Sound Basin. This map indicates an ongoing and widespread loss of spawners across much of the Puget Sound population segment, particularly within the major regional north-south corridor for transportation and development. Our findings identify current and future urbanization-related threats to wild coho, and show where green infrastructure and similar clean water strategies could prove most useful for promoting species conservation and recovery., (© 2017 by the Ecological Society of America.)

We report the development of an instrumentation and control system instantiated on a microprocessor-field programmable gate array (FPGA) device for a harmonic oscillator comprising a portion of a magnetic resonance force microscope. The specific advantages of the system are that it minimizes computation, increases maintainability, and reduces the technical barrier required to enter the experimental field of magnetic resonance force microscopy. Heterodyne digital control and measurement yields computational advantages. A single microprocessor-FPGA device improves system maintainability by using a single programming language. The system presented requires significantly less technical expertise to instantiate than the instrumentation of previous systems, yet integrity of performance is retained and demonstrated with experimental data.

Background: Though rehabilitation attempts to correct "stiff knee gait" and control for dynamic limb valgus after anterior cruciate ligament reconstruction (ACLR), impaired biomechanics often persist when an individual is cleared to return to sport (RTS). Reduced knee extension moments (KEMs) and knee flexion angles (KFAs) often continue. While at the hip, increased hip adduction angles (HADDAs) and hip internal rotation angles (HIRAs) often persist in spite of dynamic hip stabilization exercises. Sled towing and weighted vest tasks increase KEM and hip extension moments (HEMs) in healthy individuals, yet biomechanical profiles during these tasks after ACLR are unknown., Hypothesis: Weighted gait will increase KEM, HEM, hip abduction moments (HABDMs), and hip external rotation moments (HERMs) and will not increase unwanted biomechanics (limb asymmetries, HIRA, HADDA) compared with normal gait., Study Design: Controlled laboratory study., Level of Evidence: Level 4., Methods: Fourteen men and 24 women who were 5 to 12 months after ACLR, had no concomitant ligament injuries, and were cleared to RTS were recruited. Sexes were evaluated independently given the sex-specific incidence to ACL injury, reinjury, and gait responses to certain interventions. Joint moment impulses and peak angles over the first 25% of stance were compared between limbs and across tasks (eg, unweighted gait, sled 50% body weight [BW], and vest 50% BW)., Results: Men showed that weighted gait increased KEM, HEM, HERM, HADBM (vest only), HADDA, HIRA (sled only), and KFA. Asymmetrical KEM and KFA existed across tasks. Women showed that weighted gait increased KEM, HEM, HERM, HADBM (vest only), HFA (sled only), HADDA, and KFA. Asymmetrical KEM, HEM, HIRA, and KFA (sled only) existed across tasks., Conclusion: Weighted gait generally increased joint moments. Unwanted biomechanics were unique for each weighted gait task., Clinical Relevance: Though joint moments increased, both tasks created unwanted biomechanics after ACLR. Persistent hip (women only) and KEM asymmetries across tasks when cleared to RTS are concerning given the relationship among these biomechanics and decreased functional performance., Competing Interests: The following author(s) declared potential conflicts of interest: Thomas Murray, MD, Bernadette Shaw, PA-C, Erin Collins, PT, DPT, and James Townsend, PT, DPT, were supported by a grant from PPOR., (© 2016 The Author(s).)

Background: Hospital discharge data are used for occupational injury surveillance, but observed hospitalisation trends are affected by trends in healthcare practices and workers' compensation coverage that may increasingly impair ascertainment of minor injuries relative to severe injuries. The objectives of this study were to (1) describe the development of a severe injury definition for surveillance purposes and (2) assess the impact of imposing a severity threshold on estimated occupational and non-occupational injury trends., Methods: Three independent methods were used to estimate injury severity for the severe injury definition. 10 population-based hospital discharge databases were used to estimate trends (1998-2009), including the National Hospital Discharge Survey (NHDS) and State Inpatient Databases (SID) from the Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. Negative binomial regression was used to model injury trends with and without severity restriction and to test trend divergence by severity., Results: Trend estimates for occupational injuries were biased downwards in the absence of severity restriction, more so than for non-occupational injuries. Imposing a severity threshold resulted in a markedly different historical picture., Conclusions: Severity restriction can be used as an injury surveillance methodology to increase the accuracy of trend estimates, which can then be used by occupational health researchers, practitioners and policy-makers to identify prevention opportunities and to support state and national investments in occupational injury prevention efforts. The newly adopted state-based occupational health indicator, 'Work-Related Severe Traumatic Injury Hospitalizations', incorporates a severity threshold that will reduce temporal ascertainment threats to accurate trend estimates., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Coal tar sealcoats applied to asphalt surfaces in North America, east of the Continental Divide, are enriched in petroleum-derived compounds, including polycyclic aromatic hydrocarbons (PAHs). The release of PAHs and other chemicals from sealcoat has the potential to contaminate nearby water bodies, reducing the resiliency of aquatic communities. Despite this, relatively little is known about the aquatic toxicology of sealcoat-derived contaminants. We assessed the impacts of stormwater runoff from sealcoated asphalt on juvenile coho salmon (Oncorhynchus kisutch) and embryo-larval zebrafish (Danio rerio). We furthermore evaluated the effectiveness of bioretention as a green stormwater method to remove PAHs and reduce lethal and sublethal toxicity in both species. We applied a coal tar sealcoat to conventional asphalt and collected runoff from simulated rainfall events up to 7 months postapplication. Whereas sealcoat runoff was more acutely lethal to salmon, a spectrum of cardiovascular abnormalities was consistently evident in early life stage zebrafish. Soil bioretention effectively reduced PAH concentrations by an order of magnitude, prevented mortality in juvenile salmon, and significantly reduced cardiotoxicity in zebrafish. Our findings show that inexpensive bioretention methods can markedly improve stormwater quality and protect fish health.

Urban stormwater runoff is a globally significant threat to the ecological integrity of aquatic habitats. Green stormwater infrastructure methods such as bioretention are increasingly used to improve water quality by filtering chemical contaminants that may be harmful to fish and other species. Ubiquitous examples of toxics in runoff from highways and other impervious surfaces include polycyclic aromatic hydrocarbons (PAHs). Certain PAHs are known to cause functional and structural defects in developing fish hearts. Therefore, abnormal heart development in fish can be a sensitive measure of clean water technology effectiveness. Here we use the zebrafish experimental model to assess the effects of untreated runoff on the expression of genes that are classically responsive to contaminant exposures, as well as heart-related genes that may underpin the familiar cardiotoxicity phenotype. Further, we assess the effectiveness of soil bioretention for treating runoff, as measured by prevention of both visible cardiac toxicity and corresponding gene regulation. We find that contaminants in the dissolved phase of runoff (e.g., PAHs) are cardiotoxic and that soil bioretention protects against these harmful effects. Molecular markers were more sensitive than visible toxicity indicators, and several cardiac-related genes show promise as novel tools for evaluating the effectiveness of evolving stormwater mitigation strategies.

The use and interpretation of fish consumption surveys and interviews, the application of fish consumption rates for sediment evaluation and cleanup, and the development of human health water quality criteria (HH WQC) are complex and interrelated issues. The present article focuses on these issues using examples from the United States, although the issues may be relevant for other countries. Some key considerations include the fact that there are many types of fish consumption surveys (e.g., 24-h recall surveys, food frequency questionnaires, creel surveys), and these surveys have different advantages and limitations. Identification of target populations for protection, identification of the species and quantities of fish consumed, and determination of bioaccumulation assumptions are important factors when developing water quality and sediment screening levels and standards. Accounting for the cultural importance of fish consumption for some populations is an even more complex element. Discussions about HH WQC often focus only on the fish consumption rate and may not have broad public input. Some states are trying to change this through extensive public participation efforts and use of probabilistic approaches to derive HH WQC. Finally, there are limits to what WQC can achieve. Solutions beyond the establishment of WQC that target toxics reduction from other sources may provide the greatest improvements to water quality and reductions in human health risks in the future., (© 2015 SETAC.)

Background: Increased availability of prescription opioids has caused serious problems with misuse, abuse, and increased rates of morbidity and mortality. In response, Washington State enacted a law to regulate pain management and opioid prescribing practices., Objectives: The purpose of this research was to investigate healthcare professionals' practices for the care of individuals with chronic noncancer pain (CNP) who received opioid therapy before the enactment of the Washington State law., Methods: This descriptive study used a tailored design survey protocol with a 23-item questionnaire and stratified random sample of 1618 Washington State healthcare professionals. Topic areas assessed included prescribing patterns; use of best practices; consultation access; and provider education, satisfaction, and competence in prescribing opioids., Results: Only 41% of the respondents provided care for patients with CNP. Of these, nearly all (96%) managed patients with prescription opioids. Most reported "always" obtaining, evaluating, and documenting the patient's health history (86%); reviewing the patient's history for substance abuse (77.8%); and conducting ongoing interviews (57.3%). Sixty percent of the respondents self-rated being not at all, somewhat, or moderately competent to prescribe opioids. Only 8.5% reported being very or extremely satisfied working with patients with CNP., Conclusions: The enactment of Washington State's pain management law mandates all providers to adopt management and prescribing practices for patients with CNP receiving opioid medications. This study determined that these practices were not universally adopted before the law. Evaluation of the effect of this law is essential to determine if it can serve as a model for other states., Perspective: In 2010, Washington State enacted legislation on the management of CNP. The purpose of this study was to assess clinical practice among health professionals providing care to patients with CNP before implementation of the law and to discuss the potential impact of the regulation.

Weed Risk Assessment (WRA) methods for evaluating invasiveness in plants have evolved rapidly in the last two decades. Many WRA tools exist, but none were specifically designed to screen ornamental plants prior to being released into the environment. To be accepted as a tool to evaluate ornamental plants for the nursery industry, it is critical that a WRA tool accurately predicts non-invasiveness without falsely categorizing them as invasive. We developed a new Plant Risk Evaluation (PRE) tool for ornamental plants. The 19 questions in the final PRE tool were narrowed down from 56 original questions from existing WRA tools. We evaluated the 56 WRA questions by screening 21 known invasive and 14 known non-invasive ornamental plants. After statistically comparing the predictability of each question and the frequency the question could be answered for both invasive and non-invasive species, we eliminated questions that provided no predictive power, were irrelevant in our current model, or could not be answered reliably at a high enough percentage. We also combined many similar questions. The final 19 remaining PRE questions were further tested for accuracy using 56 additional known invasive plants and 36 known non-invasive ornamental species. The resulting evaluation demonstrated that when "needs further evaluation" classifications were not included, the accuracy of the model was 100% for both predicting invasiveness and non-invasiveness. When "needs further evaluation" classifications were included as either false positive or false negative, the model was still 93% accurate in predicting invasiveness and 97% accurate in predicting non-invasiveness, with an overall accuracy of 95%. We conclude that the PRE tool should not only provide growers with a method to accurately screen their current stock and potential new introductions, but also increase the probability of the tool being accepted for use by the industry as the basis for a nursery certification program.

Evidence-based practice (EBP) is the foundation of quality care, but EBP is not widely adopted. This study evaluated the impact of a hospital-wide EBP nursing project on the organizational culture of a Magnet hospital. Results of pre- and postintervention surveys suggest the intervention increased the nurses' confidence in the hospital's EBP environment. Belief in EBP was related to confidence in implementing EBP in practice.