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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: 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).)