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Many conservation plans remain unimplemented, in part because of insufficient consideration of the social processes that influence conservation decisions. Complementing social considerations with an integrated understanding of the ecology of a region can result in a more complete conservation approach. We suggest that linking conservation planning to a social-ecological systems (SES) framework can lead to a more thorough understanding of human-environment interactions and more effective integration of social considerations. By characterizing SES as a set of subsystems, and their interactions with each other and with external factors, the SES framework can improve our understanding of the linkages between social and ecological influences on the environment. Using this framework can help to identify socially and ecologically focused conservation actions that will benefit ecosystems and human communities, and assist in the development of more consistent evidence for evaluating conservation actions by comparing conservation case studies.

A focus on ecosystem services (ES) is seen as a means for improving decisionmaking. In the research to date, the valuation of the material contributions of ecosystems to human well-being has been emphasized, with less attention to important cultural ES and nonmaterial values. This gap persists because there is no commonly accepted framework for eliciting less tangible values, characterizing their changes, and including them alongside other services in decisionmaking. Here, we develop such a framework for ES research and practice, addressing three challenges: (1) Nonmaterial values are ill suited to characterization using monetary methods; (2) it is difficult to unequivocally link particular changes in socioecological systems to particular changes in cultural benefits; and (3) cultural benefits are associated with many services, not just cultural ES. There is no magic bullet, but our framework may facilitate fuller and more socially acceptable integrations of ES information into planning and management.

Ecosystem services research has been focused on the ways that humans directly benefit from goods and services, and economic valuation techniques have been used to measure those benefits. We argue that, although it is appropriate in some cases, this focus on direct use and economic quantification is often limiting and can detract from environmental research and effective management, in part by crowding out other understandings of human—environment relationships. Instead, we make the case that the systematic consideration of multiple metaphors of such relationships in assessing social—ecological systems will foster better understanding of the many ways in which humans relate to, care for, and value ecosystems. Where it is possible, we encourage a deliberative approach to ecosystem management whereby ecosystem researchers actively engage conservationists and local resource users to make explicit, through open deliberation, the types of metaphors salient to their conservation problem.

Scientists are increasingly called upon to engage in policy formulation, but the literature on engagement is strong on speculation and weak on evidence. Using a survey administered at several broadly \"ecological\" conferences, we investigated: (1) the extent to which respondents engage in policy-related activities (including reporting scientific results, interpreting science for policy makers, integrating science into decision making, taking a position on a policy issue, and acting as a decision maker); (2) what factors best explain these types of engagement; and (3) whether respondents' activity levels match their stated beliefs on such activities. Different factors explain different forms of participation. Past negative experience was identified as a barrier to taking part in policy, while self-perceived competence in navigating the science-policy interface was consistently important in explaining activity across all engagement types, highlighting the importance of training programs linking scientists to policy. Many respondents believed that scientists should interpret, integrate, and advocate, which contrasts with previous research and relatively low levels of self-reported participation in policy.

In the sustainability and conservation sciences, “social learning” is defined as a group process which depends on trust and social capital and tends to boost conservation outcomes. We term this “collaborative social learning.” Meanwhile, the behavioral sciences define social learning as the individual use of socially acquired information and seek to explain how individuals employ social learning as part of adaptive behavior. We term this “behavioral social learning.” However, the influence of behavioral social learning on ecological outcomes is poorly understood. We conducted a study of behavioral social learning among fishers in seven communities in Chile's Region V to probe its connections with ecological outcomes and collaborative social learning. We develop and employ a novel behavioral measure of individual social learning in a simple fishing game in which fishers may pay a portion of their game earnings to observe and learn from other fishers in the game. We explore the internal and external validity of the instrument. The self‐consistency of game play, learning, and participant reflections reveals strong internal validity of the learning game. Additionally, game behavior is correlated with factors such as migration history, and the perceived availability of peers from whom to learn, suggesting the method also holds external validity. We then test whether factors associated with collaborative social learning, such as social capital, are related to social learning behavior as measured by the experiment. Interestingly, many correlates of ‘collaborative social learning’ are not strongly correlated with ‘behavioral social learning’ in our sample. We argue that this disconnect can help improve our understanding of the emergence of community‐based conservation and positive ecological outcomes as well as ‘collaborative social learning’ itself. Finally, we provide guidance on how behavioral measures of social learning could benefit community‐based natural resource management and conservation.

A focus on ecosystem services (ES) is seen as a means for improving decisionmaking. In the research to date, the valuation of the material contributions of ecosystems to human well-being has been emphasized, with less attention to important cultural ES and nonmaterial values. This gap persists because there is no commonly accepted framework for eliciting less tangible values, characterizing their changes, and including them alongside other services in decisionmaking. Here, we develop such a framework for ES research and practice, addressing three challenges: (1) Nonmaterial values are ill suited to characterization using monetary methods; (2) it is difficult to unequivocally link particular changes in socioecological systems to particular changes in cultural benefits; and (3) cultural benefits are associated with many services, not just cultural ES. There is no magic bullet, but our framework may facilitate fuller and more socially acceptable integrations of ES information into planning and management.

Many conservation plans remain unimplemented, in part because of insufficient consideration of the social processes that influence conservation decisions. Complementing social considerations with an integrated understanding of the ecology of a region can result in a more complete conservation approach. We suggest that linking conservation planning to a social–ecological systems (SES) framework can lead to a more thorough understanding of human–environment interactions and more effective integration of social considerations. By characterizing SES as a set of subsystems, and their interactions with each other and with external factors, the SES framework can improve our understanding of the linkages between social and ecological influences on the environment. Using this framework can help to identify socially and ecologically focused conservation actions that will benefit ecosystems and human communities, and assist in the development of more consistent evidence for evaluating conservation actions by comparing conservation case studies.

Solid tumors have been hypothesized to contain a subset of highly aggressive cells that fuel tumor growth and metastasis. The search is on for drugs that selectively kill or diminish the malignant properties of these tumor-initiating cells (TICs; previously called “cancer stem cells”). Pattabiraman et al. hypothesized that compounds that induce TICs to undergo a phenotypic change called the mesenchymal-to-epithelial transition (MET) would therefore cause TICs to lose their tumor-initiating ability. Indeed, drugs activating the protein kinase A signaling pathway triggered an epigenetic reprogramming of TICs that resulted in the cells acquiring a more benign epithelial-like phenotype. Science , this issue p. 10.1126/science.aad3680 Tumor-initiating cells differentiate to a more benign state when treated with drugs that activate protein kinase A. The epithelial-to-mesenchymal transition enables carcinoma cells to acquire malignancy-associated traits and the properties of tumor-initiating cells (TICs). TICs have emerged in recent years as important targets for cancer therapy, owing to their ability to drive clinical relapse and enable metastasis. Here, we propose a strategy to eliminate mesenchymal TICs by inducing their conversion to more epithelial counterparts that have lost tumor-initiating ability. We report that increases in intracellular levels of the second messenger, adenosine 3′,5′-monophosphate, and the subsequent activation of protein kinase A (PKA) induce a mesenchymal-to-epithelial transition (MET) in mesenchymal human mammary epithelial cells. PKA activation triggers epigenetic reprogramming of TICs by the histone demethylase PHF2, which promotes their differentiation and loss of tumor-initiating ability. This study provides proof-of-principle for inducing an MET as differentiation therapy for TICs and uncovers a role for PKA in enforcing and maintaining the epithelial state.

Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab. NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America. Eligible patients were aged 18 years or older with American Joint Committee on Cancer 8th edition stage III–IVB p16-negative HNSCC or unfavourable stage I–III p16-positive oropharyngeal or unknown primary carcinoma, who had a contraindication to cisplatin (Eastern Cooperative Oncology Group [ECOG] performance status 2, renal or hearing impairment, peripheral neuropathy, aged at least 70 years with moderate or severe comorbidity, or aged younger than 70 years with severe comorbidity). Patients were randomly assigned (2:1) by permuted block randomisation (multiples of 6) to intravenous durvalumab 1500 mg starting 2 weeks before radiotherapy then every 4 weeks starting week 2 of radiotherapy (seven cycles) or intravenous cetuximab 400 mg/m2 1 week before radiotherapy then 250 mg/m2 weekly beginning week 1 of radiotherapy (eight cycles), with intensity-modulated radiotherapy (70 Gy in 35 fractions over 7 weeks). Stratification factors were tumour and nodal stage, ECOG performance status and comorbidity, and primary site and p16 status. The phase 2 primary endpoint was progression-free survival in the intention-to-treat population. There was one prespecified interim futility analysis at 50% of progression-free survival information. If the observed hazard ratio was 1·0 or more, favouring cetuximab, early stopping would be considered. Extended follow-up analysis was post hoc. This trial is registered with ClinicalTrials.gov, NCT03258554, and is closed to enrolment. Following a ten-patient safety lead-in, the phase 2 trial enrolled 190 patients from March 12, 2019, to July 30, 2021, 186 of whom were randomly assigned (123 to durvalumab and 63 to cetuximab). Median age was 72 years (IQR 64–77), 30 (16%) patients were women and 156 (84%) were men. Phase 2 accrual was suspended in July 30, 2021, following an interim futility analysis, and permanently closed in Sept 1, 2022. The phase 3 part of the trial was not conducted. At a median follow-up of 2·3 years (IQR 1·9–3·1) for the extended follow-up (data cutoff July 31, 2023; post-hoc analysis), 2-year progression-free survival was 50·6% (95% CI 41·5–59·8) in the durvalumab group versus 63·7% (51·3–76·1) in the cetuximab group (hazard ratio 1·33 [95% CI 0·84–2·12]; p=0·89). Adverse events were similar in both groups. The most common grade 3–4 adverse events were dysphagia (26 [22%] of 119 patients in the durvalumab group vs 18 [30%] of 61 patients in the cetuximab group), lymphopenia (33 [28%] vs 20 [33%]), and oral mucositis (13 [11%] vs 11 [18%]). Four (3%) patients in the durvalumab group and one (2%) in the cetuximab group died from treatment-related adverse events (death not otherwise specified, laryngeal oedema, lung infection, and respiratory failure in the durvalumab group and sudden death not otherwise specified in the cetuximab group). Our findings suggest that durvalumab did not improve outcomes compared with cetuximab in patients with HNSCC with contraindications to cisplatin. Further trials are needed to define the standard of care for this population. US National Cancer Institute and AstraZeneca.