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The field of MultiSector Dynamics (MSD) explores the dynamics and co‐evolutionary pathways of human and Earth systems with a focus on critical goods, services, and amenities delivered to people through interdependent sectors. This commentary lays out core definitions and concepts, identifies MSD science questions in the context of the current state of knowledge, and describes ongoing activities to expand capacities for open science, leverage revolutions in data and computing, and grow and diversify the MSD workforce. Central to our vision is the ambition of advancing the next generation of complex adaptive human‐Earth systems science to better address interconnected risks, increase resilience, and improve sustainability. This will require convergent research and the integration of ideas and methods from multiple disciplines. Understanding the tradeoffs, synergies, and complexities that exist in coupled human‐Earth systems is particularly important in the context of energy transitions and increased future shocks. Key Points Sustainability, climate change, and energy transitions are highly interdependent challenges MultiSector Dynamics (MSD) studies these challenges through the lens of complex, adaptive human‐Earth systems Confronting human‐Earth systems complexity requires a diverse, transdisciplinary workforce and community‐level open science

As per the EMA definition, adaptive pathways is a scientific concept for the development of medicines which seeks to facilitate patient access to promising medicines addressing high unmet need through a prospectively planned approach in a sustainable way. This review reports the findings of activities undertaken by the ADAPT-SMART consortium to identify enablers and explore the suitability of managed entry agreements for adaptive pathways products in Europe. We found that during 2006-2016 outcomes-based managed entry agreements were not commonly used for products with a conditional marketing authorization or authorized under exceptional circumstances. The barriers and enablers to develop workable managed entry agreements models for adaptive pathways products were discussed through interviews and a multi-stakeholder workshop with a number of recommendations made in this paper.

There is a climate change adaptation implementation gap. We have information about the likely impacts and implications, but concrete pre-emptive action is elusive. Key to addressing this are alternative planning approaches that enable decision makers to anticipate impacts and design alternate pathways depending on how conditions change, in time for adaptation actions to be implemented. Over the last ten years, dynamic adaptive pathways planning (DAPP) has been applied in Aotearoa New Zealand (A-NZ) to assist in such circumstances. Pathways planning has now been applied in diverse decision settings and has motivated the use and development of complementary methods and tools for evaluating adaptation options and pathways. Different governance and engagement models have emerged, tailored with and for different communities. DAPP research and practice in A-NZ has advanced the design of monitoring systems, decision signals and triggers, staging managed retreat over time, and serious games to prime decision makers for dealing with uncertainty. Māori (the Indigenous people of A-NZ) worldviews, knowledge and values have intersected and informed DAPP applications, but significant untapped opportunities exist. This paper presents lessons learned from these applications and further research needed. Opportunities for supporting and extending the DAPP process for adaptation decision making through governance, engagement and indigenous knowledge and values are suggested

Understanding mechanistic and cellular events underlying a toxicological outcome allows the prediction of impact of environmental stressors to organisms living in different habitats. A systems-based approach aids in characterizing molecular events, and thereby the cellular pathways that have been perturbed. However, mapping only adverse outcomes of a toxicant falls short of describing the stress or adaptive response that is mounted to maintain homeostasis on perturbations and may confer resistance to the toxic insult. Silver is a potential threat to aquatic organisms because of the increasing use of silver-based nanomaterials, which release free silver ions. The effects of silver were investigated at the transcriptome, proteome, and cellular levels of Chlamydomonas reinhardtii . The cells instigate a fast transcriptome and proteome response, including perturbations in copper transport system and detoxification mechanisms. Silver causes an initial toxic insult, which leads to a plummeting of ATP and photosynthesis and damage because of oxidative stress. In response, the cells mount a defense response to combat oxidative stress and to eliminate silver via efflux transporters. From the analysis of the perturbations of the cell’s functions, we derived a detailed mechanistic understanding of temporal dynamics of toxicity and adaptive response pathways for C. reinhardtii exposed to silver.

Payers are a major stakeholder in any considerations and initiatives concerning adaptive licensing of new medicinal products, also referred to as Medicines Adaptive Pathways to patients (MAPPs). Firstly, the scope and necessity of MAPPs need further scrutiny, especially with regard to the definition of unmet need. Conditional approval pathways already exist for new medicines for seriously debilitating or life-threatening diseases and only a limited number of new medicines are innovative. Secondly, MAPPs will result in new medicines on the market with limited evidence about their effectiveness and safety. Additional data are to be collected after approval. Consequently, adaptive pathways may increase the risk of exposing patients to ineffective or unsafe medicines. We have already seen medicines approved conventionally that subsequently proved ineffective or unsafe amongst a wider, more co-morbid population as well as medicines that could have been considered for approval under MAPPs but subsequently proved ineffective or unsafe in Phase III trials and were never licensed. Thirdly, MAPPs also put high demands on payers. Routine collection of patient level data is difficult with high transaction costs. It is not clear who will fund these. Other challenges for payers include shifts in the risk governance framework, implications for evaluation and HTA, increased complexity of setting prices, difficulty with ensuring equity in the allocation of resources, definition of responsibility and liability and implementation of stratified use. Exit strategies also need to be agreed in advance, including price reductions, rebates, or reimbursement withdrawals when price premiums are not justified. These issues and concerns will be discussed in detail including potential ways forward.

Purpose of Review Managed retreat will be inevitable where other adaptation options, such as protective structures or building restrictions, provide only temporary respite or are otherwise uneconomic, technically impractical or both. Here, we focus on the implementation of pre-emptive managed retreat, providing examples of how it can be sequenced, socialised and given the governance enablers necessary for implementation. Recent Findings Ongoing sea-level rise during the twenty-first century and beyond poses huge adaptation challenges, especially for low-lying coastal and floodplain settlements. Settlements are already functionally disrupted from repetitive non-extreme flooding and research shows that sea-level rise will impact far more people, far sooner than previously thought, as more powerful storms, heavy rainfall and rising groundwater coincide with higher tides. To date, most examples of managed retreat have been post-disaster responses following damage and disruption. Pre-emptive managed retreat, by contrast, has yet to become a well-accepted and widely practised adaptation response. Nevertheless, there are increasing examples of research and practice on how pre-emptive managed retreat can be designed, sequenced and implemented alongside other forms of adaptation within anticipatory forms of governance . Summary The current state of knowledge about managed retreat is reviewed and critical insights and lessons for governance and policy-making are given. Several novel examples from New Zealand are presented to address some of the implementation gaps. Goals and principles are enunciated to inform long-term adaptation strategies.

Medicines receiving a conditional marketing authorization through Medicines Adaptive Pathways to Patients (MAPPs) will be a challenge for payers. The \"introduction\" of MAPPs is already seen by the European Medicines Agency (EMA) as a fait accompli, with payers not consulted or involved. However, once medicines are approved through MAPPs, they will be evaluated for funding by payers through different activities. These include Health Technology Assessment (HTA) with often immature clinical data and high uncertainty, financial considerations, and negotiations through different types of agreements, which can require monitoring post launch. Payers have experience with new medicines approved through conditional approval, and the fact that MAPPs present additional challenges is a concern from their perspective. There may be some activities where payers can collaborate. The final decisions on whether to reimburse a new medicine via MAPPs will have more variation than for medicines licensed via conventional processes. This is due not only to increasing uncertainty associated with medicines authorized through MAPPs but also differences in legal frameworks between member states. Moreover, if the financial and side-effect burden from the period of conditional approval until granting full marketing authorization is shifted to the post-authorization phase, payers may have to bear such burdens. Collection of robust data during routine clinical use is challenging along with high prices for new medicines during data collection. This paper presents the concept of MAPPs and possible challenges. Concerns and potential ways forward are discussed and a number of recommendations are presented from the perspective of payers.

IntroductionThe imbalance between ecosystem service supply and demand, combined with increasing ecological vulnerability, poses a significant challenge to the sustainable development of ecologically sensitive regions. Northern Shaanxi, a typical agro-pastoral zone in China with ecological fragility, is highly susceptible to severe soil erosion, desertification, and water scarcity. These stresses are intensified by intensive human activities and climate change. Therefore, it is necessary to systematically clarify the spatial differentiation of ecosystem service value (ESV) and vulnerability in this region, and to propose regionally tailored optimization and regulation strategies.MethodsThis study introduces a “classification–simulation–strategy alignment” analytical framework to examine the interaction between ESV and ecosystem vulnerability (EV). Using Northern Shaanxi as a case study, the spatiotemporal dynamics of ESV and EV are quantitatively analyzed from 2000 to 2020. According to the spatial coupling relationship between ESV and EV, the region is divided into four functional zones: Low ESV–Low EV (general utilization areas), High ESV–Low EV (ecological stability areas), Low ESV–High EV (key restoration areas), and High ESV–High EV (core protection areas). The PLUS model is applied to simulate various future development scenarios, assess the ecological responses across these zones, and propose targeted adaptive management strategies for Northern Shaanxi.ResultsThe results indicate that ESV is generally higher in the southeast and lower in the northwest, whereas EV declines from northwest to southeast. Under future scenarios, key restoration areas and core protection areas show elevated ecological sensitivity and should be prioritized in governance efforts. Scenario simulations support the development of region-specific management strategies and contribute to a systematic governance pathway based on “classification–simulation–strategy alignment” tailored to the challenges of Northern Shaanxi.DiscussionThis study advances understanding of the coordinated evolution of ESV and EV, providing both theoretical and practical foundations for precise zoning management and adaptive ecological governance in Northern Shaanxi. The findings also offer valuable insights for other ecologically sensitive regions with similar characteristics.

An accelerated sea-level rise (SLR) may threaten the future livability of the Netherlands. Three perspectives to anticipate this SLR are elaborated here regarding technical, physical, and spatial aspects: Protect, Advance, and Accommodate. The overall objective was to explore the tools and measures that are available for adaptation, assess their spatial impacts, and identify dos and don’ts in current spatial issues like housing, climate adaptation, infrastructure, and the energy transition. Each elaboration was performed by a consortium consisting of representatives from private parties (engineering consultancy, project contractors, (landscape) architects, economists), knowledge institutes (including universities), and government, using an iterative process of model computations and design workshops. The elaborations made clear that a realistic and livable future perspective for the Dutch Delta continues to exist, even with a maximum analyzed SLR of 5 m, and will consist of a combination of elements from all three perspectives. This will require large investments and space for new and upgraded water infrastructure and will have large impacts on land use, water availability, agriculture, nature, residential buildings, shipping, and regional water systems. There is still a significant degree of uncertainty regarding future SLR; therefore, it is not advisable to make major investment decisions at this time. Nevertheless, some no-regret measures are already clear: continuation of the protection of the Randstad agglomeration (Amsterdam, The Hague, Rotterdam, and Utrecht) and its economic earning potential for future generations, adaptation of agriculture to more brackish and saline conditions, designation of space for additional future flood protection, extra storage capacity (for river discharge and increased precipitation), river discharge, and sand extraction (for future coastal maintenance). The research identified concrete actions for today’s decision-making processes, even though the time horizon of the analysis captures centuries. Including the perspectives in long term, policy planning is already necessary because the transition processes will take decades, if not more than a century, to be implemented.

Modifications to transcriptional regulators play a major role in adaptation. Here, we compared the effects of multiple beneficial mutations within and between Escherichia coli rpoB, the gene encoding the RNA polymerase β subunit, and rho, which encodes a transcriptional terminator. These two genes have harbored adaptive mutations in numerous E. coli evolution experiments but particularly in our previous large-scale thermal stress experiment, where the two genes characterized alternative adaptive pathways. To compare the effects of beneficial mutations, we engineered four advantageous mutations into each of the two genes and measured their effects on fitness, growth, gene expression and transcriptional termination at 42.2 °C. Among the eight mutations, two rho mutations had no detectable effect on relative fitness, suggesting they were beneficial only in the context of epistatic interactions. The remaining six mutations had an average relative fitness benefit of ∼20%. The rpoB mutations affected the expression of ∼1,700 genes; rho mutations affected the expression of fewer genes but most (83%) were a subset of those altered by rpoB mutants. Across the eight mutants, relative fitness correlated with the degree to which a mutation restored gene expression back to the unstressed, 37.0 °C state. The beneficial mutations in the two genes did not have identical effects on fitness, growth or gene expression, but they caused parallel phenotypic effects on gene expression and genome-wide transcriptional termination.