The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3•5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.

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The purpose of medicines is to improve patients' lives. Stakeholders involved in the development and lifecycle management of medicines agree that more effective patient involvement is needed to ensure that patient needs and priorities are identified and met. Despite the increasing number and scope of patient involvement initiatives, there is no accepted master framework for systematic patient involvement in industry-led medicines research and development, regulatory review, or market access decisions. Patient engagement is very productive in some indications, but inconsistent and fragmentary on a broader level. This often results in inefficient drug development, increasing evidence requirements, lack of patient-centered outcomes that address unmet medical needs and facilitate adherence, and consequently, lack of required therapeutic options and high costs to society and involved parties. Improved patient involvement can drive the development of innovative medicines that deliver more relevant and impactful patient outcomes and make medicine development faster, more efficient, and more productive. It can lead to better prioritization of early research; improved resource allocation; improved trial protocol designs that better reflect patient needs; and, by addressing potential barriers to patient participation, enhanced recruitment and retention. It may also improve trial conduct and lead to more focused, economically viable clinical trials. At launch and beyond, systematic patient involvement can also improve the ongoing benefit-risk assessment, ensure that public funds prioritize medicines of value to patients, and further the development of the medicine. Progress toward a universal framework for patient involvement requires a joint, precompetitive, and international approach by all stakeholders, working in true partnership to consolidate outputs from existing initiatives, identify gaps, and develop a comprehensive framework. It is essential that all stakeholders participate to drive adoption and implementation of the framework and to ensure that patients and their needs are embedded at the heart of medicines development and lifecycle management.

We consider the size and structure of the automorphism groups of a variety of empirical 'realworld' networks and find that, in contrast to classical random graph models, many real-world networks are richly symmetric. We construct a practical network automorphism group decomposition, relate automorphism group structure to network topology and discuss generic forms of symmetry and their origin in real-world networks. We also comment on how symmetry can affect network redundancy and robustness.

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ethical analysis while bringing this crucial conversation to a new audience. We are at a watershed moment in health care. Ethical considerations have rarely been so integral and essential to maximising success of a technology both empirically and clinically. The time is right to partake in thoughtful and collaborative engagement on the challenge of bias to bring about lasting change.We declare no competing interests.

In recent years, numerous journals, regulators and ethics guidelines have adopted policies for prospective registration of clinical trials and full reporting of results. Whereas at one time, investigators published controlled clinical trials at their discretion, policies now compel prospective registration and deposition of trial results-including those that are negative and inconclusive-in publicly accessible databases 1 . In May, an editorial in Nature Biotechnology also supported the full disclosure of trial results in response to a call for more openness from European regulators 2 . In the following correspondence, we examine whether arguments that justify trial registration also hold for preclinical studies aimed at supporting trials. We argue that the high rate of failure in translating basic research into medical therapies raises concerns about human protections and inefficiencies in the research enterprise; registration and reporting of preclinical studies would partly address these concerns. We close by suggesting that funding agencies and others establish working groups to explore mechanisms for reconciling preclinical registration with the strategic imperatives in drug development.When registration and public deposition of results ('good disclosure practice') were canonized as ethical principles, two main arguments were offered. First, good disclosure practice respects the altruism of human subjects by helping ensure that studies see the light of day. Publication is the first step in a process through which findings in isolated settings are synthesized into collective knowledge. If this process is interrupted by nonpublication, burdens endured by human volunteers lose their moral justification. The second argument rested on protecting downstream users-patients and institutions whose interests are bound up with an unimpeded flow of findings. Absent good disclosure practice, researchers coming forward with unfavorable findings are at a reputational and funding disadvantage relative to those withholding them. This incentivizes biased reporting. Biased reporting potentially

One contribution of 9 to a theme issue 'Antimicrobial resistance: addressing the threat to global health'. The antibacterial therapeutic area has been described as the perfect storm. Resistance is increasing to the point that our hospitals encounter patients infected with untreatable pathogens, the overall industry pipeline is described as dry and most multinational pharmaceutical companies have withdrawn from the area. Major contributing factors to the declining antibacterial industry pipeline include scientific challenges, clinical/regulatory hurdles and low return on investment. This paper examines these challenges and proposes approaches to address them. There is a need for a broader scientific agenda to explore new approaches to discover and develop antibacterial agents. Additionally, ideas of how industry and academia could be better integrated will be presented. While promising progress in the regulatory environment has been made, more streamlined regulatory paths are still required and the solutions will lie in global harmonization and clearly defined guidance. Creating the right incentives for antibacterial research and development is critical and a new commercial model for antibacterial agents will be proposed. One key solution to help resolve both the problem of antimicrobial resistance (AMR) and lack of new drug development are rapid, cost-effective, accurate point of care diagnostics that will transform antibacterial prescribing and enable more cost-effective and efficient antibacterial clinical trials. The challenges of AMR are too great for any one group to resolve and success will require leadership and partnerships among academia, industry and governments globally.