International treaties have mostly failed to produce their intended effects.

There are over 250,000 international treaties that aim to foster global cooperation. But are treaties actually helpful for addressing global challenges? This systematic field-wide evidence synthesis of 224 primary studies and meta-analysis of the higher-quality 82 studies finds treaties have mostly failed to produce their intended effects. The only exceptions are treaties governing international trade and finance, which consistently produced intended effects. We also found evidence that impactful treaties achieve their effects through socialization and normative processes rather than longer-term legal processes and that enforcement mechanisms are the only modifiable treaty design choice with the potential to improve the effectiveness of treaties governing environmental, human rights, humanitarian, maritime, and security policy domains. This evidence synthesis raises doubts about the value of international treaties that neither regulate trade or finance nor contain enforcement mechanisms.

The primate cortical LFP exhibits multiple spectral and temporal gradients and widespread task dependence during visual short-term memory.

Although cognitive functions are hypothesized to be mediated by synchronous neuronal interactions in multiple frequency bands among widely distributed cortical areas, we still lack a basic understanding of the distribution and task dependence of oscillatory activity across the cortical map. Here, we ask how the spectral and temporal properties of the local field potential (LFP) vary across the primate cerebral cortex, and how they are modulated during visual short-term memory. We measured the LFP from 55 cortical areas in two macaque monkeys while they performed a visual delayed match to sample task. Analysis of peak frequencies in the LFP power spectra reveals multiple discrete frequency bands between 3 and 80 Hz that differ between the two monkeys. The LFP power in each band, as well as the sample entropy, a measure of signal complexity, display distinct spatial gradients across the cortex, some of which correlate with reported spine counts in cortical pyramidal neurons. Cortical areas can be robustly decoded using a small number of spectral and temporal parameters, and significant task-dependent increases and decreases in spectral power occur in all cortical areas. These findings reveal pronounced, widespread, and spatially organized gradients in the spectral and temporal activity of cortical areas. Task-dependent changes in cortical activity are globally distributed, even for a simple cognitive task.NEW & NOTEWORTHY We recorded extracellular electrophysiological signals from roughly the breadth and depth of a cortical hemisphere in nonhuman primates (NHPs) performing a visual memory task. Analyses of the band-limited local field potential (LFP) power displayed widespread, frequency-dependent cortical gradients in spectral power. Using a machine learning classifier, these features allowed robust cortical area decoding. Further task dependence in LFP power were found to be widespread, indicating large-scale gradients of LFP activity, and task-related activity.

Classifying European cigarette consumption trajectories from 1970 to 2015.

OBJECTIVES: To systematically code and classify longitudinal cigarette consumption trajectories in European countries since 1970. DESIGN: Blinded duplicate qualitative coding of periods of year-over-year relative increase, plateau, and decrease of national per capita cigarette consumption and categorisation of historical cigarette consumption trajectories based on longitudinal patterns emerging from the data. SETTING: 41 countries or former countries in the European region for which data are available between 1970 and 2015. RESULTS: Regional trends in longitudinal consumption patterns identify stable or decreasing consumption throughout Northern, Western and Southern European countries, while Eastern and Southeastern European countries experienced much greater instability. The 11 emergent classes of historical cigarette consumption trajectories were also regionally clustered, including a distinctive inverted U or sine wave pattern repeatedly emerging from former Soviet and Southeastern European countries. CONCLUSIONS: The open-access data produced by this study can be used to conduct comparative international evaluations of tobacco control policies by separating impacts likely attributable to gradual long-term trends from those more likely attributable to acute short-term events. The complex, regionally clustered historical trajectories of cigarette consumption in Europe suggest that the enduring normative frame of a gently sloping downward curve in cigarette consumption can offer a false sense of security among policymakers and can distract from plausible causal mechanisms among researchers. These multilevel and multisectoral causal mechanisms point to the need for a greater understanding of the political economy of regional and global determinants of cigarette consumption.

Beyond MPOWER: a systematic review of population-level factors that affect European tobacco smoking rates.

BACKGROUND: Population-level factors within and beyond the scope of the World Health Organization's (WHO) MPOWER policy package have significant impacts on smoking rates. However, no synthesis of the existing evidence exists. This systematic review identifies population-level factors that influence cigarette smoking rates in European countries. METHODS: We searched the ProQuest database collection for original, peer-reviewed quantitative evaluations that investigated the effects of population-level exposures on smoking rates in European countries. Of the 3122 studies screened, 62 were ultimately included in the review. A standardized data extraction form was used to identify key characteristics of each study including publication year, years evaluated, countries studied, population characteristics, study design, data sources, analytic methods, exposure studied, relevant covariates and effects on tobacco smoking outcomes. RESULTS: One hundred and fifty-five population-level exposures were extracted from the 62 studies included in the review, 99 of which were related to WHO MPOWER measures. An additional 56 exposures fell into eight policy realms: economic crises, education policy, macro-economic factors, non-MPOWER tobacco regulations, population welfare, public policy, sales to minors and unemployment rates. About one-half of the MPOWER exposures affected smoking rates (55/99) and did so in an overwhelmingly positive way (55/55). Over three-quarters of the non-MPOWER exposures were associated with statistically significant changes in smoking outcomes (43/56), with about two-thirds of these exposures leading to a decrease in smoking (29/43). CONCLUSIONS: Population-level factors that fall outside of the WHO's MPOWER measures are an understudied research area. The impacts of these factors on tobacco control should be considered by policymakers.

Exploring Models for an International Legal Agreement on the Global Antimicrobial Commons: Lessons from Climate Agreements.

An international legal agreement governing the global antimicrobial commons would represent the strongest commitment mechanism for achieving collective action on antimicrobial resistance (AMR). Since AMR has important similarities to climate change-both are common pool resource challenges that require massive, long-term political commitments-the first article in this special issue draws lessons from various climate agreements that could be applicable for developing a grand bargain on AMR. We consider the similarities and differences between the Paris Climate Agreement and current governance structures for AMR, and identify the merits and challenges associated with different international forums for developing a long-term international agreement on AMR. To be effective, fair, and feasible, an enduring legal agreement on AMR will require a combination of universal, differentiated, and individualized requirements, nationally determined contributions that are regularly reviewed and ratcheted up in level of ambition, a regular independent scientific stocktake to support evidence informed policymaking, and a concrete global goal to rally support.

Governing the Global Antimicrobial Commons: Introduction to Special Issue.

Antimicrobial resistance is one of the greatest public health crises of our time. The natural biological process that causes microbes to become resistant to antimicrobial drugs presents a complex social challenge requiring more effective and sustainable management of the global antimicrobial commons-the common pool of effective antimicrobials. This special issue of Health Care Analysis explores the potential of two legal approaches-one long-term and one short-term-for managing the antimicrobial commons. The first article explores the lessons for antimicrobial resistance that can be learned from recent climate change agreements, and the second article explores how existing international laws can be adapted to better support global action in the short-term.

Making Use of Existing International Legal Mechanisms to Manage the Global Antimicrobial Commons: Identifying Legal Hooks and Institutional Mandates.

Antimicrobial resistance (AMR) is an urgent threat to global public health and development. Mitigating this threat requires substantial short-term action on key AMR priorities. While international legal agreements are the strongest mechanism for ensuring collaboration among countries, negotiating new international agreements can be a slow process. In the second article in this special issue, we consider whether harnessing existing international legal agreements offers an opportunity to increase collective action on AMR goals in the short-term. We highlight ten AMR priorities and several strategies for achieving these goals using existing "legal hooks" that draw on elements of international environmental, trade and health laws governing related matters that could be used as they exist or revised to include AMR. We also consider the institutional mandates of international authorities to highlight areas where additional steps could be taken on AMR without constitutional changes. Overall, we identify 37 possible mechanisms to strengthen AMR governance using the International Health Regulations, the Agreement on the Application of Sanitary and Phytosanitary Measures, the Agreement on Trade-Related Aspects of Intellectual Property Rights, the Agreement on Technical Barriers to Trade, the International Convention on the Harmonized Commodity Description and Coding System, and the Basel, Rotterdam, and Stockholm conventions. Although we identify many shorter-term opportunities for addressing AMR using existing legal hooks, none of these options are capable of comprehensively addressing all global governance challenges related to AMR, such that they should be pursued simultaneously with longer-term approaches including a dedicated international legal agreement on AMR.

Evaluating official development assistance-funded granting mechanisms for global health and development research that is initiated in high-income countries.

BACKGROUND: Several countries allocate official development assistance (ODA) for research on global health and development issues that is initiated in the donor country. The integration of such research within domestic research systems aligns with efforts to coordinate ODA investments with science, technology and innovation policies towards achieving the Sustainable Development Goals (SDGs). METHODS: Through a document synthesis and interviews with research funders in ODA donor and recipient countries, we evaluated the performance of this funding approach across seven donor-country programmes from five donor countries and examined the institutional design elements that increase its chances of advancing development goals and addressing global challenges. RESULTS: We found that carefully designed programmes provide a promising pathway to producing valuable and contextually relevant knowledge on global health and development issues. To achieve these outcomes and ensure they benefit ODA-receiving countries, programmes should focus on recipient-country priorities and absorptive capacity; translate research on global public goods into context-appropriate technologies; plan and monitor pathways to impact; structure equitable partnerships; strengthen individual and institutional capacity; and emphasize knowledge mobilization. CONCLUSIONS: Global health and development research programmes and partnerships have an important role to play in achieving the SDGs and addressing global challenges. Governments should consider the potential of ODA-funded research programmes to address gaps in their global health and development frameworks. In the absence of concrete evidence of development impact, donor countries should consider making increases in ODA allocations for research additional to more direct investments that have demonstrated effectiveness in ODA-receiving countries.

A virus unites the world while national border closures divide it: Epidemiologic, legal, and political analysis on border closures during COVID-19.

This article critically examines the use of national border closures at the outset of the COVID-19 pandemic. After explaining why targeted border closures generally do not work and how they violated international law at the time, we examine the unprecedented case of total border closures. Positing that since the current instruments and institutions of global health governance did not anticipate this phenomenon, the legality of total border closures rests on less certain grounds. Then, after asking why nearly every government implemented some form of border closure in March 2020 if neither science nor law provided adequate motivation for their use, we conclude that in the face of a global health emergency, border closures represent an opportunity for political leaders to show determined action, redirect blame to other jurisdictions, and reinforce nationalism. We proceed to argue that both targeted and total border closures have profound legal, epidemiological, and political significance as performances that contradict global realities while undermining notions of global solidarity. Such political theatre means that citizens must weigh these consequences against any perceived benefits of border closures as they would any other politically driven government action, and contest and challenge them appropriately. Citizens must not unduly defer to scientists or lawyers on early COVID-19 border closures because these were primarily political-not scientific or legal-decisions. In this vein, we conclude with some guiding political considerations for scrutinizing government decisions to close borders and observations for the future of global health cooperation during infectious disease outbreaks.

Lessons learned from COVID-19 for the post-antibiotic future.

INTRODUCTION: COVID-19 has rapidly and radically changed the face of human health and social interaction. As was the case with COVID-19, the world is similarly unprepared to respond to antimicrobial resistance (AMR) and the challenges it will produce. COVID-19 presents an opportunity to examine how the international community might better respond to the growing AMR threat. MAIN BODY: The impacts of COVID-19 have manifested in health system, economic, social, and global political implications. Increasing AMR will also present challenges in these domains. As seen with COVID-19, increasing healthcare usage and resource scarcity may lead to ethical dilemmas about prioritization of care; unemployment and economic downturn may disproportionately impact people in industries reliant on human interaction (especially women); and international cooperation may be compromised as nations strive to minimize outbreaks within their own borders. CONCLUSION: AMR represents a slow-moving disaster that offers a unique opportunity to proactively develop interventions to mitigate its impact. The world's attention is currently rightfully focused on responding to COVID-19, but there is a moral imperative to take stock of lessons learned and opportunities to prepare for the next global health emergency.

Artificial intelligence in health care: laying the Foundation for Responsible, sustainable, and inclusive innovation in low- and middle-income countries.

The World Health Organization and other institutions are considering Artificial Intelligence (AI) as a technology that can potentially address some health system gaps, especially the reduction of global health inequalities in low- and middle-income countries (LMICs). However, because most AI-based health applications are developed and implemented in high-income countries, their use in LMICs contexts is recent and there is a lack of robust local evaluations to guide decision-making in low-resource settings. After discussing the potential benefits as well as the risks and challenges raised by AI-based health care, we propose five building blocks to guide the development and implementation of more responsible, sustainable, and inclusive AI health care technologies in LMICs.

Using a rapid environmental scan methodology to map country-level global health research expertise in Canada.

BACKGROUND: Many countries are currently rethinking their global health research funding priorities. When resources are limited, it is important to understand and use information about existing research strengths to inform research strategies and investments and to drive impact. This study describes a method to rapidly assess a country's global health research expertise and applies this method in the Canadian context. METHODS: We developed a three-pronged rapid environmental scan to evaluate Canadian global health research expertise that focused on research funding inputs, research activities and research outputs. We assessed research funding inputs from Canada's national health research funding agency and identified the 30 Canadian universities that received the most global health research funding. We systematically searched university websites and secondary databases to identify research activities, including research centres, research chairs and research training programmes. To evaluate research outputs, we searched PubMed to identify global health research publications by Canadian university-affiliated researchers. We used these three perspectives to develop a more nuanced understanding of Canadian strengths in global health research from different perspectives. RESULTS: Canada's main global health research funder, the Canadian Institutes of Health Research, invested a total of $314 M from 2000 to 2016 on global health research grants. This investment has contributed to Canada's wealth of global health research expertise, including 12 training programmes, 27 Canada Research Chairs, 6 research centres and 30 WHO Collaborating Centres across 27 universities. Research activities were concentrated in Canada's biggest cities and most commonly focused on health equity and globalisation issues. Canadian-affiliated researchers have contributed to a research output of 822 unique publications on PubMed. There is an opportunity to build global health expertise in regions not already concentrated with research activity, focusing on transnational risks and neglected conditions research. CONCLUSIONS: Our three-pronged approach allowed us to rapidly identify clear geographic and substantive areas of strength in Canadian global health research, including urban regions and research focused on health equity and globalisation topics. This information can be used to support research policy directives, including to inform a Canadian global health research strategy, and to allow relevant academic institutions and funding organisations to make more strategic decisions regarding their future investments.

Government policy interventions to reduce human antimicrobial use: A systematic review and evidence map.

BACKGROUND: Growing political attention to antimicrobial resistance (AMR) offers a rare opportunity for achieving meaningful action. Many governments have developed national AMR action plans, but most have not yet implemented policy interventions to reduce antimicrobial overuse. A systematic evidence map can support governments in making evidence-informed decisions about implementing programs to reduce AMR, by identifying, describing, and assessing the full range of evaluated government policy options to reduce antimicrobial use in humans. METHODS AND FINDINGS: Seven databases were searched from inception to January 28, 2019, (MEDLINE, CINAHL, EMBASE, PAIS Index, Cochrane Central Register of Controlled Trials, Web of Science, and PubMed). We identified studies that (1) clearly described a government policy intervention aimed at reducing human antimicrobial use, and (2) applied a quantitative design to measure the impact. We found 69 unique evaluations of government policy interventions carried out across 4 of the 6 WHO regions. These evaluations included randomized controlled trials (n = 4), non-randomized controlled trials (n = 3), controlled before-and-after designs (n = 7), interrupted time series designs (n = 25), uncontrolled before-and-after designs (n = 18), descriptive designs (n = 10), and cohort designs (n = 2). From these we identified 17 unique policy options for governments to reduce the human use of antimicrobials. Many studies evaluated public awareness campaigns (n = 17) and antimicrobial guidelines (n = 13); however, others offered different policy options such as professional regulation, restricted reimbursement, pay for performance, and prescription requirements. Identifying these policies can inform the development of future policies and evaluations in different contexts and health systems. Limitations of our study include the possible omission of unpublished initiatives, and that policies not evaluated with respect to antimicrobial use have not been captured in this review. CONCLUSIONS: To our knowledge this is the first study to provide policy makers with synthesized evidence on specific government policy interventions addressing AMR. In the future, governments should ensure that AMR policy interventions are evaluated using rigorous study designs and that study results are published. PROTOCOL REGISTRATION: PROSPERO CRD42017067514.

Canada's global health role: supporting equity and global citizenship as a middle power.

Canada's history of nation building, combined with its status as a so-called middle power in international affairs, has been translated into an approach to global health that is focused on equity and global citizenship. Canada has often aspired to be a socially progressive force abroad, using alliance building and collective action to exert influence beyond that expected from a country with moderate financial and military resources. Conversely, when Canada has primarily used economic self-interest to define its global role, the country's perceived leadership in global health has diminished. Current Prime Minister Justin Trudeau's Liberal federal government has signalled a return to progressive values, driven by appreciation for diversity, equality, and Canada's responsibility to be a good global citizen. However, poor coordination of efforts, limited funding, and the unaddressed legacy of Canada's colonisation of Indigenous peoples weaken the potential for Canadians to make meaningful contributions to improvement of global health equity. Amid increased nationalism and uncertainty towards multilateral commitments by some major powers in the world, the Canadian federal government has a clear opportunity to convert its commitments to equity and global citizenship into stronger leadership on the global stage. Such leadership will require the translation of aspirational messages about health equity and inclusion into concrete action at home and internationally.

Evidence-based guidelines for supportive care of patients with Ebola virus disease.

The 2013-16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive care to patients admitted to Ebola treatment units. Key recommendations include administration of oral and, as necessary, intravenous hydration; systematic monitoring of vital signs and volume status; availability of key biochemical testing; adequate staffing ratios; and availability of analgesics, including opioids, for pain relief.

How law can help solve the collective action problem of antimicrobial resistance.

Antimicrobial resistance is a global collective action problem with dire consequences for human health. This article considers how domestic and international legal mechanisms can be used to address antimicrobial resistance and overcome the governance and political economy challenges that accelerate it.

A population health perspective on artificial intelligence.

The burgeoning field of Artificial Intelligence (AI) has the potential to profoundly impact the public's health. Yet, to make the most of this opportunity, decision-makers must understand AI concepts. In this article, we describe approaches and fields within AI and illustrate through examples how they can contribute to informed decisions, with a focus on population health applications. We first introduce core concepts needed to understand modern uses of AI and then describe its sub-fields. Finally, we examine four sub-fields of AI most relevant to population health along with examples of available tools and frameworks. Artificial intelligence is a broad and complex field, but the tools that enable the use of AI techniques are becoming more accessible, less expensive, and easier to use than ever before. Applications of AI have the potential to assist clinicians, health system managers, policy-makers, and public health practitioners in making more precise, and potentially more effective, decisions.

Delays in Global Disease Outbreak Responses: Lessons from H1N1, Ebola, and Zika.

In global disease outbreaks, there are significant time delays between the source of an outbreak and collective action. Some delay is necessary, but recent delays have been extended by insufficient surveillance capacity and time-consuming efforts to mobilize action. Three public health emergencies of international concern (PHEICs)-H1N1, Ebola, and Zika-allow us to identify and compare sources of delays and consider seven hypotheses about what influences the length of delays. These hypotheses can then motivate further research that empirically tests them. The three PHEICs suggest that deferred global mobilization is a greater source of delay than is poor surveillance capacity. These case study outbreaks support hypotheses that we see quicker responses for novel diseases when outbreaks do not coincide with holidays and when US citizens are infected. They do not support hypotheses that we see quicker responses for more severe outbreaks or those that threaten larger numbers of people. Better understanding the reason for delays can help target policy interventions and identify the kind of global institutional changes needed to reduce the spread and severity of future PHEICs.

Mapping educational opportunities for healthcare workers on antimicrobial resistance and stewardship around the world.

BACKGROUND: Antimicrobial resistance is an important global issue facing society. Healthcare workers need to be engaged in solving this problem, as advocates for rational antimicrobial use, stewards of sustainable effectiveness, and educators of their patients. To fulfill this role, healthcare workers need access to training and educational resources on antimicrobial resistance. METHODS: To better understand the resources available to healthcare workers, we undertook a global environmental scan of educational programs and resources targeting healthcare workers on the topic of antimicrobial resistance and antimicrobial stewardship. Programs were identified through contact with key experts, web searching, and academic literature searching. We summarized programs in tabular form, including participating organizations, region, and intended audience. We developed a coding system to classify programs by program type and participating organization type, assigning multiple codes as necessary and creating summary charts for program types, organization types, and intended audience to illustrate the breadth of available resources. RESULTS: We identified 94 educational initiatives related to antimicrobial resistance and antimicrobial stewardship, which represent a diverse array of programs including courses, workshops, conferences, guidelines, public outreach materials, and online-resource websites. These resources were developed by a combination of government bodies, professional societies, universities, non-profit and community organizations, hospitals and healthcare centers, and insurance companies and industry. Most programs either targeted healthcare workers collectively or specifically targeted physicians. A smaller number of programs were aimed at other healthcare worker groups including pharmacists, nurses, midwives, and healthcare students. CONCLUSIONS: Our environmental scan shows that there are many organizations working to develop and share educational resources for healthcare workers on antimicrobial resistance and antimicrobial stewardship. Governments, hospitals, and professional societies appear to be driving action on this front, sometimes working with other types of organizations. A broad range of resources have been made freely available; however, we have noted several opportunities for action, including increased engagement with students, improvements to pre-service education, recognition of antimicrobial resistance courses as continuing medical education, and better platforms for resource-sharing online.