Governing Antimicrobial Resistance (AMR) in a Changing Climate: A Participatory Scenario Planning Approach Applied to Sweden in 2050

Background: Antimicrobial resistance (AMR) is a growing global crisis with long-term and unpredictable health, social and economic impacts, with which climate change is likely to interact. Understanding how to govern AMR amidst evolving climatic changes is critical. Scenario planning offers a suitable approach. By envisioning alternative futures, stakeholders more effectively can identify consequences, anticipate problems, and better determine how to intervene. This study explored future worlds and actions that may successfully address AMR in a changing climate in a high-income country, using Sweden as the case.Methods: We conducted online scenario-building workshops and interviews with eight experts who explored: (1) how promising interventions (taxation of antimicrobials at point of sale, and infection prevention measures) could each combat AMR in 2050 in Sweden given our changing climate; and (2) actions to take starting in 2030 to ensure success in 2050. Transcripts were thematically analyzed to produce a narrative of participant validated alternative futures.Results: Recognizing AMR to be a global problem requiring global solutions, participants looked beyond Sweden to construct three alternative futures: (1) “Tax Burn Out” revealed taxation of antimicrobials as a low-impact intervention that creates inequities and thus would fail to address AMR without other interventions, such as infection prevention measures. (2) “Addressing the Basics” identified infection prevention measures as highly impactful at containing AMR in 2050 because they would contribute to achieving the Sustainable Development Goals (SDGs), which would be essential to tackling inequities underpinning AMR and climate change, and help to stabilize climate-induced mass migration and conflicts; and (3) ”Siloed Nations” described a movement toward nationalism and protectionism that would derail the “Addressing the Basics” scenario, threatening health and wellbeing of all. Several urgent actions were identified to combat AMR long-term regardless which future un-folds, such as global collaboration, and a holistic approach where AMR and climate change are addressed as interlinked issues.Conclusion: Our participatory scenario planning approach enabled participants from different sectors to create shared future visions and identify urgent actions to take that hinge on global collaboration, addressing AMR and climate change together, and achieving the SDGs to combat AMR under a changing climate

Factors impacting antimicrobial resistance in the South East Asian food system and potential places to intervene: A participatory, one health study

BackgroundWith AMU projected to increase, South East Asia (SEA) is at high risk of experiencing disproportionate health, social, and economic burdens due to antimicrobial resistance (AMR). Our objective was to identify factors influencing AMR in SEA’s food system and places for intervention by integrating the perspectives of experts from the region to inform policy and management decisions.Materials and methodsWe conducted two 6.5 h workshops and two 90-min interviews involving 18 AMR and other disciplinary experts from human, animal, and environment sectors who brainstormed the factors influencing AMR and identified leverage points (places) for intervention. Transcripts and workshop materials were coded for factors and their connections and transcribed into a causal loop diagram (CLD). Thematic analysis described AMR dynamics in SEA’s food system and leverage points for intervention. The CLD and themes were confirmed via participant feedback.ResultsParticipants constructed a CLD of AMR in the SEA food system that contained 98 factors interlinked by 362 connections. CLD factors reflected eight sub-areas of the SEA food system (e.g., government). Seven themes [e.g., antimicrobial and pesticide use and AMR spread (n = 40 quotes)], six “overarching factors” that impact the entire AMR system [e.g., the drive to survive (n = 12 quotes)], and 10 places for intervention that target CLD factors (n = 5) and overarching factors (n = 2) emerged from workshop discussions.ConclusionThe participant derived CLD of factors influencing AMR in the SEA food system demonstrates that AMR is a product of numerous interlinked actions taken across the One Health spectrum and that finding solutions is no simple task. Developing the model enabled the identification of potentially promising leverage points across human, animal, and environment sectors that, if comprehensively targeted using multi-pronged interventions, could evoke system wide changes that mitigate AMR. Even targeting some leverage points for intervention, such as increasing investments in research and capacity building, and setting and enforcing regulations to control antimicrobial supply, demand, and use could, in turn, shift mindsets that lead to changes in more difficult to alter leverage points, such as redefining the profit-driven intent that drives system behavior in ways that transform AMU and sustainably mitigate AMR

Neutralising antibodies block the function of Rh5/Ripr/CyRPA complex during invasion of <i>Plasmodium falciparum</i> into human erythrocytes

An effective vaccine is a priority for malaria control and elimination. The leading candidate in the Plasmodium falciparum blood stage is PfRh5. PfRh5 assembles into trimeric complex with PfRipr and PfCyRPA in the parasite, and this complex is essential for erythrocyte invasion. In this study, we show that antibodies specific for PfRh5 and PfCyRPA prevent trimeric complex formation. We identify the EGF-7 domain on PfRipr as a neutralising epitope and demonstrate that antibodies against this region act downstream of complex formation to prevent merozoite invasion. Antibodies against the C-terminal region of PfRipr were more inhibitory than those against either PfRh5 or PfCyRPA alone, and a combination of antibodies against PfCyRPA and PfRipr acted synergistically to reduce invasion. This study supports prioritisation of PfRipr for development as part of a next-generation antimalarial vaccine

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Evolution and Structural Organization of the C Proteins of <i>Paramyxovirinae</i>

<div><p>The phosphoprotein (P) gene of most <i>Paramyxovirinae</i> encodes several proteins in overlapping frames: P and V, which share a common N-terminus (PNT), and C, which overlaps PNT. Overlapping genes are of particular interest because they encode proteins originated <i>de novo</i>, some of which have unknown structural folds, challenging the notion that nature utilizes only a limited, well-mapped area of fold space. The C proteins cluster in three groups, comprising measles, Nipah, and Sendai virus. We predicted that all C proteins have a similar organization: a variable, disordered N-terminus and a conserved, α-helical C-terminus. We confirmed this predicted organization by biophysically characterizing recombinant C proteins from Tupaia paramyxovirus (measles group) and human parainfluenza virus 1 (Sendai group). We also found that the C of the measles and Nipah groups have statistically significant sequence similarity, indicating a common origin. Although the C of the Sendai group lack sequence similarity with them, we speculate that they also have a common origin, given their similar genomic location and structural organization. Since C is dispensable for viral replication, unlike PNT, we hypothesize that C may have originated <i>de novo</i> by overprinting PNT in the ancestor of <i>Paramyxovirinae</i>. Intriguingly, in measles virus and Nipah virus, PNT encodes STAT1-binding sites that overlap different regions of the C-terminus of C, indicating they have probably originated independently. This arrangement, in which the same genetic region encodes simultaneously a crucial functional motif (a STAT1-binding site) and a highly constrained region (the C-terminus of C), seems paradoxical, since it should severely reduce the ability of the virus to adapt. The fact that it originated twice suggests that it must be balanced by an evolutionary advantage, perhaps from reducing the size of the genetic region vulnerable to mutations.</p></div

Alignment of the region of PNT of the measles and Nipah groups containing STAT1-binding sites, corrected by using the C frame.

<p>Conventions are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090003#pone-0090003-g002" target="_blank">Figure 2</a>. This reliable alignment of PNT is based on an alignment of the C frame by the procedure described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090003#pone-0090003-g008" target="_blank">Figure 8</a>. The [Y/H]DH[S/G]GE motifs common to the STAT1-binding sites of <i>measles virus</i> and <i>Nipah virus</i> PNT are underlined. Note that contrary to the alignment of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090003#pone-0090003-g007" target="_blank">Figure 7</a>, here they are not aligned together. Y110 of <i>measles virus</i> PNT and Y116 of <i>Nipah virus</i> PNT, which were suggested to be analogous (see text) are in bold.</p

Alignment of the C proteins of the measles and Nipah groups.

<p>Conventions are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090003#pone-0090003-g002" target="_blank">Figure 2</a>. Several positions appear conserved but have not been indicated, because their alignment is not reliable (see text).</p

Circular Dichroism (CD) spectra of the C proteins of hPIV1 and Tupaia PMV.

<p>Circular Dichroism (CD) spectra of the C proteins of hPIV1 and Tupaia PMV.</p