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Dimerization of the thrombopoietin receptor (TpoR) is necessary for receptor activation and downstream signaling through activated Janus kinase 2. We have shown previously that different orientations of the transmembrane (TM) helices within a receptor dimer can lead to different signaling outputs. Here we addressed the structural basis of activation for receptor mutations S505N and W515K that induce myeloproliferative neoplasms. We show using in vivo bone marrow reconstitution experiments that ligand-independent activation of TpoR by TM asparagine (Asn) substitutions is proportional to the proximity of the mutation to the intracellular membrane surface. Solid-state NMR experiments on TM peptides indicate a progressive loss of helical structure in the juxtamembrane (JM) R/KWQFP motif with either proximity of Asn substitutions to the cytosolic boundary or mutation of W515 in the motif. Mutational studies in the TpoR cytosolic JM region show that the helical loss by itself can induce activation, but is localized to a maximum of 6 amino acids downstream of W515, the rest of the region until Box 1 requiring helicity for receptor function. The constitutive activation of TpoR mutants S505N and W515K can be inhibited by rotation of TM helices within the TpoR dimer, which also restores helicity around W515. Together these data allow us to develop a general model for activation and to explain the critical role of the JM W515 residue in the regulation of receptor activity.(Total manuscript without References and Figure Legends 6507 words, main text (without methods and materials):)

As I understand it, the central aim of the field of CSR is to reconcile (in the sense of “consilience”) methods and theories from the natural sciences with research on religion, which though defined in various ways, is usually understood as a universal human phenomenon. This does not necessarily mean religion is innate, but like all universal human phenomena, there will be an evolutionary story to tell about how it, or its constituent elements, came about. The stories are usually about the phenomena of religion writ-large, variously defined, rarely reaching the granularity to make claims about specific historical and cultural circumstances where religion is most relevant to agents. I challenge all scholars of religion to make their metaphysics explicit.

In 2013, a Lancet Infectious Diseases Commission described the state of antimicrobial resistance worldwide. Since then, greater awareness of the public health ramifications of antimicrobial resistance has led to national actions and global initiatives, including a resolution at the high-level meeting of the UN General Assembly in 2016. Progress in addressing this issue has ranged from a ban on irrational drug combinations in India to commitments to ban colistin as a growth promoter in animals, improve hospital infection control, and implement better antimicrobial stewardship. Funds have been mobilised, and regulatory barriers to new antibiotic development have been relaxed. These efforts have been episodic and uneven across countries, however. Sustained funding for antimicrobial resistance and globally harmonised targets to monitor progress are still urgently needed. Except for in a few leading countries, antimicrobial resistance has not captured the sustained focus of national leaders and country-level actors, including care providers.

Philadelphia-negative classical Myeloproliferative Neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF), are clonal hemopathies that emerge in the hematopoietic stem cell (HSC) compartment. MPN driver mutations are restricted to specific exons (14 and 12) of Janus kinase 2 (JAK2), thrombopoietin receptor (MPL/TPOR) and calreticulin (CALR) genes, are involved directly in clonal myeloproliferation and generate the MPN phenotype. As a result, an increased number of fully functional erythrocytes, platelets and leukocytes is observed in the peripheral blood. Nevertheless, the complexity and heterogeneity of MPN clinical phenotypes cannot be solely explained by the type of driver mutation. Other factors, such as additional somatic mutations affecting epigenetic regulators or spliceosomes components, mutant allele burdens and modifiers of signaling by driver mutants, clonal architecture and the order of mutation acquisition, signaling events that occur downstream of a driver mutation, the presence of specific germ-line variants, the interaction of the neoplastic clone with bone marrow microenvironment and chronic inflammation, all can modulate the disease phenotype, influence the MPN clinical course and therefore, might be useful therapeutic targets.

An approach to understanding religion that draws on both humanities and natural science but rejects approaches that employ simple monisms and radical dualisms. In Beyond Heaven and Earth, Gabriel Levy argues that collective religious narratives and beliefs are part of nature; they are the basis for the formation of the narratives and beliefs of individuals. Religion grows out of the universe, but to make sense of it we have to recognize the paradox that the universe is both mental and material (or neither). We need both humanities and natural science approaches to study religion and religious meaning, Levy contends, but we must also recognize the limits of these approaches. First, we must make the dominant metaphysics that undergird the various disciplines of science and humanities more explicit, and second, we must reject those versions of metaphysics that maintain simple monisms and radical dualisms. Bringing Donald Davidson's philosophy—a form of pragmatism known as anomalous monism—to bear on religion, Levy offers a blueprint for one way that the humanities and natural sciences can have a mutually respectful dialogue. Levy argues that in order to understand religions we have to take their semantic content seriously. We need to rethink such basic concepts as narrative fiction, information, agency, creativity, technology, and intimacy. In the course of his argument, Levy considers the relation between two closely related semantics, fiction and religion, and outlines a new approach to information. He then applies his theory to discrete cases: ancient texts, modern media, and intimacy.

Objectives: Optimal treatment of carbapenem-resistant Gram-negative bacteria (CR-GNB) infections is uncertain because of the lack of good-quality evidence and the limited effectiveness of available antibiotics. The aim of this survey was to investigate clinicians' prescribing strategies for treating CR-GNB infections worldwide. Methods: A 36-item questionnaire was developed addressing the following aspects of antibiotic prescribing: respondent's background, diagnostic and therapeutic availability, preferred antibiotic strategies and rationale for selecting combination therapy. Prescribers were recruited following the snowball sampling approach, and a post-stratification correction with inverse proportional weights was used to adjust the sample's representativeness. Results: A total of 1012 respondents from 95 countries participated in the survey. Overall, 298 (30%) of the respondents had local guidelines for treating CR-GNB at their facility and 702 (71%) had access to Infectious Diseases consultation, with significant discrepancies according to country economic status: 85% (390/502) in high-income countries versus 59% (194/283) in upper-medium-income countries and 30% (118/196) in lower-middle-income countries/lower-income-countries). Targeted regimens varied widely, ranging from 40 regimens for CR-Acinetobacter spp. to more than 100 regimens for CR-Enterobacteriaceae. Although the majority of respondents acknowledged the lack of evidence behind this choice, dual combination was the preferred treatment scheme and carbapenem-polymyxin was the most prescribed regimen, irrespective of pathogen and infection source. Respondents noticeably disagreed around the meaning of ‘combination therapy’ with 20% (150/783) indicating the simple addition of multiple compounds, 42% (321/783) requiring the presence of in vitro activity and 38% (290/783) requiring in vitro synergism. Conclusions: Management of CR-GNB infections is far from being standardized. Strategic public health focused randomized controlled trials are urgently required to inform evidence-based treatment guidelines.

BACKGROUND: Variation in the approaches taken to contain the SARS-CoV-2 (COVID-19) pandemic at country level has been shaped by economic and political considerations, technical capacity, and assumptions about public behaviours. To address the limited application of learning from previous pandemics, this study aimed to analyse perceived facilitators and inhibitors during the pandemic and to inform the development of an assessment tool for pandemic response planning. METHODS: A cross-sectional electronic survey of health and non-health care professionals (5 May - 5 June 2020) in six languages, with respondents recruited via email, social media and website posting. Participants were asked to score inhibitors (-10 to 0) or facilitators (0 to +10) impacting country response to COVID-19 from the following domains - Political, Economic, Sociological, Technological, Ecological, Legislative, and wider Industry (the PESTELI framework). Participants were then asked to explain their responses using free text. Descriptive and thematic analysis was followed by triangulation with the literature and expert validation to develop the assessment tool, which was then compared with four existing pandemic planning frameworks. RESULTS: 928 respondents from 66 countries (57% health care professionals) participated. Political and economic influences were consistently perceived as powerful negative forces and technology as a facilitator across high- and low-income countries. The 103-item tool developed for guiding rapid situational assessment for pandemic planning is comprehensive when compared to existing tools and highlights the interconnectedness of the 7 domains. CONCLUSIONS: The tool developed and proposed addresses the problems associated with decision making in disciplinary silos and offers a means to refine future use of epidemic modelling.

Additional material: Online Supplementary Document available at http://jogh.org/documents/2021/jogh-11-05011-s001.pdf . Copyright © 2021 The Author(s). Background: Variation in the approaches taken to contain the SARS-CoV-2 (COVID-19) pandemic at country level has been shaped by economic and political considerations, technical capacity, and assumptions about public behaviours. To address the limited application of learning from previous pandemics, this study aimed to analyse perceived facilitators and inhibitors during the pandemic and to inform the development of an assessment tool for pandemic response planning. Methods A cross-sectional electronic survey of health and non-health care professionals (5 May - 5 June 2020) in six languages, with respondents recruited via email, social media and website posting. Participants were asked to score inhibitors (−10 to 0) or facilitators (0 to +10) impacting country response to COVID-19 from the following domains - Political, Economic, Sociological, Technological, Ecological, Legislative, and wider Industry (the PESTELI framework). Participants were then asked to explain their responses using free text. Descriptive and thematic analysis was followed by triangulation with the literature and expert validation to develop the assessment tool, which was then compared with four existing pandemic planning frameworks. Results 928 respondents from 66 countries (57% health care professionals) participated. Political and economic influences were consistently perceived as powerful negative forces and technology as a facilitator across high- and low-income countries. The 103-item tool developed for guiding rapid situational assessment for pandemic planning is comprehensive when compared to existing tools and highlights the interconnectedness of the 7 domains. Conclusions The tool developed and proposed addresses the problems associated with decision making in disciplinary silos and offers a means to refine future use of epidemic modelling. This study did not receive any external funding.

Background Point prevalence surveys (PPSs) on antibiotic use are useful for understanding different aspects related to prescription patterns in hospitals. Methods An adaptation of the WHO methodology for a PPS on antibiotic use was applied. Hospital wards were divided into medical (MED), surgical (SUR), ICUs, gynaecology and obstetrics (GO), high-risk (HR) and mixed wards (MIX). A web application (RedCap©) through a mobile device was used for data collection. Results Between December 2018 and August 2019, 5444 patients in 33 hospitals in five countries were included (10 hospitals in Cuba, 7 in Paraguay, 6 in El Salvador, 5 in Mexico and 5 in Peru). Of these patients, 54.6% received at least one antibiotic, with variations between and within hospitals and countries. Antibiotics were more frequently used in ICUs (67.2%), SUR (64.5%) and MED wards (54.2%), with 51.2% of antibiotics prescribed for community-acquired infections (CAIs), 22.9% for healthcare-associated infections (HAIs), 11.1% for surgical prophylaxis and 6.1% for unknown reasons. Adherence to guidelines was observed in 68.6% of cases (72.8% for CAIs, 72.4% for HAIs and 44.3% for prophylaxis). Third-generation cephalosporins were the class of antibiotics most frequently used (26.8%), followed by carbapenems (10.3%) and fluoroquinolones (8%). Targeted treatments were achieved in 17.3% of cases. Conclusions Antibiotic use was generally higher than that published in other studies. There is an urgent need to promote and strengthen the antimicrobial stewardship programmes in Latin America.

Metatarsophalangeal arthritis of the first ray of the foot, also known as hallux rigidus, is an invalidating cause of walking that is still underestimated. It is associated to a local deformation of the first ray with a limitation of the dorsal mobilization of the joint, affecting thus the propulsion of the foot. Several stages of the disease exist, and symptoms as well as the treatment will depend on the moment of the consultation. In this paper, we present the different clinical pictures and adapted treatments according to the stage of the disease, and we share our results of a new modality of surgery that conserves the articular mobility of the joint.L’arthrose métatarsophalangienne du premier rayon du pied, connue également sous le nom de « hallux rigidus », est une pathologie invalidante de la marche encore sous-estimée. Elle est associée à une déformation localisée du premier rayon et à une limitation de la flexion dorsale au niveau de l’articulation, affectant ainsi la propulsion. Plusieurs stades de cette maladie existent, et les symptômes ainsi que leurs traitements dépendront du moment de consultation. Dans cet article, nous présentons les différents symptômes et traitements de cette arthrose, adaptés selon le stade en partageant notre expérience avec les nouveautés technologiques conservatrices du mouvement articulaire et leur résultat à moyen terme.

Congenital amegakaryocytic thrombocytopenia (CAMT) is a severe inherited thrombocytopenia due to loss-of-function mutations affecting the thrombopoietin (TPO) receptor, MPL. Here, we report a new homozygous MPL variant responsible for CAMT in 1 consanguineous family. The propositus and her sister presented with severe thrombocytopenia associated with mild anemia. Next-generation sequencing revealed the presence of a homozygous MPLR464G mutation resulting in a weak cell-surface expression of the receptor in platelets. In cell lines, we observed a defect in MPLR464G maturation associated with its retention in the endoplasmic reticulum. The low cell-surface expression of MPLR464G induced very limited signaling with TPO stimulation, leading to survival and reduced proliferation of cells. Overexpression of a myeloproliferative neoplasm–associated calreticulin (CALR) mutant did not rescue trafficking of MPLR464G to the cell surface and did not induce constitutive signaling. However, it unexpectedly restored a normal response to eltrombopag (ELT), but not to TPO. This effect was only partially mimicked by the purified recombinant CALR mutant protein. Finally, the endogenous CALR mutant was able to restore the megakaryocyte differentiation of patient CD34+ cells carrying MPLR464G in response to ELT.

BackgroundHealthcare professionals are increasingly expected to lead antimicrobial stewardship (AMS) initiatives. This role in complex healthcare environments requires specialized training.ObjectivesLittle is known about the types of AMS training programmes available to clinicians seeking to play a lead role in AMS. We aimed to identify clinicians’ awareness of AMS training programmes, characteristics of AMS training programmes available and potential barriers to participation.MethodsAMS training programmes available were identified by members of the ESCMID Study Group for Antimicrobial Stewardship (ESGAP) via an online survey and through an online search in 2018. Individual training programme course coordinators were then contacted (September–October 2018) for data on the target audience(s), methods of delivery, intended outcomes and potential barriers to accessing the training programme.ResultsA total of 166/250 ESGAP members (66%) responded to the survey, nominating 48 unique AMS training programmes. An additional 32 training programmes were identified through an online search. AMS training programmes were from around the world. Less than half (44.4%) of respondents were aware of one or more AMS training programmes available, with pharmacists more aware compared with medical doctors and other professionals (73% versus 46% and 25%, respectively). AMS training programmes were most commonly delivered online (59%) and aimed at medical doctors (46%). Training costs and a lack of recognition by health professional societies were the most frequently cited barriers to participation in AMS training programmes.ConclusionsThe development of a systematic inventory of AMS training programmes around the globe identifies opportunities and limitations to current training available. Improving access and increasing awareness amongst target participants will support improved education in AMS.

Background Inappropriate antibiotic use represents a major global threat. Sepsis and bacterial lower respiratory tract infections (LRTIs) have been linked to antimicrobial resistance, carrying important consequences for patients and health systems. Procalcitonin-guided algorithms may represent helpful tools to reduce antibiotic overuse but the financial burden is unclear. The aim of this study was to estimate the healthcare and budget impact in Argentina of using procalcitonin-guided algorithms to guide antibiotic prescription. Methods A decision tree was used to model health and cost outcomes for the Argentinean health system, over a one-year duration. Patients with suspected sepsis in the intensive care unit and hospitalized patients with LRTI were included. Model parameters were obtained from a focused, non-systematic, local and international bibliographic search, and validated by a panel of local experts. Deterministic and probabilistic sensitivity analyses were performed to analyze the uncertainty of parameters. Results The model predicted that using procalcitonin-guided algorithms would result in 734.5 [95% confidence interval (CI): 1,105.2;438.8] thousand fewer antibiotic treatment days, 7.9 [95% CI: 18.5;8.5] thousand antibiotic-resistant cases avoided, and 5.1 [95% CI: 6.7;4.2] thousand fewer Clostridioides difficile cases. In total, this would save $422.4 US dollars (USD) [95% CI: $935;$267] per patient per year, meaning cost savings of $83.0 [95% CI: $183.6;$57.7] million USD for the entire health system and $0.4 [95% CI: $0.9;$0.3] million USD for a healthcare provider with 1,000 cases per year of sepsis and LRTI patients. The sensitivity analysis showed that the probability of cost-saving for the sepsis patient group was lower than for the LRTI patient group (85% vs. 100%). Conclusions Healthcare and financial benefits can be obtained by implementing procalcitonin-guided algorithms in Argentina. Although we found results to be robust on an aggregate level, some caution must be used when focusing only on sepsis patients in the intensive care unit.

Objectives/Purpose The costs attributable to antimicrobial resistance (AMR) remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR across human, animal, and environmental health; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network has developed a framework to help guide AMR costing exercises in any part of the world as a first step towards more comprehensive analyses for comparing AMR interventions at the local level as well as more harmonized analyses for quantifying the full economic burden attributable to AMR at the global level.Methods GAP-ON€ (funded under the JPIAMR 8th call (Virtual Research Institute) is composed of 19 international networks and institutions active in the field of AMR. For this project, the Network operated by means of Delphi rounds, teleconferences and face-to-face meetings. The resulting costing framework takes a bottom-up approach to incorporate all relevant costs imposed by an AMR bacterial microbe in a patient, in an animal, or in the environment up through to the societal level. Results The framework itemizes the epidemiological data as well as the direct and indirect cost components needed to build a realistic cost picture for AMR. While the framework lists a large number of relevant pathogens for which this framework could be used to explore the costs, the framework is sufficiently generic to facilitate the costing of other resistant pathogens, including those of other aetiologies. Conclusion In order to conduct cost-effectiveness analyses to choose amongst different AMR-related interventions at local level, the costing of AMR should be done according to local epidemiological priorities and local health service norms. Yet the use of a common framework across settings allows for the results of such studies to contribute to cumulative estimates that can serve as the basis of broader policy decisions at the international level such as how to steer R&D funding and how to prioritize AMR amongst other issues. Indeed, it is only by building a realistic cost picture that we can make informed decisions on how best to tackle major health threats.

Introduction: Carbapenemases are β-lactamases able to hydrolyze a wide range of β-lactam antibiotics, including carbapenems. Carbapenemase production in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter spp., with and without the co-expression of other β-lactamases is a serious public health threat. Carbapenemases belong to three main classes according to the Ambler classification: class A, class B, and class D. Areas covered: Carbapenemase-bearing pathogens are endemic in Latin America. In this review, we update the status of carbapenemases in Latin America and the Caribbean. Expert opinion: Understanding the current epidemiology of carbapenemases in Latin America and the Caribbean is of critical importance to improve infection control policies limiting the dissemination of multi-drug-resistant pathogens and in implementing appropriate antimicrobial therapy.

Objectives/PurposeThe costs attributable to antimicrobial resistance (AMR) across human, animal, and environmental health remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network aimed to develop a global, One Health AMR Cost Framework, that can be used by countries, regions, and other entities to quantify the economic burden attributable to AMR.MethodsGAP-ON€ (funded under the JPIAMR 8th call (Virtual Research Institute) is composed of 19 international networks and institutions active in the field of AMR. It operated by means of Delphi rounds, teleconferences (TCs) and face-to-face (F2F) meetings. It assumes a bottom-up cost estimate, at the National level, with a global scope across all One Health Areas.ResultsThe resulting framework consists of the epidemiological data and the direct and indirect cost components, linked by the likelihood of each AMR-related health state that imposes such costs, across all One Health Areas for a large number of relevant pathogens. It represents a first step towards more comprehensive analyses for comparing cost-effectiveness of AMR interventions at the local level as well as more harmonised analyses at the global level.ConclusionThis is the first full AMR costing framework to be developed for bacterial pathogens in human and animal health and the environment. It aims to provide guidance on the data items necessary to calculate AMR costs in a global, One Health perspective to facilitate harmonized, full economic analyses. It is only through building a realistic cost picture that we can make informed decisions about potential strategies and political priorities.

Mutations in the MPL gene encoding the human thrombopoietin receptor (TpoR) drive sporadic and familial essential thrombocythemias (ETs). We identified 2 ET patients harboring double mutations in cis in MPL, namely, L498W-H499C and H499Y-S505N. Using biochemical and signaling assays along with partial saturation mutagenesis, we showed that L498W is an activating mutation potentiated by H499C and that H499C and H499Y enhance the activity of the canonical S505N mutation. L498W and H499C can activate a truncated TpoR mutant, which lacks the extracellular domain, indicating these mutations act on the transmembrane (TM) cytosolic domain. Using a protein complementation assay, we showed that L498W and H499C strongly drive dimerization of TpoR. Activation by tryptophan substitution is exquisitely specific for position 498. Using structure-guided mutagenesis, we identified upstream amino acid W491 as a key residue required for activation by L498W or canonical activating mutations such as S505N and W515K, as well as by eltrombopag. Structural data point to a common dimerization and activation path for TpoR via its TM domain that is shared between the small-molecule agonist eltrombopag and canonical and novel activating TpoR mutations that all depend on W491, a potentially accessible extracellular residue that could become a target for therapeutic intervention.

Background: Variation in the approaches taken to contain the SARS-CoV-2 (COVID-19) pandemic at country level has been shaped by economic and political considerations, technical capacity, and assumptions about public behaviours. To address the limited application of learning from previous pandemics, this study aimed to analyse perceived facilitators and inhibitors during the pandemic and to inform the development of an assessment tool for pandemic response planning. Methods: A cross-sectional electronic survey of health and non-healthcare professionals (5 May - 5 June 2020) in six languages, with respondents recruited via email, social media and website posting. Participants were asked to score inhibitors (-10 to 0) or facilitators (0 to +10) impacting country response to COVID-19 from the following domains – Political, Economic, Sociological, Technological, Ecological, Legislative, and wider Industry (the PESTELI framework). Participants were then asked to explain their responses using free text. Descriptive and thematic analysis was followed by triangulation with the literature and expert validation to develop the assessment tool, which was then compared with four existing pandemic planning frameworks. Findings: 928 respondents from 66 countries (57% healthcare professionals) participated. Political and economic influences were consistently perceived as powerful negative forces and technology as a facilitator across high- and low-income countries. The 103-item tool developed for guiding rapid situational assessment for pandemic planning is comprehensive when compared to existing tools and highlights the interconnectedness of the 7 domains. Interpretation: The tool developed and proposed addresses the problems associated with decision making in disciplinary silos and offers a means to refine future use of epidemic modelling. Funding Statement: This study did not receive any external funding. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the Joint Research Compliance Office, Imperial College London (ICREC reference: 20IC5947).

[Objectives/purpose] The costs attributable to antimicrobial resistance (AMR) remain theoretical and largely unspecified. Current figures fail to capture the full health and economic burden caused by AMR across human, animal, and environmental health; historically many studies have considered only direct costs associated with human infection from a hospital perspective, primarily from high-income countries. The Global Antimicrobial Resistance Platform for ONE-Burden Estimates (GAP-ON€) network has developed a framework to help guide AMR costing exercises in any part of the world as a first step towards more comprehensive analyses for comparing AMR interventions at the local level as well as more harmonized analyses for quantifying the full economic burden attributable to AMR at the global level., [Methods] GAP-ON€ (funded under the JPIAMR 8th call (Virtual Research Institute) is composed of 19 international networks and institutions active in the field of AMR. For this project, the Network operated by means of Delphi rounds, teleconferences and face-to-face meetings. The resulting costing framework takes a bottom-up approach to incorporate all relevant costs imposed by an AMR bacterial microbe in a patient, in an animal, or in the environment up through to the societal level., [Results] The framework itemizes the epidemiological data as well as the direct and indirect cost components needed to build a realistic cost picture for AMR. While the framework lists a large number of relevant pathogens for which this framework could be used to explore the costs, the framework is sufficiently generic to facilitate the costing of other resistant pathogens, including those of other aetiologies., [Conclusion] In order to conduct cost-effectiveness analyses to choose amongst different AMR-related interventions at local level, the costing of AMR should be done according to local epidemiological priorities and local health service norms. Yet the use of a common framework across settings allows for the results of such studies to contribute to cumulative estimates that can serve as the basis of broader policy decisions at the international level such as how to steer R&D funding and how to prioritize AMR amongst other issues. Indeed, it is only by building a realistic cost picture that we can make informed decisions on how best to tackle major health threats., The creation of the GAP-ONE Network was supported under the framework of the Joint Programming Initiative on Antimicrobial Resistance and funded by the Italian Ministry of Health, within the JPIAMR 8th call, Virtual Research Initiative, 2018.