| 1. |
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| 2. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 5. |
- Carlsson, Sigrid, 1982, et al.
(författare)
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Who and when should we screen for prostate cancer? Interviews with key opinion leaders.
- 2015
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Ingår i: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer screening using prostate-specific antigen (PSA) is highly controversial. In this Q & A, Guest Editors for BMC Medicine's 'Spotlight on Prostate Cancer' article collection, Sigrid Carlsson and Andrew Vickers, invite some of the world's key opinion leaders to discuss who, and when, to screen for prostate cancer. In response to the points of view from the invited experts, the Guest Editors summarize the experts' views and give their own personal opinions on PSA screening.
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| 6. |
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| 7. |
- Bruinsma, Sophie M, et al.
(författare)
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Expert consensus document : Semantics in active surveillance for men with localized prostate cancer - results of a modified Delphi consensus procedure
- 2017
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Ingår i: Nature Reviews Urology. - : Springer Science and Business Media LLC. - 1759-4820 .- 1759-4812. ; 14:5, s. 312-322
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Forskningsöversikt (refereegranskat)abstract
- Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if ≥70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.
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| 8. |
- Carroll, Harriet A., et al.
(författare)
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Hydration status affects thirst and salt preference but not energy intake or postprandial ghrelin in healthy adults : A randomised crossover trial
- 2019
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Ingår i: Physiology and Behavior. - : Elsevier BV. - 0031-9384. ; 212
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few studies have investigated the effect of hydration status on appetite for food in healthy adults. Prior work suggests hydration status does not alter appetite or energy intake, with mixed findings regarding appetite hormone secretion. However, an extensive investigation into both the psychological and physiological appetitive responses to hydration status has never been conducted. Objective: To investigate the effect of hydration status on multiple facets of appetite. Design: After 3 days pre-trial standardization, a range of appetite tasks were conducted when hypohydrated (HYPO) and euhydrated (EUHY) in 16 healthy participants (8 men). Hydration status was manipulated via dehydration in a heat tent for 60 min and subsequent fluid restriction (HYPO) or replacement (EUHY). The next day, a food reward computer task was completed followed by an ad libitum pasta meal. Pre- and post-prandial visual analogue scales assessing hunger, fullness, and flavour desires (sweet, salty, savoury and fatty) were additionally completed. Blood samples were taken the previous day before the hydration interventions in a euhydrated state, and in the fasted and post-prandial state during HYPO and EUHY. Results: HYPO induced -1.9 ± 1.2% body mass change, compared to -0.2 ± 0.6%, with accompanying changes in markers of hypohydration which were not seen during EUHY. A higher desire for foods was associated with a higher water content but the association was weaker in EUHY compared to HYPO, (β= -0.33 mm/g of food water content, p < 0.001) in the food reward task. Visual analogue scales showed similar hunger and fullness between interventions, but during HYPO there was consistently higher thirst (average range in difference 27–32 mm across all time points) and lower fasted desire for salt (−23, 95% CI −10, −35 mm). Ad libitum energy intake (HYPO 1953 ± 742 kJ, EUHY 2027 ± 926 kJ; p = 0.542) and post-prandial ghrelin concentrations (HYPO 180 ± 65 pg mL−1, EUHY 188 ± 71 pg mL−1; p = 0.736) were similar by hydration status. Conclusions: An acute manipulation to hydration status altered desire for salt and foods of differing water contents, but did not influence energy intake at an ad libitum pasta meal. Further research should investigate whether these appetites would alter food choice.
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| 9. |
- Carroll, Joseph, et al.
(författare)
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Biocultural Theory: The Current State of Knowledge
- 2017
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Ingår i: Evolutionary Behavioral Sciences. - : American Psychological Association (APA). - 2330-2925 .- 2330-2933. ; 11:1, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Biocultural theory is an integrative research program designed to investigate the causal interactions between biological adaptations and cultural constructions. From the biocultural perspective, cultural processes are rooted in the biological necessities of the human life cycle: specifically human forms of birth, growth, survival, mating, parenting, and sociality. Conversely, from the biocultural perspective, human biological processes are constrained, organized, and developed by culture, which includes technology, culturally specific socioeconomic and political structures, religious and ideological beliefs, and artistic practices such as music, dance, painting, and storytelling. Establishing biocultural theory as a program that self-consciously encompasses the different particular forms of human evolutionary research could help scholars and scientists envision their own specialized areas of research as contributions to a coherent, collective research program. This article argues that a mature biocultural paradigm needs to be informed by at least 7 major research clusters: (a) gene-culture coevolution; (b) human life history theory; (c) evolutionary social psychology; (d) anthropological research on contemporary hunter-gatherers; (e) biocultural socioeconomic and political history; (f) evolutionary aesthetics; and (g) biocultural research in the humanities (religions, ideologies, the history of ideas, and the arts). This article explains the way these research clusters are integrated in biocultural theory, evaluates the level of development in each cluster, and locates current biocultural theory within the historical trajectory of the social sciences and the humanities.
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| 10. |
- Mah, Jean K, et al.
(författare)
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A multinational study on motor function in early-onset FSHD.
- 2018
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Ingår i: Neurology. - 1526-632X. ; 90:15
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Tidskriftsartikel (refereegranskat)abstract
- To investigate motor function associations with age, sex, and D4Z4 repeats among participants with early-onset facioscapulohumeral muscular dystrophy (FSHD) type 1 as defined by weakness onset before 10 years of age.We collected standardized motor assessments, including manual muscle testing (MMT), quantitative muscle testing, functional motor evaluations, and clinical severity scores (CSSs), at 12 Cooperative International Neuromuscular Research Group centers. To measure associations, we used linear regression models adjusted for sex, evaluation age, age at onset of weakness, and D4Z4 repeats.Among 52 participants (60% female, mean age 22.9 ± 14.7 years), weakness was most pronounced in the shoulder and abdominal musculature. Older enrollment age was associated with greater CSSs (p = 0.003). When adjusted for enrollment age, sex, and D4Z4 repeats, younger age at onset of facial weakness was associated with greater CSSs, slower velocities in timed function tests, and lower MMT scores (p < 0.05).Significant clinical variability was observed in early-onset FSHD. Earlier age at onset of facial weakness was associated with greater disease severity. Longitudinal assessments are needed to determine the rate of disease progression in this population.
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| 11. |
- Marini, Lorenzo, et al.
(författare)
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Climate drivers of bark beetle outbreak dynamics in Norway spruce forests
- 2017
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Ingår i: Ecography. - : Wiley. - 0906-7590 .- 1600-0587. ; 40:12, s. 1426-1435
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Tidskriftsartikel (refereegranskat)abstract
- Bark beetles are among the most devastating biotic agents affecting forests globally and several species are expected to be favored by climate change. Given the potential interactions of insect outbreaks with other biotic and abiotic disturbances, and the potentially strong impact of changing disturbance regimes on forest resources, investigating climatic drivers of destructive bark beetle outbreaks is of paramount importance. We analyzed 17 time-series of the amount of wood damaged by Ips typographus, the most destructive pest of Norway spruce forests, collected across 8 European countries in the last three decades. We aimed to quantify the relative importance of key climate drivers in explaining timber loss dynamics, also testing for possible synergistic effects. Local outbreaks shared the same drivers, including increasing summer rainfall deficit and warm temperatures. Large availability of storm-felled trees in the previous year was also strongly related to an increase in timber loss, likely by providing an alternative source of breeding material. We did not find any positive synergy among outbreak drivers. On the contrary, the occurrence of large storms reduced the positive effect of warming temperatures and rainfall deficit. The large surplus of breeding material likely boosted I. typographus population size above the density threshold required to colonize and kill healthy trees irrespective of other climate triggers. Importantly, we found strong negative density dependence in I. typographus that may provide a mechanism for population decline after population eruptions. Generality in the effects of complex climatic events across different geographical areas suggests that the large-scale drivers can be used as early warning indicators of increasing local outbreak probability. Ecography
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| 12. |
- Søgaard Jørgensen, Peter, et al.
(författare)
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Antibiotic and pesticide susceptibility and the Anthropocene operating space
- 2018
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 1:11, s. 632-641
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Forskningsöversikt (refereegranskat)abstract
- Rising levels of antimicrobial and pesticide resistance increasingly undermine human health and systems for biomass production, and emphasize the sustainability challenge of preserving organisms susceptible to these biocides. In this Review, we introduce key concepts and examine dynamics of biocide susceptibility that must be governed to address this challenge. We focus on the impact of biocides on the capacity of susceptible organisms to prevent spread of resistance, and we then review how biocide use affects a broader suite of ecosystem services. Finally, we introduce and assess the state of what we term the Anthropocene operating space of biocide susceptibility, a framework for assessing the potential of antibiotic and pesticide resistance to undermine key functions of human society. Based on current trends in antibiotic, insecticide and herbicide resistance, we conclude that the states of all six assessed variables are beyond safe zones, with three variables surpassed regionally or globally.
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| 13. |
- Søgaard Jørgensen, Peter, et al.
(författare)
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Changing antibiotic resistance : sustainability transformation to a pro-microbial planet
- 2017
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 25, s. 66-76
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Forskningsöversikt (refereegranskat)abstract
- Decades of overuse, misuse, and environmental antibiotic pollution has increased the global pool of resistant bacteria. With estimates of hundreds of thousands of annual human deaths and a lack of new drugs to replace old ones, antimicrobial resistance probably constitutes one of the greatest human health and sustainability challenges of the 21st century. To safeguard treatable infections, a deliberate social-ecological transformation is needed toward stewardship of the global microbiome and long-term sustainable use of antibiotics. We review the foundation for such a transformation using recent insights from sustainability science, evolutionary biology and health, and the understanding of human interactions with microbes as two intertwined complex adaptive systems. A coherent strategy should acknowledge humans as the source of the world's strongest evolutionary force, reflect that antibiotics are building blocks of modern health systems, and strive to build social-ecological resilience to minimize levels of resistance and avoid over dependency on innovation of new drugs. Bottom up opportunities for seeding the transformation include participatory monitoring and stewardship of our personal and environmental microbiomes, as well as collective consumer action. Top down priorities include regular international institutions to coordinate multi-level action.
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| 14. |
- Søgaard Jørgensen, Peter, et al.
(författare)
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Evolution in the Anthropocene : Informing Governance and Policy
- 2019
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Ingår i: Annual Review of Ecology, Evolution and Systematics. - : Annual Reviews. - 1543-592X .- 1545-2069. ; 50, s. 527-546
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Forskningsöversikt (refereegranskat)abstract
- The Anthropocene biosphere constitutes an unprecedented phase in the evolution of life on Earth with one species, humans, exerting extensive control. The increasing intensity of anthropogenic forces in the twenty-first century has widespread implications for attempts to govern both human-dominated ecosystems and the last remaining wild ecosystems. Here, we review how evolutionary biology can inform governance and policies in the Anthropocene, focusing on five governance challenges that span biodiversity, environmental management, food and other biomass production, and human health. The five challenges are: (a) evolutionary feedbacks, (b) maintaining resilience, (c) alleviating constraints, (d) coevolutionary disruption, and (e) biotechnology. Strategies for governing these dynamics will themselves have to be coevolutionary, as eco-evolutionary and social dynamics change in response to each other.
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| 15. |
- Van Hemelrijck, Mieke, et al.
(författare)
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Reasons for Discontinuing Active Surveillance : Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 75:3, s. 523-531
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Tidskriftsartikel (refereegranskat)abstract
- Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4–28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0–13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5–2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4–2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for <5 yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4–28.6%) at 5 yr and 38.2% (95% CI: 36.7–39.9%) at 10 yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up. Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. Patient summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5 yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS.
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| 16. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 17. |
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| 18. |
- Wernli, Didier, et al.
(författare)
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Mapping global policy discourse on antimicrobial resistance
- 2017
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Ingår i: BMJ Global Health. - : BMJ. - 2059-7908. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- The rising importance of antimicrobial resistance (AMR) to the global health agenda is associated with a growing number of parties voicing their concern about the issue. With more recommendations and policies appearing, understanding the policy process requires making sense of the views, values, interests and goals of each participant. Policy frame analysis provides a method to understand both the scientific view and the actions advocated by global health actors to tackle AMR. Here we review and refine policy frame analyses of AMR using a deductive approach. Among several policy frames previously defined in the field of global health, we identify 'AMR as healthcare', 'AMR as development', 'AMR as innovation' and 'AMR as security' as frequent frames used in dealing with AMR. In addition, we found that 'AMR as One Health' constitutes a recent framing of the topic that seeks to provide an integrated understanding between human and animal health. Each frame originates in distinct scientific fields, conceptualises the main causes of AMR and prioritises different interventions and measurements. Better understanding and integration of these frames into an overarching social and ecological framework will support policy progress in tackling AMR.
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