| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 3. |
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| 4. |
- Ashbolt, N. J., et al.
(författare)
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Human Health Risk Assessment (HHRA) for Environmental Development and Transfer of Antibiotic Resistance
- 2013
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:9, s. 993-1001
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. OBJECTIVE: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of anti-biotic treatment caused by antibiotic-resistant pathogens. METHODS: The authors participated in a workshop held 4-8 March 2012 in Quebec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development "hot spots," exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. DISCUSSION: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental " hot spot" compartments; and c) modifying traditional dose-response approaches to address doses of ARB for various health outcomes and pathways. CONCLUSIONS: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multi-criteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.
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| 5. |
- Botvinik-Nezer, Rotem, et al.
(författare)
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Variability in the analysis of a single neuroimaging dataset by many teams
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
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Tidskriftsartikel (refereegranskat)abstract
- Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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| 6. |
- Pruden, A., et al.
(författare)
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Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment
- 2013
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:8, s. 878-885
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. OBJECTIVE: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. METHODS: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. DISCUSSION: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stake-holders and promote action. CONCLUSIONS: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action.
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| 7. |
- West, Jay B., et al.
(författare)
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Comparison and evaluation of retrospective intermodality image registration techniques
- 1997
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Ingår i: SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. ; , s. 332-347
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Konferensbidrag (refereegranskat)abstract
- All retrospective image registration methods have attached to them some intrinsic estimate of registration error. However, this estimate of accuracy may not always be a good indicator of the distance between actual and estimated positions of targets within the cranial cavity. This paper describes a project whose principal goal is to use a prospective method based on fiducial markers as a ’gold standard’ to perform an objective, blinded evaluation of the accuracy of several retrospective image-to-image registration techniques. Image volumes of three modalities – CT, MR, and PET – were taken of patients undergoing neurosurgery at Vanderbilt University Medical Center. These volumes had all traces of the fiducial markers removed, and were provided to project collaborators outside Vanderbilt, who then performed retrospective registrations on the volumes, calculating transformations from CT to MR and/or from PET to MR, and communicated their transformations to Vanderbilt where the accuracy of each registration was evaluated. In this evaluation the accuracy is measured at multiple ’regions of interest,’ i.e. areas in the brain which would commonly be areas of neurological interest. A region is defined in the MR image and its centroid C is determined. Then the prospective registration is used to obtain the corresponding point C’ in CT or PET. To this point the retrospective registration is then applied, producing C’ in MR. Statistics are gathered on the target registration error (TRE), which is the disparity between the original point C and its corresponding point C’. A second goal of the project is to evaluate the importance of correcting geometrical distortion in MR images, by comparing the retrospective TRE in the rectified images, i.e., those which have had the distortion correction applied, with that of the same images before rectification. This paper presents preliminary results of this study along with a brief description of each registration technique and an estimate of both preparation and execution time needed to perform the registration.
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| 8. |
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| 9. |
- Devaux, Yvan, et al.
(författare)
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Association of circulating MicroRNA-124-3p levels with outcomes after out-of-hospital cardiac arrest : A substudy of a randomized clinical trial
- 2016
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Ingår i: JAMA Cardiology. - : American Medical Association (AMA). - 2380-6583. ; 1:3, s. 305-313
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The value of microRNAs (miRNAs) as biomarkers has been investigated in various clinical contexts. Initial small-scale studies suggested that miRNAs might be useful indicators of outcome after cardiac arrest. OBJECTIVE: To address the prognostic value of circulating miRNAs in a large cohort of comatose patients with out-of-hospital cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: This substudy of the Target Temperature Management After Cardiac Arrest (TTM) trial, a multicenter randomized, parallel-group, assessor-blinded clinical trial, compared the 6-month neurologic outcomes and survival of patients with cardiac arrest after targeted temperature management at 33°C or 36°C. Five hundred seventy-nine patients who survived the first 24 hours after the return of spontaneous circulation and who had blood samples available for miRNA assessment were enrolled from 29 intensive care units in 9 countries from November 11, 2010, to January 10, 2013. Final follow-up was completed on July 3, 2013, and data were assessed from February 1, 2014, to February 1, 2016. INTERVENTIONS: Blood sampling at 48 hours after the return of spontaneous circulation. MAINOUTCOMES AND MEASURES: The primary end point was poor neurologic outcomeat6 months (cerebral performance category score, 3 [severe neurologic sequelae], 4 [coma], or 5 [death]). The secondary end point was survival until the end of the trial. Circulating levels of miRNAs were measured by sequencing and polymerase chain reaction. RESULTS: Of the 579 patients (265 men [80.3%]; mean [SD] age, 63 [12] years), 304 patients (52.5%) hada poor neurologic outcomeat 6months. Inthe discovery phase with short RNA sequencing in 50 patients, the brain-enriched miR-124-3p level was identified as a candidate prognostic variable for neurologic outcomes. In the validation cohort of 529 patients, mean (SD) levels of miR-124-3p were higher in patients with a poor outcome (8408 [12 465] copies/μL) compared with patients with a good outcome (1842 [3025] copies/μL; P < .001). The miR-124-3p level was significantly associated with neurologic outcomes in the univariable analysis (odds ratio, 6.72; 95% CI, 4.53-9.97). In multivariable analyses using logistic regression, miR-124-3p levels were independently associated with neurologic outcomes (odds ratio, 1.62; 95% CI, 1.13-2.32). In Cox proportional hazards models, higher levels of miR-124-3p were significantly associated with lower survival (hazard ratio, 1.63; 95% CI, 1.37-1.93). CONCLUSIONS AND RELEVANCE: Levels of miR-124-3p can be used as prognostication tools for neurologic outcome and survival after out-of-hospital cardiac arrest. Thus, miRNA levels may aid in tailoring health care for patients with cardiac arrest.
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| 10. |
- Finley, R. L., et al.
(författare)
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The Scourge of Antibiotic Resistance: The Important Role of the Environment
- 2013
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 57:5, s. 704-710
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Forskningsöversikt (refereegranskat)abstract
- Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, beta-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.
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