| 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. |
- 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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| 4. |
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| 5. |
- 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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| 6. |
- 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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| 7. |
- Kepp, Kasper P., et al.
(författare)
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Panel stacking is a threat to consensus statement validity
- 2024
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier. - 0895-4356 .- 1878-5921. ; 173
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Tidskriftsartikel (refereegranskat)abstract
- Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.
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| 8. |
- 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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| 9. |
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| 10. |
- Bellani, Gabriele, et al.
(författare)
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Shape effects on turbulent modulation by large nearly neutrally buoyant particles
- 2012
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Ingår i: Journal of Fluid Mechanics. - : Cambridge University Press (CUP). - 0022-1120 .- 1469-7645. ; 712, s. 41-60
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Tidskriftsartikel (refereegranskat)abstract
- We investigate dilute suspensions of Taylor-microscale-sized particles in homogeneous isotropic turbulence. In particular, we focus on the effect of particle shape on particle-fluid interaction. We conduct laboratory experiments using a novel experimental technique to simultaneously measure the kinematics of fluid and particle phases. This uses transparent particles having the same refractive index as water, whose motion we track via embedded optical tracers. We compare the turbulent statistics of a single-phase flow to the turbulent statistics of the fluid phase in a particle-laden suspension. Two suspensions are compared, one in which the particles are spheres and the other in which they are prolate ellipsoids with aspect ratio 2. We find that spherical particles at volume fraction phi(v) = 0.14% reduce the turbulent kinetic energy (TKE) by 15% relative to the single-phase flow. At the same volume fraction (and slightly smaller total surface area), ellipsoidal particles have a much smaller effect: they reduce the TKE by 3% relative to the single-phase flow. Spectral analysis shows the details of TKE reduction and redistribution across spatial scales: spherical particles remove energy from large scales and reinsert it at small scales, while ellipsoids remove relatively less TKE from large scales and reinsert relatively more at small scales. Shape effects are far less evident in the statistics of particle rotation, which are very similar for ellipsoids and spheres. Comparing these with fluid enstrophy statistics, we find that particle rotation is dominated by velocity gradients on scales much larger than the particle characteristic length scales.
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| 11. |
- Bellani, Gabriele, et al.
(författare)
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Turbulence modulation and rotational dynamics of large nearly neutrally buoyant particles in homogeneous isotropic turbulence
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This paper is an experimental investigation of turbulence modulation effects by Taylor-scale size particles in the dilute regime. Experiments are performed on a turbulence tank able to provide Homogeneous Isotropic Turbulence at Reλ ≈ 270. A novel experimental technique capable of simultaneously measuring rotational rates of arbitrarily shaped particles and fluid velocity using standard Stereoscopic Particle Image Velocimetry (Stereo-PIV) and Index-of-Refracion matching is presented here. Particles of the same IoR of water with embedded tracers allowed the measurement of the velocity of the portion of particles in the measurement plane. A novel algorithm based on the assumption of solid body rotation, is then used to extract particle rotation rates. We compare the results from two particle shapes to the single phase measurements: spherical and ellipsoidal particles with aspect ratio 2. It is found that spherical particles provide a 15% turbulence reduction, about five times more than what is provided by ellipsoidal particles at the same volume fraction (φv ≈ 0.1%), and with less particle surface area available. These result suggest that there might be an turbulence production mechanism for ellipsoidal particles that is not present for spheres. This hypothesis is supported by spectral analysis. Pivoting effect is observed for both spherical and ellipsoidal particles, but for the latter, the reduction in the small wavenumber region is less evident. Preliminary results of statistics of rotational rates shows that ellipsoidal particles tend to have an enhanced rotational velocity as compared to spheres.
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| 12. |
- 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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| 13. |
- MacKinnon, M. C., et al.
(författare)
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Increasing incidence and antimicrobial resistance in Escherichia coli bloodstream infections: a multinational population-based cohort study
- 2021
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Ingår i: Antimicrobial Resistance and Infection Control. - : Springer Science and Business Media LLC. - 2047-2994. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Escherichia coli is an important pathogen in humans and is the most common cause of bacterial bloodstream infections (BSIs). The objectives of our study were to determine factors associated with E. coli BSI incidence rate and third-generation cephalosporin resistance in a multinational population-based cohort. Methods We included all incident E. coli BSIs (2014-2018) from national (Finland) and regional (Australia [Canberra], Sweden [Skaraborg], and Canada [Calgary, Sherbrooke, and western interior]) surveillance. Incidence rates were directly age and sex standardized to the European Union 28-country 2018 population. Multivariable negative binomial and logistic regression models estimated factors significantly associated with E. coli BSI incidence rate and third-generation cephalosporin resistance, respectively. The explanatory variables considered for inclusion in both models were year (2014-2018), region (six areas), age (< 70-years-old and >= 70-years-old), and sex (female and male). Results We identified 31,889 E. coli BSIs from 40.7 million person-years of surveillance. Overall and third-generation cephalosporin-resistant standardized rates were 87.1 and 6.6 cases/100,000 person-years, respectively, and increased 14.0% and 40.1% over the five-year study. Overall, 7.8% (2483/31889) of E. coli BSIs were third-generation cephalosporin-resistant. Calgary, Canberra, Sherbrooke, and western interior had significantly lower E. coli BSI rates compared to Finland. The significant association between age and E. coli BSI rate varied with sex. Calgary, Canberra, and western interior had significantly greater odds of third-generation cephalosporin-resistant E. coli BSIs compared to Finland. Compared to 2014, the odds of third-generation cephalosporin-resistant E. coli BSIs were significantly increased in 2016, 2017, and 2018. The significant association between age and the odds of having a third-generation cephalosporin-resistant E. coli BSI varied with sex. Conclusions Increases in overall and third-generation cephalosporin-resistant standardized E. coli BSI rates were clinically important. Overall, E. coli BSI incidence rates were 40-104% greater than previous investigations from the same study areas. Region, sex, and age are important variables when analyzing E. coli BSI rates and third-generation cephalosporin resistance in E. coli BSIs. Considering E. coli is the most common cause of BSIs, this increasing burden and evolving third-generation cephalosporin resistance will have an important impact on human health, especially in aging populations.
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| 14. |
- MacKinnon, M. C., et al.
(författare)
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Mortality in Escherichia coli bloodstream infections: a multinational population-based cohort study
- 2021
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Ingår i: Bmc Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Escherichia coli is the most common cause of bloodstream infections (BSIs) and mortality is an important aspect of burden of disease. Using a multinational population-based cohort of E. coli BSIs, our objectives were to evaluate 30-day case fatality risk and mortality rate, and determine factors associated with each. Methods During 2014-2018, we identified 30-day deaths from all incident E. coli BSIs from surveillance nationally in Finland, and regionally in Sweden (Skaraborg) and Canada (Calgary, Sherbrooke, western interior). We used a multivariable logistic regression model to estimate factors associated with 30-day case fatality risk. The explanatory variables considered for inclusion were year (2014-2018), region (five areas), age (< 70-years-old, >= 70-years-old), sex (female, male), third-generation cephalosporin (3GC) resistance (susceptible, resistant), and location of onset (community-onset, hospital-onset). The European Union 28-country 2018 population was used to directly age and sex standardize mortality rates. We used a multivariable Poisson model to estimate factors associated with mortality rate, and year, region, age and sex were considered for inclusion. Results From 38.7 million person-years of surveillance, we identified 2961 30-day deaths in 30,923 incident E. coli BSIs. The overall 30-day case fatality risk was 9.6% (2961/30923). Calgary, Skaraborg, and western interior had significantly increased odds of 30-day mortality compared to Finland. Hospital-onset and 3GC-resistant E. coli BSIs had significantly increased odds of mortality compared to community-onset and 3GC-susceptible. The significant association between age and odds of mortality varied with sex, and contrasts were used to interpret this interaction relationship. The overall standardized 30-day mortality rate was 8.5 deaths/100,000 person-years. Sherbrooke had a significantly lower 30-day mortality rate compared to Finland. Patients that were either >= 70-years-old or male both experienced significantly higher mortality rates than those < 70-years-old or female. Conclusions In our study populations, region, age, and sex were significantly associated with both 30-day case fatality risk and mortality rate. Additionally, 3GC resistance and location of onset were significantly associated with 30-day case fatality risk. Escherichia coli BSIs caused a considerable burden of disease from 30-day mortality. When analyzing population-based mortality data, it is important to explore mortality through two lenses, mortality rate and case fatality risk.
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