| 1. |
- Fatsis-Kavalopoulos, Nikos, et al.
(författare)
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Potential risks of treating bacterial infections with a combination of β-lactam and aminoglycoside antibiotics : A systematic quantification of antibiotic interactions in E. coli blood stream infection isolates
- 2022
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 78
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTreatment of Blood Stream Infections (BSIs) with a combination of a β-lactam and an aminoglycoside antibiotic is widely used in intensive care units (ICUs) around the world. However, no studies have systematically examined how these drugs interact and potentially influence the antimicrobial efficacy of the overall treatment.MethodsWe collected 500 E. coli isolates from the Uppsala University hospital that were isolated from blood of patients with suspicion of infection. Of those we tested the efficacy of combinations of 2 common β-lactam antibiotics (Ampicillin and Cefotaxime) combined with 2 common aminoglycosides (Gentamicin and Tobramycin) on 254 isolates. The efficacy of all 4 pairwise combinations in inhibiting bacterial growth was then examined on all susceptible strains. That was done by quantifying the Fractional Inhibitory index (FICi), a robust metric for antibiotic combinatorial behaviour, of all possible treatments on every strain. When non additive interactions were identified, results of the original screen were verified with time kill assays. Finally, combination behaviours were analysed for potential cross correlations.FindingsOut of the 4 antibiotic combinations screened none exhibited synergistic effects on any of the 254 strains. On the contrary all 4 exhibited important antagonistic effects on several isolates. Specifically, the combinations of AMP-GEN and CTX-GEN were antagonistic in 1.97% and 1.18% of strains respectively. Similarly, the combinations of AMP-TOB were antagonistic on 0.78% of all strains. PCA analysis revealed that an important factor on the responses to the combination treatments was the choice of a specific aminoglycoside over another. Subsequent cross correlation analysis revealed that the interaction profiles of combinations including the same aminoglycoside are significantly correlated (Spearman's cross correlation test p<0.001).InterpretationThe findings of this study elucidate potential risks of the common combination treatment for blood stream infections. They also demonstrate, previously unquantified metrics on how antibiotics in combination therapies are not interchangeable with others of the same class. Finally, they reiterate the need for case-by-case testing of antibiotic interactions in a clinical setting.
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| 2. |
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| 3. |
- Gorshunov, B. P., et al.
(författare)
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Subterahertz electrodynamics of (TMTSF)(2)X (X = ClO4, PF6) salts
- 2013
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Ingår i: Journal of Experimental and Theoretical Physics. - 1063-7761 .- 1090-6509. ; 116:3, s. 460-466
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Tidskriftsartikel (refereegranskat)abstract
- The terahertz-subterahertz spectra of the complex permittivity and dynamic conductivity of polycrystalline (TMTSF)(2)ClO4 and (TMTSF)(2)PF6 samples are measured quantitatively. The spectra of (TMTSF)(2)ClO4 have absorption lines at frequencies of 7 and 30 cm(-1). The obtained temperature dependences of the line parameters in the range 5-300 K cast some doubt on the earlier concept of their phonon origin. An excitation is detected at temperatures below 20 K in the frequency range near 30 cm(-1), and its nature is related to the activation of a transverse acoustic phonon caused by the folding of the Brillouin zone due to the ordering of noncentrosymmetrical anions below 20 K. An increase in the carrier relaxation rate is found in this temperature range, which indicates a close relation between the electron and phonon subsystems in (TMTSF)(2)ClO4. Sings of additional low-energy excitations that should manifest themselves at frequencies below 1-2 cm(-1) are detected. (TMTSF)(2)PF6 containing centrosymmetrical anions has no absorption lines in the frequency range 3-20 cm(-1) and the temperature range 5-300 K.
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| 4. |
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| 5. |
- Fatsis-Kavalopoulos, Nikos
(författare)
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Precise cell manipulations and imaging of cellular responses : Methods developed using microfluidic, 3D-printing and microfabrication technologies
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is at the heart of biological and medical research to try and understand how cells communicate with each other, and how cells respond to alterations in their environment, including treatment with different drugs. There is in this context a continued need for better methods that allow researchers to precisely manipulate cells and their microenvironment and to study the resulting responses using high-resolution live microscopy. This thesis presents the development and implementation of several devices that addresses these needs.A novel microfluidic device called the cell assembly generator (CAGE) was created to generate precisely composed cell clusters of different cell types; the first of its kind. Experimental evidence demonstrated that the CAGE chip can be used to study paracrine signalling in tailor-made cancer cell clusters composed of up to five cells.A high-throughput microfluidic chip for rapid phenotypic antibiotic susceptibility testing was developed and tested using 21 clinical isolates of Klebsiella pneumoniae, Staphylococcus aureus and Escherichia coli against a panel of antibiotics. Stable minimum inhibitory concentration values were obtained from this system within 2-4 hours with high accuracy to the standard method.3D-printing was used to create a modular and affordable time-lapse imaging and incubation system, called ATLIS. This system enables researchers to convert simple inverted microscopes into live cell imaging systems, where images and movies of living cells can be recorded using a regular smartphone.Finally, a strategy was developed for the generation of modular microfluidic systems using 3D-printed moulds for PDMS casting, to enable studies of leukocyte adherence to differentially treated endothelial cell populations in the same field of view and under the same conditions.
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| 6. |
- Guyader, Hugo, 1990-, et al.
(författare)
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Institutional Logics at Play in a Mobility-as-a-Service Ecosystem
- 2021
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Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 13:15
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Tidskriftsartikel (refereegranskat)abstract
- The last decade has brought the transport sector to the forefront of discussions on sustainability and digital innovations: practitioners, researchers, and regulators alike have witnessed the emergence of a wide diversity of shared mobility services. Based on a longitudinal case study of a regional Mobility-as-a-Service (MaaS) ecosystem in Sweden, constituted of a document analysis and 24 semi-structured interviews with 18 representatives from regional authorities, mobility service providers, and other stakeholders from the public and private sectors, this study examines the co-existing and competing institutional logics at play, identified as State logic, Market logic, Sustainability logic, Experimental logic, and Service logic. The analysis reveals that these institutional logics pertain to tensions in the collaboration within the ecosystem’s stakeholders in terms of: (1) finding a common vision and scope for MaaS, (2) establishing a sustainable business model, (3) triggering a behavioral change regarding car travel, (4) being able to find one’s role within the project and to consequently collaborate with other stakeholders, and (5) managing uncertainty through testing and experimenting innovative solutions, which ultimately yielded key learnings about MaaS and the shared mobility ecosystem and its stakeholders. These case study findings, based on an institutional logics framework, provide a novel perspective on emerging ecosystems, from which implications for MaaS developers and further research on shared mobility are drawn.
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| 7. |
- Jones, A Wayne, et al.
(författare)
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Drug poisoning deaths in Sweden show a predominance of ethanol in mono-intoxications, adverse drug-alcohol interactions and poly-drug use
- 2011
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Ingår i: FORENSIC SCIENCE INTERNATIONAL. - : Elsevier Science B.V., Amsterdam.. - 0379-0738. ; 206:1-3, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Over a 10-year period (1998-2007) all deaths in Sweden classified by forensic pathologists as fatal drug poisonings (N = 6894) were retrieved from a toxicology database (TOXBASE) belonging to the National Board of Forensic Medicine. The deaths were further classified as suicides N = 2288 (33%), undetermined N = 2260 (33%) and accidental N = 2346 (34%). The average age (+/- SD) of all victims was 49.1 +/- 15.9 years and men 47.4 +/- 15.6 years were 5-year younger than women 52.2 +/- 15.8 years (p andlt; 0.01). Most of the deceased (78%) were poly-drug users although a single drug (mono-intoxications) was found in 22% of all poisoning deaths (p andlt; 0.001). The number of drugs in blood samples varied from 1 to 12 with a median of 3-4 per case. Mono-intoxication deaths were mostly ethanol-related (N = 976) and the mean and median blood-alcohol concentration (BAC) was 3.06 g/L and 3.10 g/L, respectively. The BAC decreased as the number of additional drugs in blood increased from 2.15 g/L with one drug to 1.25 g/L with 6 or more drugs. The mean (median) concentrations of non-alcohol drugs in mono-intoxication deaths were morphine (N = 93) 0.5 mg/L (0.2 mg/L), amphetamine (N = 39) 2.0 mg/L (1.2 mg/L), dextropropoxyphene (N = 33) 3.9 mg/L (2.9 mg/L), dihydro-propiomazine (N = 32) 1.6 mg/L (1.0 mg/L) and 7-amino-flunitrazepam (N = 28), 0.4 mg/L (0.3 mg/ L). Elevated blood morphine in these poisoning deaths mostly reflected abuse of heroin as verified by finding 6-monoacetyl morphine (6-MAM) in the blood samples. When investigating drug poisoning deaths a comprehensive toxicological analysis is essential although the results do not reveal the extent of prior exposure to drugs or the development of pharmacological tolerance. The concentrations of drugs determined in post-mortem blood are one element in the case. The autopsy report, the police investigation, the findings at the scene and eye-witness statements should all be carefully considered when the cause and manner of death are determined.
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| 8. |
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| 9. |
- Murphy, Laurel E., et al.
(författare)
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Folate and vitamin B-12 in idiopathic male infertility
- 2011
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Ingår i: Asian Journal of Andrology. - : Medknow. - 1008-682X .- 1745-7262. ; 13:6, s. 856-861
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Tidskriftsartikel (refereegranskat)abstract
- Although methylenetetrahydrofolate reductase, a folate enzyme gene, has been associated with idiopathic male infertility, few studies have examined other folate-related metabolites and genes. We investigated whether idiopathic male infertility is associated with variants in folate, vitamin B-12 (B12) and total homocysteine (tHcy)-related genes and measured these metabolites in blood. We conducted a case-control study that included 153 men with idiopathic infertility and 184 fertile male controls recruited at the Fertility Center and Antenatal Care Center, University Hospital, Malmo and Lund, Sweden. Serum folate, red cell folate (RCF), serum B12, plasma tHcy and semen quality were measured. Subjects were genotyped for 20 common variants in 12 genes related to folate/B12/homocysteine metabolism. Metabolite concentrations and genotype distributions were compared between cases and controls using linear and logistic regression with adjustment for covariates. The phosphatidylethanolamine N-methyltransferase (PEMT) M175V and TCblR rs173665 polymorphisms were significantly associated with infertility (P=0.01 and P=0.009, respectively), but not with semen quality. Among non-users of supplements, infertile men had lower serum folate concentrations than fertile men (12.89 vs. 14.73 nmol l(-1); P=0.02), but there were no significant differences in RCF, B12 or tHcy. Folate, B12 and tHcy concentrations were not correlated with any semen parameters. This study provides little support for low folate or B12 status in the pathogenesis of idiopathic male infertility. Although additional data are needed to confirm these initial findings, our results suggest that PEMT and TCblR, genes involved in choline and B12 metabolism, merit further investigation in idiopathic male infertility. Asian Journal of Andrology (2011) 13, 856-861; doi: 10.1038/aja.2011.96; published online 22 August 2011
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| 10. |
- Serdyuk, Yuriy, 1963, et al.
(författare)
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Computer Simulations of Discharges along Insulator Surfaces
- 2017
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Ingår i: Annual Report - Conference on Electrical Insulation and Dielectric Phenomena, CEIDP. - 0084-9162. ; Volume 2017-October, s. 26-29
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Konferensbidrag (refereegranskat)abstract
- Development of streamer discharges in air along surfaces of solid insulators is analyzed by means of computer simulations utilizing drift-diffusion model of charge transport in discharge plasma. The results are presented for smooth cylindrical insulator and insulator with a shed. Variations of electron densities, space charges and electric fields profiles during discharge propagation are reported. The influence of a protective shed on the insulator on the discharge development is highlighted.
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