| 1. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 2. |
- Suzuki, Chikako, et al.
(författare)
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Impact of the first tumor response at eight weeks on overall survival in metastatic breast cancer patients treated with first-line combination chemotherapy
- 2013
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Ingår i: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 30:1
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this was to determine whether the change of size observed at the first response evaluation after initiation of first-line combination chemotherapy correlates with overall survival (OS) in patients with metastatic breast cancer (MBC). The change in size of tumors derived from measurements according to Response Evaluation Criteria In Solid Tumors (RECIST) at the first evaluation on computed tomography (CT) was obtained from a multicenter, randomized phase III trial ("TEX trial," n = 287) comparing treatment with a combination of epirubicin and paclitaxel alone or with capecitabine (TEX). Cox regression and Kaplan-Meier analyses were performed to evaluate the correlations between the first change in tumor size, response according to RECIST and OS. Data from CT evaluations of 233 patients were available. Appearance of new lesions or progression of non-target lesions (new/non-target) indicated short OS by univariable regression analysis (HR 3.76, 95 % CI 1.90-7.42, p andlt; 0.001). A decrease by andgt;30 % at this early time point was prognostic favorable (HR 0.69, 95 % CI 0.49-0.98, p = 0.04) and not significantly less than the best overall response according to RECIST. After adjustment for previous adjuvant treatment and the treatment given within the frame of the randomized trial, OS was still significantly shorter in patients with new/non-target lesions after a median 8 weeks of treatment (HR 4.41, 95 % CI 2.74-7.11, p andlt; 0.001). Disease progression at the first evaluation correlates with OS in patients with MBC treated with first-line combination chemotherapy. The main reason for early disease progression was the appearance of new lesions or progression of non-target lesions. These patients had poor OS even though more lines of treatment were available. Thus, these factors should be focused on in the response evaluations besides tumor size changes.
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| 3. |
- Bengtsson, Stina, et al.
(författare)
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Sequence types and plasmid carriage of uropathogenic Escherichia coli devoid of phenotypically detectable resistance
- 2012
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 67:1, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Plasmids play a major role in the dissemination of antibiotic resistance, and several studies have shown the association between specific resistance mechanisms and certain plasmid types and/or Escherichia coli lineages. This study describes the distribution of plasmids, replicon types, sequence types (STs) and ST complexes (STCs) of E. coli devoid of phenotypic resistance to 24 antibiotics. Methods Eighty E. coli isolates from urinary tract infections from four European countries were selected because of their lack of phenotypically detectable antibiotic resistance. The isolates were characterized to the phylogenetic group level using PCR and to ST by multilocus sequence typing. Plasmid carriage was assessed using S1 nuclease PFGE profiling and PCR-based replicon typing. Results Plasmids were detected in only 38/80 (47%) of the isolates; one (n = 18), two (n = 14), three (n = 5) and four (n = 1) plasmids. Six different replicon types were identified, the most common being a combination of IncFII and IncFIB. Most isolates belonged to phylogenetic group B2 and STC73 (n = 20), STC95 (n = 7) and ST420 (n = 6). A high proportion of STC73 isolates (75%) was devoid of plasmids. No association could be found between specific STs and replicon type. Conclusions A large proportion of E. coli strains phenotypically devoid of antibiotic resistance were plasmid naive. Those isolates that harboured plasmids displayed replicon types similar to those of resistant isolates, but the distributions of STs and STCs were different. This may indicate chromosomally encoded mechanisms important for the stabilization of plasmids harbouring antibiotic resistance.
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| 4. |
- Brolund, Alma, et al.
(författare)
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Molecular Characterisation of Trimethoprim Resistance in Escherichia coli and Klebsiella pneumoniae during a 2 year intervention on Trimethoprim use
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:2, s. e9233-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Trimethoprim resistance is increasing in Enterobacteriaceae. In 2004-2006 an intervention on trimethoprim use was conducted in Kronoberg County, Sweden, resulting in 85% reduction in trimethoprim prescriptions. We investigated the distribution of dihydrofolate reductase (dfr)-genes and integrons in Escherichia coli and Klebsiella pneumoniae and the effect of the intervention on this distribution. METHODOLOGY/PRINCIPAL FINDINGS: Consecutively isolated E. coli (n = 320) and K. pneumoniae (n = 54) isolates phenotypically resistant to trimethoprim were studied. All were investigated for the presence of dfrA1, dfrA5, dfrA7, dfrA8, dfrA12, dfrA14, dfrA17 and integrons class I and II. Isolates negative for the seven dfr-genes (n = 12) were also screened for dfr2d, dfrA3, dfrA9, dfrA10, dfrA24 and dfrA26. These genes accounted for 96% of trimethoprim resistance in E. coli and 69% in K. pneumoniae. The most prevalent was dfrA1 in both species. This was followed by dfrA17 in E. coli which was only found in one K. pneumoniae isolate. Class I and II Integrons were more common in E. coli (85%) than in K. pneumoniae (57%). The distribution of dfr-genes did not change during the course of the 2-year intervention. CONCLUSIONS/SIGNIFICANCE: The differences observed between the studied species in terms of dfr-gene and integron prevalence indicated a low rate of dfr-gene transfer between these two species and highlighted the possible role of narrow host range plasmids in the spread of trimethoprim resistance. The stability of dfr-genes, despite large changes in the selective pressure, indirectly suggests a low fitness cost of dfr-gene carriage.
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| 5. |
- Finné, Martin, et al.
(författare)
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Climate in the eastern Mediterranean, and adjacent regions, during the past 6000 years - A review
- 2011
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 0305-4403 .- 1095-9238. ; 38:12, s. 3153-3173
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Forskningsöversikt (refereegranskat)abstract
- The eastern Mediterranean, with its long archaeological and historical records, provides a unique opportunity to study human responses to climate variability. We review paleoclimate data and reconstructions from the region with a focus on the last 6000 years. We aim to provide an up-to-date source of information on climate variability and to outline present limitations and future opportunities. The review work is threefold: (1) literature review, (2) spatial and temporal analysis of proxy records, and (3) statistical estimation of uncertainties in present paleoclimate reconstructions (temperature, C). On a regional scale the review reveals a wetter situation from 6000 to 5400 yrs BP (note: all ages in this paper are in calibrated years before present (i.e. before 1950), abbreviated yrs BP, unless otherwise stated). This is followed by a less wet period leading up to one of fully-developed aridity from c. 4600 yrs BP. There is a need for more high-resolution paleoclimate records, in order to (i) better understand regional patterns and trends versus local climate variability and to (ii) fill the gap of data from some regions, such as the Near East, Greece and Egypt. Further, we evaluate the regional occurrence of a proposed widespread climate event at 4200 yrs BP. This proposed climate anomaly has been used to explain profound changes in human societies at different locations in the region around this time. We suggest that although aridity was widespread around 4200 yrs BP in the eastern Mediterranean region, there is not enough evidence to support the notion of a climate event with rapidly drying conditions in this region.
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| 6. |
- Finné, Martin, 1981-
(författare)
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Climate in the eastern Mediterranean during the Holocene and beyond – A Peloponnesian perspective
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis contributes increased knowledge about climate variability during the late Quaternary in the eastern Mediterranean. Results from a paleoclimate review reveal that regional wetter conditions from 6000 to 5400 years BP were replaced by a less wet period from 5400 to 4600 years BP and to fully arid conditions around 4600 years BP. The data available, however, show that there is not enough evidence to support the notion of a widespread climate event with rapidly drying conditions in the region around 4200 years ago. The review further highlights the lack of paleoclimate data from the archaeologically rich Peloponnese Peninsula. This gap is addressed in this thesis by the provision of new paleoclimate records from the Peloponnese. One stalagmite from Kapsia Cave and two stalagmites from Glyfada Cave were dated and analyzed for stable oxygen (δ18O) and carbon (δ13C) isotopes. The Glyfada record covers a period from ~78 ka to ~37 ka and shows that the climate in this region responded rapidly to changes in temperatures over Greenland. During Greenland stadial (interstadial) conditions colder (warmer) and drier (wetter) conditions are reflected by depleted (enriched) δ13C-values in the speleothems. The Kapsia record covers a period from ~2900 to ~1100 years BP. A comparison between the modern stalagmite top isotopes and meteorological data shows that a main control on stalagmite δ18O is wet season precipitation amount. The δ18O record from Kapsia indicates cyclical humidity changes of close to 500 years, with rapid shifts toward wetter conditions followed by slowly developing aridity. Superimposed on this signal is a centennial signal of precipitation variability. A second speleothem from Kapsia with multiple horizons of fine sediments from past flood events intercalated with the calcite is used to develop a new, quick and non-destructive method for tracing flood events in speleothems by analyzing a thick section with an XRF core scanner.
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| 7. |
- Finné, Martin, et al.
(författare)
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Speleothem evidence for late Holocene climate variability and floods in Southern Greece
- 2014
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Ingår i: Quaternary Research. - : Cambridge University Press (CUP). - 0033-5894 .- 1096-0287. ; 81:2, s. 213-227
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Tidskriftsartikel (refereegranskat)abstract
- We present stable isotope data (delta O-18, delta C-13) from a detrital rich stalagmite from Kapsia Cave, the Peloponnese, Greece. The cave is rich in archeological remains and there are reasons to believe that flooding of the cave has directly affected humans using the cave. Using a combination of U-Th and C-14 dating to constrain a site-specific correction factor for (Th-232/U-238) detrital molar ratio, a linear age model was constructed. The age model shows that the stalagmite grew during the period from ca. 950 BC to ca. AD 830. The stable oxygen record from Kapsia indicates cyclical changes of close to 500 yr in precipitation amount, with rapid shifts towards wetter conditions followed by slowly developing aridity. Superimposed on this signal, wetter conditions are inferred around 850, 700, 500 and 400-100 BC, and around AD 160-300 and AD 770; and driest conditions are inferred to have occurred around 450 BC, AD 100-150 and AD 650. Detrital horizons in the stalagmite indicate that three major floods took place in the cave at 500 BC, 70 BC and AD 450. The stable carbon isotope record reflects changes in biological activity being a result of both climate and human activities. (c) 2014 University of Washington.
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| 8. |
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| 9. |
- Johansson, Åsa, et al.
(författare)
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The detection and verification of carbapenemases using ertapenem and Matrix Assisted Laser Desorption Ionization-Time of Flight
- 2014
-
Ingår i: BMC Microbiology. - : BioMed Central. - 1471-2180. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The increase in carbapenemase producing Enterobacteriaceae and Pseudomonas aeruginosa is a significant threat to modern medicine. A rapid detection of carbapenemase production in Klebsiella pneumoniae and Pseudomonas aeruginosa is of importance for the institution of correct antibiotic treatment and infection control measures.Results: Standardised inoculums of K. pneumoniae or P. aeruginosa were incubated at 37 degrees C with ertapenem in 15 and 120 min followed by centrifugation. The supernatant was applied on a steel target plate, covered with HCCA matrix and analysed using a Microflex(TM) (Bruker Daltonics) in the mass range of 4-600 Da. The assay detected and separated KPC from other carbapenemases in K. pneumoniae after only 15 min incubation. In P. aeruginosa, however, only 8/14 isolates of VIM-producing P. aeruginosa were detected. None of the tested carbapenemase negative isolates displayed a pattern of hydrolysis of ertapenem.Conclusions: This assay allows for a very rapid detection and verification of KPC (45 min including the preparation steps) and MBL production (150 min) in K. pneumoniae and can be performed using standard matrix. However, the study revealed the need for optimization of the substrate/species combination in assays for the detection of carbapenemases in P. aeruginosa using MALDI-TOF.
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| 10. |
- Jonsson, Jonas, et al.
(författare)
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Instrumentation and vehicle platform of a miniaturized submersible for exploration of terrestrial and extraterrestrial aqueous environments
- 2012
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Ingår i: Acta Astronautica. - : Elsevier BV. - 0094-5765 .- 1879-2030. ; 79, s. 203-211
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Tidskriftsartikel (refereegranskat)abstract
- An example of an extraterrestrial environment likely to support life is the vast liquid body believed to hide underneath the frozen crust of Jupiter's moon Europa. The hypothetical exploration of this, as well as the more accessible subglacial lakes on Earth, has been used as model applications for the development of a heavily miniaturized, yet qualified, submersible with the potential to be deployable either in itself through a long and narrow borehole or as the daughter craft of an ice-penetrating cryobot.Onboard the submersible, which is only 20 cm in length and 5 cm in diameter, accommodation of a versatile set of sensors and instruments capable of characterizing and imaging the surroundings, and even collecting water samples with microorganisms for return, is facilitated through the use of miniaturization technologies. For instance, together with a small camera, a laser-based, microoptic device enables the 3-D reconstruction of imaged objects for topographical measurements. As a complement, when the water is turbid or a longer range is wanted, the world's smallest side-scanning sonar, exhibiting centimeter resolution and a range of over 30 m, has been developed. The work on miniaturizing a CTD, which is a widely employed oceanographic instrument used to measure and correlate conductivity, temperature, and depth, has commenced. Furthermore, a device employing acoustics to trap microscopic particles and organisms, and, by this, enrich water samples, is under development. To ensure that the gathered samples are pristine until analyzed at the end of a mission, the device is equipped with high-pressure, latchable valves.Remote operation and transfer of measurement data and images, or even live streaming of video, is made possible through a kilometer-long fiber optic cable being reeled out from the vehicle underway and tethering it to a terminal. To extend the missions, the same fiber shall also be capable of charging the onboard batteries.In this paper, the vehicle and its subsystems are summarized. Subsystems essential for the vehicle's operation, e.g., hull structure, communication and power management, are treated separately from those of more mission-specific nature, like the instruments mentioned above.
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| 11. |
- Jonsson, Jonas, et al.
(författare)
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Miniaturized submersible for exploration of aqueous environments on Earth and beyond
- 2011
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Konferensbidrag (refereegranskat)abstract
- Some of the most likely environments to support extraterrestrial life in our solar system are the ice-covered moons, suchas Europa, thought to harbor a liquid ocean underneath its frozen crust. Exploration, however, necessitates an ice-penetratingcryobot, or a long and narrow borehole, and the subsequent deployment of a small submersible, a hydrobot, with severe sizerestrictions imposed on its scientific payload. As a stepping stone for exploration of such environments, a small instrumentladenedsubmersible vehicle is currently under development.Employment of a large set of instruments capable of characterizing the aqueous environment, imaging the surroundingsand collecting microorganisms is essential for the determination of habitability. Despite the submersible being only 20 cm inlength and 5 cm in diameter, a high degree of functionality is facilitated here through the use of miniaturization technologies. Forinstance, a compact laser-illuminated diffractive optical element, paired with a high-resolution camera, enable photogrammetryand the reconstruction of objects’ shapes in 3-D space. Also for imaging, the world’s smallest side-scanning sonar has beendeveloped to acoustically image, either where water is too turbid for the camera, or where longer range is necessary. Currently,the sonar exhibits centimeter resolution and ranges over 30 meters. On the sensor side, a most vital oceanographic instrument, theCTD, used to measure the conductivity, temperature, and depth of water, has been heavily miniaturized and preliminaryevaluated. Additionally, a water sampler combining integrated selection and enriching capabilities to filter out and accommodate,e.g., microbes in the size range of 1-10 μm, is under development. Among other parts, its high-pressure valves and microfluidicacoustic traps have already been realized.For remote operation and upload of measurement data or images, or even live streaming of video, the submersible will betethered with a bi-directionally transmitting fiber optic cable, also capable of charging the onboard batteries for long missions.The one kilometer long fiber will be fitted within the hull, and by reeling out the fiber from the submersible, drag will be reduced.Herein, test results and images of the vehicle and its complete, and continuously developed, subsystems are presented.The vehicle, and its subsystems as stand-alone instruments, will enable the exploration of previously unreachable analogenvironments on Earth, vital to the field of astrobiology, and act as a forerunner to a submersible hydrobot that can explore icecoveredoceans elsewhere in our solar system.
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| 12. |
- Jonsson, Jonas, et al.
(författare)
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Miniaturized submersible for exploration of small aqueous environments
- 2011
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Ingår i: Oceans’11 MTS/IEEE Kona, Hilton Waikoloa Village, Kona, Hawai‘i September 19-22, 2011.
-
Konferensbidrag (refereegranskat)abstract
- Remotely operated vehicles (ROVs) are commonlyused for sub-surface exploration. However, multi-functionalROVs tend to be fairly large, while preferred small and compactROVs suffer from limited functionality. The Deeper Access,Deeper Understanding (DADU) project aims to develop a smallsubmersible concept using miniaturization technologies to enablea high functionality. An operator is able to maneuver the vehiclewith five degrees of freedom using eight small thrusters, while aset of accelerometers and gyros monitor the orientation of thesubmersible. A single fiber optic cable will connect thesubmersible to a control station and enable simultaneous dataand command transfers. Rechargeable battery packs providepower to the submersibles subsystems during operation. Thesewill be rechargeable through the fiber connection. A forwardlooking camera is aided by a laser topography measurementsystem, where distances, sizes and shapes of objects in view canbe determined to within 0.5 cm. For murkier environments, orwhen a more extensive mapping of the surroundings is needed,the small high-frequency side-scanning sonar can be used.Salinity calculations of the water will be available throughmeasurements of the conductivity, temperature and depth.Samples of water and particles within it will be enabled through awater sampler with an enriching capability. Flow sensors will beable to measure the water movement around the submersible’shull. The submersible and its subsystems are under continuousdevelopment. The vehicle itself, and its subsystems as stand-aloneinstruments, will enable the exploration of previouslyunreachable submerged environments, such as the sub-glaciallakes found in Iceland and Antarctica, or other submerged smallenvironments, such as pipe and cave systems.
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| 13. |
- Karah, Nabil, et al.
(författare)
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Plasmid-mediated quinolone resistance determinants qnr and aac(6')-Ib-cr in Escherichia coli and Klebsiella spp. from Norway and Sweden
- 2010
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Ingår i: Diagnostic microbiology and infectious disease. - : Elsevier BV. - 0732-8893 .- 1879-0070. ; 66:4, s. 425-431
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of the plasmid-mediated quinolone resistance genes qnr and aac(6')-Ib-cr was investigated among clinical isolates of Escherichia coli and Klebsiella spp. selected from 2 collections of consecutive isolates collected in 2004 to 2005 in Norway (n = 2479) and Sweden (n = 2980) and 1 group of extended-spectrum beta-lactamase (ESBL)-producing isolates collected in 2003 in Norway (n = 71). A total of 414 isolates was selected for screening based on resistance to nalidixic acid and/or reduced susceptibility/resistance to ciprofloxacin. The prevalence of both qnr and aac(6')-Ib-cr was higher among the ESBL producers (9.1% and 52.3%, respectively) than in the consecutive isolates (1.1% and 3.2%, respectively). qnrS1 was detected in 6 isolates, whereas qnrB1 and qnrB7 were detected in 2 isolates. The genetic structure surrounding qnrS1 was similar to previously described structures. In 2 isolates, qnrS1 was located on conjugative IncN-type plasmids of approximately 140 kb.
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| 14. |
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| 15. |
- Muhammad, Ibrahim, et al.
(författare)
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Characterisation of blaTEM genes and types of β-lactamase plasmids in Neisseria gonorrhoeae - the prevalent and conserved blaTEM-135 has not recently evolved and existed in the Toronto plasmid from the origin
- 2014
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major concern worldwide. It has been recently feared that the blaTEM-1 gene is, via blaTEM-135, evolving into an extended-spectrum β-lactamase (ESBL), which could degrade all cephalosporins including ceftriaxone. The aims of the present study were to characterize the blaTEM genes, types of β-lactamase plasmids, the degradation of ampicillin by TEM-135 compared to TEM-1, and to perform molecular epidemiological typing of β-lactamase-producing N. gonorrhoeae strains internationally.METHODS: β-lactamase producing N. gonorrhoeae isolates (n = 139) cultured from 2000 to 2011 in 15 countries were examined using antibiograms, blaTEM gene sequencing, β-lactamase plasmid typing, and N. gonorrhoeae multiantigen sequence typing (NG-MAST). Furthermore, the blaTEM gene was sequenced in the first described Toronto plasmid (pJD7), one of the first Asian plasmids (pJD4) and African plasmids (pJD5) isolated in Canada. The degradation of ampicillin by TEM-135 compared to TEM-1 was examined using a MALDI-TOF MS hydrolysis assay.RESULTS: Six different blaTEM sequences were identified (among isolates with 125 different NG-MAST STs), i.e. blaTEM-1 (in 104 isolates), blaTEM-135 (in 30 isolates), and four novel blaTEM sequences (in 5 isolates). The blaTEM-1 allele was only found in the African and Asian plasmids, while all Rio/Toronto plasmids possessed the blaTEM-135 allele. Most interesting, the first described gonococcal Toronto plasmid (pJD7), identified in 1984, also possessed the highly conserved blaTEM-135 allele. The degradation of ampicillin by TEM-135 compared to TEM-1 was indistinguishable in the MALDI-TOF MS hydrolysis assay.CONCLUSIONS: blaTEM-135, encoding TEM-135, is predominantly and originally associated with the Rio/Toronto plasmid and prevalent among the β-lactamase producing gonococcal strains circulating globally. blaTEM-135 does not appear, as previously hypothesized, to have recently evolved due to some evolutionary selective pressure, for example, by the extensive use of extended-spectrum cephalosporins worldwide. On the contrary, the present study shows that blaTEM-135 existed in the Toronto plasmid from its discovery and that blaTEM-135 is highly conserved (not further evolved in the past >30 years). Nevertheless, international studies for monitoring the presence of different blaTEM alleles, the possible evolution of the blaTEM-135 allele, and the types of β-lactamase producing plasmids, remain imperative.
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| 16. |
- Poulsen, Hanna O., et al.
(författare)
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High genetic diversity of nitrofurantoin- or mecillinam-resistant Escherichia coli indicates low propensity for clonal spread
- 2013
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 68:9, s. 1974-1977
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Tidskriftsartikel (refereegranskat)abstract
- The empirical treatment with trimethoprim or ciprofloxacin of urinary tract infections (UTIs) is now questioned, partly due to the global expansion of a few resistant clonal groups of Escherichia coli. In this study we investigated the clonal structure of 34 strains of E. coli (collected from non-pregnant women aged 1865 years with uncomplicated UTIs in Europe and Canada) resistant to either of two other common treatment alternatives for uncomplicated UTIs, mecillinam or nitrofurantoin, using multilocus sequence typing (MLST). The 34 isolates were, despite high levels of multiresistance, distributed all over the E. coli genetic diversity spectrum with little association of antibiotic resistance to specific clonal groups. The results of this study indicate a low probability of a future clonal spread of resistance to mecillinam and nitrofurantoin.
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| 17. |
- Rondahl, E., et al.
(författare)
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The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer
- 2014
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Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 60:2, s. 172-173
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hepatitis C diagnostics involve antibody screening and confirmation of current infection by detection of HCV RNA positivity. In screening instruments with fixed pipetting needle, there is a risk of sample carry-over contamination. Objectives: The aim of this study was to evaluate the risk of such contamination in a proposed clinical setting. Study design: In the present study, known HCV RNA positive (n= 149) and negative (n= 149) samples were analysed by anti-HCV Abbott in an Architect instrument in an alternating fashion in order to test for contamination. Results: In subsequent retesting of the previously HCV RNA-negative samples, six samples (4%) were positive by the Cobas Taqman assay with a maximum level of 33. IU/mL. The results show that there is a risk for transfer of HCV in the Architect instrument but they also show that the levels of HCV RNA observed are low. Conclusions: We conclude that complementary HCV RNA testing on samples identified as anti-HCV positive by screening can be recommended because the complementary results are reliable in the majority of cases when either HCV RNA is negative or HCV RNA is positive with a level >1000. IU/mL. In a minority of cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination should be suspected and a new sample requested for HCV RNA testing. This strategy would reduce the need for obtaining a new sample from the vast majority of patients with a newly discovered HCV antibody positivity. © 2014 The Authors.
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| 18. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 19. |
- Sundqvist, Kyle, 1978, et al.
(författare)
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The pumpistor: A linearized model of a flux-pumped superconducting quantum interference device for use as a negative-resistance parametric amplifier
- 2013
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 103:102603
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Tidskriftsartikel (refereegranskat)abstract
- We describe a circuit model for a flux-driven Superconducting QUantum Interference Device (SQUID). This is useful for developing insight into how these devices perform as active elements in parametric amplifiers. The key concept is that frequency mixing in a flux-pumped SQUID allows for the appearance of an effective negative resistance. In the three-wave, degenerate case treated here, a negative resistance appears only over a certain range of allowed input signal phase. This model readily lends itself to testable predictions of more complicated circuits.
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| 20. |
- Sundqvist, Martin, 1974-
(författare)
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Antibiotic Resistance and Population Dynamics of Escherichia coli in Relation to a Large Scale Antibiotic Consumption Intervention
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistance challenges the practice and development of modern medicine. The aim of this thesis was to test the hypothesis that antibiotic resistance is reversible once the selection pressure of an antibiotic is removed. A decisive reduction (85%) in trimethoprim and trimethoprim-sulfamethoxazole over 24 months in Kronoberg County, Sweden, is described. The resistance baseline prior to the intervention and the effects of the intervention on resistance levels, trimethoprim resistance genes (dfr-genes) and population structure in Escherichia coli were studied. The effects of different algorithms for excluding patient duplicate isolates were small but systematic. An identical algorithm was used throughout. The drastic decrease in the use of trimethoprim containing drugs did not result in a corresponding decrease in trimethoprim resistance. This was true both for total trimethoprim resistance and for trimethoprim mono-resistance. The distributions of E. coli phenotypes, dfr-genes and E. coli sequence types were stable. The marginal effect on resistance rates was explained by a low fitness cost of trimethoprim resistance observed in vitro and the high levels of associated resistance in trimethoprim resistant isolates. Trimethoprim resistance was, although widespread in the E. coli population, more common in certain E. coli sequence types. The distributions of dfr-genes were different in E. coli and K. pneumoniae and between different E. coli sequence types. These results indicate mechanisms related to the genetic back-bone of E coli to be important for the acquisition and persistence of antibiotic resistance. The findings of this thesis indicates that, at least for some classes of antibiotics, we may have overestimated the usefulness of a strategy for reversing antimicrobial resistance based on the fitness cost of resistance. We have equally underestimated the conserving effects of associated resistance. The stability of the dfr-genes and E. coli sequence types underlines the importance of associated resistance and successful lineages in the spread and maintenance of antibiotic resistance in E. coli.
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| 21. |
- Sundqvist, Martin, et al.
(författare)
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Little evidence for reversibility of trimethoprim resistance after a drastic reduction in trimethoprim use
- 2010
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 65:2, s. 350-360
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Tidskriftsartikel (refereegranskat)abstract
- The worldwide rapid increase in antibiotic-resistant bacteria has made efforts to prolong the lifespan of existing antibiotics very important. Antibiotic resistance often confers a fitness cost in the bacterium. Resistance may thus be reversible if antibiotic use is discontinued or reduced. To examine this concept, we performed a 24 month voluntary restriction on the use of trimethoprim-containing drugs in Kronoberg County, Sweden. The intervention was performed on a 14 year baseline of monthly data on trimethoprim resistance and consumption. A three-parameter mathematical model was used to analyse the intervention effect. The prerequisites for reversion of resistance (i.e. fitness cost, associated resistance and clonal composition) were studied on subsets of consecutively collected Escherichia coli from urinary tract infections. The use of trimethoprim-containing drugs decreased by 85% during the intervention. A marginal but statistically significant effect on the increase in trimethoprim resistance was registered. There was no change in the clonal composition of E. coli and there was no measurable fitness cost associated with trimethoprim resistance in clinical isolates. The frequency of associated antibiotic resistances in trimethoprim-resistant isolates was high. A lack of detectable fitness cost of trimethoprim resistance in vitro together with a strong co-selection of other antibiotics could explain the rather disappointing effect of the intervention. The result emphasizes the low possibility of reverting antibiotic resistance once established and the urgent need for the development of new antibacterial agents.
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| 22. |
- Sundqvist, Martin, 1959-, et al.
(författare)
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Med en examen från Karlstads universitet : Alumner inom hälsa, natur- och teknikvetenskap Examen 2007–2010
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- En alumnstudie inom fakultetens område genomfördes hösten 2013. I rapporten redovisas resultaten av de enkäter till alumner som tagit examen från följande program under åren 2007-2010:BiologiprogrammetBiovetenskapligt program: Biomedicinsk analytiker och ReceptarieCivilingenjörsprogrammet DatateknikCivilingenjörsprogrammet Energi- och MiljöteknikCivilingenjörsprogrammet Industriell ekonomiCivilingenjörsprogrammet KemiteknikCivilingenjörsprogrammet MaskinteknikCivilingenjörsprogrammet Teknisk fysikHögskoleingenjörsprogrammet i elektroteknikHögskoleingenjörsprogrammet i byggteknik, inriktning husbyggnadHögskoleingenjörsprogrammet i energi- och miljöteknikHögskoleingenjörsprogrammet i innovationsteknik och designHögskoleingenjörsprogrammet i maskinteknikDataingenjörMiljövetarprogrammetAlumnerna har jobb (98,5 %), och nästan alltid inom det område som man utbildat sig.Alumnerna är i huvudsak nöjda med Kau och med sin utbildningDen viktigaste framgångsfaktorn som nämns av många alumner är lärarnas kompentens, engagemang, hjälpsamhet och tillgänglighet.Universitetets studiemiljö i vid bemärkelse lyfts fram. Det vill säga, lokaler, gruppstorlekar, gemenskap, bemötande, administration och campus.Samverkan med arbetslivet i form av praktik, studiebesök, skarpa ”case-jobb” finns med både som en styrka och som något det borde finnas mer av. Detta är uppenbarligen ett område som engagerar många.
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| 23. |
- Sundqvist, Martin, 1974-
(författare)
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Reversibility of antibiotic resistance
- 2014
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Ingår i: Upsala Journal of Medical Sciences. - : Informa Healthcare. - 0300-9734 .- 2000-1967. ; 119:2, s. 142-148
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Forskningsöversikt (refereegranskat)abstract
- Although theoretically attractive, the reversibility of resistance has proven difficult in practice, even though antibiotic resistance mechanisms induce a fitness cost to the bacterium. Associated resistance to other antibiotics and compensatory mutations seem to ameliorate the effect of antibiotic interventions in the community. In this paper the current understanding of the concepts of reversibility of antibiotic resistance and the interventions performed in hospitals and in the community are reviewed.
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| 24. |
- Sundqvist, Martin, 1959-
(författare)
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Utresande studenter från Fakulteten för Hälsa, Natur- och Teknikvetenskap 2008-2013 : Varför valde de att studera utomlands?
- 2014
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Rapport (populärvet., debatt m.m.)abstract
- En enkätundersökning genomfördes under VT2014 bland studenter som tidigare deltagit i någon form av internationellt utbyte under åren 2008-2013. Undersökningen omfattade de studenter som bedrivit huvudelen av sina studier vid Fakulteten för hälsa, natur- och teknikvetenskap. Det betyder att studenter från följande program kom att ingå i undersökningen: Samtliga Ingenjörsprogram, Sjuksköterskeutbildningen, Tandhygienistutbildningen, Lärarutbildning, Biovetenskapligt program, Miljövetenskapligt program och Matematikekonomiprogrammet.Svarsfrekvensen blev på ett utskick, utan påminnelse, 159 av 429, d.v.s. 37 %. Det kan visserligen sägas vara i underkant för att göra säkra statistiska analyser. Men det var ju inte heller det vi var ute efter. Vi ville ju inte jämföra grupper med varandra utan bara få veta varför studenter valt att resa utomlands under sin studietid och därför var alla svar lika värdefulla. De viktigaste slutsatserna blev attDrivkraften för att delta i internationella utbyten under studietiden är sökandet efter bra upplevelser och personlig utveckling snarare än efter sådant som direkt gynnar den framtida karriären.Etablerade och organiserade utbyten med bra stöd och bra ”service” genererar stora volymer utbyte under förutsättning att information och ”marknadsföring” är tillräcklig.
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| 25. |
- Sundqvist, Martin, 1974-, et al.
(författare)
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Within-Population Distribution of Trimethoprim Resistance in Escherichia coli before and after a Community-Wide Intervention on Trimethoprim Use
- 2014
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 58:12, s. 7492-7500
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Tidskriftsartikel (refereegranskat)abstract
- A 2-year prospective intervention on the prescription of trimethoprim reduced the use by 85% in a health care region with 178,000 inhabitants. Here, we performed before-and-after analyses of the within-population distribution of trimethoprim resistance in Escherichia coli. Phylogenetic and population genetic methods were applied to multilocus sequence typing data of 548 consecutively collected E. coli isolates from clinical urinary specimens. Results were analyzed in relation to antibiotic susceptibility and the presence and genomic location of different trimethoprim resistance gene classes. A total of 163 E. coli sequence types (STs) were identified, of which 68 were previously undescribed. The isolates fell into one of three distinct genetic clusters designated BAPS 1 (E. coli phylogroup B2), BAPS 2 (phylogroup A and B1), and BAPS 3 (phylogroup D), each with a similar frequency before and after the intervention. BAPS 2 and BAPS 3 were positively and BAPS 1 was negatively associated with trimethoprim resistance (odds ratios of 1.97, 3.17, and 0.26, respectively). In before-and-after analyses, trimethoprim resistance frequency increased in BAPS 1 and decreased in BAPS 2. Resistance to antibiotics other than trimethoprim increased in BAPS 2. Analysis of the genomic location of different trimethoprim resistance genes in isolates of ST69, ST58, and ST73 identified multiple independent acquisition events in isolates of the same ST. The results show that despite a stable overall resistance frequency in E. coli before and after the intervention, marked within-population changes occurred. A decrease of resistance in one major genetic cluster was masked by a reciprocal increase in another major cluster.
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