| 1. |
- Nelson, G., et al.
(författare)
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QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy
- 2021
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 284:1, s. 56-73
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Tidskriftsartikel (refereegranskat)abstract
- A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
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| 2. |
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| 3. |
- Boehm, U., et al.
(författare)
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QUAREP-LiMi: a community endeavor to advance quality assessment and reproducibility in light microscopy
- 2021
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; :18, s. 1423-1426
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Tidskriftsartikel (refereegranskat)abstract
- The community-driven initiative Quality Assessment and Reproducibility for Instruments & Images in Light Microscopy (QUAREP-LiMi) wants to improve reproducibility for light microscopy image data through quality control (QC) management of instruments and images. It aims for a common set of QC guidelines for hardware calibration and image acquisition, management and analysis.
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| 4. |
- Boushel, Robert, et al.
(författare)
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Low-intensity training increases peak arm VO2 by enhancing both convective and diffusive O2 delivery.
- 2014
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 211:1, s. 122-134
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Tidskriftsartikel (refereegranskat)abstract
- AIM: It is an ongoing discussion the extent to which oxygen delivery and oxygen extraction contribute to an increased muscle oxygen uptake during dynamic exercise. It has been proposed that local muscle factors including the capillary bed and mitochondrial oxidative capacity play a large role in prolonged low-intensity training of a small muscle group when the cardiac output capacity is not directly limiting. The purpose of this study was to investigate the relative roles of circulatory and muscle metabolic mechanisms by which prolonged low-intensity exercise training alters regional muscle VO2 .METHODS: In nine healthy volunteers (seven males, two females), haemodynamic and metabolic responses to incremental arm cycling were measured by the Fick method and biopsy of the deltoid and triceps muscles before and after 42 days of skiing for 6 h day(-1) at 60% max heart rate.RESULTS: Peak pulmonary VO2 during arm crank was unchanged after training (2.38 ± 0.19 vs. 2.18 ± 0.2 L min(-1) pre-training) yet arm VO2 (1.04 ± 0.08 vs. 0.83 ± 0.1 L min(1) , P < 0.05) and power output (137 ± 9 vs. 114 ± 10 Watts) were increased along with a higher arm blood flow (7.9 ± 0.5 vs. 6.8 ± 0.6 L min(-1) , P < 0.05) and expanded muscle capillary volume (76 ± 7 vs. 62 ± 4 mL, P < 0.05). Muscle O2 diffusion capacity (16.2 ± 1 vs. 12.5 ± 0.9 mL min(-1) mHg(-1) , P < 0.05) and O2 extraction (68 ± 1 vs. 62 ± 1%, P < 0.05) were enhanced at a similar mean capillary transit time (569 ± 43 vs. 564 ± 31 ms) and P50 (35.8 ± 0.7 vs. 35 ± 0.8), whereas mitochondrial O2 flux capacity was unchanged (147 ± 6 mL kg min(-1) vs. 146 ± 8 mL kg min(-1) ).CONCLUSION: The mechanisms underlying the increase in peak arm VO2 with prolonged low-intensity training in previously untrained subjects are an increased convective O2 delivery specifically to the muscles of the arm combined with a larger capillary-muscle surface area that enhance diffusional O2 conductance, with no apparent role of mitochondrial respiratory capacity.
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| 5. |
- Castellani, Carlo, et al.
(författare)
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Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice
- 2008
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Ingår i: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993 .- 1873-5010. ; 7:3, s. 179-96
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Tidskriftsartikel (refereegranskat)abstract
- It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings. Although the diagnosis of CF is usually straightforward, care needs to be exercised in the use and interpretation of genetic tests: genotype information is not the final arbiter of a clinical diagnosis of CF or CF transmembrane conductance regulator (CFTR) protein related disorders. The diagnosis of these conditions is primarily based on the clinical presentation, and is supported by evaluation of CFTR function (sweat testing, nasal potential difference) and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF or CFTR-related disorders. Broad genotype/phenotype associations are useful in epidemiological studies, but CFTR genotype does not accurately predict individual outcome. The use of CFTR genotype for prediction of prognosis in people with CF at the time of their diagnosis is not recommended. The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients.
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| 8. |
- Gumpert, H., et al.
(författare)
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Transfer and Persistence of a Multi-Drug Resistance Plasmid in situ of the Infant Gut Microbiotain the Absence of Antibiotic Treatment
- 2017
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The microbial ecosystem residing in the human gut is believed to play an important role in horizontal exchange of virulence and antibiotic resistance genes that threatens human health. While the diversity of gut-microorganisms and their genetic content has been studied extensively, high-resolution insight into the plasticity, and selective forces shaping individual genomes is scarce. In a longitudinal study, we followed the dynamics of co-existing Escherichia coli lineages in an infant not receiving antibiotics. Using whole genome sequencing, we observed large genomic deletions, bacteriophage infections, as well as the loss and acquisition of plasmids in these lineages during their colonization of the human gut. In particular, we captured the exchange of multidrug resistance genes, and identified a clinically relevant conjugative plasmid mediating the transfer. This resistant transconjugant lineage was maintained for months, demonstrating that antibiotic resistance genes can disseminate and persist in the gut microbiome; even in absence of antibiotic selection. Furthermore, through in vivo competition assays, we suggest that the resistant transconjugant can persist through a fitness advantage in the mouse gut in spite of a fitness cost in vitro. Our findings highlight the dynamic nature of the human gut microbiota and provide the first genomic description of antibiotic resistance gene transfer between bacteria in the unperturbed human gut. These results exemplify that conjugative plasmids, harboring resistance determinants, can transfer and persists in the gut in the absence of antibiotic treatment.
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| 9. |
- Larsson, Gerry, et al.
(författare)
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Refinement of the questionnaire 'quality of care from the patient's perspective' using structural equation modelling
- 1998
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712 .- 0000-0000. ; 12:2, s. 111-118
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Tidskriftsartikel (refereegranskat)abstract
- In 1994, the questionnaire 'Quality of Care from the Patient's Perspective' (QPP) was developed using a conventional factor analytical approach (Wilde et al. 1994). The items and conceptual framework of this questionnaire were derived from a theoretical model, which, in turn, was developed from qualitative patient interviews, using a grounded theory method of analysis (Wilde et al. 1993). The aims of this study were to develop further the dimensionality of the QPP using structural equation modelling combined with advances in factor analysis modelling, and to refine the instrument. This comparatively new methodology extracts more information out of questionnaire data and is considered to be superior to traditional scaling methods. The sample consisted of 611 somatic inpatients from four departments at a Swedish hospital. Data collected with the QPP were explored with the new tool tracing the dimensions postulated in the theoretical model underlying the QPP. A nested factor model was developed fulfilling statistical criteria for adjustment between model and data. The model consists of a general factor and 16 subordinate factors. Most of the original QPP scales were reproduced with the new statistical technique. However, some content changes were made which appear to bring the QPP scales closer to patients' meaning representations of the area. Some changes were also made to the response format, changes which appear to strengthen the psychometric properties of the instrument. The refined QPP will hopefully contribute to a more differentiated picture of quality of care when applied in the field. All scales, items, and response formats of the revised QPP are presented in an appendix.
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| 11. |
- Rosenkilde, Carola E. H., et al.
(författare)
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Collateral sensitivity constrains resistance evolution of the CTX-M-15 beta-lactamase
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance is a major challenge to global public health. Discovery of new antibiotics is slow and to ensure proper treatment of bacterial infections new strategies are needed. One way to curb the development of antibiotic resistance is to design drug combinations where the development of resistance against one drug leads to collateral sensitivity to the other drug. Here we study collateral sensitivity patterns of the globally distributed extended-spectrum beta-lactamase CTX-M-15, and find three non-synonymous mutations with increased resistance against mecillinam or piperacillin-tazobactam that simultaneously confer full susceptibility to several cephalosporin drugs. We show in vitro and in mice that a combination of mecillinam and cefotaxime eliminates both wild-type and resistant CTX-M-15. Our results indicate that mecillinam and cefotaxime in combination constrain resistance evolution of CTX-M-15, and illustrate how drug combinations can be rationally designed to limit the resistance evolution of horizontally transferred genes by exploiting collateral sensitivity patterns.
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| 12. |
- Schult, A. L., et al.
(författare)
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Women require routine opioids to prevent painful colonoscopies: a randomised controlled trial
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:12, s. 1480-1489
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Tidskriftsartikel (refereegranskat)abstract
- Background Women are at high risk for painful colonoscopy. Pain, but also sedation, are barriers to colorectal cancer (CRC) screening participation. In a randomised controlled trial, we compared on-demand with pre-colonoscopy opioid administration to control pain in women at CRC screening age. Methods Women, aged 55-79 years, attending colonoscopy at two Norwegian endoscopy units were randomised 1:1:1 to (1) fentanyl on-demand, (2) fentanyl prior to colonoscopy, or (3) alfentanil on-demand. The primary endpoint was procedural pain reported by the patients on a validated four-point Likert scale and further dichotomized for the study into painful (moderate or severe pain) and non-painful (slight or no pain) colonoscopy. Secondary endpoints were: willingness to repeat colonoscopy, adverse events, cecal intubation time and rate, and post-procedure recovery time. Results Between June 2017 and May 2020, 183 patients were included in intention-to-treat analyses in the fentanyl on-demand group, 177 in the fentanyl prior to colonoscopy group, and 179 in the alfentanil on-demand group. Fewer women receiving fentanyl prior to colonoscopy reported a painful colonoscopy compared to those who were given fentanyl on-demand (25.2% vs. 44.1%, p < .001). There was no difference in the proportion of painful colonoscopies between fentanyl on-demand and alfentanil on-demand (44.1% vs. 39.5%, p = .40). No differences were observed for adverse events or any of the other secondary endpoints between the three groups. Conclusions Fentanyl prior to colonoscopy provided better pain control than fentanyl or alfentanil on-demand. Fentanyl before colonoscopy should be recommended to all women at screening age.
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| 13. |
- Sommer, Morten O. A., et al.
(författare)
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Prediction of antibiotic resistance : time for a new preclinical paradigm?
- 2017
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Ingår i: Nature Reviews Microbiology. - : Springer Science and Business Media LLC. - 1740-1526 .- 1740-1534. ; 15:11, s. 688-695
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Forskningsöversikt (refereegranskat)abstract
- Predicting the future is difficult, especially for evolutionary processes that are influenced by numerous unknown factors. Still, this is what is required of drug developers when they assess the risk of resistance arising against a new antibiotic candidate during preclinical development. In this Opinion article, we argue that the traditional procedures that are used for the prediction of antibiotic resistance today could be markedly improved by including a broader analysis of bacterial fitness, infection dynamics, horizontal gene transfer and other factors. This will lead to more informed preclinical decisions for continuing or discontinuing the development of drug candidates.
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| 14. |
- Svedberg, Gudrun, 1962-
(författare)
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Entreprenörskapets avtryck i klassrummets praxis : om villkor och lärande i gymnasieskolans entreprenörskapsprojekt
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Entrepreneurship has been entered on a supranational political agenda, in the EU and the OECD, and been emphatically described as a fundamental skill and a concern for schools and education. The agenda is reflected to a varying extent at the national and regional political levels. My aim is to describe, analyze and gain knowledge of what entrepreneurship in the Swedish upper secondary schools imply in practice, against the background of a local context. In particular, the conditions for learning. My approach is ethnographically inspired and this multiple case study is limited to two upper secondary school programmes. Data has been collected through observations, video recordings, informal conversations with pupils and teachers and formal conversations with headmasters. The material is analyzed in terms of three socioculturally inspiring foci. By means of a cultural-institutional focus, the stability and changeability of the programmes were elucidated. The previous institutional frameworks have been partially questioned by the teachers in the field, which has resulted in the following: In one of the upper secondary schools a new locally adapted programme has been composed, and courses and subjects have been integrated in a new way in the other school’s existing programme. The changes in the upper secondary programmes are to a great extent an example of a meeting between top-down and bottom-up initiatives. The changes of the institutional frameworks are connected to a discursive shift of the responsibility for pupils’ learning and education from teachers to pupils and also to teacher’s ambition to adapt interest- and experience-related teaching. In a situated focus, both programmes were identified as communities of practice with a joint enterprise, mutual engagement and a shared repertoire. These three dimensions were useful for examining specific aspects of the teaching. There has above all been an altered balance between reification and participation in the teaching as well as boundary crossing both outside the community of practice and within the community. Different conditions for learning were identified through an interpersonal focus. Both collaborative learning and cooperative learning were useful, but not sufficient concepts for describing the various forms of team learning. The conditions of cooperation and the pupils’ communication patterns revealed yet another form of team learning, which I call comparative learning. If the risk of everyday concepts getting the upper hand and trivialization can be avoided in team learning, there is in all these learning processes a potential for the pupils being able to develop strategies for handling complex tasks, taking initiatives and responsibility, cooperating and learning from one another in various different ways. In this way entrepreneurship has had an impact on the practice of the classrooms.
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| 15. |
- Taube, Karin, et al.
(författare)
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Gender differences at the Item Level
- 1996
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Ingår i: Are girls better readers?. - Amsterdam : Intern. Ass. for the Evaluation of Ed.Achievement. - 9789051665161
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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