| 1. |
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| 2. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 5. |
- Delabrouille, J., et al.
(författare)
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Exploring cosmic origins with CORE : Survey requirements and mission design
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- Future observations of cosmic microwave background (CMB) polarisation have the potential to answer some of the most fundamental questions of modern physics and cosmology, including: what physical process gave birth to the Universe we see today? What are the dark matter and dark energy that seem to constitute 95% of the energy density of the Universe? Do we need extensions to the standard model of particle physics and fundamental interactions? Is the ACDM cosmological scenario correct, or are we missing an essential piece of the puzzle? In this paper, we list the requirements for a future CMB polarisation survey addressing these scientific objectives, and discuss the design drivers of the CORE space mission proposed to ESA in answer to the M5 call for a medium-sized mission. The rationale and options, and the methodologies used to assess the mission's performance, are of interest to other future CMB mission design studies. CORE has 19 frequency channels, distributed over a broad frequency range, spanning the 60-600 GHz interval, to control astrophysical foreground emission. The angular resolution ranges from 2' to 18', and the aggregate CMB sensitivity is about 2 mu K.arcmin. The observations are made with a single integrated focal-plane instrument, consisting of an array of 2100 cryogenically-cooled, linearly-polarised detectors at the focus of a 1.2-m aperture cross-Dragone telescope. The mission is designed to minimise all sources of systematic effects, which must be controlled so that no more than 10(-4) of the intensity leaks into polarisation maps, and no more than about 1% of E-type polarisation leaks into B-type modes. CORE observes the sky from a large Lissajous orbit around the Sun-Earth L2 point on an orbit that offers stable observing conditions and avoids contamination from sidelobe pick-up of stray radiation originating from the Sun, Earth, and Moon. The entire sky is observed repeatedly during four years of continuous scanning, with a combination of three rotations of the spacecraft over different timescales. With about 50% of the sky covered every few days, this scan strategy provides the mitigation of systematic effects and the internal redundancy that are needed to convincingly extract the primordial B-mode signal on large angular scales, and check with adequate sensitivity the consistency of the observations in several independent data subsets. CORE is designed as a near-ultimate CMB polarisation mission which, for optimal complementarity with ground-based observations, will perform the observations that are known to be essential to CMB polarisation science and cannot be obtained by any other means than a dedicated space mission. It will provide well-characterised, highly-redundant multi-frequency observations of polarisation at all the scales where foreground emission and cosmic variance dominate the final uncertainty for obtaining precision CMB science, as well as 2' angular resolution maps of high-frequency foreground emission in the 300-600 GHz frequency range, essential for complementarity with future ground-based observations with large telescopes that can observe the CMB with the same beamsize.
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| 6. |
- Natoli, P., et al.
(författare)
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Exploring cosmic origins with CORE : Mitigation of systematic effects
- 2018
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Tidskriftsartikel (refereegranskat)abstract
- We present an analysis of the main systematic effects that could impact the measurement of CMB polarization with the proposed CORE space mission. We employ timeline to-map simulations to verify that the CORE instrumental set-up and scanning strategy allow us to measure sky polarization to a level of accuracy adequate to the mission science goals. We also show how the CORE observations can be processed to mitigate the level of contamination by potentially worrying systematics, including intensity-to-polarization leakage due to bandpass mismatch, asymmetric main beams, pointing errors and correlated noise. We use analysis techniques that are well validated on data from current missions such as Planck to demonstrate how the residual contamination of the measurements by these effects can be brought to a level low enough not to hamper the scientific capability of the mission, nor significantly increase the overall error budget. We also present a prototype of the CORE photometric calibration pipeline, based on that used for Planck, and discuss its robustness to systematics, showing how CORE can achieve its calibration requirements. While a fine-grained assessment of the impact of systematics requires a level of knowledge of the system that can only be achieved in a future study phase, the analysis presented here strongly suggests that the main areas of concern for the CORE mission can be addressed using existing knowledge, techniques and algorithms.
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| 7. |
- Kueppers, Michael, et al.
(författare)
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Triple F-a comet nucleus sample return mission
- 2009
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Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 23:3, s. 809-847
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Tidskriftsartikel (refereegranskat)abstract
- The Triple F (Fresh From the Fridge) mission, a Comet Nucleus Sample Return, has been proposed to ESA's Cosmic Vision program. A sample return from a comet enables us to reach the ultimate goal of cometary research. Since comets are the least processed bodies in the solar system, the proposal goes far beyond cometary science topics (like the explanation of cometary activity) and delivers invaluable information about the formation of the solar system and the interstellar molecular cloud from which it formed. The proposed mission would extract three sample cores of the upper 50 cm from three locations on a cometary nucleus and return them cooled to Earth for analysis in the laboratory. The simple mission concept with a touch-and-go sampling by a single spacecraft was proposed as an M-class mission in collaboration with the Russian space agency ROSCOSMOS.
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| 8. |
- Hillier, Ladeana W, et al.
(författare)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 9. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 10. |
- Zumla, A, et al.
(författare)
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Towards host-directed therapies for tuberculosis
- 2015
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Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1784 .- 1474-1776. ; 14:8, s. 511-
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Tidskriftsartikel (refereegranskat)
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| 11. |
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| 13. |
- Cauchoix, M., et al.
(författare)
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The repeatability of cognitive performance : a meta-analysis
- 2018
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 373:1756
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Tidskriftsartikel (refereegranskat)abstract
- Behavioural and cognitive processes play important roles in mediating an individual's interactions with its environment. Yet, while there is a vast literature on repeatable individual differences in behaviour, relatively little is known about the repeatability of cognitive performance. To further our understanding of the evolution of cognition, we gathered 44 studies on individual performance of 25 species across six animal classes and used meta-analysis to assess whether cognitive performance is repeatable. We compared repeatability (R) in performance (1) on the same task presented at different times (temporal repeatability), and (2) on different tasks that measured the same putative cognitive ability (contextual repeatability). We also addressed whether R estimates were influenced by seven extrinsic factors (moderators): type of cognitive performance measurement, type of cognitive task, delay between tests, origin of the subjects, experimental context, taxonomic class and publication status. We found support for both temporal and contextual repeatability of cognitive performance, with mean R estimates ranging between 0.15 and 0.28. Repeatability estimates were mostly influenced by the type of cognitive performance measures and publication status. Our findings highlight the widespread occurrence of consistent inter-individual variation in cognition across a range of taxa which, like behaviour, may be associated with fitness outcomes. This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.
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| 14. |
- Dunham, I, et al.
(författare)
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The DNA sequence of human chromosome 22
- 1999
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 402:6761, s. 489-495
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Dierig, A., et al.
(författare)
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A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis
- 2023
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Ingår i: Trials. - : BMC. - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin.Methods: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course.Discussion: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages.
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| 16. |
- Bick, Ulrich, et al.
(författare)
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Image-guided breast biopsy and localisation : recommendations for information to women and referring physicians by the European Society of Breast Imaging
- 2020
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Ingår i: Insights into Imaging. - : Springer Science and Business Media LLC. - 1869-4101. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- We summarise here the information to be provided to women and referring physicians about percutaneous breast biopsy and lesion localisation under imaging guidance. After explaining why a preoperative diagnosis with a percutaneous biopsy is preferred to surgical biopsy, we illustrate the criteria used by radiologists for choosing the most appropriate combination of device type for sampling and imaging technique for guidance. Then, we describe the commonly used devices, from fine-needle sampling to tissue biopsy with larger needles, namely core needle biopsy and vacuum-assisted biopsy, and how mammography, digital breast tomosynthesis, ultrasound, or magnetic resonance imaging work for targeting the lesion for sampling or localisation. The differences among the techniques available for localisation (carbon marking, metallic wire, radiotracer injection, radioactive seed, and magnetic seed localisation) are illustrated. Type and rate of possible complications are described and the issue of concomitant antiplatelet or anticoagulant therapy is also addressed. The importance of pathological-radiological correlation is highlighted: when evaluating the results of any needle sampling, the radiologist must check the concordance between the cytology/pathology report of the sample and the radiological appearance of the biopsied lesion. We recommend that special attention is paid to a proper and tactful approach when communicating to the woman the need for tissue sampling as well as the possibility of cancer diagnosis, repeat tissue sampling, and or even surgery when tissue sampling shows a lesion with uncertain malignant potential (also referred to as “high-risk” or B3 lesions). Finally, seven frequently asked questions are answered.
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| 17. |
- Moles, A. T., et al.
(författare)
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Putting plant resistance traits on the map : A test of the idea that plants are better defended at lower latitudes
- 2011
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 191:3, s. 777-788
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Tidskriftsartikel (refereegranskat)abstract
- It has long been believed that plant species from the tropics have higher levels of traits associated with resistance to herbivores than do species from higher latitudes. A meta-analysis recently showed that the published literature does not support this theory. However, the idea has never been tested using data gathered with consistent methods from a wide range of latitudes. • We quantified the relationship between latitude and a broad range of chemical and physical traits across 301 species from 75 sites world-wide. • Six putative resistance traits, including tannins, the concentration of lipids (an indicator of oils, waxes and resins), and leaf toughness were greater in high-latitude species. Six traits, including cyanide production and the presence of spines, were unrelated to latitude. Only ash content (an indicator of inorganic substances such as calcium oxalates and phytoliths) and the properties of species with delayed greening were higher in the tropics. • Our results do not support the hypothesis that tropical plants have higher levels of resistance traits than do plants from higher latitudes. If anything, plants have higher resistance toward the poles. The greater resistance traits of high-latitude species might be explained by the greater cost of losing a given amount of leaf tissue in low-productivity environments. © 2011 New Phytologist Trust.
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| 18. |
- Evangelou, Evangelos, et al.
(författare)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 19. |
- Sullivan, Nicola J., et al.
(författare)
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Developing a mealybug pheromone monitoring tool to enhance IPM practices in New Zealand vineyards
- 2023
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Ingår i: Journal of Pest Science. - : Springer. - 1612-4758 .- 1612-4766. ; 96, s. 29-39
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Tidskriftsartikel (refereegranskat)abstract
- Mealybugs are phloem-feeding insects found on many crops worldwide. In New Zealand vineyards, they transmit the economically important Grapevine leafroll-associated virus 3 (GLRaV-3). For some mealybug species, synthetic sex pheromones have been commercialised, and are used as monitoring tools. The mealybugs Pseudococcus longispinus and Pseudococcus calceolariae are major pests in many New Zealand vineyards. We present work on the development of a combined P. longispinus and P. calceolariae pheromone lure. The optimal dose for monitoring P. longispinus was found to be 10 mu g of the (S)-(+)-enantiomer, either alone or in the racemic mixture. Addition of the corresponding alcohol did not improve trap catch of P. longispinus. Both the P. longispinus and the P. calceolariae pheromone lures remained active in the field for 90 days. Combining the 2 species' pheromones had no negative effects on male mealybug trap catch for either species. We conclude that the pheromone ester alone is the best lure for the male P. longispinus. Combining the two mealybug species' pheromones into a single lure provides the New Zealand viticultural industry with an efficient monitoring tool. Late-vintage deployment of baited lures will provide information on mealybug abundance and local distribution that will inform the scope of future insecticide programmes, to target areas based on need rather than an area-wide application by default.
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| 20. |
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| 21. |
- Testa, G, et al.
(författare)
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Living Donor Uterus Transplantation: A Single Center's Observations and Lessons Learned From Early Setbacks to Technical Success.
- 2017
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Ingår i: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. - : Elsevier BV. - 1600-6143. ; 17:11, s. 2901-2910
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Tidskriftsartikel (refereegranskat)abstract
- Uterus transplantation is a vascularized composite allograft transplantation. It allows women who do not have a uterus to become pregnant and deliver a baby. In this paper, we analyze the first five cases of living donor uterus transplantation performed in the United States. The first three recipients lost their uterus grafts at days 14, 12, and 6, respectively, after transplant. Vascular complications, related to both inflow and outflow problems, were identified as the primary reason for the graft losses. Two recipients, at 6 and 3mo, respectively, after transplant, have functioning grafts with regular menstrual cycles. Ultimate success will be claimed only after a live birth. This paper is an in-depth analysis of evaluation, surgical technique, and follow-up of these five living donor uterus transplants. The lessons learned were instrumental in allowing us to evolve from failure to technical and functional success. We aim to share our conclusions and build on knowledge in the evolving field of uterus transplantation.
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| 26. |
- Boita, Joana, et al.
(författare)
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Validation of a candidate instrument to assess image quality in digital mammography using ROC analysis
- 2021
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Ingår i: European Journal of Radiology. - : Elsevier BV. - 1872-7727 .- 0720-048X. ; 139
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo validate a candidate instrument, to be used by different professionals to assess image quality in digital mammography (DM), against detection performance results.MethodsA receiver operating characteristics (ROC) study was conducted to assess the detection performance in DM images with four different image quality levels due to different quality issues. Fourteen expert breast radiologists from five countries assessed a set of 80 DM cases, containing 60 lesions (40 cancers, 20 benign findings) and 20 normal cases. A visual grading analysis (VGA) study using a previously-described candidate instrument was conducted to evaluate a subset of 25 of the images used in the ROC study. Eight radiologists that had participated in the ROC study, and seven expert breast-imaging physicists, evaluated this subset. The VGA score (VGAS) and the ROC and visual grading characteristics (VGC) areas under the curve (AUCROC and AUCVGC) were compared.ResultsNo large differences in image quality among the four levels were detected by either ROC or VGA studies. However, the ranking of the four levels was consistent: level 1 (partial AUCROC: 0.070, VGAS: 6.77) performed better than levels 2 (0.066, 6.15), 3 (0.061, 5.82), and 4 (0.062, 5.37). Similarity between radiologists’ and physicists’ assessments was found (average VGAS difference of 10 %).ConclusionsThe results from the candidate instrument were found to correlate with those from ROC analysis, when used by either observer group. Therefore, it may be used by different professionals, such as radiologists, radiographers, and physicists, to assess clinically-relevant image quality variations in DM.
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| 27. |
- Chen, Z. X., et al.
(författare)
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RNA helicase a is a downstream mediator of KIF1Bβ tumor-suppressor function in neuroblastoma
- 2014
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Ingår i: Cancer Discovery. - 2159-8274 .- 2159-8290. ; 4:4, s. 434-451
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Tidskriftsartikel (refereegranskat)abstract
- Inherited KIF1B loss-of-function mutations in neuroblastomas and pheochromocytomas implicate the kinesin KIF1B as a 1p36.2 tumor suppressor. However, the mechanism of tumor suppression is unknown. We found that KIF1B isoform β (KIF1Bβ) interacts with RNA helicase A (DHX9), causing nuclear accumulation of DHX9, followed by subsequent induction of the proapoptotic XIAP-associated factor 1 (XAF1) and, consequently, apoptosis. Pheochromocytoma and neuroblastoma arise from neural crest progenitors that compete for growth factors such as nerve growth factor (NGF) during development. KIF1Bβ is required for developmental apoptosis induced by competition for NGF. We show that DHX9 is induced by and required for apoptosis stimulated by NGF deprivation. Moreover, neuroblastomas with chromosomal deletion of 1p36 exhibit loss of KIF1Bβ expression and impaired DHX9 nuclear localization, implicating the loss of DHX9 nuclear activity in neuroblastoma pathogenesis. SIGNIFICANCE: KIF1Bβ has neuroblastoma tumor-suppressor properties and promotes and requires nuclear-localized DHX9 for its apoptotic function by activating XAF1 expression. Loss of KIF1Bβ alters subcellular localization of DHX9 and diminishes NGF dependence of sympathetic neurons, leading to reduced culling of neural progenitors, and, therefore, might predispose to tumor formation.
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| 28. |
- Litjens, Carlijn H. C., et al.
(författare)
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Protein binding of rifampicin is not saturated when using high-dose rifampicin
- 2019
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Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 74:4, s. 986-990
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Tidskriftsartikel (refereegranskat)abstract
- Background Higher doses of rifampicin are being investigated as a means to optimize response to this pivotal TB drug. It is unknown whether high-dose rifampicin results in saturation of plasma protein binding and a relative increase in protein-unbound (active) drug concentrations. Objectives To assess the free fraction of rifampicin based on an in vitro experiment and data from a clinical trial on high-dose rifampicin. Methods Protein-unbound rifampicin concentrations were measured in human serum spiked with increasing total concentrations (up to 64mg/L) of rifampicin and in samples obtained by intensive pharmacokinetic sampling of patients who used standard (10mg/kg daily) or high-dose (35mg/kg) rifampicin up to steady-state. The performance of total AUC(0-24) to predict unbound AUC(0-24) was evaluated. Results The in vitro free fraction of rifampicin remained unaltered (approximate to 9%) up to 21mg/L and increased up to 13% at 41mg/L and 17% at 64mg/L rifampicin. The highest (peak) concentration in vivo was 39.1mg/L (high-dose group). The arithmetic mean percentage unbound to total AUC(0-24)in vivo was 13.3% (range=8.1%-24.9%) and 11.1% (range=8.6%-13.6%) for the standard group and the high-dose group, respectively (P=0.214). Prediction of unbound AUC(0-24) based on total AUC(0-24) resulted in a bias of -0.05% and an imprecision of 13.2%. Conclusions Plasma protein binding of rifampicin can become saturated, but exposures after high-dose rifampicin are not high enough to increase the free fraction in TB patients with normal albumin values. Unbound rifampicin exposures can be predicted from total exposures, even in the higher dose range.
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| 33. |
- Aurora, P., et al.
(författare)
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Multiple breath inert gas washout as a measure of ventilation distribution in children with cystic fibrosis
- 2004
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Ingår i: Thorax. - : BMJ. - 0040-6376. ; 59:12, s. 1068-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple breath inert gas washout (MBW) has been suggested as a tool for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to compare the relative sensitivity of MBW and spirometry for detecting abnormal lung function in school age children with CF and to compare MBW results obtained from healthy children in the UK with those recently reported from Sweden. METHODS: Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow when 25% of forced vital capacity remains to be expired (MEF25) were compared with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22 children with CF aged 6-16 years and in 33 healthy controls. RESULTS: LCI was higher in children with CF than in healthy controls (mean difference 5.1 (95% CI of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference -2.3 (95% CI -2.9 to -1.7) and -1.8 (95% CI -2.4 to -1.3), respectively; p<0.001 for all). There was a significant negative correlation between LCI and FEV1 (r2 = 0.62) and MEF25 (r2 = 0.46). However, while normal (> or =-1.96 z-scores) FEV1 and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF, respectively, all but one of these children had an abnormally increased LCI. LCI was repeatable in both groups (within subject CV for three measurements 6% for CF and 5% for healthy children). In healthy subjects LCI was independent of age and virtually identical in the British and Swedish children (mean difference 0.1 (95% CI -0.1 to 0.4), p = 0.38) CONCLUSIONS: MBW is reproducible between laboratories, generates normal ranges which are constant over childhood, and is more frequently abnormal than spirometry in children with CF.
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| 34. |
- Aurora, P., et al.
(författare)
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Multiple-breath washout as a marker of lung disease in preschool children with cystic fibrosis
- 2005
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Ingår i: Am J Respir Crit Care Med. - 1073-449X. ; 171:3, s. 249-56
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Tidskriftsartikel (refereegranskat)abstract
- Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group successfully completed all measures, with success on first visit being between 68 and 86% for all three measures. Children with CF had significantly higher lung clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p < 0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001), and significantly lower forced expired volume in 0.5 seconds (-0.49 z-scores [-0.95, -0.03], p < 0.05). Abnormal lung function results were identified in 22 (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%) of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who were infected with Pseudomonas aeruginosa had significantly higher lung clearance index, but no significant difference in other lung function measures, when compared with noninfected children. Most preschool children can perform multiple-breath washout, plethysmography, and spirometry at first attempt. Multiple-breath washout detects abnormal lung function in children with CF more readily than plethysmography or spirometry.
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| 37. |
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| 38. |
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| 39. |
- Blom, L, et al.
(författare)
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Gender-specific differences and burn outcome
- 2017
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Ingår i: Burns : journal of the International Society for Burn Injuries. - : Elsevier BV. - 1879-1409. ; 43:4, s. 889-890
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 40. |
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| 41. |
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| 45. |
- Boita, Joana, et al.
(författare)
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Development and content validity evaluation of a candidate instrument to assess image quality in digital mammography : A mixed-method study
- 2021
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Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X. ; 134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To develop a candidate instrument to assess image quality in digital mammography, by identifying clinically relevant features in images that are affected by lower image quality. Methods: Interviews with fifteen expert breast radiologists from five countries were conducted and analysed by using adapted directed content analysis. During these interviews, 45 mammographic cases, containing 44 lesions (30 cancers, 14 benign findings), and 5 normal cases, were shown with varying image quality. The interviews were performed to identify the structures from breast tissue and lesions relevant for image interpretation, and to investigate how image quality affected the visibility of those structures. The interview findings were used to develop tentative items, which were evaluated in terms of wording, understandability, and ambiguity with expert breast radiologists. The relevance of the tentative items was evaluated using the content validity index (CVI) and modified kappa index (k*). Results: Twelve content areas, representing the content of image quality in digital mammography, emerged from the interviews and were converted into 29 tentative items. Fourteen of these items demonstrated excellent CVI ≥ 0.78 (k* > 0.74), one showed good CVI < 0.78 (0.60 ≤ k* ≤ 0.74), while fourteen were of fair or poor CVI < 0.78 (k* ≤ 0.59). In total, nine items were deleted and five were revised or combined resulting in 18 items. Conclusions: By following a mixed-method methodology, a candidate instrument was developed that may be used to characterise the clinically-relevant impact that image quality variations can have on digital mammography.
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| 46. |
- Boita, Joana, et al.
(författare)
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How does image quality affect radiologists’ perceived ability for image interpretation and lesion detection in digital mammography?
- 2021
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 31:7, s. 5335-5343
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study how radiologists’ perceived ability to interpret digital mammography (DM) images is affected by decreases in image quality. Methods: One view from 45 DM cases (including 30 cancers) was degraded to six levels each of two acquisition-related issues (lower spatial resolution and increased quantum noise) and three post-processing-related issues (lower and higher contrast and increased correlated noise) seen during clinical evaluation of DM systems. The images were shown to fifteen breast screening radiologists from five countries. Aware of lesion location, the radiologists selected the most-degraded mammogram (indexed from 1 (reference) to 7 (most degraded)) they still felt was acceptable for interpretation. The median selected index, per degradation type, was calculated separately for calcification and soft tissue (including normal) cases. Using the two-sided, non-parametric Mann-Whitney test, the median indices for each case and degradation type were compared. Results: Radiologists were not tolerant to increases (medians: 1.5 (calcifications) and 2 (soft tissue)) or decreases (median: 2, for both types) in contrast, but were more tolerant to correlated noise (median: 3, for both types). Increases in quantum noise were tolerated more for calcifications than for soft tissue cases (medians: 3 vs. 4, p = 0.02). Spatial resolution losses were considered less acceptable for calcification detection than for soft tissue cases (medians: 3.5 vs. 5, p = 0.001). Conclusions: Perceived ability of radiologists for image interpretation in DM was affected not only by image acquisition-related issues but also by image post-processing issues, and some of those issues affected calcification cases more than soft tissue cases. Key Points: • Lower spatial resolution and increased quantum noise affected the radiologists’ perceived ability to interpret calcification cases more than soft tissue lesion or normal cases. • Post-acquisition image processing-related effects, not only image acquisition-related effects, also impact the perceived ability of radiologists to interpret images and detect lesions. • In addition to current practices, post-acquisition image processing-related effects need to also be considered during the testing and evaluation of digital mammography systems.
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| 48. |
- Cederström, B., et al.
(författare)
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Lesion characterization in spectral photon-counting tomosynthesis
- 2017
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Ingår i: Medical Imaging 2017. - : SPIE - International Society for Optical Engineering. - 9781510607095
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Konferensbidrag (refereegranskat)abstract
- It has previously been shown that 2D spectral mammography can be used to discriminate between (likely benign) cystic and (potentially malignant) solid lesions in order to reduce unnecessary recalls in mammography. One limitation of the technique is, however, that the composition of overlapping tissue needs to be interpolated from a region surrounding the lesion. The purpose of this investigation was to demonstrate that lesion characterization can be done with spectral tomosynthesis, and to investigate whether the 3D information available in tomosynthesis can reduce the uncertainty from the interpolation of surrounding tissue. A phantom experiment was designed to simulate a cyst and a tumor, where the tumor was overlaid with a structure that made it mimic a cyst. In 2D, the two targets appeared similar in composition, whereas spectral tomosynthesis revealed the exact compositional difference. However, the loss of discrimination signal due to spread from the plane of interest was of the same strength as the reduction of anatomical noise. Results from a preliminary investigation on clinical tomosynthesis images of solid lesions yielded results that were consistent with the phantom experiments, but were still to some extent inconclusive. We conclude that lesion characterization is feasible in spectral tomosynthesis, but more data, as well as refinement of the calibration and discrimination algorithms, are needed to draw final conclusions about the benefit compared to 2D.
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| 49. |
- Crilly, J., et al.
(författare)
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Staff perceptions of the emergency department working environment: An international cross-sectional survey
- 2019
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Ingår i: EMA - Emergency Medicine Australasia. - : Wiley. - 1742-6731 .- 1742-6723. ; 31:6, s. 1082-91
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aims of this study were to describe clinical staff perceptions of their ED working environment and to explore associations between staff demographics, coping styles and the work environment. Methods: A cross-sectional study was conducted in one Swedish ED and two Australian EDs in 2015–2016. Descriptive statistics were used to explore stressors, coping styles and aspects of the working environment for the combined cohort and the cohort split by age, sex, professional role, years of employment in the ED and country. Regression analyses examined the impact of coping style and demographic characteristics on staff perceptions of the working environment. Results: Two hundred and six ED staff completed the survey (response rate: 64%). Factors most stressful for ED staff included death or sexual abuse of a child, heavy workload and poor skill mix. Staff perceptions of the working environment differed based on age, sex, country, tenure and job role. Regression analysis of perceptions of the work environment on demographics and coping strategies revealed that negative coping strategies were associated with low self-realisation, high workload, high conflict and high nervousness. Active coping and positive thinking were associated with increased self-realisation. Positive thinking was associated with lower levels of conflict. Conclusions: Employees engaging in positive coping strategies had more positive perceptions of the work environment, while those engaging in maladaptive coping strategies reported negative perceptions of the work environment. These data suggest that strategies that promote the use of active coping and positive thinking should be encouraged and warrant further research in the ED. © 2019 Australasian College for Emergency Medicine
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