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- Gossec, L., et al.
(författare)
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European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies : 2015 update
- 2016
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Books. - 0003-4967 .- 1468-2060. ; 75:3, s. 499-510
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since the publication of the European League Against Rheumatism recommendations for the pharmacological treatment of psoriatic arthritis (PsA) in 2012, new evidence and new therapeutic agents have emerged. The objective was to update these recommendations.METHODS: A systematic literature review was performed regarding pharmacological treatment in PsA. Subsequently, recommendations were formulated based on the evidence and the expert opinion of the 34 Task Force members. Levels of evidence and strengths of recommendations were allocated.RESULTS: The updated recommendations comprise 5 overarching principles and 10 recommendations, covering pharmacological therapies for PsA from non-steroidal anti-inflammatory drugs (NSAIDs), to conventional synthetic (csDMARD) and biological (bDMARD) disease-modifying antirheumatic drugs, whatever their mode of action, taking articular and extra-articular manifestations of PsA into account, but focusing on musculoskeletal involvement. The overarching principles address the need for shared decision-making and treatment objectives. The recommendations address csDMARDs as an initial therapy after failure of NSAIDs and local therapy for active disease, followed, if necessary, by a bDMARD or a targeted synthetic DMARD (tsDMARD). The first bDMARD would usually be a tumour necrosis factor (TNF) inhibitor. bDMARDs targeting interleukin (IL)12/23 (ustekinumab) or IL-17 pathways (secukinumab) may be used in patients for whom TNF inhibitors are inappropriate and a tsDMARD such as a phosphodiesterase 4-inhibitor (apremilast) if bDMARDs are inappropriate. If the first bDMARD strategy fails, any other bDMARD or tsDMARD may be used.CONCLUSIONS: These recommendations provide stakeholders with an updated consensus on the pharmacological treatment of PsA and strategies to reach optimal outcomes in PsA, based on a combination of evidence and expert opinion. © 2015 BMJ Publishing Group Ltd & European League Against Rheumatism.
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- Larsson, Anders, 1957, et al.
(författare)
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1060 nm VCSELs for long-reach optical interconnects
- 2018
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Ingår i: Optical Fiber Technology. - : Elsevier BV. - 1095-9912 .- 1068-5200. ; 44, s. 36-42
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Tidskriftsartikel (refereegranskat)abstract
- Reach extension of high capacity optical interconnects based on vertical-cavity surface-emitting lasers (VCSELs) and multimode fibers (MMFs), as needed for large-scale data centers, would benefit from high-speed GaAs-based VCSELs at 1060 nm. At this wavelength, the chromatic dispersion and attenuation of the optical fiber are much reduced in comparison with 850 nm. We present single and multimode 1060 nm VCSELs based on designs derived partly from our high-speed 850 nm VCSEL designs. The single-mode VCSEL, with a modulation bandwidth exceeding 22 GHz, supports back-to-back data rates up to 50 Gbps at 25 °C and 40 Gbps at 85 °C under binary NRZ (OOK) modulation. Using mode-selective launch, we demonstrate error-free 25 Gbps transmission over 1000 m of 1060 nm optimized MMF. Higher data rates and/or longer distances will be possible with equalization, forward-error-correction, and/or multilevel modulation.
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| 8. |
- Sharma, S., et al.
(författare)
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Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades
- 2017
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 91:14
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Tidskriftsartikel (refereegranskat)abstract
- The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby to lead to immune evasion. To address this hypothesis, we measured the ability of human sera collected between 1979 and 2010 to block glycan binding of four pandemic GII. 4 noroviruses isolated in the last 4 decades. In total, 268 sera were investigated for 50% blocking titer (BT50) values of virus-like particles (VLPs) against pig gastric mucin (PGM) using 4 VLPs that represent different GII. 4 norovirus variants identified between 1987 and 2012. Pre- and postpandemic sera (sera collected before and after isolation of the reference NoV strain) efficiently prevented binding of VLP strains MD145 (1987), Grimsby (1995), and Houston (2002), but not the Sydney (2012) strain, to PGM. No statistically significant difference in virus-blocking titers was observed between pre- and postpandemic sera. Moreover, paired sera showed that blocking titers of >= 160 were maintained over a 6-year period against MD145, Grimsby, and Houston VLPs. Significantly higher serum blocking titers (geometric mean titer [GMT], 1,704) were found among IgA-deficient individuals than among healthy blood donors (GMT, 90.9) (P < 0.0001). The observation that prepandemic sera possess robust blocking capacity for viruses identified decades later suggests a common attachment factor, at least until 2002. Our results indicate that serum IgG possesses antibody-blocking capacity and that blocking titers can be maintained for at least 6 years against 3 decades of pandemic GII. 4 NoV. IMPORTANCE Human noroviruses (NoVs) are the major cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) in saliva and gut recognize NoV and are the proposed ligands that facilitate infection. Polymorphisms in HBGA genes, and in particular a nonsense mutation in FUT2 (G428A), result in resistance to global dominating GII. 4 NoV. The emergence of new pandemic GII. 4 strains occurs at intervals of several years and is proposed to be attributable to epochal evolution, including amino acid changes and immune evasion. However, it remains unclear whether exposure to a previous pandemic strain stimulates immunity to a pandemic strain identified decades later. We found that prepandemic sera possess robust virus-blocking capacity against viruses identified several decades later. We also show that serum lacking IgA antibodies is sufficient to block NoV VLP binding to HBGAs. This is essential, considering that 1 in every 600 Caucasian children is IgA deficient.
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| 9. |
- Simpanen, Ewa, 1987, et al.
(författare)
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1060 nm single and multimode VCSELs for up to 50 Gb/s modulation
- 2017
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Ingår i: Proceedings of IEEE Photonics Conference 2017. - : IEEE. - 9781509065776 ; 2017-January, s. 65-66
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Konferensbidrag (refereegranskat)abstract
- We present the design and performance of 1060 nm VCSELs with up to 50 Gb/s intrinsic speed and demonstrate 25 Gb/s transmission over 1000 m of 1060 nm optimized MMF using a single-mode VCSEL and mode-selective launch.
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- Glimelius, B, et al.
(författare)
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The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of chemotherapy effects in some major tumour types--summary and conclusions
- 2001
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X. ; 40, s. 135-
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Forskningsöversikt (refereegranskat)abstract
- This report by The Swedish Council on Technology Assessment in Health Care (SBU) reviews, classifies, and grades the scientific literature on cancer chemotherapy in some major tumour types, describes the practice of chemotherapy in Sweden, compares practice with scientific knowledge, and analyses the costs and cost-effectiveness of chemotherapy. The report is intended primarily for decision-makers at various levels, both practitioners and administrators. It is also of interest for the medical profession. The extensive body of scientific literature was reviewed according to strict criteria that reflected the scientific weight of the literature. Sixteen experts representing different disciplines (oncology, surgery, internal medicine, health economy and quality of life research) participated in the literature review. Each section was discussed within the project group and was reviewed by at least one, but usually two international researchers. Additional input was provided by national experts representing different scientific disciplines. For the final evaluation to be as close to the objective truth as possible, a concerted effort was made to guarantee objectivity and thorough assessment of current knowledge about the effects of chemotherapy on the selected cancers. The tumour types selected for this assessment include firstly those types where three investigations had shown an increased use of chemotherapy in Sweden during the latest decade. These were non-small cell lung cancer (NSCLC), gastric cancer, pancreatic cancer, colorectal cancer and urinary bladder cancer. Secondly, the two tumour types comprising the greatest number of patients treated with chemotherapy in Sweden, breast cancer and haematological malignancies, were included. Among the haematological malignancies, the most prevalent ones, acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), Hodgkin's disease (HD), aggressive non-Hodgkin's lymphoma (NHL) of the large B-cell type and indolent NHL of follicular type were evaluated. These constitute about 75%, of all haematological malignancies. Thirdly, ovarian cancer was included since chemotherapy has been extensively used and since, at the time of the planning of this overview, a group of very expensive drugs, the taxanes, had preliminarily shown promising results. A wealth of scientific literature has been published on cancer therapy. The review presented in this report is limited to scientific studies judged to be important for evaluating chemotherapy efficacy. Assessments of the content and quality of these studies, and a critical summary of the results in all stages of the selected tumours, have never before been attempted in this way. However, similar comprehensive overviews of certain stages of the tumours have previously been made. These overviews were also critically evaluated. Totally 1,496 studies involving 558,743 patients were reviewed. The survey of practice of chemotherapy use involved all departments of surgery, urology, gynaecology, internal medicine including haematologic units, pulmonary medicine and general and gynaecologic oncology at 16 hospitals in two health care regions in Sweden, covering 39% of the Swedish population. During the 4 weeks of the survey, all patients with the diagnoses concerned who received chemotherapy were registered. The study included 1,590 patients. The working group's general conclusions are summarised in the following points: The literature on the effects of chemotherapy is extensive. Chemotherapy has a well-documented role in the curative and palliative treatment of patients with several types of cancer. The use of chemotherapy is of utmost importance for the possibility of cure in certain tumour types. In other tumours, chemotherapy increases the possibility of cure when added to local and regional treatments, particularly surgery. In the instances of no possibility of cure, chemotherapy may to a variable extent improve both patient survival and well-being. In Sweden chemotherapy is largely used in accordance with that documented in the scientific literature. The extent of both over- and under-treatment seems to be limited but cannot be excluded at the individual patient level. The literature-based knowledge is scientifically of lower quality in the most chemotherapy sensitive tumours than in tumours showing more limited sensitivity. In the more sensitive tumours, positive effects on a symptomatic stage and survival were seen several decades ago. In those days, clinical treatment studies did not fulfil the current high quality requirements. Small life-prolonging effects of chemotherapy are sometimes very well documented in large, high quality scientific studies. Some of these s
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- Mohammed Taha, Hiba, et al.
(författare)
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The NORMAN Suspect List Exchange (NORMAN-SLE) : facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry
- 2022
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 34:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA’s CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/).
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| 26. |
- Simpanen, Ewa, 1987, et al.
(författare)
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1060 nm single-mode vertical-cavity surface-emitting laser operating at 50 Gbit/s data rate
- 2017
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Ingår i: Electronics Letters. - : Institution of Engineering and Technology (IET). - 1350-911X .- 0013-5194. ; 53:13, s. 869-870
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Tidskriftsartikel (refereegranskat)abstract
- An energy efficient 1060 nm GaAs-based oxide-confined vertical-cavity surface-emitting laser designed for high-speed modulation and singlemode emission has been developed. A record data rate of 50 Gbit/ s at an energy dissipation of 100 fJ/ bit is demonstrated for a device with > 50 dB side-mode-suppression and 0.2 mA threshold current, making this laser a promising light source for long-reach optical interconnects.
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| 27. |
- Simpanen, Ewa, 1987, et al.
(författare)
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1060 nm VCSEL for up to 40 Gbit/s Data Transmission
- 2016
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Ingår i: Conference Digest - IEEE International Semiconductor Laser Conference. - 0899-9406. - 9784885523069 ; , s. Article no 7765757-
-
Konferensbidrag (refereegranskat)abstract
- A GaAs-based 1060 nm VCSEL with strained InGaAs/GaAsP QWs, doped DBRs, a short optical cavity, and multiple oxide apertures is presented. Modulation up to 40 Gbit/s at 25°C and 30 Gbit/s at 85°C is demonstrated.
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| 31. |
- Antonsson, J B, et al.
(författare)
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Changes in gut intramucosal pH and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage.
- 1995
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Ingår i: Critical Care Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0090-3493 .- 1530-0293. ; 23:11, s. 1872-81
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To establish the relationship between gut intramucosal pH and blood flow to the gut, gut oxygen delivery, and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage.DESIGN: Prospective, controlled study.SETTING: Experimental laboratory in a university teaching hospital.SUBJECTS: Thirty pigs of both sexes, weighing 15 to 22 kg.INTERVENTIONS: Animals were anesthetized, intubated, and mechanically ventilated. A flow probe was placed around the superior mesenteric artery for registration of blood flow. A tonometer was placed in the lumen of midileum for calculation of gut intramucosal pH. Hourly, for 5 hrs, blood samples were taken from mixed venous, mesenteric venous, and arterial blood. Five animals served as controls, ten animals had peritonitis induced by fecal instillation in the abdominal cavity, five were bled stepwise, five were bled rapidly (to a mean arterial pressure of 30 mm Hg), and five were bled rapidly and reinfused after 3 hrs.MEASUREMENTS AND MAIN RESULTS: Both peritonitis and hemorrhage caused decreases in gut blood flow and intramucosal pH. In mild peritonitis, the intramucosal pH decrease preceded that of blood flow. In all experimental groups, oxygen delivery decreased over time; in both mild and severe peritonitis, this decrease was preceded by a decrease of intramucosal pH. Intramucosal pH correlated well with gut oxygen extraction ratio in peritonitis (r2 = .86). In hemorrhage, there was a correlation of r2 = .66, but in intramucosal pH of < 7.12, a further decrease was accompanied only by minor changes in extraction ratio.CONCLUSIONS: Since a reduction in blood flow was preceded by a decrease in intramucosal pH, low intramucosal pH in peritonitis cannot be explained by low flow alone. Gut oxygen delivery proved to be a poor indicator of gut acidosis (i.e., low intramucosal pH). In peritonitis, a decreasing intramucosal pH was associated with an increasing oxygen extraction ratio. In hemorrhage, this association had a sharp deflection point below which a further decrease in intramucosal pH occurred concomitantly with an unchanged gut oxygen extraction ratio. Increased extraction ratio was not sufficient, not even initially, to maintain aerobic metabolism (i.e., unchanged intramucosal pH).
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| 36. |
- Blomqvist, P, et al.
(författare)
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Untitled - Introduction
- 2000
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Ingår i: ACTA ORTHOPAEDICA SCANDINAVICA. - 0001-6470. ; 71
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 40. |
- Bychkov, D, et al.
(författare)
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Deep learning based tissue analysis predicts outcome in colorectal cancer
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 3395-
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Tidskriftsartikel (refereegranskat)abstract
- Image-based machine learning and deep learning in particular has recently shown expert-level accuracy in medical image classification. In this study, we combine convolutional and recurrent architectures to train a deep network to predict colorectal cancer outcome based on images of tumour tissue samples. The novelty of our approach is that we directly predict patient outcome, without any intermediate tissue classification. We evaluate a set of digitized haematoxylin-eosin-stained tumour tissue microarray (TMA) samples from 420 colorectal cancer patients with clinicopathological and outcome data available. The results show that deep learning-based outcome prediction with only small tissue areas as input outperforms (hazard ratio 2.3; CI 95% 1.79–3.03; AUC 0.69) visual histological assessment performed by human experts on both TMA spot (HR 1.67; CI 95% 1.28–2.19; AUC 0.58) and whole-slide level (HR 1.65; CI 95% 1.30–2.15; AUC 0.57) in the stratification into low- and high-risk patients. Our results suggest that state-of-the-art deep learning techniques can extract more prognostic information from the tissue morphology of colorectal cancer than an experienced human observer.
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| 46. |
- Dent, R. M., et al.
(författare)
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Large-scale insertional mutagenesis of Chlamydomonas supports phylogenomic functional prediction of photosynthetic genes and analysis of classical acetate-requiring mutants
- 2015
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Ingår i: The Plant Journal. - : John Wiley & Sons. - 0960-7412 .- 1365-313X. ; 82:2, s. 337-351
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydomonas reinhardtii is a unicellular green alga that is a key model organism in the study of photosynthesis and oxidative stress. Here we describe the large-scale generation of a population of insertional mutants that have been screened for phenotypes related to photosynthesis and the isolation of 459 flanking sequence tags from 439 mutants. Recent phylogenomic analysis has identified a core set of genes, named GreenCut2, that are conserved in green algae and plants. Many of these genes are likely to be central to the process of photosynthesis, and they are over-represented by sixfold among the screened insertional mutants, with insertion events isolated in or adjacent to 68 of 597 GreenCut2 genes. This enrichment thus provides experimental support for functional assignments based on previous bioinformatic analysis. To illustrate one of the uses of the population, a candidate gene approach based on genome position of the flanking sequence of the insertional mutant CAL027_01_20 was used to identify the molecular basis of the classical C. reinhardtii mutation ac17. These mutations were shown to affect the gene PDH2, which encodes a subunit of the plastid pyruvate dehydrogenase complex. The mutants and associated flanking sequence data described here are publicly available to the research community, and they represent one of the largest phenotyped collections of algal insertional mutants to date.
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| 47. |
- Dulio, Valeria, et al.
(författare)
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Beyond target chemicals : updating the NORMAN prioritisation scheme to support the EU chemicals strategy with semi-quantitative suspect/non-target screening data
- 2024
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Ingår i: Environmental Sciences Europe. - : Springer Nature. - 2190-4707 .- 2190-4715. ; 36:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prioritisation of chemical pollutants is a major challenge for environmental managers and decision-makers alike, which is essential to help focus the limited resources available for monitoring and mitigation actions on the most relevant chemicals. This study extends the original NORMAN prioritisation scheme beyond target chemicals, presenting the integration of semi-quantitative data from retrospective suspect screening and expansion of existing exposure and risk indicators. The scheme utilises data retrieved automatically from the NORMAN Database System (NDS), including candidate substances for prioritisation, target and suspect screening data, ecotoxicological effect data, physico-chemical data and other properties. Two complementary workflows using target and suspect screening monitoring data are applied to first group the substances into six action categories and then rank the substances using exposure, hazard and risk indicators. The results from the ‘target’ and ‘suspect screening’ workflows can then be combined as multiple lines of evidence to support decision-making on regulatory and research actions.Results: As a proof-of-concept, the new scheme was applied to a combined dataset of target and suspect screening data. To this end, > 65,000 substances on the NDS, of which 2579 substances supported by target wastewater monitoring data, were retrospectively screened in 84 effluent wastewater samples, totalling > 11 million data points. The final prioritisation results identified 677 substances as high priority for further actions, 7455 as medium priority and 326 with potentially lower priority for actions. Among the remaining substances, ca. 37,000 substances should be considered of medium priority with uncertainty, while it was not possible to conclude for 19,000 substances due to insufficient information from target monitoring and uncertainty in the identification from suspect screening. A high degree of agreement was observed between the categories assigned via target analysis and suspect screening-based prioritisation. Suspect screening was a valuable complementary approach to target analysis, helping to prioritise thousands of substances that are insufficiently investigated in current monitoring programmes.Conclusions: This updated prioritisation workflow responds to the increasing use of suspect screening techniques. It can be adapted to different environmental compartments and can support regulatory obligations, including the identification of specific pollutants in river basins and the marine environments, as well as the confirmation of environmental occurrence levels predicted by modelling tools. Graphical Abstract: (Figure presented.)
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| 50. |
- Feng, L, et al.
(författare)
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Technique for strand-specific gene-expression analysis and monitoring of primer-independent cDNA synthesis in reverse transcription
- 2012
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Ingår i: BioTechniques. - : Future Science Ltd. - 1940-9818 .- 0736-6205. ; 52:4, s. 263-
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Tidskriftsartikel (refereegranskat)abstract
- Primer-independent cDNA synthesis during reverse transcription hinders quantitative analysis of bidirectional mRNA synthesis in eukaryotes as well as in cells infected with RNA viruses. We report a simple RT-PCR-based assay for strand-specific gene-expression analysis. By modifying the cDNA sequence during reverse transcription, the opposite strands of target sequences can be simultaneously detected by postamplification melting curve analysis and primer-initiated transcripts are readily distinguished from nonspecifically primed cDNA. We have utilized this technique to optimize the specificity of reverse transcription on a panel of 15 target genes. Primer-independent reverse transcription occurred for all target sequences when reverse transcription was performed at 42°C and accounted for 11%–57% of the final PCR amplification products. By raising the reaction temperature to 55°C, the specificity of reverse transcription could be increased without significant loss of sensitivity. We have also demonstrated the utility of this technique for analysis of (+) and (-) RNA synthesis of influenza A virus in infected cells. Thus, this technique represents a powerful tool for analysis of bidirectional RNA synthesis.
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