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- Piehl, F., et al.
(författare)
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Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis The RINOMAX Randomized Clinical Trial
- 2022
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157.
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown. OBJECTIVE To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden. Key inclusion criteria were age older than 18 years, onset of generalized symptoms within 12 months or less, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more. Patients were screened from October 20, 2016, to March 2, 2020. Key exclusion criteria included pure ocular MG, suspected thymoma, previous thymectomy, and prior noncorticosteroid immunosuppressants or high doses of corticosteroids. INTERVENTIONS Participants were randomized 1:1 without stratification to a single intravenous infusion of 500 mg of rituximab or matching placebo. MAIN OUTCOMES AND MEASURES Minimal disease manifestations at 16 weeks defined as a QMG score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment. RESULTS Of 87 potentially eligible patients, 25 were randomized to rituximab (mean [SD] age, 67.4 [13.4] years; 7 [28%] female) and 22 to placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). Compared with placebo, a greater proportion with rituximab met the primary end point; 71% (17 of 24) in the rituximab group vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary end points, comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between groups with censoring for rescue treatment (per-protocol analysis) but were in favor of active treatment when rescue treatment was taken into account by worst rank imputation (post hoc analysis). Rescue treatments were also more frequent in the placebo arm (rituximab: 1 [4%]; placebo, 8 [36%]). One patient in the placebo arm had a myocardial infarction with cardiac arrest and 1 patient in the active arm experienced a fatal cardiac event. CONCLUSIONS AND RELEVANCE A single dose of 500 mg of rituximab was associated with greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo. Further studies are needed to address long-term benefit-risk balance with this treatment.
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- Dufva, R
(författare)
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Blood parasites, health, reproductive success, and egg volume in female Great Tits Parus major
- 1996
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Ingår i: JOURNAL OF AVIAN BIOLOGY. - : MUNKSGAARD INT PUBL LTD. - 0908-8857. ; 27:1, s. 83-87
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The effect of different genera of blood parasites on female Great Tits Parus major was studied in central Sweden. Haemoproteus, Leucocytozoon, Hepatozoon, Plasmodium and Trypanosoma were found, but only the last mentioned had any measurable effect on the
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- Hedman, J., et al.
(författare)
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Applying a customised DNA polymerase blend in forensic DNA profiling
- 2011
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Ingår i: Book of Abstracts. ; , s. 161-
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Konferensbidrag (refereegranskat)abstract
- Crime scene stains often contain extraneous compounds that may interfere with PCR-based DNA analysis,resulting in partial or negative/blank DNA profiles. Extensive DNA purification may remove PCR inhibitors, butinvolve a risk of DNA loss and introduction of contaminations. Customising the chemical content of the PCRreaction is a strategy that may increase PCR inhibitor tolerance without manipulating the sample. Previously wehave shown that crime scene stain analysis can be significantly improved by replacing the commonly used DNApolymerase AmpliTaq Gold with either individual alternative DNA polymerases or a blend of such enzymes [1,2].Here we present the validation of AmpFℓSTR SGM Plus with a modified PCR chemistry for routine casework,applying a 1:1 blend of the DNA polymerases ExTaq Hot Start and PicoMaxx High Fidelity. Allele callings areidentical to standard analysis, and stutters sizes and balance values are indistinguishable. The modified chemistryprovides increased resistance to PCR inhibitors, resulting in an elevated number of detected alleles for crimescene stains of both blood and secretion/saliva. Additionally, the detection limit is improved.[1] Hedman, J., Nordgaard, A., Rasmusson, B., Ansell, R. and Rådström, P. (2009) Improved forensic DNA analysis through the use of alternativeDNA polymerases and statistical modeling of DNA profiles. Biotechniques, 47, 951-958.[2] Hedman, J., Nordgaard, A., Dufva, C., Rasmusson, B., Ansell, R. and Rådström, P. (2010) Synergy between
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- Moller, AP, et al.
(författare)
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Host immune function and sexual selection in birds
- 1998
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Ingår i: JOURNAL OF EVOLUTIONARY BIOLOGY. - : BLACKWELL SCIENCE LTD. - 1010-061X. ; 11:6, s. 703-719
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Parasites have been hypothesized to affect sexual selection of their hosts, if secondary sexual characters reliably signal absence of infectious parasites, superior parenting ability caused by the absence of parasites, or heritable resistance to parasites
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- Zor, K., et al.
(författare)
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A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection
- 2014
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 4:109, s. 63761-63771
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Tidskriftsartikel (refereegranskat)abstract
- Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivation and electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in both applications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring.
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