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1.
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2.
  • Abbasi, R., et al. (author)
  • Limits on a muon flux from Kaluza-Klein dark matter annihilations in the Sun from the IceCube 22-string detector
  • 2010
  • In: Physical Review D. - 1550-7998 .- 1550-2368. ; 81:5, s. 057101-
  • Journal article (peer-reviewed)abstract
    • A search for muon neutrinos from Kaluza-Klein dark matter annihilations in the Sun has been performed with the 22-string configuration of the IceCube neutrino detector using data collected in 104.3 days of live time in 2007. No excess over the expected atmospheric background has been observed. Upper limits have been obtained on the annihilation rate of captured lightest Kaluza-Klein particle (LKP) WIMPs in the Sun and converted to limits on the LKP-proton cross sections for LKP masses in the range 250-3000 GeV. These results are the most stringent limits to date on LKP annihilation in the Sun.
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3.
  • Abbasi, R., et al. (author)
  • Measurement of sound speed vs. depth in South Pole ice for neutrino astronomy
  • 2010
  • In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 33:5-6, s. 277-286
  • Journal article (peer-reviewed)abstract
    • We have measured the speed of both pressure waves and shear waves as a function of depth between 80 and 500 m depth in South Pole ice with better than 1% precision. The measurements were made using the South Pole Acoustic Test Setup (SPATS), an array of transmitters and sensors deployed in the ice at the South Pole in order to measure the acoustic properties relevant to acoustic detection of astrophysical neutrinos. The transmitters and sensors use piezoceramics operating at similar to 5-25 kHz. Between 200 m and 500 m depth, the measured profile is consistent with zero variation of the sound speed with depth, resulting in zero refraction, for both pressure and shear waves. We also performed a complementary study featuring an explosive signal propagating vertically from 50 to 2250 m depth, from which we determined a value for the pressure wave speed consistent with that determined for shallower depths, higher frequencies, and horizontal propagation with the SPATS sensors. The sound speed profile presented here can be used to achieve good acoustic source position and emission time reconstruction in general, and neutrino direction and energy reconstruction in particular. The reconstructed quantities could also help separate neutrino signals from background. (C) 2010 Elsevier B.V. All rights reserved.
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4.
  • Abbasi, R., et al. (author)
  • Measurement of the atmospheric neutrino energy spectrum from 100 GeV to 400 TeV with IceCube
  • 2011
  • In: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998 .- 1550-2368. ; 83:1, s. 012001-
  • Journal article (peer-reviewed)abstract
    • A measurement of the atmospheric muon neutrino energy spectrum from 100 GeV to 400 TeV was performed using a data sample of about 18 000 up-going atmospheric muon neutrino events in IceCube. Boosted decision trees were used for event selection to reject misreconstructed atmospheric muons and obtain a sample of up-going muon neutrino events. Background contamination in the final event sample is less than 1%. This is the first measurement of atmospheric neutrinos up to 400 TeV, and is fundamental to understanding the impact of this neutrino background on astrophysical neutrino observations with IceCube. The measured spectrum is consistent with predictions for the atmospheric nu(mu) + (nu) over bar (mu) flux.
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5.
  • Abbasi, R., et al. (author)
  • Search for point sources of high energy neutrinos with final data from AMANDA-II
  • 2009
  • In: Physical Review D. - 1550-7998 .- 1550-2368. ; 79, s. 062001-
  • Journal article (peer-reviewed)abstract
    • We present a search for point sources of high energy neutrinos using 3.8 yr of data recorded by AMANDA-II during 2000-2006. After reconstructing muon tracks and applying selection criteria designed to optimally retain neutrino-induced events originating in the northern sky, we arrive at a sample of 6595 candidate events, predominantly from atmospheric neutrinos with primary energy 100 GeV to 8 TeV. Our search of this sample reveals no indications of a neutrino point source. We place the most stringent limits to date on E(-2) neutrino fluxes from points in the northern sky, with an average upper limit of E(2)Phi(nu mu)+nu(tau)<= 5.2x10(-11) TeV cm(-2) s(-1) on the sum of nu(mu) and nu(tau) fluxes, assumed equal, over the energy range from 1.9 TeV to 2.5 PeV.
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6.
  • Abbasi, R., et al. (author)
  • The energy spectrum of atmospheric neutrinos between 2 and 200 TeV with the AMANDA-II detector
  • 2010
  • In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:1, s. 48-58
  • Journal article (peer-reviewed)abstract
    • The muon and anti-muon neutrino energy spectrum is determined from 2000-2003 AMANDA telescope data using regularised unfolding. This is the first measurement of atmospheric neutrinos in the energy range 2-200 TeV. The result is compared to different atmospheric neutrino models and it is compatible with the atmospheric neutrinos from pion and kaon decays. No significant contribution from charm had-ron decays or extraterrestrial neutrinos is detected. The capabilities to improve the measurement of the neutrino spectrum with the successor experiment IceCube are discussed.
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7.
  • Abbasi, R., et al. (author)
  • Calibration and characterization of the IceCube photomultiplier tube
  • 2010
  • In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 618:1-3, s. 139-152
  • Journal article (peer-reviewed)abstract
    • Over 5000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-in. diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts. (C) 2010 Elsevier B.V. All rights reserved.
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8.
  • Abbasi, R., et al. (author)
  • Measurement of acoustic attenuation in South Pole ice
  • 2011
  • In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:6, s. 382-393
  • Journal article (peer-reviewed)abstract
    • Using the South Pole Acoustic Test Setup (SPATS) and a retrievable transmitter deployed in holes drilled for the IceCube experiment, we have measured the attenuation of acoustic signals by South Pole ice at depths between 190 m and 500 m. Three data sets, using different acoustic sources, have been analyzed and give consistent results. The method with the smallest systematic uncertainties yields an amplitude attenuation coefficient alpha = 3.20 +/- 0.57 km(-1) between 10 and 30 kHz, considerably larger than previous theoretical estimates. Expressed as an attenuation length, the analyses give a consistent result for lambda equivalent to 1/alpha of similar to 300 m with 20% uncertainty. No significant depth or frequency dependence has been found.
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9.
  • Abbasi, R., et al. (author)
  • SEARCH FOR HIGH-ENERGY MUON NEUTRINOS FROM THE "NAKED-EYE" GRB 080319B WITH THE IceCube NEUTRINO TELESCOPE
  • 2009
  • In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 701:2, s. 1721-1731
  • Journal article (peer-reviewed)abstract
    • We report on a search with the IceCube detector for high-energy muon neutrinos from GRB 080319B, one of the brightest gamma-ray bursts (GRBs) ever observed. The fireball model predicts that a mean of 0.1 events should be detected by IceCube for a bulk Lorentz boost of the jet of 300. In both the direct on-time window of 66 s and an extended window of about 300 s around the GRB, no excess was found above background. The 90% CL upper limit on the number of track-like events from the GRB is 2.7, corresponding to a muon neutrino fluence limit of 9.5 x 10(-3) erg cm(-2) in the energy range between 120 TeV and 2.2 PeV, which contains 90% of the expected events.
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10.
  • Abbasi, R., et al. (author)
  • Search for relativistic magnetic monopoles with the AMANDA-II neutrino telescope
  • 2010
  • In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 69:3-4, s. 361-378
  • Journal article (peer-reviewed)abstract
    • We present the search for Cherenkov signatures from relativistic magnetic monopoles in data taken with the AMANDA-II detector, a neutrino telescope deployed in the Antarctic ice cap at the Geographic South Pole. The non-observation of a monopole signal in data collected during the year 2000 improves present experimental limits on the flux of relativistic magnetic monopoles: Our flux limit varies between 3.8x10(-17) cm(-2) s(-1) sr(-1) (for monopoles moving at the vacuum speed of light) and 8.8x10(-16) cm(-2) s(-1) sr(-1) (for monopoles moving at a speed beta=v/c=0.76, just above the Cherenkov threshold in ice). These limits apply to monopoles that are energetic enough to penetrate the Earth and enter the detector from below the horizon. The limit obtained for monopoles reaching the detector from above the horizon is less stringent by roughly an order of magnitude, due to the much larger background from down-going atmospheric muons. This looser limit is however valid for a larger class of magnetic monopoles, since the monopoles are not required to pass through the Earth.
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11.
  • Achterberg, A., et al. (author)
  • Multiyear search for a diffuse flux of muon neutrinos with AMANDA-II
  • 2007
  • In: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998. ; 76:4, s. 042008-
  • Journal article (peer-reviewed)abstract
    • A search for TeV-PeV muon neutrinos from unresolved sources was performed on AMANDA-II data collected between 2000 and 2003 with an equivalent live time of 807 days. This diffuse analysis sought to find an extraterrestrial neutrino flux from sources with nonthermal components. The signal is expected to have a harder spectrum than the atmospheric muon and neutrino backgrounds. Since no excess of events was seen in the data over the expected background, an upper limit of E-2 Phi(90%C.L.)< 7.4x10(-8) GeV cm(-2) s(-1) sr(-1) is placed on the diffuse flux of muon neutrinos with a Phi proportional to E-2 spectrum in the energy range 16 TeV to 2.5 PeV. This is currently the most sensitive Phi proportional to E-2 diffuse astrophysical neutrino limit. We also set upper limits for astrophysical and prompt neutrino models, all of which have spectra different from Phi proportional to E-2.
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12.
  • Abbasi, R, et al. (author)
  • Extending the Search for Neutrino Point Sources with IceCube above the Horizon
  • 2009
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:22, s. 221102-
  • Journal article (peer-reviewed)abstract
    • Point source searches with the IceCube neutrino telescope have been restricted to one hemisphere, due to the exclusive selection of upward going events as a way of rejecting the atmospheric muon background. We show that the region above the horizon can be included by suppressing the background through energy-sensitive cuts. This improves the sensitivity above PeV energies, previously not accessible for declinations of more than a few degrees below the horizon due to the absorption of neutrinos in Earth. We present results based on data collected with 22 strings of IceCube, extending its field of view and energy reach for point source searches. No significant excess above the atmospheric background is observed in a sky scan and in tests of source candidates. Upper limits are reported, which for the first time cover point sources in the southern sky up to EeV energies.
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  • Bouyoucef, S E, et al. (author)
  • Poster Session 2 : Monday 4 May 2015, 08
  • 2015
  • In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
  • Journal article (peer-reviewed)
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  • Bachar-Wikstrom, Etty, et al. (author)
  • Identification of Novel Glycans in the Mucus Layer of Shark and Skate Skin
  • 2023
  • In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - 1661-6596 .- 1422-0067. ; 24:18
  • Journal article (peer-reviewed)abstract
    • The mucus layer covering the skin of fish has several roles, including protection against pathogens and mechanical damage. While the mucus layers of various bony fish species have been investigated, the composition and glycan profiles of shark skin mucus remain relatively unexplored. In this pilot study, we aimed to explore the structure and composition of shark skin mucus through histological analysis and glycan profiling. Histological examination of skin samples from Atlantic spiny dogfish (Squalus acanthias) sharks and chain catsharks (Scyliorhinus retifer) revealed distinct mucin-producing cells and a mucus layer, indicating the presence of a functional mucus layer similar to bony fish mucus albeit thinner. Glycan profiling using liquid chromatography-electrospray ionization tandem mass spectrometry unveiled a diverse repertoire of mostly O-glycans in the mucus of the two sharks as well as little skate (Leucoraja erinacea). Elasmobranch glycans differ significantly from bony fish, especially in being more sulfated, and some bear resemblance to human glycans, such as gastric mucin O-glycans and H blood group-type glycans. This study contributes to the concept of shark skin having unique properties and provides a foundation for further research into the functional roles and potential biomedical implications of shark skin mucus glycans.
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17.
  • Bachar-Wikstrom, Etty, et al. (author)
  • Mass Spectrometry Analysis of Shark Skin Proteins
  • 2023
  • In: International Journal of Molecular Sciences. - 1661-6596 .- 1422-0067. ; 24:23
  • Journal article (peer-reviewed)abstract
    • The mucus layer covering the skin of fish has several roles, including protection against pathogens and mechanical damage in which proteins play a key role. While proteins in the skin mucus layer of various common bony fish species have been explored, the proteins of shark skin mucus remain unexplored. In this pilot study, we examine the protein composition of the skin mucus in spiny dogfish sharks and chain catsharks through mass spectrometry (NanoLC-MS/MS). Overall, we identified 206 and 72 proteins in spiny dogfish (Squalus acanthias) and chain catsharks (Scyliorhinus retifer), respectively. Categorization showed that the proteins belonged to diverse biological processes and that most proteins were cellular albeit a significant minority were secreted, indicative of mucosal immune roles. The secreted proteins are reviewed in detail with emphasis on their immune potentials. Moreover, STRING protein–protein association network analysis showed that proteins of closely related shark species were more similar as compared to a more distantly related shark and a bony fish, although there were also significant overlaps. This study contributes to the growing field of molecular shark studies and provides a foundation for further research into the functional roles and potential human biomedical implications of shark skin mucus proteins.
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  • Bergman, Lina, 1985, et al. (author)
  • Multi-Fetal Pregnancy, Preeclampsia, and Long-Term Cardiovascular Disease
  • 2020
  • In: Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0194-911X .- 1524-4563. ; 76:1, s. 167-175
  • Journal article (peer-reviewed)abstract
    • This Swedish register-based cohort study determined the separate and joint contribution of preeclampsia and multi-fetal pregnancy on a woman's risk of cardiovascular disease (CVD) later in life. The study included 892 425 first deliveries between 1973 and 2010 of women born 1950 until 1971, identified in the Swedish Medical Birth Register. A composite outcome of CVD was retrieved through linkage with the National Patient and Cause of Death Registers. Cox proportional hazard regression was used to assess the risk of CVD in women who had preeclampsia in a singleton or multi-fetal pregnancy, adjusting for potential confounders, and presented as adjusted hazard ratios. Compared with women who had a singleton pregnancy without preeclampsia (the referent group), women with preeclampsia in a singleton pregnancy had an increased risk of CVD (adjusted hazard ratio 1.75 [95% CI, 1.64-1.86]). Women who had a multi-fetal pregnancy without or with preeclampsia did not have an increased risk of future CVD (adjusted hazard ratios 0.94 [95% CI, 0.79-1.10] and 1.25 [95% CI, 0.83-1.86], respectively). As opposed to preeclampsia in a first singleton pregnancy, preeclampsia in a first multi-fetal pregnancy was not associated with increased risk of future CVD. This may support the theory that preeclampsia in multi-fetal pregnancies more often occurs as a result of the larger pregnancy-related burden on the maternal cardiovascular system and excessive placenta-shed inflammatory factors, rather than the woman's underlying cardiovascular phenotype.
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  • Franzen-Rohl, E., et al. (author)
  • Herpes simplex virus specific T cell response in a cohort with primary genital infection correlates inversely with frequency of subsequent recurrences
  • 2017
  • In: Sexually Transmitted Infections. - : BMJ. - 1368-4973 .- 1472-3263. ; 93:3
  • Journal article (peer-reviewed)abstract
    • Objectives During the last decades, a changing epidemiological pattern of genital herpes simplex virus (HSV) infection has emerged. Primary infection is now caused as often by HSV-1 as by HSV-2. Once established, HSV can be reactivated leading to recurrent mucocutaneous lesions as well as meningitis. Why some otherwise immune-competent individuals experience severe and frequent recurrences is not known, and the immunological mechanism underlying recurrent symptomatic HSV infection is not fully understood. In this study, we investigate and characterise the immune response of patients with first episode of HSV genital infection and its relation to the frequency of symptomatic recurrences. Methods In this cohort study, clinical and immunological data were collected from 29 patients who were followed 1 year after presenting with a first episode of genital or meningeal HSV infection. They were classified by PCR and serology as those with primary HSV-1, primary HSV-2 and non-primary HSV-2 infection. Results HSV-specific interleukin(Il)-4 and II-10 responses at first visit were higher in primary infected HSV-2 infected patients experiencing lower numbers of recurrences during subsequent year. Conclusions The median number of recurrences following primary HSV-2 genital infection may partly be predicted by the strength of an early HSV-specific IL-4 and IL-10 response.
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  • Gustafson, Stefan, et al. (author)
  • ICAM-1 is a cell-surface receptor for hyaluronan.
  • 1995
  • In: 6th Interscience World Conference on Inflammation, Antirheumatics, Analgesics, Immunomodulators, Geneva, Switzerland, 28-30 March, Abstract. ; 160, s. 28-
  • Review (other academic/artistic)
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  • Hillborg, H., et al. (author)
  • Crosslinked polydimethylsiloxane exposed to oxygen plasma studied by neutron reflectometry and other surface specific techniques
  • 2000
  • In: Polymer. - 0032-3861 .- 1873-2291. ; 41:18, s. 6851-6863
  • Journal article (peer-reviewed)abstract
    • Spin-coated specimens of crosslinked polydimethylsiloxane (PDMS) exposed to radio-frequency (RF) and microwave (MW) oxygen plasma were studied by specular neutron reflectometry, X-ray photoelectron spectroscopy (XPS), Wilhelmy balance, contact angle measurements, scanning electron microscopy and atomic force microscopy. Neutron reflectometry and XPS showed that the oxygen plasma led to the formation of a smooth (<10 nm), oxidised surface layer with a thickness of 130-160 nm. The oxidised layer contained a mixture of the original polymer and silicon bonded to three or four oxygen atoms (SiOx). The oxidised layer was thinner after longer plasma exposure, indicating a decrease in specific volume due to a conversion of the polymer structure to an inorganic SiOx-rich structure. The formation of the SiOx-containing layer with low segmental mobility was further confirmed by the small hysteresis in the Wilhelmy balance measurements. The similarity in the hydrophobicity recovery kinetics of specimens aged in dry air, dry argon and vacuum and XPS data showed that the hydrophobicity recovery is not due to contamination through adsorption from the atmosphere but due to migration of low molar mass PDMS species to the surface. Scanning electron microscopy also showed the presence of surface cracks in heavily oxidised specimens.
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  • Millischer, V., et al. (author)
  • Improving lithium dose prediction using population pharmacokinetics and pharmacogenomics: a cohort genome-wide association study in Sweden
  • 2022
  • In: Lancet Psychiatry. - 2215-0374. ; 9:6, s. 447-457
  • Journal article (peer-reviewed)abstract
    • Background Lithium is the most effective treatment for bipolar disorder, resulting in strong suicide prevention effects. The therapeutic range of lithium, however, is narrow and treatment initiation requires individual titration to address inter-individual variability. We aimed to improve lithium dose prediction using clinical and genomic data. Methods We performed a population pharmacokinetic study followed by a genome-wide association study (GWAS), including two clinical Swedish cohorts. Participants in cohort 1 were from specialised outpatient clinics at Huddinge Hospital, in Stockholm, Sweden, and participants in cohort 2 were identified using the Swedish National Quality Registry for Bipolar disorder (BipolaR). Patients who received a lithium dose corresponding to at least one tablet of lithium sulphate (6 mmol) per day and had clinically relevant plasma concentrations of lithium were included in the study. Data on age, sex, bodyweight, height, creatinine concentration, estimated glomerular filtration rate (eGFR), lithium preparation, number of tablets of lithium per day, serum lithium concentration, and medications affecting kidney function (C09 antihypertensives, C03 [except C03D] sodium-retaining diuretics, and non-steroidal anti-inflammatory drugs) were obtained retrospectively for several timepoints when possible from electronic health records, BipolaR, and the Swedish prescription registry. The median time between timepoints was 1.07 years for cohort 1 and 1.09 years for cohort 2. The primary outcome of interest was the natural logarithm of total body clearance for lithium (CLLi) associated with the clinical variables. The residual effects after accounting for age and sex, representing the individual-level effects (CLLi,age/sex), were used as the dependent variable in a GWAS. Findings 2357 patients who were administered lithium (1423 women [60.4%] and 934 men [39.6%]; mean age 53.6 years [range 17-89], mainly of European descent) were included and 5627 data points were obtained. Age (variance explained [R-2]: R-cohort1(2)=0.41 and R-cohort2(2)=0.31; both p<0.0001), sex (R-cohort1(2)=0.0063 [p=0.045] and R-cohort2(2)=0.026 [p<0.0001]), eGFR (R-cohort1(2)=0.38 and R-cohort2(2)=0.0; both p<0.0001), comedication with diuretics (R-cohort1(2)=0.0058 [p=0.014] and R-cohort2(2)=0.0026 [p<0.0001]), and agents acting on the renin-aldosterone-angiotensin system (R-cohort1(2)=0.028 and R-cohort2(2)=0.015; both p<0.0001) were clinical predictors of CLLi. Notably, an association between CLLi and serum lithium was observed, with a lower CLLi being associated with higher serum lithium (R-cohort1(2)=0.13 and R-cohort2(2)=0.15; both p<0.0001). In a GWAS of CLLi,age/sex, one locus was associated with a change in CLLi (rs583503; beta=-0.053 [95% CI -0.071 to -0.034]; p<0.00000005). We also found enrichment of the associations with genes expressed in the medulla (p=0.0014, corrected FDR=0.04) and cortex of the kidney (p=0.0015, corrected FDR=0.04), as well as associations with polygenic risk scores for eGFR (p value threshold: 0.05, p=0.01), body-mass index (p value threshold: 0.05, p=0.00025), and blood urea nitrogen (p value threshold: 0.001, p=0.00043). The model based on six clinical predictors explained 61.4% of the variance in CLLi in cohort 1 and 49.8% in cohort 2. Adding genetic markers did not lead to major improvement of the models: within the subsample of genotyped individuals, the variance explained only increased from 59.32% to 59.36% in cohort 1 and from 49.21% to 50.03% in cohort 2 when including rs583503 and the four first principal components. Interpretation Our model predictors could be used clinically to better guide lithium dosage, shortening the time to reach therapeutic concentrations, thus improving care. Identification of the first genomic locus and PRS to be associated with CLLi introduces the opportunity of individualised medicine in lithium treatment. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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  • Taghavi, K., et al. (author)
  • Colposcopy telemedicine: live versus static swede score and accuracy in detecting CIN2+, a cross-sectional pilot study
  • 2018
  • In: Bmc Womens Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 18:1
  • Journal article (peer-reviewed)abstract
    • Background: This cross-sectional pilot study evaluates diagnostic accuracy of live colposcopy versus static image Swede-score evaluation for detecting significant precancerous cervical lesions greater than, or equal to grade 2 severity (CIN2+). Methods: VIA or HrHPV positive women were examined using a mobile colposcope, in a rural clinic in Kolkata, India. Live versus static Swede-score colposcopy assessments were made independently. All assessments were by gynecologists, junior or expert. Static image assessors were blinded to live scoring, patient information and final histopathology result. Primary outcome was the ability to detect CIN2+ lesions verified by directed biopsies. Diagnostic accuracy was calculated for live versus static Swede-score in detecting CIN2+ lesions, as well as for interclass correlation. Results: 495 images from 94 VIA positive women were evaluated in this study. Thirteen women (13.9%) had CIN2+ on biopsy. No significant difference was found in the detection of CIN2+ lesions between live and static assessors (area under curve = 0.69 versus 0.71, p = 0.63). A Swede-score of 4+, had a sensitivity of 76.9% (95% CI 46.2-95.0%) and 84.6% (95% CI 54.6-98.1%), for live-and static-image assessment respectively. The corresponding positive predictive values were found to be 90.9% (95% CI 75.7-98.1%) and 92.6% (95% CI 75.7-99.1%). The interclass correlation was good (kappa statistic = 0.60) for the senior static assessors. Conclusions: Swede-score evaluation of static colposcopy images was found to reliably detect CIN2+ lesions in this study. Larger studies are needed to further develop the colposcopy telemedicine concept which may offer reliable guidance in management where direct specialist input is not available. Trial registration: Ethical approval of the study was obtained by the Chittaranjan National Cancer Institute (CNCI) Human Research Ethics Committee (4.311/27/2014).
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  • Tan, Lionel K.K., et al. (author)
  • Vaccine-induced, but not natural immunity, against the Streptococcal inhibitor of complement protects against invasive disease
  • 2021
  • In: npj Vaccines. - : Springer Science and Business Media LLC. - 2059-0105. ; 6
  • Journal article (peer-reviewed)abstract
    • Highly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full-length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole-blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We, therefore, propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full-length SIC permits the development of protective antibodies against all SIC domains.
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  • Enblad, Gunilla, et al. (author)
  • A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia
  • 2018
  • In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 24:24, s. 6185-6194
  • Journal article (peer-reviewed)abstract
    • Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective for patients with CD19(+) B-cell malignancies. Most studies have investigated the second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR receptor. Here, we describe the first clinical phase I/IIa trial using third-generation CAR T cells targeting CD19 to evaluate safety and efficacy.Patients and Methods: Fifteen patients with B-cell lymphoma or leukemia were treated with CAR T cells. The patients with lymphoma received chemotherapy during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled before and at multiple time points after CAR infusion to evaluate the persistence of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry, and a proteomic array.Results: Treatment with third-generation CAR T cells was generally safe with 4 patients requiring hospitalization due to adverse reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma were in remission at 3 months. Two patients are still alive. Best predictor of response was a good immune status prior to CAR infusion with high IL12, DC-Lamp, Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived suppressor cells (MDSCs; CD14(+)CD33(+)HLA(-)DR(-)) and low levels of IL6, IL8, NAP3, sPDL1, and sPDL2.Conclusions: Third-generation CARs may be efficient in patients with advanced B-cell lymphoproliferative malignancy with only modest toxicity. Immune profiling pre- and posttreatment can be used to find response biomarkers.
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