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1.
  • Agevik, Niklas, et al. (author)
  • On Loudspeaker Linearization Using Pre-Distortion
  • 2004
  • In: European DSP Education & Research Symposium (EDERS).
  • Conference paper (peer-reviewed)abstract
    • In this paper we present a system for linearizing the combined output of a stereo amplifier and loudspeaker through pre-distortion. Removal of room cancellation effects is also discussed. The system uses white noise to estimate an FIR model with the Recursive Least Squares algorithm and experiments show that this can significantly improve the linearity of the sound system. We show that the system can be extended with a nonlinear model and that this indeed can be implemented on a TexasInstruments TMS320C6701 DSP with excellent performance.
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2.
  • Alvez, Maria Bueno, et al. (author)
  • Next generation pan-cancer blood proteome profiling using proximity extension assay
  • 2023
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Journal article (peer-reviewed)abstract
    • A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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3.
  • Jemt, Anders, 1985-, et al. (author)
  • Evaluation of methods for whole genome and transcriptome sequencing from nanograms of FFPE samples
  • Other publication (other academic/artistic)abstract
    • The most widely used method for the preservation of clinical tissue specimens is formalin fixation and paraffin embedding (FFPE). Simultaneous analysis of RNA and DNA from samples preserved using this method have long proved problematic, primarily due to lack of material. Here, we describe an attempt to build a complete analysis package for RNA and DNA extracted from single tissue sections. The workflow includes quality control of the extracted material, library preparation and data analysis. We extract DNA with varying integrity from FFPE sections and subject them to whole genome sequencing using two library preparation methods, Illumina TruSeq Nano using the Illumina NeoPrep and Rubicon Genomics ThruPlex. We are able to obtain some usable data, albeit with high duplication rates, demonstrating both the possibilities and challenges of sequencing damaged DNA. Two different approaches to transcriptome sequencing are assessed, the TruSeq RNA Access library preparation kit from Illumina and the SMARTer Stranded Total RNA-Seq Kit - Pico Input from Clonetech. The sequence capture approach of the TruSeq kit is shown to be more robust to low integrity RNA compared to the SMARTer kit. However, the SMARTer kit needs much less starting material and is able to yield data about all transcripts, not just protein coding mRNA.
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4.
  • Rahm, Henrik, et al. (author)
  • Drömmen om företaget
  • 2016
  • In: Svenskans beskrivning 34 : förhandlingar vid trettiofjärde sammankomsten för svenskans beskrivning, Lund den 22-24 oktober 2014 - förhandlingar vid trettiofjärde sammankomsten för svenskans beskrivning, Lund den 22-24 oktober 2014. - 1102-3619 .- 0347-8971. - 9789187833779 - 9789187833786 ; 34, s. 399-411
  • Book chapter (peer-reviewed)
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5.
  • Abrego, Nerea, et al. (author)
  • Airborne DNA reveals predictable spatial and seasonal dynamics of fungi
  • 2024
  • In: Nature. - 0028-0836 .- 1476-4687. ; 631, s. 835-842
  • Journal article (peer-reviewed)abstract
    • Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.
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6.
  • Adamsson, Jenni, 1977, et al. (author)
  • Immune Responses Against Helicobacter pylori in Gastric Cancer Patients and in Risk Groups for Gastric Cancer.
  • 2013
  • In: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 18:1, s. 73-82
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: It has previously been reported that weak serum IgG but elevated IgA antibody responses against H.pylori may be associated with risk of gastric cancer (GC) development. To search for potential immunologic markers for GC, we analyzed antibody responses against H.pylori in risk groups of cancer development. MATERIAL AND METHODS: Sera and stomach biopsies collected from H.pylori-infected GC patients as well as from patients with gastric ulcer (GU), atrophic gastritis, intestinal metaplasia (IM) and duodenal ulcer and from H.pylori-infected control subjects without atrophy or IM, and in addition from H.pylori-negative subjects were analyzed for IgG and IgA antibodies against three different H.pylori antigen preparations, that is, membrane protein (MP), urease, and CagA. RESULTS: We observed an increased serum IgA/IgG titer ratio against H.pylori anti-MP in GC and GU patients, and against CagA in Hp-infected GC patients and risk groups. Female patients with GC had a higher serum anti-MP IgA/IgG titer ratio and a higher proportion of poorly differentiated cancer compared with male patients. As earlier observed, the non-tumorous mucosa of H.pylori-infected GC patients contained considerably lower levels of total IgA and H.pylori-specific IgA compared with H.pylori-infected controls. Similarly, we observed decreased specific mucosal anti-MP IgA response in patients with IM. CONCLUSION: We observed several differences in local and systemic immunologic responses against H.pylori in H.pylori-infected GC patients and putative GC risk group patients compared with H.pylori-infected controls. These findings may be of importance in efforts to identify risk groups of GC or early stages of GC.
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7.
  • Agebjörn, Anders, et al. (author)
  • Kvinna – motsatsen till man? : Ordet kvinna:s semantik
  • 2016
  • In: Svenskans beskrivning 34 : Förhandlingar vid Trettiofjärde sammankomsten Lund den 22–24 oktober 2014 - Förhandlingar vid Trettiofjärde sammankomsten Lund den 22–24 oktober 2014. - 0347-8971. - 9789187833779 - 9789187833786 ; 74, s. 61-77
  • Conference paper (peer-reviewed)
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8.
  • Allen-Perkins, Alfonso, et al. (author)
  • CropPol : a dynamic, open and global database on crop pollination
  • 2022
  • In: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 103:3
  • Journal article (peer-reviewed)abstract
    • Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved.
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9.
  • Anderson, Henrik, 1975- (author)
  • Development of Electroacoustic Sensors for Biomolecular Interaction Analysis
  • 2009
  • Doctoral thesis (other academic/artistic)abstract
    • Biomolecular interaction analysis to determine the kinetics and affinity between interacting partners is important for the fundamental understanding of biology, as well as for the development of new pharmaceutical substances. A quartz crystal microbalance instrument suitable for kinetics and affinity analyses of interaction events was developed. The functionality of the sensor system was demonstrated by development of an assay for relative affinity determination of lectin-carbohydrate interactions.Sensor surfaces allowing for effective immobilization of one interacting partner is a key functionality of a biosensor. Here, three different surfaces and immobilization methods were studied. First, optimized preparation conditions for sensor surfaces based on carboxyl-terminated self assembled monolayers were developed and were demonstrated to provide highly functional biosensor surfaces with low non-specific binding. Second, a method allowing for immobilization of very acidic biomolecules based on the use of an electric field was developed and evaluated. The electric field made it possible to immobilize the highly acidic C-peptide on a carboxylated surface. Third, a method for antibody immobilization on a carboxyl surface was optimized and the influence of immobilization pH on the immobilization level and antigen binding capacity was thoroughly assessed. The method showed high reproducibility for a set of antibodies and allowed for antibody immobilization also at low pH.Three broadly different strategies to increase the sensitivity of electroacoustic sensors were explored. A QCM sensor with small resonator electrodes and reduced flow cell dimensions was demonstrated to improve the mass transport rate to the sensor surface. The use of polymers on QCM sensor surfaces to enhance the sensor response was shown to increase the response of an antibody-antigen model system more than ten-fold. Moreover, the application of high frequency thin film bulk acoustic resonators for biosensing was evaluated with respect to sensing range from the surface. The linear detection range of the thin film resonator was determined to be more than sufficient for biosensor applications involving, for instance, antibody-antigen interactions. Finally, a setup for combined frequency and resistance measurements was developed and was found to provide time resolved data suitable for kinetics determination.
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10.
  • Bengtsson, Staffan, et al. (author)
  • Brandskyddsteknisk projektering
  • 2005
  • In: Brandskyddshandboken - En handbok för projektering av brandskydd i byggnader. - 1402-3504. ; , s. 21-49
  • Book chapter (other academic/artistic)
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11.
  • Bommarco, Riccardo, et al. (author)
  • Drastic historic shifts in bumble-bee community composition in Sweden
  • 2012
  • In: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954 .- 0962-8452. ; 279:1727, s. 309-315
  • Journal article (peer-reviewed)abstract
    • The species richness of flower-visiting insects has declined in past decades, raising concerns that the ecosystem service they provide by pollinating crops and wild plants is threatened. The relative commonness of different species with shared ecological traits can play a pervasive role in determining ecosystem functioning, but information on changes in abundances of pollinators over time is lacking. We gathered data on relative abundances of bumble-bee species in Swedish red clover fields during three periods in the last 70 years (1940s, 1960s and present), and on clover seed yields since 1921. We found drastic decreases in bumble-bee community evenness, with potential consequences for level and stability of red clover seed yield. The relative abundances of two short-tongued bumble-bees have increased from 40 per cent in the 1940s to entirely dominate present communities with 89 per cent. Average seed yield declined in recent years and variation in yield doubled, suggesting that the current dependence on few species for pollination has been especially detrimental to stability in seed yield. Our results suggest a need to develop management schemes that promote not only species-rich but also more evenly composed communities of service-providing organisms.
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12.
  • De Vito, Luca, et al. (author)
  • A bayesian filtering - Approach for calibrating a look-up table used for ADC error correction
  • 2005
  • In: Instrumentation and Measurement Technology Conference, 2005. IMTC 2005. Proceedings of the IEEE. - : IEEE. - 9780780388796 ; , s. 293-297
  • Conference paper (peer-reviewed)abstract
    • The paper presents a new method for the correction of non-linearity errors in ADCs. The method has been designed to allow self calibration in systems where an internal signal can be generated, such as base stations for mobile communications. The method has been implemented and tested in simulation on the behavioral model of a commercial ADCs, and on a hardware setup composed by a data acquisition board and a distorting circuit.
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13.
  • De Vito, Luca, et al. (author)
  • Bayesian calibration of a lookup table for ADC error correction
  • 2007
  • In: IEEE Transactions on Instrumentation and Measurement. - 0018-9456 .- 1557-9662. ; 56:3, s. 873-878
  • Journal article (peer-reviewed)abstract
    • This paper presents a new method for the correction of nonlinearity errors in analog-to-digital converters (ADCs). The method has been designed to allow a self-calibration in systems where an internal signal can be generated, such as base stations for mobile communications. The method has been implemented and tested in simulation on the behavioral model of commercial ADCs and on a hardware setup composed by a data acquisition board and a distorting circuit.
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16.
  • Englund, Mikael C. O., 1971, et al. (author)
  • The establishment of 20 different human embryonic stem cell lines and subclones; a report on derivation, culture, characterisation and banking.
  • 2010
  • In: In vitro cellular & developmental biology. Animal. - : Springer Science and Business Media LLC. - 1543-706X .- 1071-2690. ; 46:3-4, s. 217-30
  • Journal article (peer-reviewed)abstract
    • This report summarises our efforts in deriving, characterising and banking of 20 different human embryonic stem cell lines. We have derived a large number of human embryonic stem cell lines between 2001 and 2005. One of these cell lines was established under totally xeno-free culture conditions. In addition, several subclones have been established, including a karyoptypical normal clone from a trisomic mother line. A master cell banking system has been utilised in concert with an extensive characterisation programme, ensuring a supply of high quality pluripotent stem cells for further research and development. In this report we also present the first data on a proprietary novel antibody, hES-Cellect, that exhibits high specificity for undifferentiated hES cells. In addition to the traditional manual dissection approach of propagating hES cells, we here also report on the successful approaches of feeder-free cultures as well as single cell cultures based on enzymatic digestion. All culture systems used as reported here have maintained the hES cells in a karyotypical normal and pluripotent state. These systems also have the advantage of being the principal springboards for further scale up of cultures for industrial or clinical applications that would require vastly more cells that can be produced by mechanical means.
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17.
  • Essving, Per, 1960-, et al. (author)
  • Local Infiltration Analgesia Versus Intrathecal Morphine for Postoperative Pain Management After Total Knee Arthroplasty : A Randomized Controlled Trial
  • 2011
  • In: Anesthesia and Analgesia. - : Lippincott, Williams and Wilkins. - 0003-2999 .- 1526-7598. ; 113:4, s. 926-933
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Local infiltration analgesia (LIA)-using a combination of local anesthetics, nonsteroidal anti-inflammatory drugs, and epinephrine, injected periarticularly during surgery-has become popular in postoperative pain management after total knee arthroplasty (TKA). We compared intrathecal morphine with LIA after TKA. less thanbrgreater than less thanbrgreater thanMETHODS: In this double-blind study, 50 patients scheduled to undergo TKA under spinal anesthesia were randomized into 2 groups: group M, 0.1 mg morphine was injected intrathecally together with the spinal anesthetic and in group L, LIA using ropivacaine, ketorolac, and epinephrine was infiltrated in the knee during the operation, and 2 bolus injections of the same mixture were given via an intraarticular catheter postoperatively. Postoperative pain, rescue analgesic requirements, mobilization, and home readiness were recorded. Patient-assessed health quality was recorded using the Oxford Knee Score and EQ-5D during 3 months follow-up. The primary endpoint was IV morphine consumption the first 48 postoperative hours. less thanbrgreater than less thanbrgreater thanRESULTS: Mean morphine consumption was significantly lower in group L than in group M during the first 48 postoperative hours: 26 +/- 15 vs 54 +/- 29 mg, i.e., a mean difference for each 24-hour period of 14.2 (95% confidence interval [CI] 7.6 to 20.9) mg. Pain scores at rest and on movement were lower during the first 48 hours in group L than in group M (P andlt; 0.001). Pain score was also lower when walking in group L than in group M at 24 hours and 48 hours postoperatively (P andlt; 0.001). In group L, more patients were able to climb stairs at 24 hours: 50% (11 of 22) versus 4% (1 of 23), i.e., a difference of 46% (95% CI 23.5 to 68.5) and at 48 hours: 70% (16 of 23) versus 22% (5 of 23), i.e., a difference of 48% (95% CI 23 to 73). Median (range) time to fulfillment of discharge criteria was shorter in group L than in group M, 51 (24-166) hours versus 72 (51-170) hours. The difference was 23 (95% CI 18 to 42) hours (P = 0.001). Length of hospital stay was also shorter in group L than in group M: median (range) 3 (2-17) versus 4 (2-14) days (P = 0.029). Patient satisfaction was greater in group L than in group M (P = 0.001), but no differences were found in knee function, side effects, or in patient-related outcomes, Oxford Knee score, or EQ-5D. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: LIA technique provided better postoperative analgesia and earlier mobilization, resulting in shorter hospital stay, than did intrathecal morphine after TKA.
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18.
  • Essving, Per, 1960-, et al. (author)
  • Minimally invasive surgery did not improve outcome compared to conventional surgery following unicompartmental knee arthroplasty using local infiltration analgesia A randomized controlled trial with 40 patients
  • 2012
  • In: Acta Orthopaedica. - New York, USA : Informa Healthcare. - 1745-3674 .- 1745-3682. ; 83:6, s. 634-641
  • Journal article (peer-reviewed)abstract
    • Background and purpose: There has recently been interest in the advantages of minimally invasive surgery (MIS) over conventional surgery, and on local infiltration analgesia (LIA) during knee arthroplasty. In this randomized controlled trial, we investigated whether MIS would result in earlier home-readiness and reduced postoperative pain compared to conventional unicompartmental knee arthroplasty (UKA) where both groups received LIA.Patients and methods: 40 patients scheduled for UKA were randomized to a MIS group or a conventional surgery (CON) group. Both groups received LIA with a mixture of ropivacaine, ketorolac, and epinephrine given intra-and postoperatively. The primary endpoint was home-readiness (time to fulfillment of discharge criteria). The patients were followed for 6 months.Results: We found no statistically significant difference in home-readiness between the MIS group (median (range) 24 (21-71) hours) and the CON group (24 (21-46) hours). No statistically significant differences between the groups were found in the secondary endpoints pain intensity, morphine consumption, knee function, hospital stay, patient satisfaction, Oxford knee score, and EQ-5D. The side effects were also similar in the two groups, except for a higher incidence of nausea on the second postoperative day in the MIS group.Interpretation: Minimally invasive surgery did not improve outcome after unicompartmental knee arthroplasty compared to conventional surgery, when both groups received local infiltration analgesia. The surgical approach (MIS or conventional surgery) should be selected according to the surgeon's preferences and local hospital policies.
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19.
  • Essving, Per, 1960-, et al. (author)
  • Minimally invasive surgery did not improve outcome compared to conventional surgery following unicompartmental knee arthroplasty when using local infiltration analgesia
  • Other publication (other academic/artistic)abstract
    • Background and purpose: There has recently been focus on the advantages of minimally invasive surgery (MIS) over conventional surgery and on local infiltration analgesia (LIA) during knee arthroplasty. This prospective randomized controlled trial investigated whether MIS would result in earlier home readiness and reduced postoperative pain compared to conventional unicompartmental knee arthroplasty (UKA) where both groups received LIA. Patients and methods: 40 patients scheduled for UKA were randomized to group MIS or group CON (conventional surgery). Both groups received LIA, with a mixture of ropivacaine, ketorolac, and epinephrine, intra- and postoperatively. The primary endpoint was home readiness (time to fulfillment of discharge criteria). The patients were followed for 6 months. Results: We found no statistically significant difference in home readiness between group MIS, median (range) 24 (21–71) h compared to group CON, 24 (21–46) h. No statistically significant differences between the groups were found in the secondary endpoints: pain intensity, morphine consumption, knee function, hospital stay, patient satisfaction, Oxford Knee Score and EQ-5D. The side effects between the groups were also similar, except a higher incidence of nausea on the second postoperative day in group MIS compared with group CON. Interpretation: Minimally invasive surgery did not improve outcome after unicompartmental knee arthroplasty compared to conventional surgery, when both groups received local infiltration analgesia. The surgical approach (MIS or conventional surgery) should be selected according to surgeon’s preferences and local hospital policies. ClinicalTrials.gov. (Identifier NCT00991445). 
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20.
  • Falconer, Henrik, et al. (author)
  • Robot-assisted approach to cervical cancer (RACC) : an international multi-center, open-label randomized controlled trial
  • 2019
  • In: International Journal of Gynecological Cancer. - : BMJ Publishing Group Ltd. - 1048-891X .- 1525-1438. ; 29:6, s. 1072-1076
  • Journal article (peer-reviewed)abstract
    • Background: Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival.Primary Objective: To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy.Study Hypothesis: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes.Trial Design: Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden.Major Inclusion/Exclusion Criteria: Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years.Primary Endpoint: Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer.Sample Size: The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (alpha) of 5% and a power (1-beta) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients.Estimated Dates for Completing Accrual and Presenting Results: Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.
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21.
  • Franklin, Oskar, et al. (author)
  • Plasma micro-RNA alterations appear late in pancreatic cancer
  • 2018
  • In: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 267:4, s. 775-781
  • Journal article (peer-reviewed)abstract
    • Objectives: The aim of this research was to study whether plasma microRNAs (miRNA) can be used for early detection of pancreatic cancer (PC) by analyzing prediagnostic plasma samples collected before a PC diagnosis. Background: PC has a poor prognosis due to late presenting symptoms and early metastasis. Circulating miRNAs are altered in PC at diagnosis but have not been evaluated in a prediagnostic setting. Methods: We first performed an initial screen using a panel of 372 miRNAs in a retrospective case-control cohort that included early-stage PC patients and healthy controls. Significantly altered miRNAs at diagnosis were then measured in an early detection case-control cohort wherein plasma samples in the cases are collected before a PC diagnosis. Carbohydrate antigen 19–9 (Ca 19–9) levels were measured in all samples for comparison. Results: Our initial screen, including 23 stage I-II PC cases and 22 controls, revealed 15 candidate miRNAs that were differentially expressed in plasma samples at PC diagnosis. We combined all 15 miRNAs into a multivariate statistical model, which outperformed Ca 19–9 in receiver-operating characteristics analysis. However, none of the candidate miRNAs, individually or in combination, were significantly altered in prediagnostic plasma samples from 67 future PC patients compared with 132 matched controls. In comparison, Ca 19–9 levels were significantly higher in the cases at <5 years before diagnosis. Conclusion: Plasma miRNAs are altered in PC patients at diagnosis, but the candidate miRNAs found in this study appear late in the course of the disease and cannot be used for early detection of the disease.
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22.
  • Funestrand, Henrik, et al. (author)
  • Substandard and falsified medical products are a global public health threat. A pilot survey of awareness among physicians in Sweden
  • 2019
  • In: Journal of Public Health. - : Oxford University Press (OUP). - 1741-3850 .- 1741-3842. ; 41:1, s. 95-102
  • Journal article (peer-reviewed)abstract
    • BackgroundSubstandard and falsified medical products are a public health threat, primarily associated with low- and middle-income countries. Today, the phenomenon also exists in high-income countries. Increased Internet access has opened a global market. Self-diagnosis and self-prescription have boosted the market for unregulated websites with access to falsified medicines.AimTo describe the state of knowledge and experience on SF medical products among emergency physicians (EPs) and general practitioners (GPs) in Sweden.MethodsAn online survey with anonymous answers from 100 EPs and 100 GPs. Physicians were recruited from TNS SIFO’s medical database. The term in the survey was ‘illegal and falsified medicines’ which was common in Sweden at that time. It corresponds well with the term ‘substandard and falsified medical products’ that the WHO launched shortly after our data collection. We report our results with this term.ResultsIn Sweden, 78.5% of the physicians had heard the term ‘illegal and falsified medicines’ and 36.5% had met patients they suspected had taken it. Physicians lacked awareness of the use of the reporting system and wanted more knowledge about how to deal with patients who have possibly used falsified medicines.ConclusionsTo meet the public health threat of SF medical products, physicians need more knowledge.
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24.
  • Gulliksson, Mats, et al. (author)
  • Psychosocial factors during the first year after a coronary heart disease event in cases and referents : Secondary Prevention in Uppsala Primary Health Care Project (SUPRIM)
  • 2007
  • In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261 .- 1471-2261. ; 7, s. 36-
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: A large number of studies have reported on the psychosocial risk factor pattern prior to coronary heart disease events, but few have investigated the situation during the first year after an event, and none has been controlled. We therefore performed a case-referent study in which the prevalence of a number of psychosocial factors was evaluated. METHODS: Three hundred and forty-six coronary heart disease male and female cases no more than 75 years of age, discharged from hospital within the past 12 months, and 1038 referents from the general population, matched to the cases by age, sex and place of living, received a postal questionnaire in which information on lifestyle, psychosocial and quality of life measures were sought. RESULTS: The cases were, as expected, on sick leave to a larger extent than the referents, reported poorer fitness, poorer perceived health, fewer leisure time activities, but unexpectedly reported better social support, and more optimistic views of the future than the referents. There were no significant case-referent differences in everyday life stress, stressful life events, vital exhaustion, depressive mood, coping or life orientation test. However, women reported less favourable situations than men regarding stressful life events affecting others, vital exhaustion, depressive mood, coping, self-esteem, sleep, and symptom reporting, and female cases reported the most unfavourable situation of all groups. CONCLUSION: In this first controlled study of the situation during the first year after a CHD event disease and gender status both appeared to be determinants of psychological well-being, with gender status apparently the strongest. This may have implications for cardiac rehabilitation programmes.
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25.
  • Gulliksson, Mats, et al. (author)
  • Randomized Controlled Trial of Cognitive Behavioral Therapy vs Standard Treatment to Prevent Recurrent Cardiovascular Events in Patients With Coronary Heart Disease Secondary Prevention in Uppsala Primary Health Care Project (SUPRIM)
  • 2011
  • In: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 171:2, s. 134-140
  • Journal article (peer-reviewed)abstract
    • Background: Psychosocial factors are independently associated with increased risk of cardiovascular disease(CVD) morbidity and mortality, but the effects of psychosocial factor intervention on CVD are uncertain. We performed a randomized controlled clinical trial of cognitive behavioral therapy (CBT) to measure its effects on CVD recurrence. Methods: The study included 362 women and men 75 years or younger who were discharged from the hospital after a coronary heart disease event within the past 12 months. Patients were randomized to receive traditional care (reference group, 170 patients) or traditional care plus a CBT program (intervention group, 192 patients), focused on stress management, with 20 two-hour sessions during 1 year. Median attendance at each CBT session was 85%. Outcome variables were all-cause mortality, hospital admission for recurrent CVD, and recurrent acute myocardial infarction. Results: During a mean 94 months of follow-up, the intervention group had a 41% lower rate of fatal and non-fatal first recurrent CVD events (hazard ratio [95% confidence interval], 0.59 [0.42-0.83]; P=.002), 45% fewer recurrent acute myocardial infarctions (0.55 [0.36-0.85]; P=.007), and a nonsignificant 28% lower all-cause mortality (0.72 [0.40-1.30]; P=.28) than the reference group after adjustment for other outcome-affecting variables. In the CBT group there was a strong dose-response effect between intervention group attendance and outcome. During the first 2 years of follow-up, there were no significant group differences in traditional risk factors. Conclusions: A CBT intervention program decreases the risk of recurrent CVD and recurrent acute myocardial infarction. This may have implications for secondary preventive programs in patients with coronary heart disease.
  •  
26.
  • Gunnarsson, Rebeqa, et al. (author)
  • Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia
  • 2011
  • In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 96:8, s. 1161-1169
  • Journal article (peer-reviewed)abstract
    • Background High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic profiles from sequential patients' samples allows detection of clonal evolution. Design and Methods We screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia from a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples obtained after 5-9 years. Results At diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number neutral loss of heterozygosity on 13q, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (n=10) did not acquire additional aberrations. The most common secondary event, del(13q), was detected in 6/12 (50%) of all patients with acquired alterations. Interestingly, aberrations on, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated IGHV. Conclusions Whole-genome screening revealed a high frequency of genomic aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution was associated with other markers of aggressive disease and commonly included the known recurrent aberrations.
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27.
  • Gunnarsson, Rebeqa, et al. (author)
  • Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia
  • 2018
  • In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 32:10, s. 2117-2125
  • Journal article (peer-reviewed)abstract
    • High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.
  •  
28.
  • Guoqiang, Zhang, 1980-, et al. (author)
  • Adaptive Playout Scheduling for Voice over IP : Event-Triggered Control Policy
  • In: IEEE Multimedia. - 1070-986X .- 1941-0166.
  • Journal article (other academic/artistic)abstract
    • We study adaptive-playout scheduling for Voice over IP using the frame-work of stochastic impulse control theory. We use the Wiener process tomodel the fluctuation of the buffer length in the absence of control. In thiscontext, the control signal consists of length units that correspond to insert-ing or dropping a pitch cycle. We define an optimality criterion that hasan adjustable trade-off between average buffering delay and average controlsignal (the length of the pitch cycles added plus the length of the pitch cyclesdropped), and show that a band control policy is optimal for this criterion.The band control policy maintains the buffer length within a band regionby imposing impulse control (inserted or dropped pitch cycles) whenever thebounds of the band are reached. One important property of the band controlpolicy is that it incurs no packet-loss through buffering if there are no out-of-order packet-arrivals. Experiments performed on both synthetic and realnetwork-delay traces show that the proposed playout scheduling algorithmoutperforms two recent algorithms in most cases.
  •  
29.
  • Hartman, Henrik, et al. (author)
  • Experimental oscillator strengths for forbidden lines in complex spectra
  • 2005
  • In: Physica Scripta. - 0281-1847. ; T119, s. 40-44
  • Conference paper (peer-reviewed)abstract
    • In dilute astrophysical plasmas, such as planetary nebulae and H II regions, strong lines appear that only have weak, if any, correspondence to the spectrum of laboratory light sources. Some of these are parity forbidden lines, i.e. emission from long-lived metastable states that cannot decay via normal electric dipole (E1) routes but only via the slower M1 and E2 transitions. The long lifetime of the upper levels and their sensitivity to collisions make the lines good diagnostics of the emitting plasma, but then the transition probability, or A-value, of these lines must be known. We report on a technique to experimentally determine A-values for forbidden lines using the method of combining the lifetime of the upper level with the branching fractions for the different decay channels. The lifetime is measured using the laser probing technique (LPT) on a stored ion beam. Since these lines are rarely produced in laboratory plasmas, we use astrophysical spectra to determine the branching fractions (BF). The lifetime and the BF then give the A-value, which is one quantity needed for modeling the spectrum of the plasma emitting the forbidden lines. The present measurements are performed within the FERRUM project, an international collaboration producing and evaluating transition probabilities for iron group element lines of astrophysical importance [Johansson, P. I. S. et al., Physica Scripta T100, 71 (2002).]
  •  
30.
  • Hartman, Henrik, et al. (author)
  • The FERRUM project : experimentally determined metastable lifetimes and transition probabilities for forbidden [Ti II] lines observed in eta Carinae
  • 2005
  • In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 361:1, s. 206-210
  • Journal article (peer-reviewed)abstract
    • In the spectrum of an emission-line region ejected from the massive star Eta Carinae, called the strontium filament (SrF), forbidden lines from many elements, in particular [Sr II] and [Ti II], are observed. These lines are strong in this specific region and valuable for plasma diagnostics. Forbidden lines are not easily produced in laboratory light sources and the atomic parameters for these lines can thus not be measured in a straightforward way. We use a combination of laboratory and astrophysical measurements to determine transition probabilities for the [Ti II] lines. Lifetimes for metastable levels in Ti II are measured using a laser probing technique on a stored ion beam at CRYRING, MSL, Stockholm. Branching fractions from some of these levels are derived from Hubble Space Telescope/STIS spectra of the SrF. The astrophysical branching fractions are combined with the experimental lifetimes to determine absolute transition probabilities. We report lifetimes for the Ti II levels b(4)P(3/2), b(2)P(1/2), c(2)D(3/2) and c(2)D(5/2), in the range 0.29-17 s, and transition probabilities for eight parity-forbidden lines from the levels c(2)D(3/2) and c(2)D(5/2), along with uncertainty estimates.
  •  
31.
  • Hartman, Henrik, et al. (author)
  • The FERRUM project : experimental and theoretical transition rates of forbidden [Sc II] lines and radiative lifetimes of metastable ScII levels
  • 2008
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 480:2, s. 575-580
  • Journal article (peer-reviewed)abstract
    • Context. In many plasmas, long-lived metastable atomic levels are depopulated by collisions (quenched) before they decay radiatively. In low-density regions, however, the low collision rate may allow depopulation by electric dipole (E1) forbidden radiative transitions, so-called forbidden lines (mainly M1 and E2 transitions). If the atomic transition data are known, these lines are indicators of physical plasma conditions and used for abundance determination. Aims. Transition rates can be derived by combining relative intensities between the decay channels, so-called branching fractions (BFs), and the radiative lifetime of the common upper level. We use this approach for forbidden [Sc II] lines, along with new calculations. Methods. Neither BFs for forbidden lines, nor lifetimes of metastable levels, are easily measured in a laboratory. Therefore, astrophysical BFs measured in Space Telescope Imaging Spectrograph (STIS) spectra of the strontium filament of Eta Carinae are combined with lifetime measurements using a laser probing technique on a stored ion-beam (CRYRING facility, MSL, Stockholm). These quantities are used to derive the absolute transition rates (A-values). New theoretical transition rates and lifetimes are calulated using the CIV3 code. Results. We report experimental lifetimes of the Sc II levels 3d(2) a(3)P(0,1,2) with lifetimes 1.28, 1.42, and 1.24 s, respectively, and transition rates for lines from these levels down to 3d4s a(3)D in the region 8270-8390 angstrom. These are the most important forbidden [Sc II] transitions. New calculations for lines and metastable lifetimes are also presented, and are in good agreement with the experimental data.
  •  
32.
  • Hartman, Henrik, et al. (author)
  • The FERRUM project: an extremely long radiative lifetime in Ti II measured in an ion storage ring
  • 2003
  • In: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 36, s. 197-202
  • Journal article (peer-reviewed)abstract
    • We have extended the laser probing technique at the CRYRING storage ring to measurement of the extremely long lifetime (28 s) of the metastable 3d2(3P)4s b 4P5/2 level in Ti II. The result obtained demonstrates the power of this method for investigation of such long-lived levels. This is the first experimental lifetime investigation of metastable states in Ti II.
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33.
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34.
  • Herlemann, Daniel P. R., et al. (author)
  • Metagenomic De Novo Assembly of an Aquatic Representative of the Verrucomicrobial Class Spartobacteria
  • 2013
  • In: mBio. - 2161-2129 .- 2150-7511. ; 4:3, s. e00569-12-
  • Journal article (peer-reviewed)abstract
    • The verrucomicrobial subdivision 2 class Spartobacteria is one of the most abundant bacterial lineages in soil and has recently also been found to be ubiquitous in aquatic environments. A 16S rRNA gene study from samples spanning the entire salinity range of the Baltic Sea indicated that, in the pelagic brackish water, a phylotype of the Spartobacteria is one of the dominating bacteria during summer. Phylogenetic analyses of related 16S rRNA genes indicate that a purely aquatic lineage within the Spartobacteria exists. Since no aquatic representative from the Spartobacteria has been cultured or sequenced, the metabolic capacity and ecological role of this lineage are yet unknown. In this study, we reconstructed the genome and metabolic potential of the abundant Baltic Sea Spartobacteria phylotype by metagenomics. Binning of genome fragments by nucleotide composition and a self-organizing map recovered the near-complete genome of the organism, the gene content of which suggests an aerobic heterotrophic metabolism. Notably, we found 23 glycoside hydrolases that likely allow the use of a variety of carbohydrates, like cellulose, mannan, xylan, chitin, and starch, as carbon sources. In addition, a complete pathway for sulfate utilization was found, indicating catabolic processing of sulfated polysaccharides, commonly found in aquatic phytoplankton. The high frequency of glycoside hydrolase genes implies an important role of this organism in the aquatic carbon cycle. Spatiotemporal data of the phylotype's distribution within the Baltic Sea indicate a connection to Cyanobacteria that may be the main source of the polysaccharide substrates. IMPORTANCE The ecosystem roles of many phylogenetic lineages are not yet well understood. One such lineage is the class Spartobacteria within the Verrucomicrobia that, despite being abundant in soil and aquatic systems, is relatively poorly studied. Here we circumvented the difficulties of growing aquatic Verrucomicrobia by applying shotgun metagenomic sequencing on a water sample from the Baltic Sea. By using a method based on sequence signatures, we were able to in silico isolate genome fragments belonging to a phylotype of the Spartobacteria. The genome, which represents the first aquatic representative of this clade, encodes a diversity of glycoside hydrolases that likely allow degradation of various complex carbohydrates. Since the phylotype cooccurs with Cyanobacteria, these may be the primary producers of the carbohydrate substrates. The phylotype, which is highly abundant in the Baltic Sea during summer, may thus play an important role in the carbon cycle of this ecosystem.
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35.
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36.
  • Hjalmarson, Åke, et al. (author)
  • Recent astronomy highlights from the Odin satellite
  • 2005
  • In: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 36, s. 1031-1047
  • Journal article (peer-reviewed)abstract
    • Astronomy highlights, mainly from the third year of Odin observations time shared 50/50% with aeronomy are presented: the very low O2 abundance limits achieved, the highly pressure broadened absorption lines of H2O, H218O, and CO (5 → 4) in the atmosphere of Mars, the high precision H2O and H218O observations of comets, the detections of NH3 and H2O around the C-rich star IRC+10216 (CW Leo) and of H2O around the O-rich star W Hya, NH3 and H2O observations of infall/outflow interactions, observations of H2O, H218O, H217O as well as NH3 and 15NH3 in multiple absorptions towards Sgr B2, and in emission towards Orion KL, the H2O detection of several new outflows in the DR21 W75S region. We also discuss the results of deconvolution of high S/N H2O, CO and 13CO (5 → 4) maps of the Orion KL region to 40″ resolution (the beam size of the Herschel telescope) and the first results from our ongoing “spectral scan” of Orion KL in bands around 555 and 570 GHz. Finally, a search for primordial molecules is presented.
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37.
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38.
  • Holm, Lisa, et al. (author)
  • Lexikala profiler i några nutida romaner
  • 2016
  • In: Svenskans beskrivning 34 : Förhandlingar vid trettiofjärde sammankomsten. Lund den 22–24 oktober 2014 - Förhandlingar vid trettiofjärde sammankomsten. Lund den 22–24 oktober 2014. - 0347-8971. - 9789187833779 ; 74, s. 201-213
  • Conference paper (peer-reviewed)
  •  
39.
  • Holmén, Nathalie, 1979, et al. (author)
  • Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity.
  • 2006
  • In: Inflammatory bowel diseases. - 1078-0998. ; 12:6, s. 447-56
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Factors determining the extension and degree of inflammation in the colonic mucosa of patients with ulcerative colitis (UC) are largely unknown, but CD4+CD25high regulatory T cells (Tregs) have been implicated to play an important role in suppressing inflammation. Therefore, the aims of this study were to determine whether colonic Tregs have suppressive effects on colonic effector T cells in UC and to analyze the association between segmental colonic Treg distribution and disease activity. MATERIALS AND METHODS: The suppressive activity of colonic CD4+CD25high Tregs from patients with active UC was determined in coculture assays measuring proliferation and cytokine production. The frequency of Tregs and the expression of the Treg marker FOXP3 were analyzed with flow cytometry and RT-PCR in isolated cells and the whole mucosa from patients with active and inactive disease, as well as healthy mucosa. RESULTS: Colonic CD4+CD25high T cells from patients with UC suppressed the proliferation and cytokine secretion of colonic effector CD4+ T cells. Healthy controls but not patients with UC had lower Treg frequencies in the sigmoid than in the ascending colon. Patients with UC with active disease had increased frequency of colonic Tregs. The frequency of Tregs was positively correlated with colonic disease activity and serum C-reactive protein. CONCLUSIONS: Colonic CD4+CD25high Tregs are able to suppress colonic effector T cell activity in vitro, and the Treg frequency in the inflamed intestine increases with disease activity in patients with active UC. This suggests that Tregs may be outnumbered by other inflammatory cells or that their suppressive activity may be influenced by the in vivo environment.
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40.
  • Händel, Peter, 1962-, et al. (author)
  • Adaptively calibrating analog-to-digital conversion with correction table indexing
  • 2000
  • Patent (pop. science, debate, etc.)abstract
    • Methods, systems, and arrangements enable true wide-band calibration of analog-to-digital conversion (ADC) using correction table indexing (350, 660). The frequency of an analog input signal that corresponds to a digital output sample is accounted for, at least partially, when accessing a correction table (350, 660) during the creation and use thereof. For example, in addition to at least a portion of a current sample, at least portion(s) of previous and/or subsequent samples may be used to build (805) (e.g., by bit concatenation) an index for addressing a correction table memory. In effect, compensation may be achieved for ADC errors that are frequency dependent. This correction table (350; 660) indexing may advantageously be employed along with a scheme that estimates (1020A) one or more parameters of the analog input signal in the digital domain on a sample-by-sample basis in order to reconstruct the analog input signal in the digital domain.
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41.
  • Jiao, Xiang, et al. (author)
  • PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1
  • 2017
  • In: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 8:61, s. 102769-102782
  • Journal article (peer-reviewed)abstract
    • Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.
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42.
  • Jungebluth, Philipp, et al. (author)
  • Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite : a proof-of-concept study
  • 2011
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9808, s. 1997-2004
  • Journal article (peer-reviewed)abstract
    • Background Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. Methods A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 mu g/kg) and epoetin beta (40 000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. Findings We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after trans plantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Post-operatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. Interpretation Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome.
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43.
  • Kindlund, Bert, 1969, et al. (author)
  • FOXP3-expressing CD4(+) T-cell numbers increase in areas of duodenal gastric metaplasia and are associated to CD4(+) T-cell aggregates in the duodenum of Helicobacter pylori-infected duodenal ulcer patients.
  • 2009
  • In: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 14:3, s. 192-201
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: We have previously demonstrated that Helicobacter pylori infection is associated with an increased number of CD4(+)CD25(high) regulatory T cells in the gastric and duodenal mucosa. In this study, we determined the number and localization of CD4(+) cells expressing the regulatory T-cell-specific transcription factor FOXP3 in the antrum and duodenum of duodenal ulcer patients, asymptomatic carriers, and uninfected individuals. We also determined gene expression levels of FOXP3 as well as anti- and proinflammatory cytokines before and after H. pylori eradication. METHODS: Cellular FOXP3 expression was studied by immunofluorescence and flow cytometry, and transcription levels of FOXP3, interleukin (IL)-10, transforming growth factor-beta, CD4, and interferon-gamma were analyzed by real-time reverse transcription-polymerase chain reaction. RESULTS: We found an increased (6-fold) frequency of CD4(+)FOXP3(+) T cells in H. pylori-infected gastric mucosa; interestingly 26% of these cells did not co-express CD25. The increase of FOXP3-expressing T cells in the antrum of infected individuals was dependent on the presence of H. pylori, since eradication therapy resulted in 4-fold lower levels of FOXP3 and IL-10 mRNA in the antrum. Furthermore, higher numbers of CD4(+)FOXP3(+) T cells were found in areas of duodenal gastric metaplasia in the duodenum of duodenal ulcer patients compared to duodenal gastric metaplasia of asymptomatic individuals and healthy mucosa in both patient groups. In duodenal ulcer patients, the CD4(+)FOXP3(+) T cells were more highly associated to aggregates in the duodenal mucosa. CONCLUSION: The numbers of CD4(+)FOXP3(+) T cells are increased and localized in CD4(+) T-cell aggregates in areas of duodenal gastric metaplasia in duodenal ulcer patients.
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44.
  • Knauss, Alessia, 1983, et al. (author)
  • Proving Ground Support for Automation of Testing of Active Safety Systems and Automated Vehicles
  • 2017
  • In: 4th International Symposium on Future Active Safety Technology towards Zero-Traffic-Accidents (FAST-zero).
  • Conference paper (peer-reviewed)abstract
    • Research in the area of autonomous vehicles is advancing in a fast pace. Companies focus on delivering vehicles with automated driving functions, where the driver still has to monitor the vehicle. While the advancements on algorithm development are enormous, the area of testing and verifying such kind of vehicles is still in a very early stage. Testing of active safety systems is well established already and a first step in this direction. However, the methods and techniques currently used for testing of active safety systems at the proving grounds will not scale to testing of automated vehicles. This will result in high costs and efforts – if done manually as it mianly is now. Hence, automation of testing at proving grounds is a necessary step in the direction of testing autonomous vehicles. In this paper, we present a study on the proving ground support needed for test automation of active safety and autonomous vehicle testing. We show that the focus should be on data and equipment related aspects to move in the direction of automated testing of autonomous vehicles.
  •  
45.
  • Larsson, Bengt, et al. (author)
  • Molecular oxygen in the rho Ophiuchi cloud
  • 2007
  • In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 466:3, s. 5-
  • Journal article (peer-reviewed)abstract
    • Context: Molecular oxygen, O2, has been expected historically to be an abundant component of the chemical species in molecular clouds and, as such, an important coolant of the dense interstellar medium. However, a number of attempts from both ground and from space have failed to detect O2 emission.Aims: The work described here uses heterodyne spectroscopy from space to search for molecular oxygen in the interstellar medium. Methods: The Odin satellite carries a 1.1 m sub-millimeter dish and a dedicated 119 GHz receiver for the ground state line of O2. Starting in 2002, the star forming molecular cloud core ρ Oph A was observed with Odin for 34 days during several observing runs.Results: We detect a spectral line at v_LSR =+3.5 km s-1 with Δ v_FWHM=1.5 km s-1, parameters which are also common to other species associated with ρ Oph A. This feature is identified as the O2 (NJ = 11 - 1_0) transition at 118 750.343 MHz.Conclusions: The abundance of molecular oxygen, relative to H{2} , is 5 × 10-8 averaged over the Odin beam. This abundance is consistently lower than previously reported upper limits.Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Étude Spatiale (CNES). The Swedish Space Corporation has been the industrial prime contractor and also is operating the satellite. Appendix A is only available in electronic form at http://www.aanda.org
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46.
  • Lidgard, Hans Henrik, et al. (author)
  • Are European patents obstacles to Swedish cancer research?
  • 2002
  • In: Gene technology and economy. - 9189116259 ; , s. 52-71
  • Book chapter (peer-reviewed)abstract
    • Professor Håkan Olsson, Lund has addressed the problems caused by patenting in the field of biotechnology. His article was triggered by patent protection acquired by the American company Myriad Genetics. According to HO, Myriad requires that analyses of blood to trace the occurrence of these genes should be carried out in the company’s American laboratories, at a significant cost. Profit is infringing on the freedom of academic research and HO therefore asks: • Is it reasonable to patent “inventions” in gene technology? • Can patent protection be allowed to impede urgent, serious and non-commercial research? • Can patent protection be circumvented by coercive measures? • Should patentees be able to monopolize analytical work in medical care? In this article I examine the system from a legal perspective. Are there solutions to the problems encountered by a researching physician, or must the rules be changed?
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47.
  • Lindskog, Henrik, 1977, et al. (author)
  • New insights to vascular smooth muscle cell and pericyte differentiation of mouse embryonic stem cells in vitro.
  • 2006
  • In: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 26:7, s. 1457-64
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The molecular mechanisms that regulate pericyte differentiation are not well understood, partly because of the lack of well-characterized in vitro systems that model this process. In this article, we develop a mouse embryonic stem (ES) cell-based angiogenesis/vasculogenesis assay and characterize the system for vascular smooth muscle cell (VSMC) and pericyte differentiation. METHODS AND RESULTS: ES cells that were cultured for 5 days on OP9 stroma cells upregulated their transcription of VSMC and pericyte selective genes. Other SMC marker genes were induced at a later time point, which suggests that vascular SMC/pericyte genes are regulated by a separate mechanism. Moreover, sequence analysis failed to identify any conserved CArG elements in the vascular SMC and pericyte gene promoters, which indicates that serum response factor is not involved in their regulation. Gleevec, a tyrosine kinase inhibitor that blocks platelet-derived growth factor (PDGF) spell-receptor signaling, and a neutralizing antibody against transforming growth factor (TGF) beta1, beta2, and beta3 failed to inhibit the induction of vascular SMC/pericyte genes. Finally, ES-derived vascular sprouts recruited cocultured MEF cells to pericyte-typical locations. The recruited cells activated expression of a VSMC- and pericyte-specific reporter gene. CONCLUSIONS: We conclude that OP9 stroma cells induce pericyte differentiation of cocultured mouse ES cells. The induction of pericyte marker genes is temporally separated from the induction of SMC genes and does not require platelet-derived growth factor B or TGFbeta1 signaling.
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48.
  • Lindstrand, Anna, et al. (author)
  • From cytogenetics to cytogenomics : whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability
  • 2019
  • In: Genome Medicine. - : BMC. - 1756-994X. ; 11:1
  • Journal article (peer-reviewed)abstract
    • BackgroundSince different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.MethodsWe analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n=68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n=156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.ResultsFirst, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850kb (min 500bp, max 155Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (>10kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data.Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively.ConclusionThe overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
  •  
49.
  • Lundin, Andreas, et al. (author)
  • Discriminant validity of the 12-item version of the general health questionnaire in a Swedish case-control study
  • 2017
  • In: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 71:3, s. 171-179
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The 12-item version of the General Health Questionnaire (GHQ-12) is widely used as a proxy for Affective Disorders in public health surveys, although the cut-off points for distress vary considerably between studies. The agreement between the GHQ-12 score and having a clinical disorder in the study population is usually unknown.AIMS: This study aimed to assess the criterion validity and to determine the sensitivity and specificity of the GHQ-12 in the Swedish population.METHODS: This study used 556 patient cases surveyed in specialized psychiatric care outpatient age- and sex-matched with 556 controls from the Stockholm Health Survey. Criterion validity for two scoring methods of GHQ-12 was tested using Receiver Operating Characteristics (ROC) analyses with Area Under the Curve (AUC) as a measure of agreement. Reference standard was (1) specialized psychiatric care and (2) current depression, anxiety or adjustment disorder.RESULTS: Both the Likert and Standard GHQ-12 scoring method discriminated excellently between individuals using specialized psychiatric services and healthy controls (Likert index AUC = 0.86, GHQ index AUC = 0.83), and between individuals with current disorder from healthy controls (Likert index AUC = 0.90, GHQ index AUC = 0.88). The best cut-off point for the GHQ index was ≥4 (sensitivity = 81.7 and specificity = 85.4), and for the Likert index ≥14 (sensitivity = 85.5 and specificity = 83.2).CONCLUSIONS: The GHQ-12 has excellent discriminant validity and is well suited as a non-specific measure of affective disorders in public mental health surveys.
  •  
50.
  • Lundin, Anders, et al. (author)
  • Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models
  • 2018
  • In: Stem Cell Reports. - : Cell Press. - 2213-6711. ; 10:3, s. 1030-1045
  • Journal article (peer-reviewed)abstract
    • In vivo studies of human brain cellular function face challenging ethical and practical difficulties. Animal models are typically used but display distinct cellular differences. One specific example is astrocytes, recently recognized for contribution to neurological diseases and a link to the genetic risk factor apolipoprotein E (APOE). Current astrocytic in vitro models are questioned for lack of biological characterization. Here, we report human induced pluripotent stem cell (hiPSC)-derived astroglia (NES-Astro) developed under defined conditions through long-term neuroepithelial-like stem (ltNES) cells. We characterized NES-Astro and astrocytic models from primary sources, astrocytoma (CCF-STTG1), and hiPSCs through transcriptomics, proteomics, glutamate uptake, inflammatory competence, calcium signaling response, and APOE secretion. Finally, we assess modulation of astrocyte biology using APOE-annotated compounds, confirming hits of the cholesterol biosynthesis pathway in adult and hiPSC-derived astrocytes. Our data show large diversity among astrocytic models and emphasize a cellular context when studying astrocyte biology.
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