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1.
  • Thomas, HS, et al. (author)
  • 2019
  • swepub:Mat__t
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  • Griffin, M. J., et al. (author)
  • The Herschel-SPIRE instrument and its in-flight performance
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L3-
  • Journal article (peer-reviewed)abstract
    • The Spectral and Photometric Imaging REceiver (SPIRE), is the Herschel Space Observatory`s submillimetre camera and spectrometer. It contains a three-band imaging photometer operating at 250, 350 and 500 mu m, and an imaging Fourier-transform spectrometer (FTS) which covers simultaneously its whole operating range of 194-671 mu m (447-1550 GHz). The SPIRE detectors are arrays of feedhorn-coupled bolometers cooled to 0.3 K. The photometer has a field of view of 4' x 8', observed simultaneously in the three spectral bands. Its main operating mode is scan-mapping, whereby the field of view is scanned across the sky to achieve full spatial sampling and to cover large areas if desired. The spectrometer has an approximately circular field of view with a diameter of 2.6'. The spectral resolution can be adjusted between 1.2 and 25 GHz by changing the stroke length of the FTS scan mirror. Its main operating mode involves a fixed telescope pointing with multiple scans of the FTS mirror to acquire spectral data. For extended source measurements, multiple position offsets are implemented by means of an internal beam steering mirror to achieve the desired spatial sampling and by rastering of the telescope pointing to map areas larger than the field of view. The SPIRE instrument consists of a cold focal plane unit located inside the Herschel cryostat and warm electronics units, located on the spacecraft Service Module, for instrument control and data handling. Science data are transmitted to Earth with no on-board data compression, and processed by automatic pipelines to produce calibrated science products. The in-flight performance of the instrument matches or exceeds predictions based on pre-launch testing and modelling: the photometer sensitivity is comparable to or slightly better than estimated pre-launch, and the spectrometer sensitivity is also better by a factor of 1.5-2.
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  • Fattibene, P, et al. (author)
  • The 4th international comparison on EPR dosimetry with tooth enamel Part 1: Report on the results
  • 2011
  • In: Radiation Measurements. - : Elsevier. - 1350-4487 .- 1879-0925. ; 46:9, s. 765-771
  • Journal article (peer-reviewed)abstract
    • This paper presents the results of the 4th International Comparison of in vitro electron paramagnetic resonance dosimetry with tooth enamel, where the performance parameters of tooth enamel dosimetry methods were compared among sixteen laboratories from all over the world. The participating laboratories were asked to determine a calibration curve with a set of tooth enamel powder samples provided by the organizers. Nine molar teeth extracted following medical indication from German donors and collected between 1997 and 2007 were prepared and irradiated at the Helmholtz Zentrum Munchen. Five out of six samples were irradiated at 0.1, 0.2, 0.5, 1.0 and 1.5 Gy air kerma; and one unirradiated sample was kept as control. The doses delivered to the individual samples were unknown to the participants, who were asked to measure each sample nine times, and to report the EPR signal response, the mass of aliquots measured, and the parameters of EPR signal acquisition and signal evaluation. Critical dose and detection limit were calculated by the organizers on the basis of the calibration-curve parameters obtained at every laboratory. For calibration curves obtained by measuring every calibration sample three times, the mean value of the detection limit was 205 mGy, ranging from 56 to 649 mGy. The participants were also invited to provide the signal response and the nominal dose of their current dose calibration curve (wherever available), the critical dose and detection limit of which were also calculated by the organizers.
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  • Cherif, M. K., et al. (author)
  • Fc gamma RIIa Polymorphism and Anti-Malaria-Specific IgG and IgG Subclass Responses in Populations Differing in Susceptibility to Malaria in Burkina Faso
  • 2012
  • In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 75:6, s. 606-613
  • Journal article (peer-reviewed)abstract
    • Fc?RIIa is known to be polymorphic; and certain variants are associated with different susceptibilities to malaria. Studies involving the Fulani ethnic group reported an ethnic difference in Fc?RIIa-R131H genotype frequencies between the Fulani and other sympatric groups. No previous studies have addressed these questions in Burkina Faso. This study aimed to assess the influence of Fc?RIIa-R131H polymorphism on anti-falciparum malaria IgG and IgG subclass responses in the Fulani and the Mossi ethnic groups living in Burkina Faso. Healthy adults more than 20 years old belonging to the Mossi or the Fulani ethnic groups were enrolled for the assessment of selected parasitological, immunological and genetic variables in relation to their susceptibility to malaria. The prevalence of the Plasmodium falciparum infection frequency was relatively low in the Fulani ethnic group compared to the Mossi ethnic group. For all tested antigens, the Fulani had higher antibody levels than the Mossi group. In both ethnic groups, a similar distribution of Fc?RIIa R131H polymorphism was found. Individuals with the R allele of Fc?RIIa had higher antibody levels than those with the H allele. This study confirmed that malaria infection affected less the Fulani group than the Mossi group. Fc?RIIa-R131H allele distribution is similar in both ethnic groups, and higher antibody levels are associated with the Fc?RIIa R allele compared to the H allele.
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  • Clarke, Robert, et al. (author)
  • Lowering blood homocysteine with folic acid based supplements : Meta-analysis of randomised trials
  • 1998
  • In: British Medical Journal. - : BMJ. - 0959-8146. ; 316:7135, s. 894-898
  • Research review (peer-reviewed)abstract
    • Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B-12 or B-6. Design: Meta-analysis of randomised controlled trials that assessed the effects of folic acid based supplements on blood homocysteine concentration. Multivariate regression analysis was used to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-12 or B-6. Subjects: Individual data on 1114 people included in 12 trials. Findings: The proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pretreatment blood homocysteine concentrations (P < 0.001) and at lower pretreatment blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 μmol/l and of folate of 12 nmol/l (approximate average concentrations for Western populations), dietary folic acid reduced blood homocysteine concentrations by 25% (95% confidence interval 23% to 28%; P < 0.001), with similar effects in the range of 0.5-5 mg folic acid daily. Vitamin B-12 (mean 0.5 mg daily) produced an additional 7% (3% to 10%) reduction in blood homocysteine. Vitamin B-6 (mean 16.5 mg daily) did not have a significant additional effect. Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 μmol/l to 8-9 μmol/l). Large scale randomised trials of such regimens in high risk populations are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease.
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  • Jevnikar, Z., et al. (author)
  • Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation
  • 2019
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 143:2, s. 577-590
  • Journal article (peer-reviewed)abstract
    • Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.
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  • Muysoms, F. E., et al. (author)
  • European Hernia Society guidelines on the closure of abdominal wall incisions
  • 2015
  • In: Hernia. - : Springer Science and Business Media LLC. - 1265-4906 .- 1248-9204. ; 19:1, s. 1-24
  • Research review (peer-reviewed)abstract
    • Background The material and the surgical technique used to close an abdominal wall incision are important determinants of the risk of developing an incisional hernia. Optimising closure of abdominal wall incisions holds a potential to prevent patients suffering from incisional hernias and for important costs savings in health care. Methods The European Hernia Society formed a Guidelines Development Group to provide guidelines for all surgical specialists who perform abdominal incisions in adult patients on the materials and methods used to close the abdominal wall. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and methodological guidance was taken from Scottish Intercollegiate Guidelines Network (SIGN). The literature search included publications up to April 2014. The guidelines were written using the AGREE II instrument. An update of these guidelines is planned for 2017. Results For many of the Key Questions that were studied no high quality data was detected. Therefore, some strong recommendations could be made but, for many Key Questions only weak recommendations or no recommendation could be made due to lack of sufficient evidence. Recommendations To decrease the incidence of incisional hernias it is strongly recommended to utilise a non-midline approach to a laparotomy whenever possible. For elective midline incisions, it is strongly recommended to perform a continuous suturing technique and to avoid the use of rapidly absorbable sutures. It is suggested using a slowly absorbable monofilament suture in a single layer aponeurotic closure technique without separate closure of the peritoneum. A small bites technique with a suture to wound length (SL/WL) ratio at least 4/1 is the current recommended method of fascial closure. Currently, no recommendations can be given on the optimal technique to close emergency laparotomy incisions. Prophylactic mesh augmentation appears effective and safe and can be suggested in high-risk patients, like aortic aneurysm surgery and obese patients. For laparoscopic surgery, it is suggested using the smallest trocar size adequate for the procedure and closure of the fascial defect if trocars larger or equal to 10 mm are used. For single incision laparoscopic surgery, we suggest meticulous closure of the fascial incision to avoid an increased risk of incisional hernias.
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  • Gronwall, C, et al. (author)
  • THE RELATIONSHIP BETWEEN DIFFERENT IGG AND IGA ANTI-MODIFIED PROTEIN AUTOANTIBODIES IN RHEUMATOID ARTHRITIS
  • 2021
  • In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 206-207
  • Conference paper (other academic/artistic)abstract
    • Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), anti-acetylated (KAc), and anti-malondialdehyde acetaldehyde (MAA) modified protein antibodies, have been described. By using RA patient single-cell derived monoclonal antibodies we have previously shown that individual ACPA clones recognize small distinct citrulline-containing epitopes giving them extensive multireactivity when these epitopes are found in many peptides and proteins. Moreover, certain CCP2+ multireactive ACPA clones bind also to cabamylated and acetylated autoantigens [1].Objectives:To provide a comprehensive evaluation of serum IgG and IgA autoreactivity to different post-translational modifications in RA.Methods:We analyzed 30 different IgG and IgA AMPA reactivities to modified antigens by ELISA and autoantigen arrays, in N=1985 newly diagnosed RA patients and population controls. The study utilized both previously established (i.e IgG and IgA CCP2; IgG ACPA fine-specificities; IgG anti-Carb fibrinogen and Carb FCS; IgG and IgA Cit/Carb/KAc/Orn(Ac)-vimentin), and novel assays (e.g. IgG anti-MAA and IgG anti-acetylated histones). Association with patient characteristics such as smoking and disease activity were explored. The newly developed assays were also evaluated in SLE disease controls and CCP2+ RA-risk individuals without arthritis.Results:Carb and KAc reactivities by different assays were primarily seen in patients also positive for citrulline-reactivity. Modified vimentin (mod-Vim) peptides were used for direct comparison of different AMPA reactivities, revealing that IgA AMPA recognizing mod-Vim was mainly detected in subsets of patients with high IgG anti-Cit-Vim levels and a history of smoking. IgG acetylation reactivity was mainly detected in a subset of patients with Cit and Carb reactivity. Anti-acetylated histone 2B reactivity was RA-specific and associated with high anti-CCP2 IgG levels, multiple ACPA fine-specificities, and smoking. This reactivity was also found to be present in CCP2+ RA-risk individuals without arthritis. Our data further demonstrate that IgG autoreactivity to MAA was increased in RA compared to controls with highest levels in CCP2+ RA, but was not RA-specific, and showed low correlation with other AMPA. Anti-MAA was instead associated with disease activity and was not significantly increased in CCP2+ individuals at risk of RA. Notably, RA patients could be subdivided into four different subsets based on their AMPA IgG and IgA reactivity profiles.Conclusion:We conclude that autoantibodies exhibiting different patterns of ACPA fine-specificities as well as Carb and KAc reactivity are present in RA and may be derived from multireactive B-cell clones. Anti-Carb and anti-KAc could be considered reactivities within the “Cit-umbrella” similar to ACPA fine-specificities, while MAA is distinctly different.References:[1]Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C. Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis. Arthritis Rheumatol. 2020 Oct;72(10):1643-1657. PMID: 32501655Caroline Grönwall: None declared, Lisa Liljefors: None declared, Holger Bang Employee of: Employee at ORGENTEC Diagnostika GmbH, Aase Hensvold: None declared, Monika Hansson: None declared, Linda Mathsson-Alm Employee of: Employee at Thermo Fisher Scientific, Lena Israelsson: None declared, Anna Svärd: None declared, Cyril CLAVEL: None declared, Elisabet Svenungsson: None declared, Iva Gunnarsson: None declared, Guy Serre: None declared, Saedis Saevarsdottir: None declared, Alf Kastbom: None declared, Lars Alfredsson: None declared, Vivianne Malmström: None declared, Johan Rönnelid: None declared, Anca Catrina: None declared, Karin Lundberg: None declared, Lars Klareskog: None declared
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  • Cengiz, Y, et al. (author)
  • Randomized trial of traditional dissection with electrocautery versus ultrasonic fundus-first dissection in patients undergoing laparoscopic cholecystectomy.
  • 2005
  • In: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 92:7, s. 810-3
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: In laparoscopic cholecystectomy dissection can be with monopolar electrocautery or with ultrasonic shears, and can start at the triangle of Calot or at the fundus of the gallbladder. METHODS: Thirty-seven patients undergoing laparoscopic cholecystectomy were randomized to electrocautery dissection from the triangle of Calot and 43 to fundus-first dissection with ultrasonic shears. All procedures were strictly standardized, and patients and their postoperative carers were blinded to the operation performed. RESULTS: Ultrasonic fundus-first dissection was associated with a shorter duration of operation (mean 46 versus 61 min), fewer overnight hospital stays (two versus eight), lower pain scores 4 and 24 h after surgery, less nausea at 2, 4 and 24 h, and a shorter period of sick leave (mean 5.5 versus 9.3 days) compared with electrocautery from the triangle of Calot. CONCLUSION: Ultrasonic fundus-first dissection during laparoscopic cholecystectomy was quicker and associated with less nausea and pain than electrocautery dissection from the triangle of Calot.
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  • Janson, A R, et al. (author)
  • Laparoscopic stoma formation with a prophylactic prosthetic mesh.
  • 2010
  • In: Hernia. - : Springer. - 1265-4906 .- 1248-9204. ; 14:5, s. 495-498
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: One year after stoma formation with an open technique, the rate of parastomal hernia is almost 50%. The herniation rate can be reduced to 10% with the use of a prophylactic mesh in a sublay position. For stomas formed with a laparoscopic technique, a surgical method with the use of prophylactic mesh should be sought. METHODS: Patients with a sigmoidostomy created with a laparoscopic technique were provided with a prophylactic large-pore, low-weight mesh in a sublay position. Follow-up examination was carried out after at least 12 months. RESULTS: Between March 2003 and May 2007, a sigmoidostomy was created in 25 patients. The patients' mean age was 65 years (range 31-89), the mean body mass index was 26 (range 21-32) and 15 were female. One stoma necrosis and two minor wound infections occurred. Parastomal hernia was present in 3 of 20 patients (15%) available for follow-up examination after 11-31 months (mean 19). No fistulas or strictures had developed. No mesh infection was noted and no mesh was removed. CONCLUSION: In laparoscopic stoma formation, a prophylactic large-pore, low-weight mesh in a sublay position is an easy and safe procedure associated with a low rate of parastomal hernia.
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  • Agrawal, K., et al. (author)
  • Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance
  • 2022
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749. ; 150:6
  • Journal article (peer-reviewed)abstract
    • Background: Patients with asthma often suffer from frequent respiratory viral infections and reduced virus clearance. Lung resident memory T cells provide rapid protection against viral reinfections. Objective: Because the development of resident memory T cells relies on the lung microenvironment, we investigated the impact of allergen sensitization on the development of virus-specific lung resident memory T cells and viral clearance. Methods: Mice were sensitized with house dust mite extract followed by priming with X47 and a subsequent secondary influenza infection. Antiviral memory T-cell response and protection to viral infection was assessed before and after secondary influenza infection, respectively. Gene set variation analysis was performed on data sets from the U-BIOPRED asthma cohort using an IFN-γ–induced epithelial cell signature and a tissue resident memory T-cell signature. Results: Viral loads were higher in lungs of sensitized compared with nonsensitized mice after secondary infection, indicating reduced virus clearance. X47 priming induced fewer antiviral lung resident memory CD8 T cells and resulted in lower pulmonary IFN-γ levels in the lungs of sensitized as compared with nonsensitized mice. Using data from the U-BIOPRED cohort, we found that patients with enrichment of epithelial IFN-γ–induced genes in nasal brushings and bronchial biopsies were also enriched in resident memory T-cell–associated genes, had more epithelial CD8 T cells, and reported significantly fewer exacerbations. Conclusions: The allergen-sensitized lung microenvironment interferes with the formation of antiviral resident memory CD8 T cells in lungs and virus clearance. Defective antiviral memory response might contribute to increased susceptibility of patients with asthma to viral exacerbations.
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  • Cengiz, Yucel, et al. (author)
  • Improved outcome after laparoscopic cholecystectomy with ultrasonic dissection : a randomized multicenter trial
  • 2010
  • In: Surgical Endoscopy. - : Springer. - 0930-2794 .- 1432-2218. ; 24:3, s. 624-630
  • Journal article (peer-reviewed)abstract
    • In conventional laparoscopic cholecystectomy, dissection with electrocautery starts at the triangle of Calot. In a randomized single-center trial, the fundus-first method (dome down) using ultrasonic dissection was faster, involved less pain or nausea, and had a shorter postoperative sick leave. This may relate to the fundus-first method or to the ultrasonic dissection. In a multicenter trial, 243 elective patients were randomized to conventional laparoscopic cholecystectomy using electrocautery (n = 85) or the fundus-first method using either electrocautery (n = 81) or ultrasonic dissection (n = 77). The fundus-first method had a shorter operating time with ultrasonic dissection (58 min) than with electrocautery (74 min; p = 0.002). The fundus-first method using ultrasonic dissection compared with electrocautery or the conventional method produced less blood loss (12 vs. 53 or 36 ml; p < 0.001) and fewer gallbladder perforations (26% vs. 46% or 49%; p = 0.005). Also, the pain and nausea scores at 4 and 6 h were lower, and the sick leave was shorter (6.1 vs. 9.4 and 9 days, respectively; p < 0.001). The fundus-first method using ultrasonic dissection is associated with less blood loss, fewer gallbladder perforations, less pain and nausea, and shorter sick leave than the conventional and fundus-first method using electrocautery. The difference seems related to the use of ultrasonic dissection.
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  • Djarv, T., et al. (author)
  • Traumatic cardiac arrest in Sweden 1990-2016 : a population-based national cohort study
  • 2018
  • In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central (BMC). - 1757-7241. ; 26
  • Journal article (peer-reviewed)abstract
    • Background: Trauma is a main cause of death among young adults worldwide. Patients experiencing a traumatic cardiac arrest (TCA) certainly have a poor prognosis but population-based studies are sparse. Primarily to describe characteristics and 30-day survival following a TCA as compared with a medical out-of-hospital cardiac arrest (medical CA). Methods: A cohort study based on data from the nationwide, prospective population-based Swedish Registry for Cardiopulmonary Resuscitation (SRCR), a medical cardiac arrest registry, between 1990 and 2016. The definition of a TCA in the SRCR is a patient who is unresponsive with apnoea where cardiopulmonary resuscitation and/or defibrillation have been initiated and in whom the Emergency Medical Services (EMS, mainly a nurse-based system) reported trauma as the aetiology. Outcome was overall 30-day survival. Descriptive statistics as well as multivariable logistic regression models were used. Results: In all, between 1990 and 2016, 1774 (2.4%) cases had a TCA and 72,547 had a medical CA. Overall 30-day survival gradually increased over the years, and was 3.7% for TCAs compared to 8.2% following a medical CA (p < 0.01). Among TCAs, factors associated with a higher 30-day survival were bystander witnessed and having a shockable initial rhythm (adjusted OR 2.67, 95% C.I. 1.15-6.22 and OR 8.94 95% C.I. 4.27-18.69, respectively). Discussion: Association in registry-based studies do not imply causality but TCA had short time intervals in the chain of survival as well as high rates of bystander-CPR. C onclusion: In a medical CA registry like ours, prevalence of TCAs is low and survival is poor. Registries like ours might not capture the true incidence. However, many individuals do survive and resuscitation in TCAs should not be seen futile.
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  • Eklund, Sanna A., et al. (author)
  • Vascular risk profiles for predicting outcome and long-term mortality in patients with idiopathic normal pressure hydrocephalus : comparison of clinical decision support tools
  • 2023
  • In: Journal of Neurosurgery. - : Journal of Neurosurgery Publishing Group (JNSPG). - 0022-3085 .- 1933-0693. ; 138:2, s. 476-482
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: Vascular risk factors (VRFs) may act synergistically, and clinical decision support tools (CDSTs) have been developed that present vascular risk as a summarized score. Because VRFs are a major issue in patients with idiopathic normal pressure hydrocephalus (INPH), a CDST may be useful in the diagnostic workup. The objective was to compare 4 CDSTs to determine which one most accurately predicts short-term outcome and 10-year mortality after CSF shunt surgery in INPH patients.METHODS: One-hundred forty INPH patients who underwent CSF shunt surgery were included. For each patient, 4 CDST scores (Systematic Coronary Risk Evaluation–Older Persons [SCORE-OP], Framingham Risk Score [FRS], Revised Framingham Stroke Risk Profile, and Kiefer’s Comorbidity Index [KCI]) were estimated. Short-term outcome (3 months after CSF shunt surgery) was defined on the basis of improvements in gait, Mini-Mental State Examination score, and modified Rankin Scale score. The 10-year mortality rate after surgery was noted. The CDSTs were compared by using Cox regression analysis, receiver operating characteristic curve analysis, and the chi-square test.RESULTS: For 3 CDSTs, increased score was associated with increased risk of 10-year mortality. A 1-point increase in the FRS indicated a 2% higher risk of death within 10 years (HR 1.02, 95% CI 1.003–1.035, p = 0.021); SCORE-OP, 5% (HR 1.05, 95% CI 1.019–1.087, p = 0.002); and KCI, 12% (HR 1.12, 95% CI 1.03–1.219, p = 0.008). FRS predicted short-term outcome of surgery (p = 0.024). When the cutoff value was set to 32.5%, the positive predictive value was 80% and the negative predictive value was 48% (p = 0.012).CONCLUSIONS: The authors recommend using FRS to predict short-term outcome and 10-year risk of mortality in INPH patients. The study indicated that extensive treatment of the risk factors of INPH may decrease risk of mortality.
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  • Eklund, Sanna A., et al. (author)
  • Vascular risk profiles for predicting outcome and long-term mortality in patients with idiopathic normal pressure hydrocephalus: comparison of clinical decision support tools
  • 2023
  • In: Journal of Neurosurgery. - : AMER ASSOC NEUROLOGICAL SURGEONS. - 0022-3085 .- 1933-0693. ; 138:2, s. 476-482
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE Vascular risk factors (VRFs) may act synergistically, and clinical decision support tools (CDSTs) have been developed that present vascular risk as a summarized score. Because VRFs are a major issue in patients with idiopathic normal pressure hydrocephalus (INPH), a CDST may be useful in the diagnostic workup. The objective was to compare 4 CDSTs to determine which one most accurately predicts short-term outcome and 10-year mortality after CSF shunt surgery in INPH patients. METHODS One-hundred forty INPH patients who underwent CSF shunt surgery were included. For each patient, 4 CDST scores (Systematic Coronary Risk Evaluation-Older Persons [SCORE-OP], Framingham Risk Score [FRS], Revised Framingham Stroke Risk Profile, and Kiefers Comorbidity Index [KCI]) were estimated. Short-term outcome (3 months after CSF shunt surgery) was defined on the basis of improvements in gait, Mini-Mental State Examination score, and modified Rankin Scale score. The 10-year mortality rate after surgery was noted. The CDSTs were compared by using Cox regression analysis, receiver operating characteristic curve analysis, and the chi-square test. RESULTS For 3 CDSTs, increased score was associated with increased risk of 10-year mortality. A 1-point increase in the FRS indicated a 2% higher risk of death within 10 years (HR 1.02, 95% CI 1.003-1.035, p = 0.021); SCORE-OP, 5% (HR 1.05, 95% CI 1.019-1.087, p = 0.002); and KCI, 12% (HR 1.12, 95% CI 1.03-1.219, p = 0.008). FRS predicted short-term outcome of surgery (p = 0.024). When the cutoff value was set to 32.5%, the positive predictive value was 80% and the negative predictive value was 48% (p = 0.012). CONCLUSIONS The authors recommend using FRS to predict short-term outcome and 10-year risk of mortality in INPH patients. The study indicated that extensive treatment of the risk factors of INPH may decrease risk of mortality. Clinical trial registration no.: NCT01850914 (ClinicalTrials.gov)
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  • Frängsmyr, L., et al. (author)
  • Evolution of the carcinoembryonic antigen family. Structures of CGM9, CGM11 and pregnancy-specific glycoprotein promoters
  • 2000
  • In: Tumor Biology. - 1010-4283 .- 1423-0380. ; 21:2, s. 63-81
  • Journal article (peer-reviewed)abstract
    • Earlier studies have demonstrated that the genes of the human carcinoembryonic antigen (CEA) family can be divided into three subgroups, the CEA subgroup (n = 12), the pregnancy-specific glycoprotein (PSG) subgroup (n = 11), and a third subgroup (n = 6). To further characterize the CEA gene family, we have determined the genomic structures of CGM9 and CGM11, analyzed the promoter regions of all eleven PSGs, studied the CGM15-PSG13 intergenic region and the evolutionary relationships between the CEA family genes. CGM9, a typical CEA subgroup member, was a pseudogene with the exon structure [5'UTR-L-L/N-TM-Cyt-3'UTR]. CGM11 contained a mixture of exons derived from CEA and PSG subgroup genes. The formula of the CGM11 pseudogene was [5'UTRL- L/N-C-3'UTR]. Thus both genes lacked the IgC2-like domains typically found in CEA subfamily members. The upstream promoter regions of all eleven PSGs were characterized. All PSG promoters lacked the classical TATA and CCAAT elements, but had putative PEA3 box(es), CACCC box(es), a RARE box, and poly (dG-dT) repeats of different lengths. Five PSGs also had an SP1 site. The complete 10-kb intergenic region between CGM15 and PSG13 was sequenced. Clusters of different types of repetitive sequences were seen. The time of divergence of the CEA and PSG subfamilies was estimated to be 107.7 ± 17.1 million years, or at about the time of human-rodent divergence. Models for the evolution of CEA and PSG and the third family subgroup genes are proposed.
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37.
  • Giha, Hayder A, et al. (author)
  • Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria
  • 2010
  • In: Molecular Medicine. - : Springer Science and Business Media LLC. - 1076-1551 .- 1528-3658. ; 16:1-2, s. 27-33
  • Journal article (peer-reviewed)abstract
    • The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Sudanese donors, followed for malaria infection for 9 years, had their CRP -286 gene locus genotyped by pyrosequencing. The number of malaria episodes experienced by each individual over the study period was used as an index for malaria susceptibility. The prevalence of the CRP alleles A, C and T were 21%, 52% and 27%, respectively. Importantly, the A-allele, unlike the C- and T-alleles or CRP genotypes, was significantly associated with an increased number of malaria episodes, P = 0.007. The proportion of A-allele carriers among donors not known to have had malaria during the study period was 18%, whereas it was 43% and 63% among donors who had experienced 1-4 and > or =5 malaria episodes, respectively, over the same period (P = 0.002). Furthermore, the A-allele was associated with higher parasite counts. In conclusion, the CRP -286 A-allele was associated with an increased susceptibility to uncomplicated Plasmodium falciparum malaria.
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38.
  • Gullberg, Maria, et al. (author)
  • A single coxsackievirus B2 capsid residue controls cytolysis and apoptosis in rhabdomyosarcoma cells.
  • 2010
  • In: Journal of Virology. - 0022-538X .- 1098-5514. ; 84:12, s. 5868-5879
  • Journal article (peer-reviewed)abstract
    • Coxsackievirus B2 (CVB2), one of six human pathogens of the group B coxsackieviruses within the enterovirus genus of Picornaviridae, causes a wide spectrum of human diseases ranging from mild upper respiratory illnesses to myocarditis and meningitis. The CVB2 prototype strain Ohio-1 (CVB2O) was originally isolated from a patient with summer grippe in the 1950s. Later on, CVB2O was adapted to cytolytic replication in rhabdomyosarcoma (RD) cells. Here, we present analyses of the correlation between the adaptive mutations of this RD variant and the cytolytic infection in RD cells. Using reverse genetics, we identified a single amino acid change within the exposed region of the VP1 protein (glutamine to lysine at position 164) as the determinant for the acquired cytolytic trait. Moreover, this cytolytic virus induced apoptosis, including caspase activation and DNA degradation, in RD cells. These findings contribute to our understanding of the host cell adaptation process of CVB2O and provide a valuable tool for further studies of virus-host interactions.
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39.
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40.
  • Hardt, Uta, et al. (author)
  • Integrated single cell and spatial transcriptomics reveal autoreactive differentiated B cells in joints of early rheumatoid arthritis
  • 2022
  • In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
  • Journal article (peer-reviewed)abstract
    • B cells play a significant role in established Rheumatoid Arthritis (RA). However, it is unclear to what extent differentiated B cells are present in joint tissue already at the onset of disease. Here, we studied synovial biopsies (n = 8) captured from untreated patients at time of diagnosis. 3414 index-sorted B cells underwent RNA sequencing and paired tissue pieces were subjected to spatial transcriptomics (n = 4). We performed extensive bioinformatics analyses to dissect the local B cell composition. Select plasma cell immunoglobulin sequences were expressed as monoclonal antibodies and tested by ELISA. Memory and plasma cells were found irrespective of autoantibody status of the patients. Double negative memory B cells were prominent, but did not display a distinct transcriptional profile. The tissue architecture implicate both local B cell maturation via T cell help and plasma cell survival niches with a strong CXCL12-CXCR4 axis. The immunoglobulin sequence analyses revealed clonality between the memory B and plasma cell pools further supporting local maturation. One of the plasma cell-derived antibodies displayed citrulline autoreactivity, demonstrating local autoreactive plasma cell differentiation in joint biopsies captured from untreated early RA. Hence, plasma cell niches are not a consequence of chronic inflammation, but are already present at the time of diagnosis.
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41.
  • Hultberg, Björn, et al. (author)
  • Increased levels of plasma homocysteine are associated with nephropathy, but not severe retinopathy in type 1 diabetes mellitus
  • 1991
  • In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 51:3, s. 277-282
  • Journal article (peer-reviewed)abstract
    • The reactive vascular-injuring amino acid homocysteine was measured in plasma samples from 79 well-characterized type 1 diabetic patients and 46 control subjects. Patients with proliferative retinopathy had higher homocysteine levels (15.0 +/- 6.3 mumols l-1; mean +/- SD, p less than 0.001; n = 42) than those with progressive retinopathy during a two-year period (10.4 +/- 1.6 mumols l-1; n = 12), no or minimal retinopathy (10.7 +/- 4.3 mumols l-1; n = 25), and the control subjects (11.0 +/- 3.4 mumols l-1). Within the group of patients with proliferative retinopathy increased homocysteine levels were confined to those patients that had serum creatinine levels greater than 115 mumols l-1 and/or an albumin:creatinine clearance ratio greater than or equal to 0.02 x 10(-3) (17.0 +/- 5.9 mumols l-1; n = 23), whereas those with no or only minimal nephropathy had levels (12.1 +/- 5.5 mumols l-1; n = 18) that were not different from the control group. We conclude that neither type 1 diabetes mellitus nor diabetic retinopathy per se is associated with increased plasma homocysteine levels. In contrast, homocysteine accumulates, probably owing to reduced glomerular filtration, in diabetic patients with advanced nephropathy. This suggests that homocysteine might contribute to the accelerated development of macroangiopathy seen especially in this subgroup of diabetic patients.
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42.
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43.
  • Israelsson, Elisabeth, et al. (author)
  • Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa
  • 2009
  • In: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 8:136
  • Journal article (peer-reviewed)abstract
    • Background C-reactive protein (CRP) is an acute phase protein that can activate various immune cells and bind to certain Fcγ receptors. The latter may compete with the binding of IgG antibodies to these receptors and could thereby interfere with the antigen-specific immune response. Polymorphisms in the promoter region of the CRP gene have been strongly associated with the plasma concentration of CRP. The known lower susceptibility to malaria in the Fulani ethnic group, as compared to their sympatric neighbours in Africa, has been linked to different genetic backgrounds. The present study was performed to investigate if polymorphisms in the CRP gene could contribute to the lower susceptibility to malaria seen in the Fulani ethnic group. Methods The CRP -717 T>C, -286 C>T>A, and +1444 C>T polymorphisms were analysed in asymptomatic Fulani and non-Fulani individuals from Mali and Sudan using Pyrosequencing T and TaqMan r MGB probes. Results The rare -286 A allele, previously shown to be associated with increased CRP expression and plasma levels, was shown to be more frequent in the non-Fulani ethnic groups as compared to the sympatric Fulani ethnic group both in Mali and Sudan. The common -717 T allele was more prevalent in the non-Fulani ethnic group compared to the sympatric Fulani ethnic group, but only in Mali. The parasite prevalence was increased for the -286 A allele, but not for the -717 T allele. No differences regarding genotype frequency or parasite prevalence were seen for +1444 C>T. Conclusion This study indicate that CRP may play an important role in the immune responses to malaria, and that the -286 C/T/A CRP polymorphism may be a contributing factor to the lower susceptibility to malaria seen in the Fulani.
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44.
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45.
  • Israelsson, Leif A., et al. (author)
  • Closing midline abdominal incisions
  • 2012
  • In: Langenbeck's archives of surgery (Print). - : Springer. - 1435-2443 .- 1435-2451. ; 397:8, s. 1201-1207
  • Research review (peer-reviewed)abstract
    • The most important wound complications are surgical site infection, wound dehiscence and incisional hernia. Experimental and clinical evidences support that the development of wound complications is closely related to the surgical technique at wound closure. The suture technique monitored through the suture length-to-wound length ratio is of major importance for the development of wound complications. The risk of wound dehiscence is low with a high ratio. The ratio must be higher than 4; otherwise, the risk of developing an incisional hernia is increased four times. With a ratio higher than 4, both the rate of wound infection and incisional hernia are significantly lower if closure is done with small stitches placed 5 to 8 mm from the wound edge than with larger stitches placed more than 10 mm from the wound edge. Midline incisions should be closed in one layer by a continuous suture technique. A monofilament suture material should be used and be tied with self-locking knots. Excessive tension should not be placed on the suture. Wounds must always be closed with a suture length-to-wound length ratio higher than 4. The only way to ascertain this is to measure, calculate and document the ratio at every wound closure. A high ratio should be accomplished with many small stitches placed 5 to 8 mm from the wound edge at very short intervals.
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46.
  • Israelsson, Leif A, et al. (author)
  • Incisional hernia repair in Sweden 2002
  • 2006
  • In: Hernia. - : Springer. - 1265-4906 .- 1248-9204. ; 10:3, s. 258-261
  • Journal article (peer-reviewed)abstract
    • Incisional hernia is a common problem after abdominal surgery. The complication and recurrence rates following the different repair techniques are a matter of great concern. Our aim was to study the results of incisional hernia repair in Sweden. A questionnaire was sent to all surgical departments in Sweden requesting data concerning incisional hernia repair performed during the year 2002. Eight hundred and sixty-nine incisional hernia repairs were reported from 40 hospitals. Specialist surgeons performed the repair in 782 (83.8%) patients. The incisional hernia was a recurrence in 148 (17.0%) patients. Thirty-three per cent of the hernias were subsequent to transverse, subcostal or muscle-splitting incisions or laparoscopic procedures. Suture repair was performed in 349 (40.2%) hernias. Onlay mesh repair was more common than a sublay technique. The rate of wound infection was 9.6% after suture repair and 8.1% after mesh repair. The recurrence rate was 29.1% with suture repair, 19.3% with onlay mesh repair, and 7.3% with sublay mesh repair. This survey revealed that there is room for improvement regarding the incisional hernia surgery in Sweden. Suture repair, with its unacceptable results, is common and mesh techniques employed may not be optimal. This study has led to the instigation of a national incisional hernia register.
  •  
47.
  • Israelsson, Leif A (author)
  • Parastomal hernia treatment with prosthetic mesh repair
  • 2010
  • In: Der Chirurg. - : Springer. - 0009-4722 .- 1433-0385. ; 81:3, s. 216-221
  • Journal article (peer-reviewed)abstract
    • After stoma formation, parastomal hernia develops in 30-50% of patients, with one-third of these require operative correction. Recurrence rates are very high after suture repair of parastomal hernias or relocation of the stoma. Open or laparoscopic mesh repairs have resulted in much lower recurrence rates. Long-term follow-up of the various techniques for parastomal hernia repair is lacking, as are randomized trials. A prophylactic prosthetic mesh placed in a sublay position at the index operation has reduced the rate of parastomal hernia in randomized trials. A prophylactic mesh in an onlay position, a sublay position, and an intraperitoneal onlay position has also been associated with low herniation rates in non-randomized studies. Although several questions within this field still have to be answered, it seems obvious that use of a mesh represents a suitable measure for the prevention of parastomal hernia as well as parastomal hernia repair.
  •  
48.
  • Israelsson, Leif A (author)
  • Parastomal hernias
  • 2008
  • In: Surgical Clinics of North America. - : W.B. Saunders Co.. - 0039-6109 .- 1558-3171. ; 88:1, s. 113-125
  • Journal article (peer-reviewed)abstract
    • The incidence of parastomal hernias is probably 30% to 50%. Suture repair of a parastomal hernia or relocation of the stoma results in a high recurrence rate, whereas with mesh repair recurrence rates are lower. Several mesh repair techniques are used in open and laparoscopic surgery, but randomized trials comparing various techniques and with long-term follow-up are needed for better evidence.
  •  
49.
  • Israelsson, Leif A (author)
  • Preventing and treating parastomal hernia
  • 2005
  • In: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 29:8, s. 1086-1089
  • Journal article (peer-reviewed)abstract
    • Parastomal hernia represents a major surgical challenge. There is no uniform definition of parastomal hernia, and the true rate is therefore difficult to establish, although it is probably higher than 30%. Many surgical techniques have been tried to prevent and treat parastomal hernia; but despite these efforts, herniation continues to be a problem. The only method that has reduced the rate of parastomal hernia in a randomized trial is the use of a prophylactic prosthetic mesh. A large-pore low-weight mesh with reduced polypropylene content and a high proportion of absorbable material placed in a sublay position at the primary operation significantly reduces the rate of parastomal hernia. Recurrence rates after surgical treatment of parastomal hernia are high unless mesh is used. Relocation of the stoma, with prophylactic mesh in a sublay position at the new site and sublay mesh repairing the incisional hernia at the primary site, is the standard method for treating parastomal hernia in our department.
  •  
50.
  • Israelsson, Leif A., et al. (author)
  • Prevention of Incisional Hernias How to Close a Midline Incision
  • 2013
  • In: Surgical Clinics of North America. - : Elsevier. - 0039-6109 .- 1558-3171. ; 93:5, s. 1027-
  • Journal article (peer-reviewed)abstract
    • The development of wound complications is closely related to the surgical technique at wound closure. The risk of the suture technique affecting the development of wound dehiscence and incisional hernia can be monitored through the suture length to wound length ratio. Mid line incisions should be closed in one layer by a continuous-suture technique using a monofilament suture material tied with self-locking knots. Excessive tension should not be placed on the suture. Closure must always be with a suture length to wound length ratio higher than 4.
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