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  • Bergqvist, Jenny, et al. (author)
  • Quantitative real-time PCR analysis and microarray-based RNA expression of HER2 in relation to outcome
  • 2007
  • In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:5, s. 845-850
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Our aim was to use quantitative real-time PCR (Q-PCR) and RNA expression profiles (RNA-EPs) to investigate HER2 status in relation to outcome. PATIENTS AND METHODS: Cut-off levels for Q-PCR and RNA-EP were established in relation to immunohistochemistry (IHC) validated by FISH in a test set of frozen tissue samples from 40 primary breast cancers. The HER2 status was subsequently studied in another validation set of 306 tumors, where Q-PCR and RNA-EP results were compared with previously carried out IHC that we had validated by chromogenic in situ hybridization (CISH). RESULTS: Q-PCR and RNA-EP offered similar sensitivity (90% versus 77%), specificity (93% versus 95%), and negative (99% versus 98%) and positive (63% versus 61%) predictive values for HER2 determinations. Analyses of relapse-free survival (RFS) and overall survival on the basis of 5 and 10 years of follow-up indicated equivalent hazard ratios for all three techniques. In contrast to IHC/CISH, both Q-PCR and RNA-EP analyses of HER2 also gave statistically significant results regarding RFS and breast cancer-corrected survival after 10 years of follow-up. CONCLUSION: The use of RNA-EP and Q-PCR to analyze HER2 in frozen and formalin-fixed breast cancer samples may be an alternate approach to IHC in combination with FISH/CISH.
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  • Matikas, A., et al. (author)
  • Prognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer
  • 2021
  • In: ESMO open. - : Elsevier BV. - 2059-7029. ; 6:2
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. METHODS: Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. RESULTS: Central Ki67 counting had excellent correlation with the results of digital image analysis (r= 0.814), but not with the diagnostic samples (r= 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P= 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj= 0.50, 95% CI 0.26-0.97, P= 0.04) and OS (HRadj= 0.46, 95% CI 0.95, P= 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (pinteraction 0.04). CONCLUSION: Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies. Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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  • Belch, Jill J. F., et al. (author)
  • Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial
  • 2010
  • In: Journal of vascular surgery : official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. - : Elsevier BV. - 0741-5214. ; 52:4, s. 825-833, 833.e1-2
  • Journal article (peer-reviewed)abstract
    • The combination of clopidogrel plus ASA did not improve limb or systemic outcomes in the overall population of PAD patients requiring below-knee bypass grafting. Subgroup analysis suggests that clopidogrel plus ASA confers benefit in patients receiving prosthetic grafts without significantly increasing major bleeding risk.
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  • Dahl, O. E., et al. (author)
  • Major joint replacement. A model for antithrombotic drug development: from proof-of-concept to clinical use
  • 2008
  • In: International angiology. - 0392-9590. ; 27:1, s. 60-7
  • Journal article (peer-reviewed)abstract
    • AIM: Development of antithrombotic compounds has traditionally been performed in patients undergoing total hip and knee replacement surgery. A high number of asymptomatic deep-vein thromboses are radiologically detectable, and bleeding and other adverse events (AE) are easy to observe. However, standardization of study procedures and endpoints in early proof-of-concept studies and late pure clinical endpoint studies has been lacking. This has made comparison between studies difficult, economic analyses speculative and potential benefits of applying the drug regimen in non-selected patients uncertain. In this paper, the International Surgical Thrombosis Forum proposes a strategy for the clinical investigation of new pharmacological agents for the prophylaxis of postoperative thrombotic events. METHODS: First, dose titration safety studies of short duration, in highly selected patients using objective venographic endpoints are recommended. Bleeding should be divided into the quantified volume of surgical bleeding and other adjudicated clinical bleeding events. The number of AE should be described for each dose step and classified according to International Coding of Diagnoses (ICD). Second, a dose confirmatory study of moderate exposure period and sufficient follow-up time is recommended. The exclusion criteria should be restricted to contraindications of the compared drugs and technical procedure. RESULTS: The efficacy, bleeding and AE should be similar to those used in dose-titration studies. In addition, the failure rate of the drug to exert its effect and the net clinical benefit should be calculated. CONCLUSION: Finally, trials with simple clinical endpoints and long follow-up should be conducted to evaluate the potential benefits of the drug-regimen in non-selected populations.
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  • Lindegårdh, N, et al. (author)
  • Piperaquine, new findings
  • 2005
  • In: International Congress for Tropical medicine and Malaria. - Marseille.
  • Conference paper (peer-reviewed)
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  • Wannberg, Gudmund, et al. (author)
  • EISCAT_3D - a next-generation European radar system for upper atmosphere and geospace research
  • 2010
  • In: Radio Science Bulletin. - 1024-4530. ; :333, s. 75-88
  • Journal article (peer-reviewed)abstract
    • The EISCAT Scientifi c Association, together with a number of collaborating institutions, has recently completed a feasibility and design study for an enhanced performance research radar facility to replace the existing EISCAT UHF and VHF systems. This study was supported by EU Sixth-Framework funding. The new radar retains the powerful multi-static geometry of the EISCAT UHF, but will employ phased arrays, direct-sampling receivers, and digital beamforming and beam steering. Design goals include, inter alia, a tenfold improvement in temporal and spatial resolution, an extension of the instantaneous measurement of full-vector ionospheric drift velocities from a single point to the entire altitude range of the radar, and an imaging capability to resolve small-scale structures. Prototype receivers and beamformers are currently being tested on a 48-element, 224 MHz array (the "Demonstrator") erected at the Kiruna EISCAT site, using the EISCAT VHF transmitter as an illuminator.
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  • Berger, P., et al. (author)
  • Validation of the Simulator for Testing and Rating Endovascular SkillS (STRESS)-machine in a setting of competence testing
  • 2010
  • In: Journal of Cardiovascular Surgery. - 0021-9509 .- 1827-191X. ; 51:2, s. 253-256
  • Journal article (peer-reviewed)abstract
    • AIM: Endovascular skills are an integral part of modern-day vascular surgery. The STRESS machine has been developed to test these skills in vascular surgeons. This study aims to define an optimal pass/fail cutoff value for the STRESS test score. METHODS: The STRESS machine consists of a dry glass model of the abdominal aorta and its tributaries with various stenotic lesions, elongations, and tortuosities. A camera and computer software are used to simulate plain fluoroscopy-mode. The test subjects are given two assignments after which two reviewers use a combination of the ICEPS and MRS to produce the final total score; 43 subjects were tested. According to previous endovascular experience, subjects were classified into four groups: novice-low (no experience, less than 11 performed procedures, less than 50 assisted procedures), novice-high (11-25 performed procedures, more than 50 assisted procedures), intermediate (1-10 performed and >11-25 assisted procedures, 11-25 performed and >1-10 assisted procedures or 25-50 performed procedures) and advanced (more than 50 performed procedures). RESULTS: Test-score and noted experience showed a correlation of 0.794. All intermediate and advanced test subjects scored more than 50 points compared to 4 out of 15 novices. CONCLUSION: We demonstrated that it is possible to determine an optimal cut-off value for competence testing with the STRESS machine.
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  • Bergqvist, Joel, et al. (author)
  • Non-infectious rhinitis is more strongly associated with early-rather than late-onset of COPD: data from the European Community Respiratory Health Survey (ECRHS)
  • 2020
  • In: European Archives of Oto-Rhino-Laryngology. - : Springer Science and Business Media LLC. - 0937-4477 .- 1434-4726. ; 277, s. 1353-1359
  • Journal article (peer-reviewed)abstract
    • Purpose Chronic obstructive pulmonary disease (COPD) is associated with several co-morbidities and non-infectious rhinitis (NIR) has emerged as a new possible co-morbidity. The primary aim of this study is to confirm a previously reported association between NIR and COPD in a multicentre population over time. The secondary aim is to investigate the course over time of such an association through a comparison between early- and late-onset COPD. Methods This study is part of the European Community Respiratory Health Survey (ECRHS). A random adult population from 25 centres in Europe and one in Australia was examined with spirometry and answered a respiratory questionnaire in 1998-2002 (ECRHS II) and in 2008-2013 (ECRHS III). Symptoms of non-infectious rhinitis, hay fever and asthma, and smoking habits were reported. Subjects reporting asthma were excluded. COPD was defined as a spirometry ratio of FEV1/FVC < 0.7. A total of 5901 subjects were included. Results Non-infectious rhinitis was significantly more prevalent in subjects with COPD compared with no COPD (48.9% vs 37.1%, p < 0.001) in ECRHS II (mean age 43) but not in ECHRS III (mean age 54). In the multivariable regression model adjusted for COPD, smoking, age, BMI, and gender, non-infectious rhinitis was associated with COPD in both ECRHS II and III. Conclusion Non-infectious rhinitis was significantly more common in subjects with COPD at a mean age of 43. Ten years later, the association was weaker. The findings indicate that NIR could be associated with the early onset of COPD.
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  • Carbajal, Ricardo, et al. (author)
  • Pain Assessment In Ventilated And Non-ventilated Neonates In Nicus Across Europe : European Pain Audit In Neonates (europain Survey)
  • 2014
  • In: Archives of Disease in Childhood. - London, United Kingdom : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 99, s. A68-A68
  • Journal article (peer-reviewed)abstract
    • Background: Neonates undergo many painful procedures during their NICU stay. These may include tracheal intubation/ventilation, skin-breaking procedures, drainage/suctioning of body orifices or cavities. Inherent subjectivity and difficulties of neonatal pain assessment contribute to a wide variety of assessment tools and clinical practices. To date, these practices have been not studied at a large scale.Objective: To determine current clinical practices for neonatal pain assessment in NICUs across Europe.Methods: An epidemiological observational study on bedside pain assessment practices collected data for all neonates in participating NICUs until infants left the unit (discharge, death, transfer to another hospital) or for 28 days. Data collection occurred via an online database for 1 month at each NICU. All neonates up to a gestational age of 44 weeks were included.Results: From October 2012 to June 2013, 243 NICUs from 18 European countries collected pain assessment data in 6680 neonates. Of these, 2142 received tracheal ventilation (TV), 1496 non-invasive ventilation (NIV) and 3042 only spontaneous ventilation (SV). The median (IQR) gestational age of TV, NIV and SV neonates were 32.1 (28.1–37.4), 33.6 (31.0–36.6) and 37.9 (35.0–39.9), respectively (p < 0.001). Overall, 58.5% of TV neonates, 45.0% of NIV neonates and 30.4% of SV neonates received bedside pain assessments (p < 0.001). Fig. shows pain assessments by country.Conclusions: Over half (58.5%) of TV neonates and less than half (45.0%) of NIV neonates had pain assessments performed in European NICUs. Wide variations in the rates of pain assessment exist among countries and an important improvement seems necessary.
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  • Carbajal, Ricardo, et al. (author)
  • Sedation And Analgesia For Neonates In Nicus Across Europe : The Europain Survey
  • 2014
  • In: Archives of Disease in Childhood. - London, United Kingdom : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 99, s. A64-A64
  • Journal article (peer-reviewed)abstract
    • Background: Pain and stress induced by mechanical ventilation, invasive procedures, or painful diseases supports the use of sedation/analgesia (S/A) in newborns admitted to Neonatal Intensive Care Units (NICUs). To date, these practices have not been studied at a large scale.Objective: To determine current clinical practices regarding the use of S/A drugs in NICUs across Europe.Methods: This epidemiological observational study on bedside clinical practices regarding S/A collected data for all neonates in participating NICUs until the infant left the unit (discharge, death, transfer) or for up to 28 days. Data collection occurred via an online database for 1 month at each NICU. All neonates up to 44 weeks gestation were included.Results: From October 2012 to June 2013, 243 NICUs from 18 European countries collected data on 6680 eligible neonates. Of these, 2142 received tracheal ventilation (TV), 1496 non-invasive ventilation (NIV) and 3042 only spontaneous ventilation (SV). The median (IQR) gestational age of TV, NIV and SV neonates were 32.1 (28.1–37.4), 33.6 (31.0–36.6) and 37.9 (35.0–39.9), respectively (p < 0.001). Overall, more TV neonates [81.5% (n = 1746)] received S/A drugs than NIV neonates [17.8% (n = 266)] and SV neonates [9.3% (n = 282)]; p < 0.001. Fig. shows the rate of S/A use by country; table shows S/A drugs used.Conclusions: Most ventilated but few non-ventilated neonates (NIV and SV) receive S/A therapy in European NICUs. Wide variations in S/A use, drugs used, and mode of administration (continuous, bolus, or both) exist among countries.
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  • Costi, T. A., et al. (author)
  • Kondo Decoherence : Finding the Right Spin Model for Iron Impurities in Gold and Silver
  • 2009
  • In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 102:5, s. 056802-
  • Journal article (peer-reviewed)abstract
    • We exploit the decoherence of electrons due to magnetic impurities, studied via weak localization, to resolve a long-standing question concerning the classic Kondo systems of Fe impurities in the noble metals gold and silver: which Kondo-type model yields a realistic description of the relevant multiple bands, spin, and orbital degrees of freedom? Previous studies suggest a fully screened spin S Kondo model, but the value of S remained ambiguous. We perform density functional theory calculations that suggest S=3/2. We also compare previous and new measurements of both the resistivity and decoherence rate in quasi-one-dimensional wires to numerical renormalization group predictions for S=1/2, 1, and 3/2, finding excellent agreement forS=3/2.
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  • De Baetselier, E, et al. (author)
  • EUPRON: nurses' practice in interprofessional pharmaceutical care in Europe. A cross-sectional survey in 17 countries
  • 2020
  • In: BMJ open. - : BMJ. - 2044-6055. ; 10:6, s. e036269-
  • Journal article (peer-reviewed)abstract
    • Safe pharmaceutical care (PC) requires an interprofessional team approach, involving physicians, nurses and pharmacists. Nurses’ roles however, are not always explicit and clear, complicating interprofessional collaboration. The aim of this study is to describe nurses’ practice and interprofessional collaboration in PC, from the viewpoint of nurses, physicians and pharmacists.DesignA cross-sectional survey.SettingThe study was conducted in 17 European countries, each with their own health systems.ParticipantsPharmacists, physicians and nurses with an active role in PC were surveyed.Main outcome measuresNurses’ involvement in PC, experiences of interprofessional collaboration and communication and views on nurses’ competences.ResultsA total of 4888 nurses, 974 physicians and 857 pharmacists from 17 European countries responded. Providing patient education and information (PEI), monitoring medicines adherence (MMA), monitoring adverse/therapeutic effects (ME) and prescribing medicines were considered integral to nursing practice by 78%, 73%, 69% and 15% of nurses, respectively. Most respondents were convinced that quality of PC would be improved by increasing nurses’ involvement in ME (95%), MMA (95%), PEI (91%) and prescribing (53%). Mean scores for the reported quality of collaboration between nurses and physicians, collaboration between nurses and pharmacists and interprofessional communication were respectively <7/10, ≤4/10, <6/10 for all four aspects of PC.ConclusionsME, MMA, PEI and prescribing are part of nurses’ activities, and most healthcare professionals felt their involvement should be extended. Collaboration between nurses and physicians on PC is limited and between nurses and pharmacists even more.
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  • Francis, C. W., et al. (author)
  • Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12months : the DALTECAN Study
  • 2015
  • In: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 13:6, s. 1028-1035
  • Journal article (peer-reviewed)abstract
    • BackgroundTreatment of venous thromboembolism (VTE) in patients with cancer has a high rate of recurrence and bleeding complications. Guidelines recommend low-molecular-weight heparin (LMWH) for at least 3-6months and possibly indefinitely for patients with active malignancy. There are, however, few data supporting treatment with LMWH beyond 6months. The primary aim of the DALTECAN study (NCT00942968) was to determine the safety of dalteparin between 6 and 12months in cancer-associated VTE. MethodsPatients with active cancer and newly diagnosed VTE were enrolled in a prospective, multicenter study and received subcutaneous dalteparin for 12months. The rates of bleeding and recurrent VTE were evaluated at months 1, 2-6 and 7-12. FindingsOf 334 patients enrolled, 185 and 109 completed 6 and 12months of therapy; 49.1% had deep vein thrombosis (DVT); 38.9% had pulmonary embolism (PE); and 12.0% had both on presentation. The overall frequency of major bleeding was 10.2% (34/334). Major bleeding occurred in 3.6% (12/334) in the first month, and 1.1% (14/1237) and 0.7% (8/1086) per patient-month during months 2-6 and 7-12, respectively. Recurrent VTE occurred in 11.1% (37/334); the incidence rate was 5.7% (19/334) for month 1, 3.4% (10/296) during months 2-6, and 4.1% (8/194) during months 7-12. One hundred and sixteen patients died, four due to recurrent VTE and two due to bleeding. ConclusionMajor bleeding was less frequent during dalteparin therapy beyond 6months. The risk of developing major bleeding complications or VTE recurrence was greatest in the first month of therapy and lower over the subsequent 11 months.
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  • Korzhavyi, Pavel A., 1966-, et al. (author)
  • Defect-induced magnetic structure in (Ga1-xMnx)As
  • 2002
  • In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 88:18, s. 187202-
  • Journal article (peer-reviewed)abstract
    • We show that magnetic structures involving partial disorder of local magnetic moments on the Mn atoms in (Ga1-xMnx)As lower the total energy, compared to the case of perfect ferromagnetic ordering, when As defects on the Ga sublattice are present. Such magnetic structures are found to be stable for a range of concentrations of As antisites, and this result accounts for the observed magnetic moments and critical temperatures in (Ga1-xMnx)As . We propose an explanation for the stabilization of the partially disordered magnetic structures and conclude that the magnetization and critical temperatures should increase substantially by reducing the number of As antisite defects.
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  • Lundgren, Fredrik, et al. (author)
  • PTFE bypass to below-knee arteries : distal vein collar or not? A prospective randomised multicentre study
  • 2010
  • In: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 39:6, s. 747-754
  • Journal article (peer-reviewed)abstract
    • BackgroundPatency and limb salvage after synthetic bypass to the arteries below-knee are inferior to that which can be achieved with autologous vein. Use of a vein collar at the distal anastomosis has been suggested to improve patency and limb salvage, a problem that is analysed in this randomised clinical study.MethodsPatients with critical limb ischaemia undergoing polytetrafluoroethylene (PTFE) bypass to below-knee arteries were randomly either assigned a vein collar or not in two groups – bypass to the popliteal artery below-knee (femoro-popliteal below-knee (FemPopBK)) and more distal bypass (femoro-distal bypass (FemDist)). Follow-up was scheduled until amputation, death or at most 5 years, whichever event occurred first.ResultsIn the FemPopBK and in the FemDist groups, 115/202 and 72/150 were randomised to have a vein collar, respectively. Information was available for 345 of 352 randomised patients (98%).At 3 years, primary patency was 26% (95% confidence interval (CI) 18–38) with a vein collar and 43 (33–58) without a vein collar for femoro-popliteal bypass and 20 (11–38), and 17 (9–33) for femoro-distal bypass, respectively. The corresponding figures for limb salvage were 64 (54–75) and 61 (50–74) for femoro-popliteal bypass, and 59 (46–76) and 44 (32–61) for femoro-distal bypass with and without a vein collar, respectively. Log-rank-test for the whole Kaplan–Meier life table curve showed no statistically significant differences with or without vein collar primary patency: p = 0.0853, p = 0.228; secondary patency: p = 0.317, p = 0.280; limb salvage: p = 0.757, p = 0.187 for FemPopBK and FemDist, respectively. The use of a vein collar did not influence patency or limb salvage.ConclusionThis study failed to show any benefit for vein collar with PTFE bypass to a below-knee artery.
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