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1.
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2.
  • Arlien-Soborg, Mai C., et al. (author)
  • Acromegaly management in the Nordic countries: A Delphi consensus survey
  • 2024
  • In: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265.
  • Journal article (peer-reviewed)abstract
    • ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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3.
  • Arlien-Soborg, Mai C., et al. (author)
  • Acromegaly management in the Nordic countries: A Delphi consensus survey
  • 2024
  • In: CLINICAL ENDOCRINOLOGY. - : WILEY. - 0300-0664 .- 1365-2265.
  • Journal article (peer-reviewed)abstract
    • ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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4.
  • Arlien-Søborg, Mai C., et al. (author)
  • Acromegaly management in the nordic countries : a Delphi consensus survey
  • 2024
  • In: Clinical Endocrinology. - : John Wiley & Sons. - 0300-0664 .- 1365-2265.
  • Journal article (peer-reviewed)abstract
    • Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.Methods: A Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1−7). Consensus was defined as ≥80% of panelists rating their agreement as ≥5 or ≤3 on the Likert-type scale.Results: Consensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.Conclusion: This consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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5.
  • Holm, Magnus, et al. (author)
  • Non-Invasive Assessment of the Atrial Cycle Length during Atrial Fibrillation in Man: Introducing, Validating and Illustrating a New ECG Method
  • 1998
  • In: Cardiovascular Research. - 1755-3245. ; 38:1, s. 69-81
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Atrial fibrillation (AF) in man has previously been shown to include a wide variety of atrial activity. Assessment of the characteristics of this arrhythmia with a commonly applicable tool may therefore be important in the choice and evaluation of different therapeutic strategies. As the AF cycle length has been shown to correlate locally with atrial refractoriness and globally with the degree of atrial organization, with, in general, shorter cycle length during apparently random AF compared to more organized AF, we have developed a new method for non-invasive assessment of the AF cycle length using the surface and the esophagus (ESO) ECG. METHODS AND RESULTS: From the frequency spectrum of the residual ECG, created by suppression of the QRST complexes, the dominant atrial cycle length (DACL) was derived. By comparison with multiple intracardiac simultaneously acquired right and left AF cycle lengths in patients with paroxysmal AF, we found that the DACL in lead V1, ranging from 130 to 185 ms, well represented a spatial average of the right AF cycle lengths, whereas the DACL in the ESO ECG, ranging from 140 to 185 ms, reflected both the right and the left AF cycle length, where the influence from each structure depended on the atrial anatomy of the individual, as determined by MRI. In patients with chronic AF, the method was capable of following changes in the AF cycle length due to administration of D,L-sotalol and 5 min of ECG recording was sufficient for the DACL to be reproducible. CONCLUSIONS: We conclude that this new non-invasive method, named 'Frequency Analysis of Fibrillatory ECG' (FAF-ECG), is capable of assessing both the magnitude and the dynamics of the atrial fibrillation cycle length in man.
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6.
  • Norell Bergendahl, Margareta, et al. (author)
  • Så skapar du det innovativa företaget
  • 2008
  • In: Innovationsförmåga. - Stockholm : PIEp. - 9789197785204 ; , s. 18-39
  • Book chapter (pop. science, debate, etc.)
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7.
  • Papakokkinou, Eleni, et al. (author)
  • Excess Morbidity Persists in Patients With Cushing’s Disease During Long-term Remission : A Swedish Nationwide Study
  • 2020
  • In: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
  • Journal article (peer-reviewed)abstract
    • Context: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined.Objective: To investigate comorbidities in patients with CD.Design, setting, and patients: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status.Main outcomes: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission.Results: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission.Conclusion: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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8.
  • Ragnarsson, Oskar, 1971, et al. (author)
  • Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study
  • 2019
  • In: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 104:6, s. 2375-2384
  • Journal article (peer-reviewed)abstract
    • Context: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable. Objective: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD. Design, Patients, and Methods: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality. Results: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome. Conclusion: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
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  • Ragnarsson, Oskar, 1971, et al. (author)
  • The incidence of Cushing’s disease : a nationwide Swedish study
  • 2019
  • In: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 22:2, s. 179-186
  • Journal article (peer-reviewed)abstract
    • Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05).Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
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10.
  • Yuan, S, et al. (author)
  • Effect of dofetilide on cardiac repolarization in patients with ventricular tachycardia. A study using simultaneous monophasic action potential recordings from two sites in the right ventricle
  • 1994
  • In: European Heart Journal. - 0195-668X. ; 15:4, s. 22-514
  • Journal article (peer-reviewed)abstract
    • Monophasic action potentials (MAP) were simultaneously recorded from the right ventricular (RV) apex (RVA) and the outflow tract (RVOT) before and after an infusion of dofetilide in 10 patients with documented ventricular tachycardia. After the drug infusion, the MAP duration (MAPd), repolarization time, and corrected QT interval were significantly prolonged during sinus rhythm, RV pacing, and RV extra stimulation. The prolongation of MAPd at 90% repolarization during RV pacing at a cycle length of 500 ms was 31 +/- 6 ms (13%) and 26 +/- 7 ms (11%) at RVA and RVOT, respectively. The ventricular effective refractory period was significantly prolonged by 33 +/- 9 ms (13%) and 22 +/- 7 ms (9%) at driving cycle lengths 600 and 500 ms, respectively. The MAPd shortening with decreasing diastolic time intervals was significantly diminished by dofetilide in early extra beats during RV extra stimulation, suggesting a relatively more pronounced effect of this drug at the early diastolic phase. The dispersion of repolarization, defined as the difference in MAPd between RVA and RVOT, and the activation time were not significantly changed. In conclusion, acute administration of dofetilide in patients with ventricular tachycardia significantly prolonged the time intervals of ventricular repolarization and refractoriness in a parallel fashion, without affecting intraventricular conduction. The effect of dofetilide on MAPd prolongation appeared not to be reverse use-dependent in this study in humans. These results verify the selective class III antiarrhythmic property of dofetilide and warrant further studies in patients.
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  • Al-Shamkhi, Nasrin, 1985-, et al. (author)
  • Pituitary function before and after surgery for nonfunctioning pituitary adenomas-data from the Swedish Pituitary Register.
  • 2023
  • In: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 189:2, s. 217-224
  • Journal article (peer-reviewed)abstract
    • Data on pre- and postoperative pituitary function in nonfunctioning pituitary adenomas (NFPA) are not consistent. We aimed to investigate pituitary function before and up to 5 years after transsphenoidal surgery with emphasis on the hypothalamic-pituitary-adrenal axis (HPA).Data from the Swedish Pituitary Register was used to analyze anterior pituitary function in 838 patients with NFPA diagnosed between 1991 and 2014. Patients who were reoperated or had received radiotherapy were excluded.Preoperative ACTH, TSH, LH/FSH, and GH deficiencies were reported in 31% (236/755), 39% (300/769), 51% (378/742), and 28% (170/604) of the patients, respectively. Preoperative median tumor volume was 5.0 (2.4-9.0) cm3. Among patients with preoperative, 1 year and 5 years postoperative data on the HPA axis (n = 428), 125 (29%) were ACTH-deficient preoperatively. One year postoperatively, 26% (32/125) of them had recovered ACTH function while 23% (70/303) patients had developed new ACTH deficiency. Thus, 1 year postoperatively, 163 (38%) patients were ACTH-deficient (P < .001 vs. preoperatively). No further increase was seen 5 years postoperatively (36%, P = .096). At 1 year postoperatively, recoveries in the TSH and LH/FSH axes were reported in 14% (33/241) and 15% (46/310), respectively, and new deficiencies in 22% (88/403) and 29% (83/288), respectively.Adrenocorticotrophic hormone deficiency increased significantly at 1 year postoperatively. Even though not significant, some patients recovered from or developed new deficiency between 1 and 5 years postoperatively. This pattern was seen in all axes. Our study emphasizes that continuous individual evaluations are needed during longer follow-up of patients operated for NFPA.
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13.
  • Alaridah, Nader, et al. (author)
  • Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden
  • 2019
  • In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
  • Journal article (peer-reviewed)abstract
    • Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.
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14.
  • Albers, GW, et al. (author)
  • Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation - A Randomized trial
  • 2005
  • In: JAMA: The Journal of the American Medical Association. - 1538-3598. ; 293:6, s. 690-698
  • Journal article (peer-reviewed)abstract
    • Context Inpatients with nonvalvular atrial fibrillation, warfarin prevents ischemic stroke, but dose adjustment, coagulation monitoring, and bleeding limit its use. Objective To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism. Design, Setting, and Participants Double-blind, randomized, multicenter trial (20002001) conducted at 409 North American sites, involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors. Interventions Adjusted-dose warfarin (aiming for an international normalized ratio [INR] 2.0 to 3.0) or fixed-dose oral ximelagatran, 36 mg twice daily. Main Outcome Measures The primary end point was all strokes (ischemic or hemorrhagic) and systemic embolic events. The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0% per year according to the intention-to-treat model. Results During 6405 patient-years (mean 20 months) of follow-up, 88 patients experienced primary events. The mean (SD) INR with warfarin (2.4 [0.8]) was within target during 68% of the treatment period. The primary event rate with ximelagatran was 1.6% per year and with warfarin was 1.2% per year (absolute difference, 0.45% per year; 95% confidence interval, -0.13% to 1.03% per year; P<.001 for the pre-defined noninferiority hypothesis). When all-cause mortality was included in addition to stroke and systemic embolic events, the rate difference was 0.10% per year (95% confidence interval, -0.97% to 1.2% per year; P=.86). There was no difference between treatment groups in rates of major bleeding, but total bleeding (major and minor) was lower with ximelagatran (37% vs 47% per year; 95% confidence interval for the difference, -14% to -6.0% per year; P<.001). Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0% of patients treated with ximelagatran, usually within 6 months and typically declined whether or not treatment continued; however, one case of documented fatal liver disease and one other suggestive case occurred. Conclusions The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy, but the potential for hepatotoxicity requires further investigation.
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15.
  • Andersen, Zorana J., et al. (author)
  • Long-term Exposure to Ambient Air Pollution and Incidence of Brain Tumor : the European Study of Cohorts for Air Pollution Effects (ESCAPE)
  • 2018
  • In: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 20:3, s. 420-432
  • Journal article (peer-reviewed)abstract
    • Background: Epidemiological evidence on the association between ambient air pollution and brain tumor risk is sparse and inconsistent.Methods: In 12 cohorts from 6 European countries, individual estimates of annual mean air pollution levels at the baseline residence were estimated by standardized land-use regression models developed within the ESCAPE and TRANSPHORM projects: particulate matter (PM) ≤2.5, ≤10, and 2.5–10 μm in diameter (PM2.5, PM10, and PMcoarse), PM2.5 absorbance, nitrogen oxides (NO2 and NOx) and elemental composition of PM. We estimated cohort-specific associations of air pollutant concentrations and traffic intensity with total, malignant, and nonmalignant brain tumor, in separate Cox regression models, adjusting for risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.Results: Of 282194 subjects from 12 cohorts, 466 developed malignant brain tumors during 12 years of follow-up. Six of the cohorts also had data on nonmalignant brain tumor, where among 106786 subjects, 366 developed brain tumor: 176 nonmalignant and 190 malignant. We found a positive, statistically nonsignificant association between malignant brain tumor and PM2.5 absorbance (hazard ratio and 95% CI: 1.67; 0.89–3.14 per 10–5/m3), and weak positive or null associations with the other pollutants. Hazard ratio for PM2.5 absorbance (1.01; 0.38–2.71 per 10–5/m3) and all other pollutants were lower for nonmalignant than for malignant brain tumors.Conclusion: We found suggestive evidence of an association between long-term exposure to PM2.5 absorbance indicating traffic-related air pollution and malignant brain tumors, and no association with overall or nonmalignant brain tumors.
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  • Andersen, Zorana J., et al. (author)
  • Long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in 15 European cohorts within the ESCAPE project
  • 2017
  • In: Journal of Environmental Health Perspectives. - Research triangle park : US department of health. - 0091-6765 .- 1552-9924. ; 125:10
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent.OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women.METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts – Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2.5μm, ≤10μm, and 2.5–10μm in diameter (PM2.5, PM10, and PMcoarse, respectively); PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2.5 {hazard ratio (HR)=1.08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg/m(3)}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg/m(3)], PMcoarse[1.20 (95% CI: 0.96, 1.49 per 5 μg/m(3)], and NO(2) [1.02 (95% CI: 0.98, 1.07 per 10 μg/m(3)], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg/m(3), p=0.04].CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women.
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17.
  • Anderson, Leif G., et al. (author)
  • The effect of the Siberian tundra on the environment of the shelf seas and the Arctic Ocean
  • 1999
  • In: Ambio. - 0044-7447. ; 28:3, s. 270-280
  • Journal article (peer-reviewed)abstract
    • The Tundra Ecology -94 expedition investigated inflow of inorganic and organic carbon to the shelf seas by river runoff, and its transformation by biochemical processes in seawater and sediment. In addition, anthropogenic radionuclides, 137Cs, 90Sr, and 239,240Pu, were studied in water and sediments. The distribution of dissolved inorganic carbon indicates that the majority of the Ob and Yenisey discharges flow into the Laptev Sea before entering the central Arctic Ocean. The sediment study shows that there is a marked difference in benthic oxygen uptake, efflux of dissolved inorganic carbon and nutrients between localities. 137Cs activity from the Chernobyl accident is 30% in the Barents, Kara, and Laptev Seas. 137Cs increased from 5-8 Bq m-3 in Barents Sea, 5-13 Bq m-3 in the Kara Sea to 8-15 Bq m-3 in the Laptev Sea, but with locally low concentrations at the river mouths. Corresponding values for 90Sr were 2.5, 3, and 4 Bq m-3, respectively.
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20.
  • Ayesa Alvarez, Susana, 1970- (author)
  • Design and Synthesis of Amine Building Blocks and Protease Inhibitors
  • 2008
  • Doctoral thesis (other academic/artistic)abstract
    • The first part of this thesis addresses the design and synthesis of amine building blocks accomplished by applying two different synthetic procedures, both of which were developed using solid-phase chemistry. Chapter 1 presents the first of these methods, entailing a practical solid-phase parallel synthesis route to N-monoalkylated aminopiperidines and aminopyrrolidines achieved by selective reductive alkylation of primary and/or secondary amines. Solid-phase NMR spectroscopy was used to monitor the reactions for which a new pulse sequence was developed. The second method, reported in Chapter 2, involves a novel approach to the synthesis of secondary amines starting from reactive alkyl halides and azides. The convenient solid-phase protocol that was devised made use of the Staudinger reaction in order to accomplish highly efficient alkylations of N-alkyl phosphimines or N-aryl phosphimines with reactive alkyl halides. The second part of the thesis describes the design and synthesis of three classes of protease inhibitors targeting the cysteine proteases cathepsins S and K, and the serine protease hepatitis C virus (HCV) NS3 protease. Chapter 4 covers the design, solid-phase synthesis, and structure-activity relationships of 4-amidofurane-3-one P1-containing inhibitors of cathepsin S and the effects of P3 sulfonamide groups on the potency and selectivity towards related cathepsin proteases. This work resulted in the discovery of highly potent and selective inhibitors of cathepsin S. Two parallel solid-phase approaches to the synthesis of a series of aminoethylamide inhibitors of cathepsin K are presented in Chapter 5. Finally, Chapter 6 reports peptide-based HCV NS3 protease inhibitors containing a non-electrophilic allylic alcohol moiety as P1 group and also outlines efforts to incorporate this new template into low-molecular-weight drug-like molecules.
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21.
  • Baturova, Maria A., et al. (author)
  • Non-permanent atrial fibrillation and oral anticoagulant therapy are related to survival during 10years after first-ever ischemic stroke
  • 2017
  • In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 232, s. 134-139
  • Journal article (peer-reviewed)abstract
    • Background: Atrial fibrillation (AF) detection in ischemic stroke patients triggers initiation of oral anticoagulant therapy (OAC). However, little is known regarding whether the persistency of AF affects long-term prognosis after ischemic stroke. We aimed to assess the impact of AF types and OAC on the outcome during a 10-year follow-up (FU) after first-ever ischemic stroke. Material and methods: The study sample comprised 336 first-ever ischemic stroke patients (median age 76, interquartile range 25-75% (IQR) 67-82. years, 136 female) included in the Lund Stroke Register (LSR) in 2001-2002. At baseline, 109 patients had either permanent (n = 44) or recurrent (n = 65) AF. OAC was assessed using the Lund University Hospital anticoagulation database. All-cause mortality was assessed via linkage with the Swedish Causes of Death Register. Results: During FU, 200 patients died. AF independently predicted all-cause mortality (hazard ratio (HR) 1.52 95% CI 1.14-2.04, p = 0.005); the worst prognosis was observed for permanent AF (HR 1.86 95% CI 1.29-2.69, p = 0.001). Patients with recurrent AF receiving OAC had similar survival rates to patients without AF (HR 0.73 95% CI 0.38-1.39, p = 0.333), while prognosis was worst for patients with permanent AF without OAC (HR 2.28 95% CI 1.38-3.77, p = 0.001) and intermediate for patients with permanent AF on OAC (HR 1.57 95% CI 0.92-2.67, p = 0.099). Conclusion: All-cause mortality was independently associated with AF and was the greatest in stroke patients with permanent AF. Patients with recurrent AF receiving OAC have the most favorable outcome, similar to those without AF and significantly better than OAC-treated patients with permanent AF.
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22.
  • Baturova, Maria, et al. (author)
  • Atrial fibrillation in patients with ischaemic stroke in the Swedish national patient registers: how much do we miss?
  • 2014
  • In: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 16:12, s. 1714-1719
  • Journal article (peer-reviewed)abstract
    • Data from national discharge registers are commonly used to estimate prevalence and incidence of atrial fibrillation (AF) in epidemiology studies. However, sensitivity and specificity of register-based AF diagnosis have not been evaluated. We sought to assess the validity of AF diagnosis in the Swedish Patient Register against electrocardiography (ECG) documentation of AF.
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25.
  • Beelen, Rob, et al. (author)
  • Long-term Exposure to Air Pollution and Cardiovascular Mortality An Analysis of 22 European Cohorts
  • 2014
  • In: Epidemiology. - : Lippincott Williams & Wilkins. - 1044-3983 .- 1531-5487. ; 25:3, s. 368-378
  • Journal article (peer-reviewed)abstract
    • Background: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. Methods: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and 10 mu m to 2.5 mu m (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. Results: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 mu g/m(3) and for PM10, 1.22 (0.91-1.63) per 10 mu g/m(3). Conclusion: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.
  •  
26.
  • Biloglav, Andrea, et al. (author)
  • SFPQ-ABL1-positive B-cell precursor acute lymphoblastic leukemias
  • 2020
  • In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264.
  • Journal article (peer-reviewed)abstract
    • In recent years, a subgroup of B‐cell precursor acute lymphoblastic leukemia (BCP ALL) without an established abnormality (“B‐other”) has been shown to be characterized by rearrangements of ABL1 , ABL2 , CSF1R , or PDGFRB (a.k.a. ABL‐class genes). Using FISH with probes for these genes, we screened 55 pediatric and 50 adult B‐other cases. Three (6%) of the adult but none of the childhood B‐other cases were positive for ABL‐class aberrations. RT‐PCR and sequencing confirmed a rare SFPQ‐ABL1 fusion in one adult B‐other case with t(1;9)(p34;q34). Only six SFPQ ‐ABL1 ‐positive BCP ALLs have been reported, present case included. A review of these shows that all harbored fusions between exon 9 of SFPQ and exon 4 of ABL1 , that the fusion is typically found in adolescents/younger adults without hyperleukocytosis, and that IKZF1 deletions are recurrent. The few patients not treated with tyrosine kinase inhibitors (TKIs) and/or allogeneic stem cell transplantation relapsed, strengthening the notion that TKI should be added to the therapy of SFPQ ‐ABL1 ‐positive BCP ALL.
  •  
27.
  • Bollmann, Andreas, et al. (author)
  • Analysis of surface electrocardiograms in atrial fibrillation: techniques, research, and clinical applications
  • 2006
  • In: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 8:11, s. 911-926
  • Research review (peer-reviewed)abstract
    • Atrial. fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Neither the natural history of AF nor its response to therapy is sufficiently predictable by clinical and echocardiographic parameters. The purpose of this article is to describe technical aspects of novel electrocardiogram (ECG) analysis techniques and to present research and clinical applications of these methods for characterization of both the fibrillatory process and the ventricular response during AF Atrial fibrillatory frequency (or rate) can reliably be assessed from the surface ECG using digital signal processing (extraction of atrial, signals and spectral analysis). This measurement shows large inter-individual variability and correlates well with intra-atriat cycle length, a parameter which appears to have primary importance in AF maintenance and response to therapy. AF with a tow fibrillatory rate is more likely to terminate spontaneously and responds better to antiarrhythmic drugs or cardioversion, whereas high-rate AF is more often persistent and refractory to therapy. Ventricular responses during AF can be characterized by a variety of methods, which include analysis of heart rate variability, RR-interval histograms, Lorenz plots, and non-linear dynamics. These methods have all shown a certain degree of usefulness, either in scientific explorations of atrioventricular (AV) nodal function or in selected clinical questions such as predicting response to drugs, cardioversion, or AV nodal modification. The role of the autonomic nervous system for AF sustenance and termination, as well as for ventricular rate responses, can be explored by different ECG analysis methods. In conclusion, non-invasive characterization of atrial fibrillatory activity and ventricular response can be performed from the surface ECG in AF patients. Different signal processing techniques have been suggested for identification of underlying AF pathomechanisms and prediction of therapy efficacy.
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28.
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29.
  • Bollmann, Andreas, et al. (author)
  • Atrial fibrillatory rate and risk of left atrial thrombus in atrial fibrillation.
  • 2007
  • In: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 9:8, s. 6-621
  • Journal article (peer-reviewed)abstract
    • ims In atrial fibrillation (AF), a relation between electrocardiogram (ECG) fibrillatory wave amplitude and thrombus formation has been sought for long with conflicting results. In contrast, the possible relation between atrial fibrillatory rate obtained from the surface ECG and left atrial thrombus formation in patients with AF is unknown and was consequently evaluated in this study. Methods and results One-hundred and twenty-five patients (mean age 64 ± 12 years, 72% male) with persistent non-valvular AF (mean duration 28 ± 80 days) undergoing transesophageal echocardiography were studied. In all patients, standard 12-lead ECG recordings were acquired before the examination. Atrial fibrillatory rate was determined using spatiotemporal QRST cancellation and time–frequency analysis of lead V1. Atrial fibrillatory rate measured 401 ± 63 fibrillations per minute (fpm, range 235–566 fpm) and was related with age (R = −0.326, P < 0.001), ventricular rate (R = −0.202, P = 0.024), gender (407 ± 62 in males vs. 387 ± 64 fpm in females, P = 0.038) but not AF duration (R = 0.088, P = 0.374), presence of lone AF (408 ± 66 vs. 394 ± 58 fpm, P = 0.228), or beta-blocker or calcium channel blocker treatment (398 ± 63 vs. 405 ± 62 fpm, P = 0.556). Age was the only independent predictor of fibrillatory rate (B = −1.714, P < 0.001). In patients with left atrial thrombus (n = 10), spontaneous echo contrast (SEC) was more frequently present (70 vs. 29 %, p = 0.007) and left atrial appendage (LAA) outflow velocity was lower (26 ± 20 vs. 37 ± 15 cm/s, P = 0.012) than in patients without thrombus (n = 115). In contrast, mean fibrillatory rate, which showed a weak inverse correlation with LAA velocity (R = −0.118, P = 0.048) was not different between both groups (380 ± 56 vs. 403 ± 63 fpm, P = 0.226). Similarly, presence of thrombus and SEC combined was not related with fibrillatory rate. Conclusion Atrial fibrillatory rate obtained from surface ECG lead V1 is not a risk marker for left atrial thrombus formation in AF.
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30.
  • Bollmann, Andreas, et al. (author)
  • Atrial fibrillatory rate and risk of stroke in atrial fibrillation.
  • 2009
  • In: Europace. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 11, s. 582-586
  • Journal article (peer-reviewed)abstract
    • Aims In atrial fibrillation (AF), a relation between electrocardiogram (ECG) parameters such as fibrillatory wave amplitude and stroke has been sought with conflicting results. In this study, we tested the hypothesis that the atrial fibrillatory rate of surface ECG lead V1 is related to stroke risk and may consequently be helpful for identifying high-risk patients. Methods and results Atrial fibrillatory rate of 79 consecutive patients with AF and embolic stroke (age 83 +/- 7 years, 41% male) was compared with those of a matched AF population without stroke (n = 79). Atrial fibrillatory rate was determined from the surface ECG using spatiotemporal QRST cancellation and time-frequency analysis of lead V1. There was no significant difference in any clinical or echocardiographic variable in patients with stroke compared with AF controls without stroke. Atrial fibrillatory rate measured 373 +/- 55 fibrillations per minute (fpm; range 235-505 fpm) in the entire population. There was no fibrillatory rate difference between stroke patients (369 +/- 54 fpm, range 256-505 fpm) and AF controls without stroke (378 +/- 56 fpm, range 235-488 fpm). There was an inverse correlation between fibrillatory rate and age (R = -0.219, P = 0.006). Individuals aged >/=85 years had a significantly lower fibrillatory rate (356 +/- 44 fpm) than individuals aged 65-74 years (384 +/- 56 fpm, P = 0.033) and individuals aged 75-84 years (384 +/- 60 fpm, P = 0.016). In those subgroups, fibrillatory rates were, however, also similar in stroke patients and AF controls. Conclusion Atrial fibrillatory rate obtained from surface ECG lead V1 is not a risk marker for stroke in AF.
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31.
  • Bollmann, Andreas, et al. (author)
  • Echocardiographic and electrocardiographic predictors for atrial fibrillation recurrence following cardioversion
  • 2003
  • In: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 14:s10, s. 162-165
  • Journal article (peer-reviewed)abstract
    • Introduction: Identification of suitable candidates for cardioversion currently is not based on individual electrical and mechanical atrial remodeling. Therefore, this study analyzed the meaning of atrial fibrillatory rate obtained from the surface ECG (as a measure of electrical remodeling) and left atrial size (as measure of mechanical remodeling) for prediction of early atrial fibrillation (AF) recurrence following cardioversion. Methods and Results: Forty-four consecutive patients (26 men and 18 women, mean age 62 ± 11 years, no antiarrhythmic medication at baseline) with persistent AF were studied. Fibrillatory rate was obtained from high-gain, high-resolution surface ECG using digital signal processing (filtering, QRST subtraction, Fourier analysis) before electrical cardioversion. Univariate and multivariate regression analysis revealed larger systolic left atrial area (Beta = 0.176, P = 0.031) obtained by precardioversion echocardiogram from the apical four-chamber view and higher atrial fibrillatory rate (Beta = 0.029, P = 0.021) to be independent predictors for AF recurrence (n = 13). Stratification based on the regression equation (electromechanical index [EMI]= 0.176 systolic left atrial area + 0.029 fibrillatory rate − 17.674) allowed identification of groups at low, intermediate, or high risk. No patient with an EMI < −1.85 had early AF recurrence, as opposed to 78% with an EMI > −0.25. Intermediate results (40% recurrence rate) were obtained when the calculated EMI ranged between −1.85 and −0.25 (P < 0.001). Conclusion: Fibrillatory rate obtained from the surface ECG and systolic left atrial area obtained by echocardiography may predict early AF recurrence in patients with persistent AF. These parameters might be useful in identifying candidates with a high likelihood of remaining in sinus rhythm after cardioversion.
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32.
  • Bollmann, Andreas, et al. (author)
  • Fibrillatory rate response to candesartan in persistent atrial fibrillation.
  • 2008
  • In: Europace. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 10, s. 1138-1144
  • Journal article (peer-reviewed)abstract
    • Introduction Angiotensin-receptor blockers may exert favourable anti-arrhythmic effects in atrial fibrillation (AF), but their mechanisms are not fully understood. In this study, we tested the hypotheses that (i) candesartan reduces atrial fibrillatory rate and (ii) fibrillatory rate and its response to candesartan are related with the outcome of cardioversion. For this purpose, a post hoc subanalysis of the randomized, placebo-controlled CAPRAF (Candesartan in the Prevention of Relapsing Atrial Fibrillation) trial was performed. Methods and results Patients with AF undergoing electrical cardioversion were randomized to receive candesartan 8 mg once daily (n = 58) or matching placebo (n = 66) and no additional class I or III anti-arrhythmic drugs. Fibrillatory rate was determined from ECG lead V1 at baseline and at the day of cardioversion using spatiotemporal QRST cancellation and time-frequency analysis. The median time on treatment was 29 days. Candesartan reduced fibrillatory rate [399 +/- 48 vs. 388 +/- 49 fibrillations/min (fpm), P = 0.04], but not placebo (402 +/- 58 vs. 402 +/- 61 fpm, P = 0.986). Candesartan effects were only observed if the baseline fibrillatory rate was high [>420 fpm: 445 +/- 21 vs. 415 +/- 49 fpm, P = 0.006 vs. intermediate (360-420 fpm): 397 +/- 19 vs. 391 +/- 37 fpm, P = 0.351 vs. low (<360 fpm): 326 +/- 26 vs. 338 +/- 29 fpm, P = 0.179]. Cardioversion success was 100% in patients with an on-treatment rate <360 fpm vs. 83% in patients with higher rates (P = 0.02). Risk for AF recurrence was similar in patients with low (64%), intermediate (75%), or high on-treatment rates (63%, P = 0.446) and was also independent of candesartan effects on the fibrillatory rate. Conclusion In patients with persistent AF, candesartan decreases the fibrillatory rate, but this effect is restricted to patients with high baseline fibrillatory rates and is not associated with improved cardioversion outcome. Fibrillatory rates <360 fpm are associated with successful cardioversion, but not with AF recurrence.
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33.
  • Bollmann, A, et al. (author)
  • Frequency measures obtained from the surface electrocardiogram in atrial fibrillation research and clinical decision-making
  • 2003
  • In: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 14:s10, s. 154-161
  • Journal article (peer-reviewed)abstract
    • Frequency Measures in AF. Introduction: Frequency analysis of fibrillation (FAF) and time-frequency analysis (TFA) were developed recently in order to quantify atrial electrical remodeling in atrial fibrillation (AF) from the surface ECG. This article describes the experience with these two different frequency analysis techniques in consecutive AF patients and discusses possible applications in AF research and clinical decision-making. Methods and Results: Baseline 2-minute, high-gain, high-resolution ECG recordings using three bipolar leads were obtained from 80 consecutive patients with AF lasting >24 hours. A power spectrum was obtained using Fourier analysis following spatiotemporal QRST cancellation. The dominant fibrillatory rate (in fibrillations per minute [fpm]) was derived (FAF). Stability of the instantaneous fibrillatory rate measured in overlapping 1-second segments was expressed as the segment proportion with consecutive rate differences <6 fpm (TFA). An adequate power spectrum that could be submitted for determination of fibrillatory rate was obtained in all patients. Dominant atrial rates ranged between 288 and 534 fpm and showed a high correlation (R = 0.878-0.911, P < 0.001) when assessed from the three different leads. The average instantaneous fibrillatory rate was inversely related with its stability (R = -0.417, P < 0.001). It was closely related with the dominant fibrillatory rate obtained from FAF (R = 0.948, P < 0.001). A literature review revealed that pharmacologic or electrical cardioversion and AF pace termination success rates were highly dependent on fibrillatory rate. Conclusion: Atrial fibrillatory rate and its variability can be reliable obtained from the surface ECG in AF patients. These parameters exhibit a significant interindividual variability allowing individual quantification of the atrial electrical remodeling process and might prove useful for predicting therapy efficacy.
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34.
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35.
  • Bråbäck, Lennart, et al. (author)
  • Childhood asthma and smoking exposures before conception - a three-generational cohort study.
  • 2018
  • In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 29:4, s. 361-368
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Some human and animal studies have recently shown that maternal grandmother's smoking during pregnancy increases the risk of asthma in the grandchildren. We have investigated whether sex of the exposed parent and/or grandchild modifies the association between grandmaternal smoking and grandchild asthma.METHODS: We formed a cohort study based on linkage of national registries with prospectively collected data over three generations. Smoking habits in early pregnancy were registered since 1982 and purchases of prescribed medication since 2005. In all, 10329 children born since 2005 had information on maternal and grandmaternal smoking on both sides and were followed from birth up to 6 years of age. Ages when medication was purchased were used to classify the cohort into never, early transient (0-3 years), early persistent (0-3 and 4-6 years) and late-onset (4-6 years) phenotypes of childhood asthma.RESULTS: Maternal grandmother's smoking was associated with an increased odds of early persistent asthma after adjustment for maternal smoking and other confounders (odds ratio 1.29, 95% confidence interval 1.10-1.51). Grandchild sex did not modify the association. Paternal grandmother's smoking was not associated with any of the asthma phenotypes.CONCLUSION: Maternal but not paternal exposure to nicotine before conception was related to an increased risk of early persistent childhood asthma, but not other asthma phenotypes. Our findings are possibly consistent with a sex specific mode of epigenetic transfer. 
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36.
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37.
  • Carlsen, Hanne Krage, et al. (author)
  • Birch pollen, air pollution and their interactive effects on airway symptoms and peak expiratory flow in allergic asthma during pollen season - a panel study in Northern and Southern Sweden
  • 2022
  • In: Environmental health. - : Springer Science and Business Media LLC. - 1476-069X. ; 21:1
  • Journal article (peer-reviewed)abstract
    • Background: Evidence of the role of interactions between air pollution and pollen exposure in subjects with allergic asthma is limited and need further exploration to promote adequate preventive measures. The objective of this study was to assess effects of exposure to ambient air pollution and birch pollen on exacerbation of respiratory symptoms in subjects with asthma and allergy to birch. Methods: Thirty-seven subjects from two Swedish cities (Gothenburg and Umea) with large variation in exposure to both birch-pollen and air pollutants, participated in the study. All subjects had confirmed allergy to birch and self-reported physician-diagnosed asthma. The subjects recorded respiratory symptoms such as rhinitis or eye irritation, dry cough, dyspnoea, the use of any asthma or allergy medication and peak respiratory flow (PEF), daily for five consecutive weeks during two separate pollen seasons and a control season without pollen. Nitrogen oxides -(NOx), ozone -(O-3), particulate matter -(PM2.5), birch pollen counts, and meteorological data were obtained from an urban background monitoring stations in the study city centres. The data were analysed using linear mixed effects models. Results: During pollen seasons all symptoms and medication use were higher, and PEF was reduced in the subjects. In regression analysis, exposure to pollen at lags 0 to 2 days, and lags 0 to 6 days was associated with increased ORs of symptoms and decreased RRs for PEF. Pollen and air pollution interacted in some cases; during low pollen exposure, there were no associations between air pollution and symptoms, but during high pollen exposure, -O-3 concentrations were associated with increased OR of rhinitis or eye irritation, and -PM2.5 concentrations were associated with increased ORs of rhinitis or eye irritation, dyspnea and increased use of allergy medication. Conclusions: Pollen and air pollutants interacted to increase the effect of air pollution on respiratory symptoms in allergic asthma. Implementing the results from this study, advisories for individuals with allergic asthma could be improved, minimizing the morbidities associated with the condition.
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38.
  • Carlsen, Hanne Krage, et al. (author)
  • Indicators of residential traffic exposure: Modelled NOX, traffic proximity, and self-reported exposure in RHINE III
  • 2017
  • In: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 167, s. 416-425
  • Journal article (peer-reviewed)abstract
    • Few studies have investigated associations between self-reported and modelled exposure to traffic pollution. The objective of this study was to examine correlations between self-reported traffic exposure and modelled (a) NOX and (b) traffic proximity in seven different northern European cities; Aarhus (Denmark), Bergen (Norway), Gothenburg, Umeå, and Uppsala (Sweden), Reykjavik (Iceland), and Tartu (Estonia). We analysed data from the RHINE III (Respiratory Health in Northern Europe, www.rhine.nu) cohorts of the seven study cities. Traffic proximity (distance to the nearest road with >10,000 vehicles per day) was calculated and vehicle exhaust (NOX) was modelled using dispersion models and land-use regression (LUR) data from 2011. Participants were asked a question about self-reported traffic intensity near bedroom window and another about traffic noise exposure at the residence. The data were analysed using rank correlation (Kendall's tau) and inter-rater agreement (Cohen's Kappa) between tertiles of modelled NOX and traffic proximity tertile and traffic proximity categories (0–150 metres (m), 150–200 m, >300 m) in each centre. Data on variables of interest were available for 50–99% of study participants per each cohort. Mean modelled NOX levels were between 6.5 and 16.0 μg/m3; median traffic intensity was between 303 and 10,750 m in each centre. In each centre, 7.7–18.7% of respondents reported exposure to high traffic intensity and 3.6–16.3% of respondents reported high exposure to traffic noise. Self-reported residential traffic exposure had low or no correlation with modelled exposure and traffic proximity in all centres, although results were statistically significant (tau = 0.057–0.305). Self-reported residential traffic noise correlated weakly (tau = 0.090–0.255), with modelled exposure in all centres except Reykjavik. Modelled NOX had the highest correlations between self-reported and modelled traffic exposure in five of seven centres, traffic noise exposure had the highest correlation with traffic proximity in tertiles in three centres. Self-reported exposure to high traffic intensity and traffic noise at each participant's residence had low or weak although statistically significant correlations with modelled vehicle exhaust pollution levels and traffic proximity. © 2017
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39.
  • Carlson, Jonas, et al. (author)
  • Can Orthogonal Lead Indicators of Propensity to Atrial Fibrillation be Accurately Assessed from the 12-Lead ECG?
  • 2005
  • In: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 7:Suppl 2, s. 39-48
  • Journal article (peer-reviewed)abstract
    • Aims: When analyzing P-wave morphology, the vectorcardiogram(VCG) has been shown useful to identify indicators of propensity to atrial fibrillation (AF). Since VCG is rarely used in the clinical routine, we wanted to investigate if these indicators could be accurately determined in VCG derived from standard 12-lead ECG (dVCG).Methods: ECG and VCG recordings from 21 healthy subjects and 20 patients with a history of AF were studied. dVCG was calculated from ECG using the inverse Dower transform. Following signal averaging of P-waves, comparisons were madebetween VCG and dVCG, where three parameters characterizing signal shape and 15 parameters describing the P-wave morphology were used to assess the compatibility of the two recording techniques. The latter parameters were alsoused to compare the healthy and the AF groups.Results: After transformation, P-wave shape was convincingly preserved. P-wave morphology parameters were consistent within the respective groups when comparing VCG and dVCG, with better preservation observed in the healthy group.Conclusion VCG derived from routine 12-lead ECG may be a useful alternate method for studying orthogonal P-wave morphology.
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40.
  • Carlson, Jonas, et al. (author)
  • Classification of Electrocardiographic P-wave Morphology
  • 2001
  • In: IEEE Transactions on Biomedical Engineering. - : Institute of Electrical and Electronics Engineers (IEEE). - 1558-2531 .- 0018-9294. ; 48:4, s. 401-405
  • Journal article (peer-reviewed)abstract
    • The atrial activity of the human heart is normally visible in the electrocardiogram as a P-wave. In patients with intermittent atrial fibrillation, a different P-wave morphology can sometimes be seen, indicating atrial conduction defects. The purpose of this study was to develop a method to discriminate between such P-waves and normal ones. 20 recordings of each type were used in a classification which, based on impulse response analysis of the P-wave and linear discrimination between various parameters, produced a correct classification in 37 of the 40 recordings (sensitivity 95%, specificity 90%)
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41.
  • Carlson, Jonas, et al. (author)
  • Classification of Electrocardiographic P-wave Morphology
  • 2000
  • In: Proceedings of the 39th IEEE Conference on Decision and Control, 2000.. - 0780366387 ; 2, s. 1804-1809
  • Conference paper (other academic/artistic)abstract
    • The atrial activity of the human heart is normally visible in the ECG as a P-wave. In patients with intermittent atrial fibrilation, a different P-wave morphology can sometimes be seen, indicating atrial conduction defects. The purpose of this study was to develop a method to discriminate between such P-waves and normal ones. 20 recordings of each type were used in a classification which, based on impulse response analysis of the P-wave and linear discrimination between various parameters, produced a correct classification in 37 of the 40 recordings (sensitivity 95%, specificity 90%)
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42.
  • Carlson, Jonas, et al. (author)
  • Left Atrial Conduction along the Coronary Sinus during Ectopic Atrial Tachycardia and Atrial Fibrillation: A Study Using Correlation Function Analysis
  • 2003
  • In: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 14:10 Suppl, s. 148-153
  • Journal article (peer-reviewed)abstract
    • ntroduction: Correlation function analysis was applied to endocardial electrograms to investigate conduction patterns along the coronary sinus (CS) during sinus rhythm (SR) and atrial tachycardias. Methods and Results: Eighteen recordings were obtained from 14 patients suffering from supraventricular tachycardias. Five atrial fibrillation(AF) recordings were compared to 10 SR recordings and 3 ectopic atrial tachycardia (EAT) recordings. The maximum correlation coefficient was used to assess similarity between signals, i.e., if they originate from the samewavefront. The cumulative time delay, calculated as pairwise summation of interelectrode time delays was used as an indicator of activation sequence along CS. Method validation using SR showed right to left conduction with high correlations in 8 of 10 recordings indicating one single wavefront. EAT recordings showed consistent left to right conduction with left atrial foci and right to left with right atrial focus and lower correlations than SR. All 5 AFrecordings showed predominantly left to right conduction direction, also with correlations lower than SR.Conclusion: 1) Correlation function analysis can be used to assess agreement between signals and direction of activation spread. 2) Due to the position of CS, the results can be used to derive mechanisms of interatrial conduction. 3) Consistency in electrical activity propagation along CS iscommon in AF.
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43.
  • Carlson, Jonas, et al. (author)
  • Non-invasive assessment of direction of right atrial activation during atrial fibrillation using correlation function analysis.
  • 2007
  • In: Computers in Cardiology. - 0276-6574. ; 34, s. 277-280
  • Journal article (peer-reviewed)abstract
    • ECGs were recorded from three electrodes attached at the corners of an equilateral triangle positioned around the location of electrode V1. The atrial signal between QRST complexes was subjected to correlation function analysis to reveal differences in activation times between the electrode sites. The time differences found were used to calculate the direction of activation across the body surface. Twenty-three subjects were studied during sinus rhythm (SR), intraoperatively confirmed typical and reverse typical atrial flutter, or during paroxysmal or permanent atrial fibrillation (AF). Subjects studied during SR and patients with typical atrial flutter exhibited a uniform direction of activation, with the main vector pointing downwards. The propagation of atrial activation during permanent AF did not show a consistent direction, while patients with paroxysmal AF exhibited more uniform activation vectors, corresponding to the direction observed in patients with atrial flutter.
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44.
  • Carlsson, E, et al. (author)
  • The role of the nurse in enhancing quality of life in patients with an implantable cardioverter-defibrillator: the Swedish experience.
  • 2002
  • In: Progress in Cardiovascular Nursing. - : Wiley. - 1751-7117 .- 0889-7204. ; 17:1, s. 18-25
  • Journal article (peer-reviewed)abstract
    • During the last 10-15 years, the implantable cardioverter-defibrillator (ICD) has become an important mode of treatment for patients suffering from grave ventricular arrhythmias, but ICD implantation involves psychosocial adjustments for both patients and relatives. The aim of this pilot study was to design a plan of education and to follow a selected group of patients with interviews, observations, and a questionnaire. The goals included seeing how well they accepted their situation after the operation when they had ongoing support of the nurse, in comparison to a control group who received conventional patient education by the physician. The patients were randomly allocated into two groups. Twenty patients were recruited, 10 in the study group and 10 in the control group, between February, 1997 and April, 1998. There were 16 men (average age, 63) and four women (average age, 57). The Nottingham Health Profile was used to measure health-related quality of life. Sleep disturbances were the greatest problem in both the study group and the control group before ICD implantation. In the study group, there was a significant improvement (p<0.05) after ICD implantation in four patients. The study also revealed a difference between men and women, with women having more sleep disturbances before ICD implantation than men (p<0.05). In both groups, there was a lack of energy and emotional reactions, both before and after ICD implantation. Few considered family life a problem before or after the study. In the control group, the patients missed the lack of contact with health care personnel more than in the study group. There was also a greater need for group meetings after the hospital stay. By means of the questionnaire, interviews, and observations, it became evident that there was a great need for information, and a plan of patient education in addition to follow-up by the nurse was felt to be very important. (c)2002 CHF, Inc.
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45.
  • Casslén, Vera, et al. (author)
  • Histamine uptake by human endometrial cells expressing the organic cation transporter EMT and the vesicular monoamine transporter-2
  • 2006
  • In: Molecular Human Reproduction. - : Oxford University Press (OUP). - 1460-2407 .- 1360-9947. ; 12:8, s. 483-489
  • Journal article (peer-reviewed)abstract
    • Cellular reuptake of monoamines, which is mediated by cell membrane transporters, is followed by accumulation in vesicles by vesicular monoamine transporters (VMAT). The aim of this study was to demonstrate the presence of functional monoamine transporters with high affinity for histamine in human endometrial tissue, since histamine has been implicated as a paracrine signal during endometrial decidualization and embryo implantation. In situ hybridization with S-35-labelled cRNA probes was used for detection of the organic cationic transporter-2 (OCT-2), the extraneuronal monoamine transporter (EMT), and VMAT-2 in cryosections of normal human endometrial tissue. To identify functional transporters for histamine in endometrial cells, we incubated primary cultures of stromal cells and cultures of attached glands with H-3-labelled histamine. Cultures were pretreated with either corticosterone, a specific inhibitor of EMT, or reserpine, a specific inhibitor of VMAT-2. EMT mRNA was localized in the stroma with peak expression in the secretory phase, whereas OCT-2 mRNA was expressed by few cells in the stroma throughout the cycle. VMAT-2 mRNA was localized in the stroma during the proliferative phase and in the epithelium during the secretory phase. Thus, EMT and VMAT-2, which both have high affinity for histamine, are strongly expressed in endometrial cells. Both corticosterone and reserpine significantly reduced the uptake of H-3-histamine in stromal cells during the proliferative as well as the secretory phase. This indicates the presence of functional EMT and VMAT-2 transporter proteins throughout the cycle, even though their periods of maximal mRNA expression were limited. The results of uptake experiments with glandular epithelial cells confirmed not only the presence of functional VMAT-2 transporter protein in the secretory phase but also the absence of a histamine-specific plasma membrane transporter throughout the cycle. Thus, endometrial tissue contains both plasma membrane and vesicular membrane monoamine transporters with high affinity for histamine. They can potentially influence the reproductive process by the uptake of extracellular histamine and subsequent release on demand.
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46.
  • Cortez, Daniel, et al. (author)
  • Atrial time and voltage dispersion are both needed to predict new-onset atrial fibrillation in ischemic stroke patients
  • 2017
  • In: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 17:1
  • Journal article (peer-reviewed)abstract
    • Background: Atrial fibrillation (AF) is a known risk factor for ischemic stroke. Electrocardiographic predictors of AF in population studies such as the Framingham Heart Study, as well as in hypertensive patients have demonstrated a predictive value of the P-wave duration for development of AF. QRS vector magnitude has had a predictive value in ventricular arrhythmia development. We aimed to assess the value of the three-dimensional P-wave vector magnitude and its relationship to P-wave duration for prediction of new-onset AF after ischemic stroke. Methods: First-ever ischemic stroke patients without AF at inclusion in the Lund Stroke Register were included. Measurements of P wave duration (Pd), QRS duration, corrected QT interval, and PQ interval were performed automatically using the University of Glasgow 12-lead ECG analysis algorithm. The P-wave vector magnitude (Pvm) was calculated automatically as the square root of the sum of the squared P-wave magnitudes in leads V6, II and one half of the P-wave amplitude in V2 ( PV 6 2 + PII 2 + 0.5 PV 2 2 $$ \sqrt(PV(6)^2+(PII)^2+(\left((0.5)^(\ast )PV2\right))^2) $$ ), based on the P-wave magnitude (Pvm) as defined by the visually transformed Kors' Quasi-orthogonal method. Results: The median age was 73 (IQR 63-80) years at stroke onset (135 males, 92 females). Multivariate predictors of new-onset atrial fibrillation included age>65years, hypertension, and Pd/Pvm. A cut-off value of 870ms/mV gave sensitivity, specificity, positive and negative predictive values of 51, 79, 30 and 87%, respectively. The Pd/Pvm was the only ECG predictor of AF with a significant multivariate hazard ratio of 2.02 (95% CI 1.18 to 3.46, p=0.010). Conclusion: P-wave dispersion as measured by the Pd/Pvm was the only ECG parameter measured which independently predicted subsequent AF identification in a cohort of stroke patients. Further prospective studies in larger cohorts are needed to validate its clinical usefulness.
  •  
47.
  • Dahlström, Edmund, 1922, et al. (author)
  • Studier av arbetsbytesprocessen.
  • 1966
  • Reports (other academic/artistic)abstract
    • This Research Report consists of five artics, all of which concern the process of "Job-choice". In the first article, written by Olsson and Rundblad, a method of choice-analysis is applied, originally outlined by Boalt & Janson at the University of Stockholm. Dahlström and Sjöstrand, in the nest articles, discuss some of the methodological difficulties that arise througt the application of the Boalt - jansson-model. Dahlström here suggests a dodification of their model, which, in the fourth article, he make an attempt to test, thereby somparing his results with those obtained by Olsson - Rundblad. In the last article, finally, Dahlström suggests a more general fram of of reference for the analysis of individual choice - or change - mechanisms in the job-sphere.
  •  
48.
  • Dalenbäck, Jan-Olof, 1954, et al. (author)
  • Åtgärder för ökad energieffektivsering i bebyggelse
  • 2005
  • Reports (other academic/artistic)abstract
    • Energikommissionens betänkande ”Omställning av energisystemet” visade 1995 på en förhållandevis stor teknisk-ekonomisk potential att minska såväl den totala (TWh/år) som den specifika energianvändningen (kWh/m²/år) i bebyggelsen. En sådan utveckling förutsätter dock att nya byggnader som uppförs har lägre energibehov än befintliga samtidigt som energianvändningen i befintliga byggnader reduceras. Nya byggnaders energibehov bestäms främst av gällande regler för bygglov medan förutsättningarna för energieffektiviseringsåtgärder i befintliga byggnader är bäst i samband med underhålls- och renoveringsåtgärder. Trots något bättre ekonomiska förutsättningar än vad man antog i Energikommissionens betänkande, visar en utvärdering att det inte skett någon egentlig minskning av den specifika energianvändningen från 1993 till 2003. Sammantaget beror detta på en låg politisk ambition (ingen skärpning av krav med avseende på energianvändning i byggnader) och en generellt sett låg acceptans för energieffektivisering hos fastighetsägare (brist på incitament att minska energianvändningen). Med en uttalad ambition att erhålla en ökad energieffektivisering i bebyggelsen krävs därför en väsentlig skärpning av de krav som påverkar energianvändningen samtidigt som energieffektivisering måste stimuleras på ett mer påtagligt sätt. Ett system med kontinuerligt skärpta krav tillsammans med fastighetsekonomiska fördelar med låg energianvändning bör på sikt leda till en väsentlig energieffektivisering i bebyggelsen. Vi föreslår införande av krav med avseende på byggnaders energiprestanda vid ny- och ombyggnad och en skärpt uppföljning av desamma med hjälp av energideklarationer i anslutning till införandet av EG-direktivet om byggnaders energiprestanda. I sammanhanget föreslås dessutom tvingande krav i anslutning till befintliga byggnader med sämst energiprestanda. Vidare förslås att energieffektivisering stimuleras med riktade informationsinsatser till småhusägare respektive större fastighetsförvaltare tillsammans med införande av ett system för klassning av byggnader bland annat baserat på energiprestanda.
  •  
49.
  • Danielsson, Susanna, 1964, et al. (author)
  • Psychopathology, psychosocial functioning, and IQ before and after epilepsy surgery in children with drug-resistant epilepsy.
  • 2009
  • In: Epilepsy & Behavior. - : Elsevier BV. - 1525-5050. ; 14:2, s. 330-337
  • Journal article (peer-reviewed)abstract
    • This is a prospective study of a consecutive series of children undergoing epilepsy surgery. The main aims were to evaluate the heterogeneity with respect to psychopathology and IQ, and to use a global assessment scale (Children's Global Assessment Scale [CGAS]) to evaluate psychosocial functioning. Clinical neuropsychiatric and neuropsychological assessments were made at baseline and at the 2-year follow-up in 24 patients, and changes were analyzed at an individual level. Psychiatric disorders (mainly attention deficit hyperactivity disorder and/or autism spectrum disorders) were found in 17 of 24 at some point. All except one child with psychiatric diagnoses before surgery still had at least one diagnosis at follow-up. Intellectual ability remained stable in the majority of cases, both in individuals with and in individuals without mental retardation. The CGAS illustrated the consequences of the extensive comorbidity in this cohort. The behavioral problems had been undiagnosed despite parental concern in many cases, indicating an unrecognized need for services for children with drug-resistant epilepsy.
  •  
50.
  • Danielsson, Susanna, 1964, et al. (author)
  • Temporal Lobe Resections in Children with Epilepsy: Neuropsychiatric Status in Relation to Neuropathology and Seizure Outcome.
  • 2002
  • In: Epilepsy & behavior : E&B. - 1525-5069. ; 3:1, s. 76-81
  • Journal article (peer-reviewed)abstract
    • The purpose of this work was to relate clinical neuropsychiatric findings to histopathological diagnoses and seizure outcome in a retrospective study of 16 children undergoing temporal lobe resections due to medically intractable epilepsy. These children constitute a heterogeneous group in which neuropsychiatric symptoms were common. The results of this study indicate a correlation between malformations of cortical development, less chance of seizure freedom, and neuropsychiatric problems in children with pharmacoresistant temporal lobe epilepsy. It is important to include neuropsychiatric assessments pre- and postoperatively and to inform parents that symptoms of autism spectrum disorders may or may not be improved after epilepsy surgery.
  •  
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