| 1. |
- Leonard, Dag, et al.
(författare)
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Coronary Heart Disease in Systemic Lupus Erythematosus Is Associated With Interferon Regulatory Factor-8 Gene Variants
- 2013
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Ingår i: Circulation: Cardiovascular Genetics. - : BMJ. - 1942-325X .- 1942-3268. ; 72:Suppl. 3, s. 270-270
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Tidskriftsartikel (refereegranskat)abstract
- Background- Patients with systemic lupus erythematosus have increased morbidity and mortality in coronary heart disease (CHD). We asked whether there was a genetic influence on CHD in systemic lupus erythematosus. Methods and Results- The association between single-nucleotide polymorphisms (SNPs) and CHD in 2 populations of patients with systemic lupus erythematosus was assessed. Patients were genotyped on a custom 12k Illumina Array. The allele frequencies were compared between patients with (n=66) and without (n=509) CHD. We found 61 SNPs with an association (P<0.01) to CHD, with the strongest association for 3 SNPs located in the interferon regulatory factor-8 (IRF8) gene. Comparison of the allele frequencies of these 61 SNPs in patients with (n=27) and without (n=212) CHD in the second study population revealed that 2 SNPs, rs925994 and rs10514610 in IRF8 (linkage disequilibrium, r(2)=0.84), were associated with CHD in both study populations. Meta-analysis of the SNP rs925994 gave an odds ratio of 3.6 (2.1-6.3), P value 1.9x10(-6). The identified IRF8 allele remained as a risk factor for CHD after adjustment for traditional CHD risk factors. The IRF8 risk allele was associated with the presence of carotid plaques (P<0.001) and increased intima-media thickness (P=0.01). By electrophoretic mobility shift assays, we show weaker binding of protein to the risk allele of the highly linked SNP rs11117415, and by flow cytometry, a reduced frequency of circulating B cells was detected in patients with the IRF8 risk allele. Conclusions- There is a considerable genetic component for CHD in systemic lupus erythematosus, with IRF8 as a strong susceptibility locus.
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| 2. |
- Bengtsson, Olof, 1969-
(författare)
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Design and Characterization of RF-Power LDMOS Transistors
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In mobile communication new applications like wireless internet and mobile video have increased the demand of data-rates. Therefore, new more wideband systems are being implemented. Power amplifiers in the base-stations that simultaneously handle these wideband signals for many terminals (handhelds) need to be highly linear with a considerable band-width. In the past decade LDMOS has been the dominating technology for use in these RF-power amplifiers. In this work LDMOS transistors possible to fabricate in a normal CMOS process have been optimized and analyzed for RF-power applications. Their non-linear behavior has been explored using load-pull measurements. The mechanisms of the non-linear input capacitance have been analyzed using 2D TCAD simulations. The investigation shows that the input capacitance is a large contributor to phase distortion in the transistor. Computational load-pull TCAD methods have been developed for analysis of RF-power devices in high-efficiency operation. Methods have been developed for class-F with harmonic loading and for bias-modulation. Load-pull measurements with drain-bias modulation in a novel measurement setup have also been conducted. The investigation shows that the combination of computational load-pull of physical transistor structures and direct measurement evaluation with modified load-pull is a viable alternative for future design of RF-power devices. Simulations and measurements on the designed LDMOS shows a 10 to 15 % increase in drain efficiency in mid-power range both in simulations and measurements. The computational load-pull method has also been used to investigate the power capability of LDMOS transistors on SOI. This study indicates that either a low-resistivity or high-resistivity substrate should be used in manufacturing of RF-power LDMOS transistors on SOI to achieve optimum efficiency. Based on a proper substrate selection these devices exhibit a 10 % higher drain-efficiency mainly due to lower dissipated power in the devices.
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| 3. |
- Berntsson Svensson, Richard, 1978-, et al.
(författare)
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BAM : backlog assessment method
- 2019
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Ingår i: Lecture Notes in Business Information Processing. - Cham : Springer Verlag. - 1865-1348. - 9783030190330 ; , s. 53-68
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Konferensbidrag (refereegranskat)abstract
- The necessity of software as stand-alone products, and as central parts of non-traditional software products have changed how software products are developed. It started with the introduction of the agile manifesto and has resulted in a change of how software process improvements (SPI) are conducted. Although there are agile SPI methods and several agile practices for evaluating and improving current processes and ways-of-working, no method or practices for evaluating the backlog exists. To address this gap, the Backlog Assessment Method (BAM) was developed and applied in collaboration with Telenor Sweden. BAM enables agile organizations to assess backlogs, and assure that the backlog items are good-enough for their needs and well aligned with the decision process. The results from the validation show that BAM is feasible and relevant in an industrial environment, and it indicates that BAM is useful as a tool to perform analysis of items in a specific backlog. © The Author(s) 2019.
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| 4. |
- Hjelm-Wallén, Lena, et al.
(författare)
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Det behövs mer än värnplikt
- 2016
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Ingår i: Svenska dagbladet. - 1101-2412. ; :2016-10-07, s. 6-6
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Människors säkerhet handlar om mycket mer än det rent militära. Därför är det är dags att överväga att införa allmän medborgartjänst för alla medborgare kring tjugoårsåldern.
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| 5. |
- Jackson, Alice M., et al.
(författare)
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Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF.
- 2020
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Ingår i: Circulation. - 1524-4539. ; 142:11, s. 1040-1054
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of worsening heart failure and death in patients with heart failure and reduced ejection fraction. We examined the efficacy and tolerability of dapagliflozin in relation to background diuretic treatment and change in diuretic therapy after randomization to dapagliflozin or placebo. METHODS: We examined the effects of study treatment in the following subgroups: no diuretic and diuretic dose equivalent to furosemide $<$40, 40, and $>$40 mg daily at baseline. We examined the primary composite end point of cardiovascular death or a worsening heart failure event and its components, all-cause death and symptoms. RESULTS: Of 4616 analyzable patients, 736 (15.9%) were on no diuretic, 1311 (28.4%) were on $<$40 mg, 1365 (29.6%) were on 40 mg, and 1204 (26.1%) were taking $>$40 mg. Compared with placebo, dapagliflozin reduced the risk of the primary end point across each of these subgroups: hazard ratios were 0.57 (95% CI, 0.36-0.92), 0.83 (95% CI, 0.63-1.10), 0.77 (95% CI, 0.60-0.99), and 0.78 (95% CI, 0.63-0.97), respectively (P for interaction=0.61). The hazard ratio in patients taking any diuretic was 0.78 (95% CI, 0.68-0.90). Improvements in symptoms and treatment toleration were consistent across the diuretic subgroups. Diuretic dose did not change in most patients during follow- up, and mean diuretic dose did not differ between the dapagliflozin and placebo groups after randomization. CONCLUSIONS: The efficacy and safety of dapagliflozin were consistent across the diuretic subgroups examined in DAPA-HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
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| 6. |
- Rosell, Johan, et al.
(författare)
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Effects of adjuvant tamoxifen therapy on the incidence of secondary cancer : results from a randomized trial with long term follow-up
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUNDTamoxifen is a well-established endocrine treatment for breast cancer. We here present results with respect to second primary cancer from a large randomized trial of 5 and 2 years of adjuvant tamoxifen. Breast cancer distant recurrence and mortality are also reported.METHODSOur study included 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after 2 years of tamoxifen therapy. They were randomized to receive three more years of therapy or stop tamoxifen. In the comparison of 5 years versus 2 years of postoperative tamoxifen treatment hazard ratios were estimated using Cox regression for different follow-up periods defined as: During treatment (2-5 years) and after treatment (5-10 years, 10-15 years, > 5 years, > 10 years and > 15 years).RESULTSIn the five years group the incidence of lung cancer was halved (hazard ratio [HR], 0.45, 95% confidence interval [95% CI], 0.27-0.77 [P = .0038]), and lung cancer mortality was decreased. An increased risk was observed for endometrial cancer (HR, 1.83; 95% CI, 1.19-2.81 [P = .0059]), but this risk appeared to decrease over time. The risk of contralateral breast cancer was decreased (HR, 0.73; 95% CI, 0.56-0.96 [P = .022]), also in the period after treatment stopped. In the five years group, the risk of distant recurrence was decreased, and statistically significant reductions were observed both during treatment and in the five year period after treatment stopped. The breast cancer mortality was reduced, especially during the post-treatment phase.CONCLUSIONSIn this randomized study, tamoxifen substantially reduces the risk of new cancer both in contralateral breast and in lung up to 10 years after treatment stopped.
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| 7. |
- Rosell, Johan, et al.
(författare)
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Long-term effects on the incidence of second primary cancers in a randomized trial of two and five years of adjuvant tamoxifen
- 2017
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 56:4, s. 614-617
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tamoxifen is a well established treatment for breast cancer, but its long-term effects on the incidence of secondary cancers are not fully evaluated.Material and methods: We have studied 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after two years of tamoxifen, and who were randomized to receive totally two or five years of therapy.Results: Compared to patients randomized to two years of tamoxifen the incidence of contralateral breast cancer [hazard ratio (HR) 0.73; 95% CI 0.56-0.96] and of lung cancer (HR 0.45; 95% CI 0.27-0.77), especially squamous cell and small cell lung cancer, were reduced in the five-year group, and similar results were seen when restricting the analysis to the 10-year period after treatment stopped. An increased incidence of endometrial cancer was observed in the five-year group, but the excess risk decreased over time.Conclusion: Further studies of the effects of tamoxifen on the risk of different histological types of lung cancer are needed.
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| 8. |
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| 9. |
- Adamson, Carly, et al.
(författare)
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Efficacy of Dapagliflozin in Heart Failure with Reduced Ejection Fraction According to Body Mass Index.
- 2021
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:10, s. 1662-1672
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: In heart failure with reduced ejection fraction (HFrEF), there is an ’obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium-glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse- outcomes in Heart Failure trial (DAPA-HF). METHODS AND RESULTS: Body mass index was examined using standard categories, i.e. underweight ($<$18.5 kg/m(2) ); normal weight (18.5-24.9 kg/m(2) ); overweight (25.0-29.9 kg/m(2) ); obesity class I (30.0-34.9 kg/m(2) ); obesity class II (35.0-39.9 kg/m(2) ); and obesity class III ($>$/=40 kg/m(2) ). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal- weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16-1.71), overweight 1.18 (0.97-1.42), obesity class II/III 1.37 (1.10-1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58-0.94), overweight 0.81 (0.65-1.02), obesity class I 0.68 (0.50-0.92), obesity class II/III 0.71 (0.51-1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7-1.1) kg (P $<$ 0.001). CONCLUSION: We confirmed an ’obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.
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| 10. |
- Adamson, Carly, et al.
(författare)
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Liver Tests and Outcomes in Heart Failure with Reduced Ejection Fraction : Findings from DAPA-HF.
- 2022
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:10, s. 1856-1868
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium- glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment. METHODS AND RESULTS: We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37-2.17], p $<$ 0.001; and 1.52 [1.12-2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests. CONCLUSION: Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.
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