| 1. |
- Engström, Gunnar, et al.
(författare)
-
The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
|
|
| 2. |
- Gunnarsson, Rebeqa, et al.
(författare)
-
Mutation, methylation, and gene expression profiles in dup(1q)-positive pediatric B-cell precursor acute lymphoblastic leukemia
- 2018
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 32:10, s. 2117-2125
-
Tidskriftsartikel (refereegranskat)abstract
- High-throughput sequencing was applied to investigate the mutation/methylation patterns on 1q and gene expression profiles in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL) with/without (w/wo) dup(1q). Sequencing of the breakpoint regions and all exons on 1q in seven dup(1q)-positive cases revealed non-synonymous somatic single nucleotide variants (SNVs) in BLZF1, FMN2, KCNT2, LCE1C, NES, and PARP1. Deep sequencing of these in a validation cohort w (n = 17)/wo (n = 94) dup(1q) revealed similar SNV frequencies in the two groups (47% vs. 35%; P = 0.42). Only 0.6% of the 36,259 CpGs on 1q were differentially methylated between cases w (n = 14)/wo (n = 13) dup(1q). RNA sequencing of high hyperdiploid (HeH) and t(1;19)(q23;p13)-positive cases w (n = 14)/wo (n = 52) dup(1q) identified 252 and 424 differentially expressed genes, respectively; only seven overlapped. Of the overexpressed genes in the HeH and t(1;19) groups, 23 and 31%, respectively, mapped to 1q; 60-80% of these encode nucleic acid/protein binding factors or proteins with catalytic activity. We conclude that the pathogenetically important consequence of dup(1q) in BCP ALL is a gene-dosage effect, with the deregulated genes differing between genetic subtypes, but involving similar molecular functions, biological processes, and protein classes.
|
|
| 3. |
- Isaksson, Johan, et al.
(författare)
-
KRAS G12C mutant non-small cell lung cancer linked to female sex and high risk of CNS metastasis : Population-based demographics and survival data from the National Swedish Lung Cancer Registry
- 2023
-
Ingår i: Clinical Lung Cancer. - : Elsevier. - 1525-7304 .- 1938-0690. ; 24:6, s. 507-518
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundReal-world data on demographics related to KRAS mutation subtypes are crucial as targeted drugs against the p.G12C variant have been approved.MethodWe identified 6183 NSCLC patients with reported NGS-based KRAS status in the Swedish national lung cancer registry between 2016 and 2019. Following exclusion of other targetable drivers, three cohorts were studied: KRAS-G12C (n = 848), KRAS-other (n = 1161), and driver negative KRAS-wild-type (wt) (n = 3349).ResultsThe prevalence of KRAS mutations and the p.G12C variant respectively was 38%/16% in adenocarcinoma, 28%/13% in NSCLC-NOS and 6%/2% in squamous cell carcinoma. Women were enriched in the KRAS-G12C (65%) and KRAS-other (59%) cohorts versus KRAS-wt (48%). A high proportion of KRAS-G12C patients in stage IV (28%) presented with CNS metastasis (vs. KRAS-other [19%] and KRAS-wt [18%]). No difference in survival between the mutation cohorts was seen in stage I-IIIA. In stage IV, median overall survival (mOS) from date of diagnosis was shorter for KRAS-G12C and KRAS-other (5.8 months/5.2 months) vs. KRAS wt (6.4 months). Women had better outcome in the stage IV cohorts, except in KRAS-G12C subgroup where mOS was similar between men and women. Notably, CNS metastasis did not impact survival in stage IV KRAS-G12C, but was associated with poorer survival, as expected, in KRAS-other and KRAS-wt.ConclusionThe KRAS p.G12C variant is a prevalent targetable driver in Sweden and significantly associated with female sex and presence of CNS metastasis. We show novel survival effects linked to KRAS p.G12C mutations in these subgroups with implications for clinical practice.
|
|
| 4. |
- Johansson, Fredrik, 1983-
(författare)
-
Microscopic Simulation of Pedestrian Traffic
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There has recently been a renewed interest in planning for pedestrian traffic, primarily in connection to public transport interchange stations, since these are important for public transport to constitute an attractive alternative to car usage. This thesis concerns microscopic simulation of pedestrian traffic, which is a promising tool for analyzing and predicting the traffic situation in a given pedestrian facility; particularly powerful when the traffic is congested. Important applications of microscopic simulation include comparison of possible infrastructure designs such as proposed interchange stations, and evaluations of various traffic management solutions, for example information systems.The purpose of this thesis is to advance the capabilities of pedestrian microsimulation toward a level at which it can be reliably applied for quantitative analysis by practitioners in the field. The work is based on an established microscopic model of pedestrian dynamics, the Social Force Model (sfm), and the advances are made in a number of different areas.To be able to evaluate and compare simulated traffic situations suitable performance measures are needed. A set of local performance measures are proposed that quantifies the local delay rate density and estimates the discomfort perceived by the pedestrians.The sfm is extended to include waiting pedestrians through the introduction of a waiting model, demonstrated to be stable and free from oscillations. The inclusion of waiting pedestrians in the model is critical for accurate modelling of public transport interchange stations, where large groups of waiting pedestrians may hinder passing pedestrians if the design of the station is poor.The relaxation time of the adaptation to the preferred velocity is an important parameter in force based models of pedestrian traffic since it affects several behaviors of the simulated pedestrians, two of which are linear acceleration and turning movements. A comparison of observations of accelerating pedestrians reported in the literature and new observations of turning pedestrians indicates that no value of the relaxation time can give model behavior consistent with both sets of observations. This indicates that modifications of the model is needed to accurately reproduce the observed behavior.An important input to simulations is the preferred speed of the simulated pedestrians. The common assumption that the preferred speed distribution at a location does not vary during the day is tested through observations of pedestrian traffic at Stockholm Central Station. The results demonstrate that the preferred speeds are lower in the afternoon than in the morning, implying that the preferred speed should be treated as a source of uncertainty when applying pedestrian microsimulation.Finally, a sensitivity analysis of a simulation of the lower hall of Stockholm Central Station is performed to find the most important sources of uncertainty in the model predictions, given the available data. The results indicate that the uncertainty related to calibration is the largest of the considered potential error sources.
|
|
| 5. |
- Angelstam, Per, et al.
(författare)
-
Evidence-Based Knowledge Versus Negotiated Indicators for Assessment of Ecological Sustainability : The Swedish Forest Stewardship Council Standard as a Case Study
- 2013
-
Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 42:2, s. 229-240
-
Tidskriftsartikel (refereegranskat)abstract
- Assessing ecological sustainability involves monitoring of indicators and comparison of their states with performance targets that are deemed sustainable. First, a normative model was developed centered on evidence-based knowledge about (a) forest composition, structure, and function at multiple scales, and (b) performance targets derived by quantifying the habitat amount in naturally dynamic forests, and as required for presence of populations of specialized focal species. Second, we compared the Forest Stewardship Council (FSC) certification standards' ecological indicators from 1998 and 2010 in Sweden to the normative model using a Specific, Measurable, Accurate, Realistic, and Timebound (SMART) indicator approach. Indicator variables and targets for riparian and aquatic ecosystems were clearly under-represented compared to terrestrial ones. FSC's ecological indicators expanded over time from composition and structure towards function, and from finer to coarser spatial scales. However, SMART indicators were few. Moreover, they poorly reflected quantitative evidence-based knowledge, a consequence of the fact that forest certification mirrors the outcome of a complex social negotiation process.
|
|
| 6. |
- Avdic, Anders, 1950-
(författare)
-
Användare och utvecklare : om anveckling med kalkylprogram
- 1999
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- I avhandlingen behandlas förutsättningar och effekter av kalkylprogramanveckling (KPA). KPA utförs av anvecklare, som fungerar både som användare och utvecklare. Anvecklare har djup verksamhetskunskap och viss verktygskunskap. Systemet, som anvecklaren utvecklar med kalkylprogram, kallas kalkylsystem. Den grundläggande forskningsfrågan i avhandlingen är: "Vilka nya möjligheter får användare att utföra arbetsuppgifter då de själva kan bygga informationssystem?" Avhandlingens syfte är att formulera en begreppsmodell över vilka förutsättningar och effekter, som gäller för kalkylprogramanveckling.Avhandlingens strategi kan sägas vara kvalitativ, hermeneutisk, abduktiv och empirinära. Fyra empiriska studier har genomförts. Empiri har i stor utsträckning styrt studier av relaterad teori. Den praktikgeneriska modellen har använts som referensmodell i avhandlingen, vilket har lett till ett synsätt, som innebär att när anvecklaren anvecklar, agerar han i minst två praktiker, utvecklarpraktiken och huvudpraktiken. Varje praktik har sin uppsättning av förutsättningar, t ex kunskap, normer och verktyg.Den integrerade karaktären på anveckling, gör interaktivitet i utvecklingsarbetet möjlig, vilket i sin tur innebär att anvecklaren snabbt kan växla mellan utveckling och användning. Ökad verktygskunskap kan innebära att anvecklaren ökar sin verksamhetskunskap. Då anvecklarens verksamhetskunskap ökar, ökar möjligheterna att analysera och ifrågasätta verksamheten. Anveckling innebär också att hänsyn kan tas till svårformaliserbara mål och normer, samt att formalisering av tyst kunskap möjliggörs. Anveckling i en miljö med lokala nätverk förenklar möjligheterna att distribuera kalkylsystem för granskning och verifiering. Kalkylsystemets transparens underlättar analys och diskussion. I avhandlingen diskuteras anveckling som ett sätt att hantera kontinuerlig omvärldsförändring på ett sätt som kan innebära omprövning av normer i verksamheten. Då anveckling betraktas som en form av systemutveckling, skiljer sig anveckling starkt från traditionell systemutveckling i och med att anveckling kännetecknas av integration, medan traditionell systemutveckling kännetecknas av specialisering.
|
|
| 7. |
- Bill-Axelson, Anna, et al.
(författare)
-
Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
- 2008
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
|
|
| 8. |
- Carlsson, Gunnar E, 1930, et al.
(författare)
-
Attitudes toward dental appearance in 50- and 60-year-old subjects living in Sweden
- 2008
-
Ingår i: Journal of Esthetic and Restorative Dentistry. - : Wiley. - 1496-4155 .- 1708-8240. ; 20:1, s. 46-56
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Attitudes towards the importance of general appearance has varied much not only over time but also among groups of individuals of different age and other characteristics. Whether the situation is similar regarding dental appearance does not seem to have been studied. Purpose: The aim was to study differences in attitudes towards dental appearance between two large samples of 50- and 60-year-old subjects. Materials and Methods: Identical questionnaires were sent to all subjects born in 1942 and 1952 living in two Swedish counties in 2002 (n=17444; n50=8881; n60=8563). The final response rate was 72.2% (n=12599). In this study, responses to four statements on the importance of dental appearance have been analyzed with respect to gender and age. Results: Many of the responses to the four statements differed with gender and age. To the first statement (“To have beautiful and perfect teeth is very important for how you are treated by other people”), 73 % agreed at age 60 compared to 64 % at age 50 (P < 0.001). Approximately 90 % of the subjects agreed to the second statement (“Minor aesthetic imperfections of the teeth have no importance, only they function well”). Logistic regression indicated that several variables were significantly associated with the statements. Besides age and gender, education and self-assessed dental problems were most important. Conclusion: Attitudes towards the importance of dental appearance differed both between genders and age groups. CLINICAL SIGNIFICANCE The varying attitudes towards dental appearance in the population must be acknowledged in treatment decisions.
|
|
| 9. |
|
|
| 10. |
- Hagell, Peter, et al.
(författare)
-
Apomorphine formulation may influence subcutaneous complications from continuous subcutaneous apomorphine infusion in Parkinson's disease
- 2020
-
Ingår i: Journal of Neurology. - : D. Steinkopff-Verlag. - 0340-5354 .- 1432-1459. ; 267:11, s. 3411-3417
-
Tidskriftsartikel (refereegranskat)abstract
- Continuous subcutaneous (s.c.) apomorphine infusion is an effective therapy for Parkinson's disease (PD), but a limitation is the formation of troublesome s.c. nodules. Various chemically non-identical apomorphine formulations are available. Anecdotal experiences have suggested that shifting from one of these (Apo-Go PumpFill®; apoGPF) to another (Apomorphine PharmSwed®; apoPS) may influence the occurrence and severity of s.c. nodules. We, therefore, followed 15 people with advanced PD (median PD-duration, 15 years; median "off"-phase Hoehn and Yahr, IV) on apoGPF and with troublesome s.c. nodules who were switched to apoPS. Data were collected at baseline, at the time of switching, and at a median of 1, 2.5, and 7.3 months post-switch. Total nodule numbers (P < 0.001), size (P < 0.001), consistency (P < 0.001), skin changes (P = 0.058), and pain (P ≤ 0.032) improved over the observation period. PD severity and dyskinesias tended to improve and increase, respectively. Apomorphine doses were stable, but levodopa doses increased by 100 mg/day. Patient-reported apomorphine efficacy tended to increase and all participants remained on apoPS throughout the observation period; with the main patient-reported reason being improved nodules. These observations suggest that patients with s.c. nodules caused by apoGPF may benefit from switching to apoPS in terms of s.c. nodule occurrence and severity. Alternatively, observed benefits may have been due to the switch itself. As nodule formation is a limiting factor in apomorphine treatment, a controlled prospective study comparing local tolerance with different formulations is warranted.
|
|
