| 1. |
- Malinovschi, Andrei, 1978-, et al.
(author)
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Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry
- 2023
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In: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:4, s. 461-471
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Journal article (peer-reviewed)abstract
- RATIONALE: Post-bronchodilator (BD) spirometry is used for diagnosis of chronic obstructive pulmonary disease (COPD). However, pre-BD reference values are used for spirometry interpretation.OBJECTIVES: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or post-BD reference values generated within the Swedish CArdioPulmonary bioImage Study (SCAPIS) when interpreting post-BD spirometry in a general population.METHODS: SCAPIS reference values for post-BD and pre-BD spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or post-BD reference values, with respiratory burden in the SCAPIS general population (28,851 individuals).MEASUREMENTS AND MAIN RESULTS: Bronchodilation resulted in higher predicted median and lower limit of normal (LLN) for FEV1/FVC ratio. The prevalence of post-BD FEV1/FVC < pre-bronchodilator LLN was 4.8% and that of post-BD FEV1/FVC < post-bronchodilator LLN was 9.9% for the general population. An additional 5.1% was identified as having an abnormal post-BD FEV1/FVC ratio and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%, p<0.001) and self-reported physician-diagnosed COPD (2.8% vs. 0.5%, p<0.001) than subjects with post-BD FEV1/FVC ratio > LLN for both pre- and post-bronchodilation).CONCLUSIONS: Pre- and post-bronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of post-bronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using post-bronchodilator reference values when interpreting post-bronchodilator spirometry might enable identification of individuals with mild disease and be clinically relevant.
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| 2. |
- Engström, Gunnar, et al.
(author)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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In: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Journal article (peer-reviewed)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 3. |
- Torén, Kjell, 1952, et al.
(author)
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Chronic airflow limitation and its relation to respiratory symptoms among ever-smokers and never-smokers: a cross-sectional study
- 2020
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In: Bmj Open Respiratory Research. - : BMJ. - 2052-4439. ; 7:1
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Journal article (peer-reviewed)abstract
- Background The diagnosis of chronic obstructive pulmonary disease is based on the presence of persistent respiratory symptoms and chronic airflow limitation (CAL). CAL is based on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1:FVC) after bronchodilation, and FEV1:FVC less than the fifth percentile is often used as a cut-off for CAL. The aim was to investigate if increasing percentiles of FEV1:FVC were associated withany respiratory symptom(cough with phlegm, dyspnoea or wheezing) in a general population sample of never-smokers and ever-smokers. Methods In a cross-sectional study comprising 15 128 adults (50-64 years), 7120 never-smokers and 8008 ever-smokers completed a respiratory questionnaire and performed FEV(1)and FVC after bronchodilation. We calculated theirz-scores for FEV1:FVC and defined the fifth percentile using the Global Lung Function Initiative (GLI) reference value, GLI(5)and increasing percentiles up to GLI(25). We analysed the associations between different strata of percentiles and prevalence ofany respiratory symptomusing multivariable logistic regression for estimation of OR. Results Among all subjects, regardless of smoking habits, the odds ofany respiratory symptomwere elevated up to the GLI(15-20)strata. Among never-smokers, the odds ofany respiratory symptomwere elevated at GLI(<5)(OR 3.57, 95% CI 2.43 to 5.23) and at GLI(5-10)(OR 2.57, 95% CI 1.69 to 3.91), but not at higher percentiles. Among ever-smokers, the odds ofany respiratory symptomwere elevated from GLI(<5)(OR 4.64, 95% CI 3.79 to 5.68) up to GLI(>= 25)(OR 1.33, 95% CI 1.00 to 1.75). Conclusions The association between percentages of FEV1:FVC and respiratory symptoms differed depending on smoking history. Our results support a higher percentile cut-off for FEV1:FVC for never-smokers and, in particular, for ever-smokers.
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| 4. |
- Torén, Kjell, 1952, et al.
(author)
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The ratio FEV1/FVC and its association to respiratory symptoms-A Swedish general population study
- 2021
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In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:2, s. 181-191
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Journal article (peer-reviewed)abstract
- Chronic airflow limitation (CAL) can be defined as fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) any respiratory symptom. In a cross-sectional general population study, 15,128 adults (50-64 years of age), 7,120 never-smokers and 8,008 ever-smokers completed a respiratory questionnaire and performed FEV1 and FVC after bronchodilation. We calculated different ratios of FEV1/FVC from 0.40 to 1.0 using 0.70 as reference category. We analysed odds ratios (OR) between different ratios and any respiratory symptom using adjusted multivariable logistic regression. Among all subjects, regardless of smoking habits, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.82, OR 0.48 (95% CI 0.41-0.56). Among never-smokers, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.81, OR 0.53 (95% CI 0.41-0.70). Among ever-smokers, the odds for any respiratory symptom was lowest at FEV1/FVC = 0.81, OR 0.43 (95% CI 0.16-1.19), although the rate of inclining in odds was small in the upper part, that is FEV1/FVC = 0.85 showed similar odds, OR 0.45 (95% CI 0.38-0.55). We concluded that the odds for any respiratory symptoms continuously decreased with higher FEV1/FVC ratios and reached a minimum around 0.80-0.85, with similar results among never-smokers. These results indicate that the optimal threshold associated with respiratory symptoms may be higher than 0.70 and this should be further investigated in prospective longitudinal studies.
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| 5. |
- Bjerkeli, Per, 1977, et al.
(author)
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Water around IRAS 15398-3359 observed with ALMA
- 2016
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595, s. Art no A39-
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Journal article (peer-reviewed)abstract
- Context. Understanding how protostars accrete their mass is one of the fundamental problems of star formation. High dust column densities and complex kinematical structures make direct observations challenging. Moreover, direct observations only provide a snapshot. Chemical tracers provide an interesting alternative to characterise the infall histories of protostars. Aims. We aim to map the distribution and kinematics of gaseous water towards the low-mass embedded protostar IRAS 15398-3359. Previous observations of H13CO+ showed a depression in the abundance towards IRAS 15398-3359. This is a sign of destruction of HCO+ by an enhanced presence of gaseous water in an extended region, possibly related to a recent burst in the accretion. Direct observations of water vapour can determine the exact extent of the emission and confirm the hypothesis that HCO+ is indeed a good tracer of the water snow-line. Methods. IRAS 15398-3359 was observed using the Atacama Large Millimeter/submillimeter Array (ALMA) at 0.5? resolution in two setups at 390 and 460 GHz. Maps of HDO (101-000) and were taken simultaneously with observations of the CS (8-7) and N2H+ (5-4) lines and continuum at 0.65 and 0.75 mm. The maps were interpreted using dust radiative transfer calculations of the protostellar infalling envelope with an outflow cavity. Results. HDO is clearly detected and extended over the scales of the H13CO+ depression, although it is displaced by ~500 AU in the direction of the outflow. HO is tentatively detected towards the red-shifted outflow lobe, but otherwise it is absent from the mapped region, which suggests that temperatures are low. Although we cannot entirely exclude a shock origin, this indicates that another process is responsible for the water emission. Conclusions. Based on the temperature structure obtained from dust radiative transfer models, we conclude that the water was most likely released from the grains in an extended hour-glass configuration during a recent accretion burst. HDO is only detected in the region closest to the protostar, at distances of up to 500 AU. These signatures can only be explained if the luminosity has recently been increased by orders of magnitudes. Additionally, the densities in the outflow cones must be sufficiently low.
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| 6. |
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| 7. |
- Kihlberg, Robert, 1975-
(author)
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Influence in sensemaking during change : a study of the Swedish police reform and subsequent change work
- 2022
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Doctoral thesis (other academic/artistic)abstract
- This dissertation is based on four articles, and examines efforts of influence in processes of sensemaking during, and subsequent to, the Swedish police reform. Sensemaking – a process where individuals work to understand what is going on when they encounter confusing events – is of central importance for how organizational change unfolds. Influence in sensemaking refers to activities with capacity to shape persons preferences and perceptions, as they try to make sense. In this dissertation, the overall purpose is to increase the understanding about influence in sensemaking during micro-processes of change. The research questions address how efforts of influence in sensemaking at different organizational levels can be understood, and by which means actors attempt to influence others sensemaking. The research applies sensemaking and sensegiving as its theoretical framework. With a qualitative approach, and ethnographic methods, influence in sensemaking is examined on four levels: Article 1 examines how the strategic level of reform promote change through visual media. The results show how 44 videos function to layer meaning and construct stereotypes in attempts to influence how the sensemaking of change would take place. Article 2 reports an ethnography of middle-managers involving employees in a multivocal process that aims to influence how sensemaking evolves. This process has four features: open-endedness, low control over cues given, several sources of cues, and the encouragement of complexity and ambiguity. Article 3 studies employees working as ‘change’ agents at employee conferences. Results show that these actors exert influence in three ways: drawing on positional power, acting powerless, and by attempts to give power away. Article 4 reports an ethnography of employees enacting a change initiative. The results show how employees’ various enactments involve episodic power, which influence the sensemaking process to varying degrees and towards diverse ends. Overall, the results from the articles outlines three understandings of influence in sensemaking: top-down efforts, reflexive interactions and responsive enactments – each with particular consequences for who can take part in processes of sensemaking, organizing, and change work, when and how. For organizations, the results imply a need for managers and employees to raise awareness of others as well as one’s own influence in sensemaking, as it shapes the way they make sense of, understand, and enact organizational change. In a larger perspective, this has significance for which forms of organizing are stimulated to develop – democratic or undemocratic.
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| 8. |
- Lindberg, Johan E., et al.
(author)
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EXTERNALLY HEATED PROTOSTELLAR CORES in the OPHIUCHUS STAR-FORMING REGION
- 2017
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 835:1, s. 3-
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Journal article (peer-reviewed)abstract
- We present APEX 218 GHz observations of molecular emission in a complete sample of embedded protostars in the Ophiuchus star-forming region. To study the physical properties of the cores, we calculate H2CO and c-C3H2 rotational temperatures, both of which are good tracers of the kinetic temperature of the molecular gas. We find that the H2CO temperatures range between 16 K and 124 K, with the highest H2CO temperatures toward the hot corino source IRAS 16293-2422 (69-124 K) and the sources in the ? Oph A cloud (23-49 K) located close to the luminous Herbig Be star S1, which externally irradiates the ? Oph A cores. On the other hand, the c-C3H2 rotational temperature is consistently low (7-17 K) in all sources. Our results indicate that the c-C3H2 emission is primarily tracing more shielded parts of the envelope whereas the H2CO emission (at the angular scale of the APEX beam; 3600 au in Ophiuchus) mainly traces the outer irradiated envelopes, apart from in IRAS 16293-2422, where the hot corino emission dominates. In some sources, a secondary velocity component is also seen, possibly tracing the molecular outflow.
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| 9. |
- Lindberg, Johan, 1977-, et al.
(author)
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Effect of infliximab on mRNA expression profiles in synovial tissue of rheumatoid arthritis patients
- 2006
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 8:6, s. R179-
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Journal article (peer-reviewed)abstract
- We examined the gene expression profiles in arthroscopic biopsies retrieved from 10 rheumatoid arthritis patients before and after anti-TNF treatment with infliximab to investigate whether such profiles can be used to predict responses to the therapy, and to study effects of the therapy on the profiles. Responses to treatment were assessed using European League Against Rheumatism response criteria. Three patients were found to be good responders, five patients to be moderate responders and two patients to be nonresponders. The TNF-alpha status of the biopsies from each of the patients before treatment was also investigated immunohistochemically, and it was detected in biopsies from four of the patients, including all three of the good responders. The gene expression data demonstrate that all patients had unique gene expression signatures, with low intrapatient variability between biopsies. The data also revealed significant differences between the good responding and nonresponding patients (279 differentially expressed genes were detected, with a false discovery rate < 0.025). Among the identified genes we found that MMP-3 was significantly upregulated in good responders (log(2) fold change, 2.95) compared with nonresponders, providing further support for the potential of MMP-3 as a marker for good responses to therapy. An even more extensive list of 685 significantly differentially expressed genes was found between patients in whom TNF-alpha was found and nonresponders, indicating that TNF-alpha could be an important biomarker for successful infliximab treatment. Significant differences were also observed between biopsies taken before and after anti-TNF treatment, including 115 differentially expressed genes in the good responding group. Interestingly, the effect was even stronger in the group in which TNF-a was immunohistochemically detected before therapy. Here, 1,058 genes were differentially expressed, including many that were novel in this context (for example, CXCL3 and CXCL14). Subsequent Gene Ontology analysis revealed that several 'themes' were significantly over-represented that are known to be affected by anti-TNF treatment in inflammatory tissue; for example, immune response (GO:0006955), cell communication (GO:0007154), signal transduction (GO:0007165) and chemotaxis (GO:0006935). No genes reached statistical significance in the moderately responding or nonresponding groups. In conclusion, this pilot study suggests that further investigation is warranted on the usefulness of gene expression profiling of synovial tissue to predict and monitor the outcome of rheumatoid arthritis therapies.
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| 10. |
- Lindberg, Johan, 1977-
(author)
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Transcriptional patterns in inflammatory disease
- 2008
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Doctoral thesis (other academic/artistic)abstract
- In the studies this thesis is based upon, microarrays were applied to profilemRNA populations in biological samples to gain insights into transcriptionalpatterns and their relation to inflammatory disease.Rheumatoid arthritis (RA) is a chronic inflammatory disease, which leads todegradation of cartilage and bone. RA is characterized by synovial inflammationwith varying levels of tissue heterogeneity. This was confirmed by microarrayanalyses of multiple biopsies from the joints of 13 patients, which showed interindividualvariation in transcript populations to be higher than intra‐individualvariationTherapeutic antibodies targeting TNF‐α have revolutionized treatment of RA,although some patients do not respond well. Identification of non‐responders isimportant, not only because anti‐TNF treatment elevates the risk of infections,but also because of the cost of treatment. A proof‐of‐concept study to investigatetranscriptional effects of anti‐TNF treatment demonstrated that differencesbetween response groups could be identified and that these differences revealedbiological themes related to inflammatory disease.A subsequent study was therefore initiated with a larger cohort of 62 patients toinvestigate gene expression patterns in the synovium prior to anti‐TNFtreatment. Here, the heterogeneity was even more pronounced, thetranscriptional patterns were confounded by the presence of synovial aggregatesand only a weak therapy‐correlated signature was detected. The presence oflymphocyte aggregates was found to correlate to response to therapy, which isconsistent with previous findings indicating a higher level of inflammation ingood responding patients.Periodontitis is an inflammatory disease with many similarities to RA. Both areincurable chronic auto‐immune diseases, characterized by tissue destructionwith common genetic associations. Individuals with RA are at higher risk ofaccumulating significant periodontal problems than the general population. PGE2(prostaglandin E2) is known to stimulate inflammation and bone resorption inperiodontitis. In further studies, microarrays were applied in a time seriesdesign on human gingival fibroblats to explore the signal transduction pathwayscontrolling TNF‐α induced PGE2 synthesis in order to identify novel therapeutictargets. The JNK and NF‐kb pathways were identified as being differentiallyaffected by TNF‐a treatment. The transcriptional patterns were further verifiedusing antibodies against phosphorylated JNK/NF‐kb molecules and specificinhibitors of the JNK and NF‐kb signaling cascades.
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| 11. |
- Lindberg, Johan, 1977-, et al.
(author)
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Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology
- 2006
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 8:2
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Journal article (peer-reviewed)abstract
- In recent years microarray technology has been used increasingly to acquire knowledge about the pathogenic processes involved in rheumatoid arthritis. The present study investigated variations in gene expression in synovial tissues within and between patients with rheumatoid arthritis. This was done by applying microarray technology on multiple synovial biopsies obtained from the same knee joints. In this way the relative levels of intra-patient and inter-patient variation could be assessed. The biopsies were obtained from 13 different patients: 7 by orthopedic surgery and 6 by rheumatic arthroscopy. The data show that levels of heterogeneity varied substantially between the biopsies, because the number of genes found to be differentially expressed between pairs of biopsies from the same knee ranged from 6 to 2,133. Both arthroscopic and orthopedic biopsies were examined, allowing us to compare the two sampling methods. We found that the average number of differentially expressed genes between biopsies from the same patient was about three times larger in orthopedic than in arthroscopic biopsies. Using a parallel analysis of the tissues by immunohistochemistry, we also identified orthopedic biopsies that were unsuitable for gene expression analysis of synovial inflammation due to sampling of non-inflamed parts of the tissue. Removing these biopsies reduced the average number of differentially expressed genes between the orthopedic biopsies from 455 to 171, in comparison with 143 for the arthroscopic biopsies. Hierarchical clustering analysis showed that the remaining orthopedic and arthroscopic biopsies had gene expression signatures that were unique for each patient, apparently reflecting patient variation rather than tissue heterogeneity. Subsets of genes found to vary between biopsies were investigated for overrepresentation of biological processes by using gene ontology. This revealed representative 'themes' likely to vary between synovial biopsies affected by inflammatory disease.
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| 12. |
- Mareschal, Sylvain, et al.
(author)
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Challenging conventional karyotyping by next-generation karyotyping in 281 intensively treated patients with AML
- 2021
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In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:4, s. 1003-1016
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Journal article (peer-reviewed)abstract
- Although copy number alterations (CNAs) and translocations constitute the backbone of the diagnosis and prognostication of acute myeloid leukemia (AML), techniques used for their assessment in routine diagnostics have not been reconsidered for decades. We used a combination of 2 next-generation sequencing-based techniques to challenge the currently recommended conventional cytogenetic analysis (CCA), comparing the approaches in a series of 281 intensively treated patients with AML. Shallow whole-genome sequencing (sWGS) outperformed CCA in detecting European Leukemia Net (ELN)-defining CNAs and showed that CCA overestimated monosomies and suboptimally reported karyotype complexity. Still, the concordance between CCA and sWGS for all ELN CNA-related criteria was 94%. Moreover, using in silico dilution, we showed that 1 million reads per patient would be enough to accurately assess ELN-defining CNAs. Total genomic loss, defined as a total loss 200 Mb by sWGS, was found to be a better marker for genetic complexity and poor prognosis compared with the CCA-based definition of complex karyotype. For fusion detection, the concordance between CCA and whole-transcriptome sequencing (WTS) was 99%. WTS had better sensitivity in identifying inv(16) and KMT2A rearrangements while showing limitations in detecting lowly expressed PML-RARA fusions. Ligation-dependent reverse transcription polymerase chain reaction was used for validation and was shown to be a fast and reliable method for fusion detection. We conclude that a next-generation sequencing-based approach can replace conventional CCA for karyotyping, provided that efforts are made to cover lowly expressed fusion transcripts.
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| 13. |
- Vagnoni, Giovanni, et al.
(author)
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Predictive engine and aftertreatment control concepts for a heavy-duty long-haul truck
- 2018
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In: Aachen Colloquium Automobile and Engine Technology.
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Conference paper (peer-reviewed)abstract
- This paper considers the modular control framework for energy and emissions management developed within the IMplementation of Powertrain Control for Economic and Clean Real driving emIssion and fuel ConsUMption (IMPERIUM) project. The framework is proposed for a long haul truck equipped with a 13 L Volvo Diesel engine and it aims to improve the operating system efficiency. Its main function blocks are: Transport Mission Management, Vehicle Environment, Route Situation, Traffic Situation, Vehicle Motion Management and Device Abstractions. The focus of the paper is the development and the evaluation of three key functions of the control framework: the Integrated Engine and After-Treatment System (EATS) Supervisory Controller and two local controllers, for the engine and the after-treatment. Whilst for the last two only a brief introduction is given, for the Integrated Engine and EATS Supervisory Controller a detailed description of the Optimal Control Problem (OCP) formulation and its solution strategies is provided. A controller is proposed based on a moving horizon Nonlinear Model Predictive Control (NMPC), which is tested in a simulation environment and benchmarked against Dynamic Programming (DP) strategies.
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| 14. |
- Österroos, Albin, et al.
(author)
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Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia
- 2020
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In: Blood Cancer Journal. - : NATURE PUBLISHING GROUP. - 2044-5385. ; 10:6
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Journal article (peer-reviewed)abstract
- Relevant molecular tools for treatment stratification of patients >= 65 years with acute myeloid leukemia (AML) are lacking. We combined clinical data with targeted DNA- and full RNA-sequencing of 182 intensively and palliatively treated patients to predict complete remission (CR) and survival in AML patients >= 65 years. Intensively treated patients withNPM1andIDH2(R172)mutations had longer overall survival (OS), whereas mutatedTP53conferred lower CR rates and shorter OS.FLT3-ITDandTP53mutations predicted worse OS in palliatively treated patients. Gene expression levels most predictive of CR were combined with somatic mutations for an integrated risk stratification that we externally validated using the beatAML cohort. We defined a high-risk group with a CR rate of 20% in patients with mutatedTP53, compared to 97% CR in low-risk patients defined by high expression ofZBTB7AandEEPD1withoutTP53mutations. Patients without these criteria had a CR rate of 54% (intermediate risk). The difference in CR rates translated into significant OS differences that outperformed ELN stratification for OS prediction. The results suggest that an integrated molecular risk stratification can improve prediction of CR and OS and could be used to guide treatment in elderly AML patients.
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