| 1. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 2. |
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| 3. |
- Hasselqvist-Ax, Ingela, et al.
(författare)
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Early cardiopulmonary resuscitation in out-of-hospital cardiac arrest.
- 2015
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Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 372:24, s. 2307-15
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Tidskriftsartikel (refereegranskat)abstract
- Three million people in Sweden are trained in cardiopulmonary resuscitation (CPR). Whether this training increases the frequency of bystander CPR or the survival rate among persons who have out-of-hospital cardiac arrests has been questioned.
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| 4. |
- Hirlekar, Geir, et al.
(författare)
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Analysis of data for comorbidity and survival in out-of-hospital cardiac arrest.
- 2018
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Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 21, s. 1541-1551
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Tidskriftsartikel (refereegranskat)abstract
- The data presented in this article is supplementary to the research article titled "Comorbidity and survival in out-of-hospital cardiac arrest" (Hirlekar et al., 2018). The data contains information of how Charlson Comorbidity Index (CCI) is calculated and coded from ICD-10 codes. Multivariable logistic regression was used in the analysis of association between comorbidity and return of spontaneous circulation. We present baseline characteristics of patients found in VF/VT. All patients with non-missing data on all baseline variables are analyzed separately. We compare the baseline characteristics of patients with and without complete data set. Analysis of when comorbidity was identified in relation to outcome is also shown.
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| 5. |
- Hirlekar, Geir, et al.
(författare)
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Comorbidity and survival in out-of-hospital cardiac arrest.
- 2018
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 133, s. 118-123
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients suffering out-of-hospital cardiac arrest (OHCA) have a poor prognosis but survival among subgroups differs greatly. Previous studies have shown conflicting results on whether patient comorbidity affects outcome. The aim of this national study was to investigate the effect of comorbidity on outcome after OHCA in Sweden.METHODS: We included all patients with bystander-witnessed OHCA from 2011 to 2015 in the national Swedish Registry of Cardiopulmonary Resuscitation. In order to assess comorbidity, the database was merged with the comprehensive National Patient Registry, which includes all out-patient and in-patient care in Sweden. The Charlson comorbidity index (CCI) and the specific comorbidity conditions constituting the CCI was used to identify whether comorbidity was associated with outcome.RESULTS: A total of 12,012 patients were included in the study. Of these, 1598 patients survived to 30 days (13%). The most common comorbidities were a history of congestive heart failure (29%), myocardial infarction (24%), and diabetes without complications (23%). Renal disease (odds ratio [OR] 0.53; 95% CI 0.53‒0.72), diabetes with complications (OR 0.65; 95% CI 0.49‒0.84), diabetes without complications (OR 0.63; 95% CI 0.52‒0.75), congestive heart failure (OR 0.84; 95% CI 0.71‒0.99), and metastatic carcinoma (OR 0.61; 95% CI 0.40‒0.93) were significantly associated with a reduced chance of 30-day survival when adjusted for demographic characteristics and also resuscitation-associated factors such as shockable initial rhythm, bystander cardiopulmonary resuscitation (CPR), and place of arrest. With increasing comorbidity, the chance of 30-day survival decreased: adjusted OR was 0.82 (59% CI 0.68-0.99) for CCI 3-4, 0.62 (95% CI 0.47-0.83) for CCI 5-6, and 0.51 (95% CI 0.36-0.72) for CCI > 6, respectively, all in relation to those with CCI 0-2. Additionally, increasing morbidity was associated with reduced odds of return of spontaneous circulation (ROSC) and ROSC at hospital admission.CONCLUSION: This large national study showed that increasing comorbidity decreased the chance of survival to 30 days in OHCA. This association remained after covariate adjustment.
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| 6. |
- Karlsson, Ingemar, et al.
(författare)
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Combining augmented reality and simulation-based optimization for decision support in manufacturing
- 2017
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Ingår i: Proceedings of the 2017 Winter Simulation Conference. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538634288 - 9781538634295 - 9781538634301 ; , s. 3988-3999
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Konferensbidrag (refereegranskat)abstract
- Although the idea of using Augmented Reality and simulation within manufacturing is not a new one, the improvement of hardware enhances the emergence of new areas. For manufacturing organizations, simulation is an important tool used to analyze and understand their manufacturing systems; however, simulation models can be complex. Nonetheless, using Augmented Reality to display the simulation results and analysis can increase the understanding of the model and the modeled system. This paper introduces a decision support system, IDSS-AR, which uses simulation and Augmented Reality to show a simulation model in 3D. The decision support system uses Microsoft HoloLens, which is a head-worn hardware for Augmented Reality. A prototype of IDSS-AR has been evaluated with a simulation model depicting a real manufacturing system on which a bottleneck detection method has been applied. The bottleneck information is shown on the simulation model, increasing the possibility of realizing interactions between the bottlenecks.
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| 7. |
- Karlsson, Jacob
(författare)
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Capnodynamic determination of effective pulmonary blood flow and end expiratory lung volume : studies in children and paediatric animal models
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dynamic capnography is a haemodynamic and respiratory monitoring technique enabling continuous cardiac output (Effective Pulmonary Blood Flow, COEPBF) and end expiratory lung volume (Effective Lung Volume, ELV) assessment in mechanically ventilated subjects. The method utilizes variations in exhaled CO2, implemented via periods of deliberate changes in the respiratory pattern. The method has been validated against high precision reference methods in animal experiments. Data from these studies have pointed to a potential use also in children, a patient group suffering from the lack of reliable and easy accessible cardiac output/functional residual capacity (CO/FRC) monitoring methods. We have validated dynamic capnography in a series of paediatric clinical studies and experimental models. COEPBF was tested for agreement of absolute values and ability to detect change against suprasternal Doppler, COSSD, in anaesthetized children and against transpulmonary flow probe, COTS, in a porcine model mimicking the clinical study. COEPBF was also tested for the same qualities, against COTS and CO2 Fick (COFick) in a model of hypoxia induced pulmonary hypertension in piglets. The respiratory parameter ELV was examined for consistency against helium wash out in a paediatric rabbit model of CO2-induced pneumoperitoneum. In addition to this, the same protocol was used to determine the PEEP level associated with most favorable conditions for preservation of lung homogeneity and CO2 clearance. COEPBF showed good agreement and trending ability when compared to COTS and COFick in the experimental setting. In the clinical study, COEPBF performed in the expected way. The reference method COSSD exhibited operator dependent qualities and appeared less reliable than COEPBF. Absolute values and changes in FRC could be monitored adequately by ELV, provided the application an adequate PEEP. The adequate PEEP level was also associated with optimal preservation lung homogeneity and CO2 removal, thus suggesting the use higher level of PEEP during laparoscopy. Dynamic capnography appears to be a reliable and accurate method for continuous CO and FRC monitoring and is a promising concept for future studies.
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| 8. |
- Libungan, Berglind, et al.
(författare)
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Out-of-hospital cardiac arrest in the elderly : A large-scale population-based study.
- 2015
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is little information on elderly people who suffer from out-of-hospital cardiac arrest (OHCA).AIM: To determine 30-day mortality and neurological outcome in elderly patients with OHCA.METHODS: OHCA patients ≥ 70 years of age who were registered in the Swedish Cardiopulmonary Resuscitation Register between 1990 and 2013 were included and divided into three age categories (70-79, 80-89, and ≥ 90 years). Multiple logistic regression analyses were performed to identify independent predictors of 30-day survival.RESULTS: Altogether, 36,605 cases were included in the study. Thirty-day survival was 6.7% in patients aged 70-79 years, 4.4% in patients aged 80-89 years, and 2.4% in those over 90 years. For patients with witnessed OHCA of cardiac aetiology found in a shockable rhythm, survival was higher: 20%, 15%, and 11%, respectively. In 30-day survivors, the distribution according to the cerebral performance categories (CPC) score at discharge from hospital was similar in the three age groups. In multivariate analysis, in patients over 70 years of age, the following factors were associated with increased chance of 30-day survival: younger age, OHCA outside the home, witnessed OHCA, CPR before arrival of EMS, shockable first-recorded rhythm, and short emergency response time.CONCLUSIONS: Advanced age is an independent predictor of mortality in OHCA patients over 70 years of age. However, even in patients above 90 years of age, defined subsets with a survival rate of more than 10% exist. In survivors, the neurological outcome remains similar regardless of age.
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| 9. |
- Lundgren, Sebastian, et al.
(författare)
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The clinical importance of tumour-infiltrating macrophages and dendritic cells in periampullary adenocarcinoma differs by morphological subtype
- 2017
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dendritic cells (DC) and tumour-associated macrophages (TAM) are essential in linking the innate and adaptive immune response against tumour cells and tumour progression. These cells are also potential target for immunotherapy as well as providing a handle to investigate immune status in the tumour microenvironment. The aim of the present study was to examine their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, with particular reference to morphological subtype. Methods: The density of tolerogenic immature CD1a+ dendritic cells (DC), and MARCO+, CD68+ and CD163+ tissue-associated macrophages (TAM) was analysed by immunohistochemistry in tissue micro arrays with tumours from 175 consecutive cases of periampullary adenocarcinoma who had undergone pancreaticoduodenectomy, 110 with pancreatobiliary type (PB-type) and 65 with intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analyses were applied to determine the impact of immune cell infiltration on 5-year overall survival (OS). Results: High density of CD1a+ DCs was an independent prognostic factor for a reduced OS in PB-type but not in I-type tumours (adjusted HR = 2.35; 95% CI 1.13-4.87). High density of CD68+ and CD163+ TAM was significantly associated with poor OS in the whole cohort, however only in unadjusted analysis (HR = 1.67; 95% CI 1.06-2.63, and HR = 1.84; 95% CI 1.09-3.09, respectively) and not in strata according to morphological subtype. High density of MARCO+ macrophages was significantly associated with poor prognosis in I-type but not in PB-type tumours (HR = 2.14 95% CI 1.03-4.44), and this association was only evident in patients treated with adjuvant chemotherapy. The prognostic value of the other investigated immune cells did not differ significantly in strata according to adjuvant chemotherapy. Conclusions: The results from this study demonstrate that high infiltration of tolerogenic immature DCs independently predicts a shorter survival in patients with PB-type periampullary adenocarcinoma, and that high density of the MARCO+ subtype of TAMs predicts a shorter survival in patients with I-type tumours. These results emphasise the importance of taking morphological subtype into account in biomarker studies related to periampullary cancer, and indicate that therapies targeting dendritic cells may be of value in the treatment of PB-type tumours, which are associated with the worst prognosis.
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| 10. |
- Megquier, Kate, et al.
(författare)
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BarkBase : Epigenomic Annotation of Canine Genomes
- 2019
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Ingår i: Genes. - : MDPI. - 2073-4425. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Dogs are an unparalleled natural model for investigating the genetics of health and disease, particularly for complex diseases like cancer. Comprehensive genomic annotation of regulatory elements active in healthy canine tissues is crucial both for identifying candidate causal variants and for designing functional studies needed to translate genetic associations into disease insight. Currently, canine geneticists rely primarily on annotations of the human or mouse genome that have been remapped to dog, an approach that misses dog-specific features. Here, we describe BarkBase, a canine epigenomic resource available at barkbase.org. BarkBase hosts data for 27 adult tissue types, with biological replicates, and for one sample of up to five tissues sampled at each of four carefully staged embryonic time points. RNA sequencing is complemented with whole genome sequencing and with assay for transposase-accessible chromatin using sequencing (ATAC-seq), which identifies open chromatin regions. By including replicates, we can more confidently discern tissue-specific transcripts and assess differential gene expression between tissues and timepoints. By offering data in easy-to-use file formats, through a visual browser modeled on similar genomic resources for human, BarkBase introduces a powerful new resource to support comparative studies in dogs and humans.
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| 11. |
- Meyer-Jacob, Carsten, 1984-
(författare)
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Infrared spectroscopy as a tool to reconstruct past lake-ecosystem changes : Method development and application in lake-sediment studies
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Natural archives such as lake sediments allow us to assess contemporary ecosystem responses to climate and environmental changes in a long-term context beyond the few decades to at most few centuries covered by monitoring or historical data. To achieve a comprehensive view of the changes preserved in sediment records, multi-proxy studies – ideally in high resolution – are necessary. However, this combination of including a range of analyses and high resolution constrains the amount of material available for analyses and increases the analytical costs. Infrared spectroscopic methods are a cost-efficient alternative to conventional methods because they offer a) a simple sample pre-treatment, b) a rapid measurement time, c) the non- or minimal consumption of sample material, and d) the potential to extract quantitative and qualitative information about organic and inorganic sediment components from a single measurement.The main objective of this doctoral thesis was twofold. The first part was to further explore the potential of Fourier transform infrared (FTIR) and visible-near infrared (VNIR) spectroscopy in paleolimnological studies as a) an alternative tool to conventional methods for quantifying biogenic silica (bSi) – a common proxy of paleoproductivity in lakes – in sediments and b) as a tool to infer past lake-water total organic carbon (TOC) levels from sediments. In a methodological study, I developed an independent application of FTIR spectroscopy and PLS modeling for determining bSi in sediments by using synthetic sediment mixtures with known bSi content. In contrast to previous models, this model is independent from conventional wet-chemical techniques, which had thus far been used as the calibration reference, and their inherent measurement uncertainties. The second part of the research was to apply these techniques as part of three multi-proxy studies aiming to a) improve our understanding of long-term element cycling in boreal and arctic landscapes in response to climatic and environmental changes, and b) to assess ongoing changes, particularly in lake-water TOC, on a centennial to millennial time scale.In the first applied study, high-resolution FTIR measurements of the 318-m long sediment record of Lake El’gygytgyn provided a detailed insight into long-term climate variability in the Siberian Arctic over the past 3.6 million years. Highest bSi accumulation occurred during the warm middle Pliocene (3.6-3.3 Ma), followed by a gradual but variable decline, which reflects the first onset of glacial periods and then the finally full establishment of glacial–interglacial cycles during the Quaternary. The second applied study investigated the sediment record of Torneträsk in subarctic northern Sweden also in relation to climate change, but only over the recent post-glacial period (~10 ka). By comparing responses to past climatic and environmental forcings that were recorded in this large-lake system with those recorded in small lakes from its catchment, I determined the significance and magnitude of larger-scale changes across the study region. Three different types of response were identified over the Holocene: i) a gradual response to the early landscape development following deglaciation (~10000-5300 cal yr BP); ii) an abrupt but delayed response following climate cooling during the late Holocene, which occurred c. 1300 cal yr BP – about 1000-2000 years later than in smaller lakes from the area; and iii) an immediate response to the ongoing climate change during the past century. The rapid, recent response in a previously rather insensitive lake-ecosystem emphasizes the unprecedented scale of ongoing climate change in northern Fennoscandia. In the third applied study, VNIR-inferred lake-water TOC concentrations from lakes across central Sweden showed that the ongoing, observed increase in surface water TOC in this region was in fact preceded by a long-term decline beginning already AD 1450-1600. These dynamics coincided with early human land use activities in the form of widespread summer forest grazing and farming that ceased over the past century. The results of this study show the strong impact of past human activities on past as well as ongoing TOC levels in surface waters, which has thus far been underestimated. The research in this thesis demonstrates that infrared spectroscopic methods can be an essential component in high-resolution, multi-proxy studies of past environmental and climate changes.
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| 12. |
- Olsson, Lina, et al.
(författare)
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FINAL REPORT DENCITY UDI PHASE 2
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The DenCity Project is a collaboration project between 21 organisations that develops innovative solutions for sustainable passenger, freight and waste transport in dense urban areas, with high demands on transport efficiency, attractiveness, accessibility and sustainability.
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| 13. |
- Savage, Carl, 1975-, et al.
(författare)
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Translating ‘See-and-Treat’ to primary care : opening the gates does not cause a flood
- 2019
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Ingår i: International Journal for Quality in Health Care. - Cary, NC : Oxford University Press. - 1353-4505 .- 1464-3677. ; 31:7, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore how the See-and-Treat concept can be applied in primary care and its effect on volume and productivity. Design: An explanatory single-case study design with a mixed methods approach and presented according to the SQUIRE 2.0 guidelines. Setting: A publicly-funded, private primary care provider within the Stockholm County, which caters to a diverse patient population in terms of ethnicity, religion, socioeconomic status and care needs. Participants: CEO, center manager, four physicians, two licensed practical nurses, one medical secretary and one lab assistant. Intervention: A See-and-Treat unit was established to offer same-day service for acute unplanned visits. Standardized patient symptom forms were created that allowed patients to self-triage and then enter into a streamlined care process consisting of a quick diagnostic lab and a physician visit. Main Outcome Measures: Volume, productivity, staff perceptions and patient satisfaction were measured through data on number and type of contacts per 1000 listed patients, visits per physician, observations, interviews and a questionnaire. Results: A significant decrease in the acute and total number of visits, a continued trend of diminishing telephone contacts, and a non-significant increase in physician productivity. Patients were very satisfied, and staff perceived an improved quality of care. Conclusions: See-and-Treat appears to be a viable approach for a specific primary care patient segment interested in acute same-day-service. Opening up access and standardizing care made it possible to efficiently address these needs and engage patients. © 2019 The Author(s) 2019. Published by Oxford University Press in association with the International Society for Quality in Health Care.
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| 14. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 15. |
- Tabassum, R, et al.
(författare)
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Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
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Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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| 16. |
- Uhlén, Mathias, et al.
(författare)
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A genome-wide transcriptomic analysis of protein-coding genes in human blood cells
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 366:6472, s. 1471-
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Tidskriftsartikel (refereegranskat)abstract
- Blood is the predominant source for molecular analyses in humans, both in clinical and research settings. It is the target for many therapeutic strategies, emphasizing the need for comprehensive molecular maps of the cells constituting human blood. In this study, we performed a genome-wide transcriptomic analysis of protein-coding genes in sorted blood immune cell populations to characterize the expression levels of each individual gene across the blood cell types. All data are presented in an interactive, open-access Blood Atlas as part of the Human Protein Atlas and are integrated with expression profiles across all major tissues to provide spatial classification of all protein-coding genes. This allows for a genome-wide exploration of the expression profiles across human immune cell populations and all major human tissues and organs.
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| 17. |
- van Beest, Floris M, et al.
(författare)
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Classifying grey seal behaviour in relation to environmental variability and commercial fishing activity -a multivariate hidden Markov model
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Classifying movement behaviour of marine predators in relation to anthropogenic activity and environmental conditions is important to guide marine conservation. We studied the relationship between grey seal (Halichoerus grypus) behaviour and environmental variability in the southwestern Baltic Sea where seal-fishery conflicts are increasing. We used multiple environmental covariates and proximity to active fishing nets within a multivariate hidden Markov model (HMM) to quantify changes in movement behaviour of grey seals while at sea. Dive depth, dive duration, surface duration, horizontal displacement, and turning angle were used to identify travelling, resting and foraging states. The likelihood of seals foraging increased in deeper, colder, more saline waters, which are sites with increased primary productivity and possibly prey densities. Proximity to active fishing net also had a pronounced effect on state occupancy. The probability of seals foraging was highest <5 km from active fishing nets (51%) and decreased as distance to nets increased. However, seals used sites <5 km from active fishing nets only 3% of their time at sea highlighting an important temporal dimension in seal-fishery interactions. By coupling high-resolution oceanographic, fisheries, and grey seal movement data, our study provides a scientific basis for designing management strategies that satisfy ecological and socioeconomic demands on marine ecosystems.
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