| 1. |
- Dinesen, Peter Thisted, et al.
(författare)
-
Estimating the Impact of Education on Political Participation : Evidence from Monozygotic Twins in the United States, Denmark and Sweden
- 2016
-
Ingår i: Political Behavior. - : Springer Science and Business Media LLC. - 0190-9320 .- 1573-6687. ; 38:3, s. 579-601
-
Tidskriftsartikel (refereegranskat)abstract
- In this study we provide new evidence on the much-discussed effect of education on political participation by utilizing the quasi-experiment of twinning. By looking at the relationship between education and participation within monozygotic (MZ) twin pairs we are able to circumvent traditional sources of confounding of the relationship rooted in genes and early life family environment because MZ twins share both. The results of within-twin pair analyses based on surveys from the United States, Denmark and Sweden show that while the relationship between education and political participation is highly confounded by genes and/or familial environment in all three countries, a positive impact remains of years of education in the US and of high school completion in Denmark. No effect is found in Sweden. Robustness checks suggest that the observed effect is not confounded by within-twin pair differences in prenatal environment nor differential treatment during childhood, and, if anything, that it most likely constitutes a lower bound estimate.
|
|
| 2. |
- Ahlskog, Rafael, 1987-
(författare)
-
Essays on the collective action dilemma of vaccination
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Vaccines famously possess positive externalities that make them susceptible to the collective action dilemma: when I get vaccinated, I protect not only myself, but also those who I might otherwise have infected. Thus, some people will have an incentive to free ride on the immunity of others. In a population of rational agents, the critical level of vaccination uptake required for herd immunity will therefore be difficult to attain in the long run, which poses difficulties for disease eradication.In this doctoral dissertation, I explore different implications of the collective action dilemma of vaccination, and different ways of ameliorating it. First: given that coercion or force could solve the dilemma, and democracies may be less likely to engage in policies that violate the physical integrity of citizens, democracies may also be at a disadvantage compared to non-democracies when securing herd immunity. In essay I, I show that this is, empirically, indeed the case. Barring the use of extensive coercion therefore necessitates other solutions.In essay II, I highlight the exception to individual rationality found in other-regarding motivations such as altruism. Our moral psychology has likely evolved to take other's welfare into account, but the extent of our prosocial motivations vary: a wider form of altruism that encompasses not just family or friends, but strangers, is likely to give way to a more narrow form when humans pair-bond and have children. This dynamic is shown to apply to the sentiments underlying vaccination behavior as well: appeals to the welfare of society of getting vaccinated have positive effects on vaccination propensity, but this effect disappears in people with families and children. On this demographic, appeals to the welfare of close loved ones instead appears to have large effects.In essay III, I investigate whether the prosocial motivations underlying vaccination behavior are liable to be affected by motivation crowding - that is, whether they are crowded out when introducing economic incentives to get vaccinated. I find that on average, economic incentives do not have adverse effects, but for a small minority of highly prosocially motivated people, they might.
|
|
| 3. |
- Brauner, Susanna, et al.
(författare)
-
H1N1 vaccination in Sjogren's syndrome triggers polyclonal B cell activation and promotes autoantibody production
- 2017
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:10, s. 1755-1763
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesVaccination of patients with rheumatic disease has been reported to result in lower antibody titres than in healthy individuals. However, studies primarily include patients on immunosuppressive therapy. Here, we investigated the immune response of treatment-naive patients diagnosed with primary Sjogren's syndrome (pSS) to an H1N1 influenza vaccine.Methods Patients with Sjogren's syndrome without immunomodulatory treatment and age-matched and gender-matched healthy controls were immunised with an H1N1 influenza vaccine and monitored for serological and cellular immune responses. Clinical symptoms were monitored with a standardised form. IgG class switch and plasma cell differentiation were induced in vitro in purified naive B cells of untreated and hydroxychloroquine-treated patients and healthy controls. Gene expression was assessed by NanoString technology.ResultsSurprisingly, treatment-naive patients with Sjogren's syndrome developed higher H1N1 IgG titres of greater avidity than healthy controls on vaccination. Notably, off-target B cells were also triggered resulting in increased anti-EBV and autoantibody titres. Endosomal toll-like receptor activation of naive B cells in vitro revealed a greater propensity of patient-derived cells to differentiate into plasmablasts and higher production of class switched IgG. The amplified plasma cell differentiation and class switch could be induced in cells from healthy donors by preincubation with type 1 interferon, but was abolished in hydroxychloroquine-treated patients and after in vitro exposure of naive B cells to chloroquine.ConclusionsThis comprehensive analysis of the immune response in autoimmune patients to exogenous stimulation identifies a mechanistic basis for the B cell hyperactivity in Sjogren's syndrome, and suggests that caution is warranted when considering vaccination in non-treated autoimmune patients.
|
|
| 4. |
- Dyrskjot, Lars, et al.
(författare)
-
Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer : A Prospective Multicentre Validation Study
- 2017
-
Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:3, s. 461-469
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participants: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysis: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitations: The progression score was significantly (p < 0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guerin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p < 0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p < 0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R-2 = 0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/ 750 patients). Conclusions: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Patient summary: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.
|
|
| 5. |
- George, Julie, et al.
(författare)
-
Comprehensive genomic profiles of small cell lung cancer
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
-
Tidskriftsartikel (refereegranskat)abstract
- We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
|
|
| 6. |
- Hedegaard, Jakob, et al.
(författare)
-
Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma
- 2016
-
Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 30:1, s. 27-42
-
Tidskriftsartikel (refereegranskat)abstract
- Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal-and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
|
|
| 7. |
|
|
| 8. |
- Löfgren, Hans O., 1961-
(författare)
-
Preventive psychosocial parental and school programmes in a general population
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction Numerous preventive programmes have emerged, and need to be investigated to determine their effects on the normal population. Earlier studies have shown a decrease in depressive symptoms, positive effects on children’s disruptive behaviour problems, and an improvement in parental competence. About a fifth of the parents in previous studies had problem-oriented (targeted) reasons for enrolment, whereas the rest of the parents had general (universal) reasons. The results of those studies suggest that the programmes are cost effective in terms of Quality-Adjusted Life Years.Aim Four sub-studies were performed, and their aims were to investigate the effect of parental training programmes (PTPs) in a naturalistic setting on parents’ mental health in the general population, to investigate how PTPs affect parents’ sense of parental competence, to investigate how PTPs affect parental stress and analyse the parents open questions about the PTPs, and to investigate the feasibility and to measure the effect on depression, anxiety, and social problems of two preventive school programmes for pupils in grade 7.Method In a longitudinal quantitative study in a real-world setting, 279 parents from the general population in northern Sweden participated in five PTPs. A comparison group of 702 parents without intervention was included. Simultaneously, a community sample of 59 pupils in grade 7 participated in two preventive school programmes. Both studies were conducted from 2010 to 2013. Parents were assigned to professionally supported interventions that included 5-10 two-hour sessions. Respondents filled in a web-based questionnaire with the General Health Questionnaire (GHQ), the Parents Sense of Competence (PSOC) for parents who had children aged 0-17 years, and the Swedish Parenthood Stress Questionnaire (SPSQ) for parents who had children aged 0-10 years. The intervention groups’ results were compared to comparison group of 702 parents from northern Sweden that had not participated in any parental training programme. In the school study, one of the preventive programmes was an ongoing programme called “Life-Skills”, and the other was an implemented Canadian programme called “Choosing Healthy Actions and Thoughts” (CHAT). The pupils completed a test battery including the Sense of Coherence (SOC), the Children’s Depression Inventory (CDI), and the Youth Self-Report (YSR) instruments. Follow up of the parental programme study was done six months after the post-intervention measure, and follow up of the school study was at one year.Results The improvements in GHQ were statistically significant for the mean of the 279 parents in the intervention group compared to the mean of a comparison group of the 702 parents who did not receive any intervention. This suggests that evidence-based PTPs enhance parental well-being even for parents without problems. The intervention group showed a statistically significant improvement in parental competence compared to the comparison group over time. The intervention itself had a significant effect on parental satisfaction, but the efficacy effect was not sustained when taking into account potential confounders. In the SPSQ, the intervention group was smaller due to the fact that the instrument was not validated for children over the age of 10 and one of the parental training groups was only for parents of teenagers. A reduction of stress in the sub-scale of health problems was detected, but no other subscale showed the intervention to have a significant effect when controlling for confounding variables. In the school study, both programmes had good feasibility according to the stake- holders and had several positive mental health outcomes over time. Compared to Life-Skills, CHAT had more significant positive effects on reducing anxious/depressive symptoms and girls experienced significant positive effects on reduced anxious/depressive behaviour, while boys reduced their aggressive behaviours.Conclusions Earlier studies indicate that PTPs enhance perceived parental competence among referred parents. The present study shows that PTPs applied in the general population might also enhance perceived parental benefits such as improved health and satisfaction, suggesting that PTPs can be an important preventive strategy to enhance parenthood. The results suggest that parents who feel a need to increase their parenting competence might participate in PTPs based on lower scores than the comparison control group both before and after the intervention. The school-based programme shows that schools may be a suitable arena for preventive programmes because there was a significant short-term improvement in depression symptoms. Further studies need to explore how parents’ participation in PTPs affects children’s mental health in the general population in quantitative longitudinal studies in real-word settings. There is also a need for bigger studies and RCTs on school preventions and on how children’s health develops naturally in the population.
|
|
| 9. |
- Murton, Bramley J., et al.
(författare)
-
Geological fate of seafloor massive sulphides at the TAG hydrothermal field (Mid-Atlantic Ridge)
- 2019
-
Ingår i: Ore Geology Reviews. - : Elsevier. - 0169-1368 .- 1872-7360. ; 107, s. 903-925
-
Forskningsöversikt (refereegranskat)abstract
- Deep-sea mineral deposits potentially represent vast metal resources that could make a major contribution to future global raw material supply. Increasing demand for these metals, many of which are required to enable a low-carbon and high-technology society and to relieve pressure on land-based resources, may result in deep sea mining within the next decade. Seafloor massive sulphide (SMS) deposits, containing abundant copper, zinc, gold and silver, have been the subject of recent and ongoing commercial interest. Although many seafloor hydrothermally systems have been studied, inactive SMS deposits are likely more accessible to future mining and far more abundant, but are often obscured by pelagic sediment and hence difficult tolocate. Furthermore, SMS deposits are three dimensional. Yet, to date, very few have been explored or sampled below the seafloor. Here, we describe the most comprehensive study to date of hydrothermally extinct seafloor massive sulphide (eSMS) deposits formed at a slow spreading ridge. Our approach involved two research cruises in the summer of 2016 to the Trans-Atlantic Geotraverse (TAG) hydrothermal field at 26 N on the Mid-Atlantic Ridge. These expeditions mapped a number of hydrothermally extinct SMS deposits using an autonomous underwater vehicle and remotely operated vehicle, acquired a combination of geophysical data including sub-seafloor seismic reflection and refraction data from 25 ocean bottom instruments, and recovered core using a robotic lander-type seafloor drilling rig. Together, these results that have allowed us to construct a new generic model for extinct seafloor massive sulphide deposits indicate the presence of up to five times more massive sulphide at and below the seafloor than was previously thought.
|
|
| 10. |
- Norén, Viveca, 1972-
(författare)
-
When water becomes a threat : Risk assessment and risk management plans for floods and drinking water in Swedish practice
- 2016
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Water is an essential but vulnerable resource. A shortage of good quality drinking water is a threat to human health and society as a whole. Abundance of water in the form of floods can also be a serious threat which can have consequences for the drinking water supply. To reduce these risks there is a need for systematic risk reduction. In the last decades a risk management approach has been developed in the management of both flood and drinking water risks. This means that a reactive, ad hoc management is being replaced by a more proactive and systematic approach where risks are analysed and evaluated as a basis for prioritising counter-measures. The complex nature of water issues has also made it evident that there is a need for a holistic view of the management, involving a variety of actors and sectors. An integrated management approach to floods and water resources has emerged.This thesis aims to examine how local level risk management, especially risk assessments, of floods and drinking water supply have been or can be performed in practice in Sweden. The existing practices have been characterised in relation to current risk management frameworks. Furthermore, the thesis aims to investigate how the effects of flood on drinking water supply have been considered in risk assessment methods and in flood risk management plans, as well as whether flood and drinking water risks have been considered in an integrated manner. The studies are based on interviews with flood risk managers in Swedish municipalities and Swedish water producers as well as on document studies of risk assessment methods and flood risk management plans.There are large variations between different municipalities and water producers in how, and to what extent, risk assessments have been performed. Some have performed very little, if any, risk assessment while others have worked systematically. The tools used are often those that are promoted by national agencies and are often less advanced than those described in the literature. The risk assessments do not always cover all relevant aspects of the risk and few actors have discussed an acceptable risk level. Flood risk assessments focus mostly on the exposure of objects to flood and investigate the consequences of such an exposure only to a limited extent. The incomplete risk assessments may result in a biased view of the risk which in turn can lead to poor decision-making. The theoretical knowledge about risk management is in many cases low and there is still often a practical approach. Strategic and holistic approaches are mostly lacking.The consequences of flood on drinking water supply are not known in detail and are not considered in detail in risk assessments commonly used in Sweden. There is an awareness of the need to coordinate the management of flood and water resources. However, despite the good intentions regarding integration, there are few signs in the risk assessments and risk management plans that integration is actually occurring.Both the risk management approach and integrated management have started to be implemented in Swedish flood and drinking water risk management. It is however on a basic level and it is still a long way to go. Further guidance and knowledge about risk management as well as commitment from and collaboration among all actors concerned is needed to make this development possible.
|
|
| 11. |
- Turcot, Valerie, et al.
(författare)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
|
|
| 12. |
- Wohlgemuth-Ueberwasser, Cora C., 1973-, et al.
(författare)
-
Distribution and solubility limits of trace elements in hydrothermal black smoker sulfides : an in-situ LA-ICP-MS study
- 2015
-
Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037 .- 1872-9533. ; 159, s. 16-41
-
Tidskriftsartikel (refereegranskat)abstract
- The key for understanding the trace metal inventory of currently explored VHMS deposits lies in the understanding of trace element distribution during the formation of these deposits on the seafloor. Recrystallization processes already occurring at the seafloor might liberate trace elements to later hydrothermal alteration and removement. To investigate the distribution and redistribution of trace elements we analyzed sulfide minerals from 27 black smoker samples derived from three different seafloor hydrothermal fields: the ultramafic-hosted Logatchev hydrothermal field on the Mid-Atlantic Ridge, the basaltic-hosted Turtle Pits field on the mid-atlantic ridge, and the felsic-hosted PACMANUS field in the Manus basin (Papua New Guinea). The sulfide samples were analyzed by mineral liberation analyser for the modal abundances of sulfide minerals, by electron microprobe for major elements and by laser ablation-inductively coupled plasma-mass spectrometry for As, Sb, Se, Te, and Au. The samples consist predominantly of chalcopyrite, sphalerite, pyrite, galena and minor isocubanite as well as inclusions of tetrahedrite–tennantite. Laser ablation spectra were used to evaluate the solubility limits of trace elements in different sulfide minerals at different textures. The solubility of As, Sb, and Au in pyrite decreases with increasing degree of recrystallization. When solubility limits are reached these elements occur as inclusions in the different sulfide phases or they are expelled from the mineral phase. Most ancient VHMS deposits represent felsic or bimodal felsic compositions. Samples from the felsic-hosted PACMANUS hydrothermal field at the Pual ridge (Papua New Guinea) show high concentrations of Pb, As, Sb, Bi, Hg, and Te, which is likely the result of an additional trace element contribution derived from magmatic volatiles. Co-precipitating pyrite and chalcopyrite are characterized by equal contents of Te, while chalcopyrite that replaced pyrite (presumably during black smoker growth) is enriched in Te relative to pyrite. These higher Te concentrations may be related to higher fluid temperature.
|
|
