| 1. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Axelsson, Christer, et al.
(författare)
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PCI De Lucs. : A clinical pathway directly to the PCI lab in out of hospital cardiac arrest
- 2016
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Ingår i: American Heart Association.
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Konferensbidrag (refereegranskat)abstract
- Purpose: In Sweden, the ambulance response time from call to arrival is 11 minutes in patients with an out-of-hospital cardiac arrest (OHCA). However, there is a small group of OHCA patients (20%) in whom this delay is minimized, namely those that occur minutes before or after the arrival of the ambulance. Despite CPR and/or defibrillation within one minute, only 20% survive to hospital discharge. The objective was therefore to determine whether a pathway with direct transportation to the cath lab, using mechanical chest compression (LUCAS), could improve survival in this selected group.Aim: To describe characteristics, feasibility and outcome among a selected group of OHCA patients transported directly to the cath lab by the ambulance in a new pathwayMethod: A prospective observational study from November 2013 to November 2015Inclusion criteria: 1. Crew-witnessed cardiac arrest (CA) of cardiac origin or CA immediately defibrillated to return of spontaneous circulation (ROSC) by public access. 2. CA occurring two to three minutes before ambulance arrival where the patient had immediate bystander CPR of high quality. 4. CA occurring two to three minutes before ambulance arrival where the patient was still breathing at ambulance arrival.Exclusion criteria: Non-cardiac origin CA or high physiologic age (hospice patients)Result: Sixty-four patients fulfilled the inclusion criteria and 14 were excluded. Of the remaining 50 patients, 25 were transported with mechanical CPR to the cath lab. The time from CA to hospital was a median of 38 minutes. Survival to 30 days was 38% among all patients, 47% among VF (N=34) and 12% (N=25) among those who were transported with mechanical CPR.Conclusion: The pathway appears safe and feasible, but the inclusion criteria need to be less complex. The vast majority of survivors were found in the VF population. There were survivors (12%) among patients transported with ongoing CPR (N=25) directly to the cath lab by the ambulance.
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| 4. |
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| 5. |
- Fovaeus, Hannah, et al.
(författare)
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Out-of-hospital cardiac arrest: Survival in children and young adults over 30 years, a nationwide registry-based cohort study
- 2024
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Ingår i: Resuscitation. - 0300-9572 .- 1873-1570.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We studied short-term (30-day) and long-term (up to ten-year) survival among children and young adults following out-of-hospital cardiac arrest (OHCA) in Sweden over the course of the past 30 years. We also studied the causes of OHCA in children and examined predictors of survival. SETTING This was a nationwide, registry-based cohort study, using the Swedish Registry of Cardiopulmonary Resuscitation. Our study comprised a cohort of 4,804 individuals aged 0 to 30 years who suffered OHCA between 1990 and 2020, in whom cardiopulmonary resuscitation (CPR) was initiated. We stratified the study cohort to distinct age groups and time periods.Results: We found an increase in 30-day survival from 7% to 20% over the span of 30 years. In those under 1 year of age, survival increased from 2% to 19%. Time to CPR decreased from 14 to 2 minutes. The 10-year survival was high among those who survived 30 days. The etiology of cardiac arrests exhibited significant variations across different age groups but remained relatively consistent over time. Causes linked to mental illness constituted a substantial percentage of these cases. Compared to the reference period (1990-1994), the odds of survival in 2015-2020 was 3.00 (95% CI: 1.43, 6.94; p = 0.006).Conclusion: Survival rate after OHCA in children and young adults has increased three-fold over the past 30 years. Still overall mortality is high underscoring the need for continued efforts to mitigate risk factors and optimize survival.
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| 6. |
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| 7. |
- Holmén, Johan, et al.
(författare)
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Passive leg raising in out-of-hospital cardiac arrest.
- 2019
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 137, s. 94-101
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of passive leg raising (PLR) in cardiopulmonary resuscitation (CPR) is sometimes discussed and even recommended. The effect of this intervention has never been properly addressed. We planned to determine whether PLR in out-of-hospital cardiac arrest (OHCA) is associated with an improved survival to 30 days.METHODS: In eight districts in western Sweden, we introduced PLR within five minutes after the start of CPR, among patients with OHCA. Patients in whom PLR was not performed, within the same district, served as a control group. Thirty-day survival was the primary endpoint. A propensity score analysis, as well as a standard multivariate analysis, was used to assess possible differences between the two groups.RESULTS: We identified 3554 patients with OHCA from the eight districts. Forty-four percent were treated with PLR during CPR. Patients who received PLR differed from those who did not, by having more risk factors for an adverse outcome (fewer crew-witnessed cases, more OHCA at home, a greater need for medication and prolonged delays to treatment). The overall survival to 30 days was 7.9% among patients who received PLR versus 13.5% among those who did not. A comparison of the groups, using propensity score matching, revealed a 30 -day survival of 8.6% in the PLR group versus 8.2% in the control group (odds ratio 1.07; 95% confidence interval 0.80-1.44).CONCLUSION: In an observational study, we introduced PLR as an addition to standard treatment in patients with OHCA. We did not find any evidence that this treatment improves survival to 30 days.
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| 8. |
- Holmén, Johan, et al.
(författare)
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Shortening Ambulance Response Time Increases Survival in Out-of-Hospital Cardiac Arrest
- 2020
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Ingår i: Journal of the American Heart Association. - : Wiley Blackwell. - 2047-9980. ; 9:21
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Tidskriftsartikel (refereegranskat)abstract
- Background The ambulance response time in out-of-hospital cardiac arrest (OHCA) has doubled over the past 30 years in Sweden. At the same time, the chances of surviving an OHCA have increased substantially. A correct understanding of the effect of ambulance response time on the outcome after OHCA is fundamental for further advancement in cardiac arrest care. Methods and ResultsWe used data from the SRCR (Swedish Registry of Cardiopulmonary Resuscitation) to determine the effect of ambulance response time on 30-day survival after OHCA. We included 20 420 cases of OHCA occurring in Sweden between 2008 and 2017. Survival to 30 days was our primary outcome. Stratification and multiple logistic regression were used to control for confounding variables. In a model adjusted for age, sex, calendar year, and place of collapse, survival to 30 days is presented for 4 different groups of emergency medical services (EMS)-crew response time: 0 to 6 minutes, 7 to 9 minutes, 10 to 15 minutes, and >15 minutes. Survival to 30 days after a witnessed OHCA decreased as ambulance response time increased. For EMS response times of >10 minutes, the overall survival among those receiving cardiopulmonary resuscitation before EMS arrival was slightly higher than survival for the sub-group of patients treated with compressions-only cardiopulmonary resuscitation.ConclusionsSurvival to 30 days after a witnessed OHCA decreases as ambulance response times increase. This correlation was seen independently of initial rhythm and whether cardiopulmonary resuscitation was performed before EMS-crew arrival. Shortening EMS response times is likely to be a fast and effective way of increasing survival in OHCA.
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| 9. |
- Holmén, Johan, et al.
(författare)
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Survival in ventricular fibrillation with emphasis on the number of defibrillations in relation to other factors at resuscitation.
- 2017
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 113, s. 33-38
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Mortality after out of hospital cardiac arrest (OHCA) is high and a shockable rhythm is a key predictor of survival. A concomitant need for repeated shocks appears to be associated with less favorable outcome.AIM: To, among patients found in ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) describe: (a) factors associated with 30-day survival with emphasis on the number of defibrillatory shocks delivered; (b) the distribution of and the characteristics of patients in relation to the number of defibrillatory shocks that were delivered.METHODS: Patients who were reported to The Swedish Register for Cardiopulmonary Resuscitation (SRCR) between January 1 1990 and December 31 2015 and who were found in VF/pVT took part in the survey.RESULTS: In all there were 19,519 patients found in VF/pVT. The 30-day survival decreased with an increasing number of shocks among all patients regardless of witnessed status and regardless of time period in the survey. In a multivariate analysis there were 12 factors that were associated with the chance of 30-day survival one of which was the number of shocks that was delivered. For each shock that was added the chance of survival decreased. Factors associated with an increased 30-day survival included CPR before arrival of EMS, female sex, cardiac etiology and year of OHCA (increasing survival over years). Factors associated with a decreased chance of 30-day survival included: increasing age, OHCA at home, the use of adrenaline and intubation and an increased delay to CPR, defibrillation and EMS arrival.CONCLUSION: Among patients found in VF/pVT, 7.5% required more than 10 shocks. For each shock that was added the chance of 30-day survival decreased. There was an increase in 30-day survival over time regardless of the number of shocks. On top of the number of defibrillations, eleven further factors were associated with 30-day survival.
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| 10. |
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| 11. |
- Aamaas, Borgar, et al.
(författare)
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Elemental carbon deposition to Svalbard snow from Norwegian settlements and long-range transport
- 2011
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 63:3, s. 340-351
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Tidskriftsartikel (refereegranskat)abstract
- The impact on snow pack albedo from local elemental carbon (EC) sources in Svalbard has been investigated for the winter of 2008. Highly elevated EC concentrations in the snow are observed around the settlements of Longyearbyen and Svea (locally > 1000 ng g(-1), about 200 times over the background level), while EC concentrations similar to the background level are seen around Ny-Alesund. Near Longyearbyen and Svea, darkened snow influenced by wind transported coal dust from open coal stockpiles is clearly visible from satellite images and by eye at the ground. As a first estimate, the reduction in snow albedo caused by local EC pollution from the Norwegian settlements has been compared to the estimated reduction caused by long-range transported EC for entire Svalbard. The effect of local EC from Longyearbyen, Svea and all Norwegian settlements are estimated to 2.1%, 7.9% and 10% of the total impact of EC, respectively. The EC particles tend to stay on the surface during melting, and elevated EC concentrations due to the spring melt was observed. This accumulation of EC enhances the positive albedo feedbacks. The EC concentrations were observed to be larger in metamorphosed snow than in fresh snow, and especially around ice lenses.
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| 12. |
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| 13. |
- Brink, Johan, 1976, et al.
(författare)
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Why do firms change? Sequences of opportunity and changes in business models and capabilities in bioscience firms
- 2007
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Ingår i: RIDE working paper series. ; :84426-015, s. 47-
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Konferensbidrag (refereegranskat)abstract
- Our paper sets out to explain how firms change and acts upon additional opportunities by analysing the development of three young bioscience firms by focusing on the relationship between experimentation of their business models and the capabilities that these firms gradually develop over time. We show that only by combining the initial technological capability with a more generic business capability, these firms were able to fully develop and pursue the initially perceived opportunity. Our analysis of these bioscience firms also reveal that the linkages between the initial technological capabilities that these companies develop are only indirectly related to subsequent opportunities acted upon. As the initial opportunity increasingly becomes economically or technologically irrelevant, the more recently acquired generic capabilities provided the firms with the ability to act upon new technological opportunities. That is, the initial technological capability of the firm is frequently not directly linked to the second pursued opportunity. We infer that as these initial capabilities generally are very technologically based they are also rather specific. Instead the link is by the necessary creation of the additional, and indeed more generic, capability within the firm. As these firms develop they are hence continuously leveraging only parts of their accumulated capabilities, meaning that they are both path-dependent and path-breaking in their development. The paper argues that a firm-based analysis of the development of capabilities and business models is warranted as a complement to the numerous sector-level studies of the biosciences. The internalist perspective of the co-evolution of capabilities and business models developed here cannot be substituted by industry or environmental explanations.
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| 14. |
- Bäfver, Linda, et al.
(författare)
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Slambränsleblandningar : Förbränning och fosforutvinning
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- For sustainable phosphorus recycling, the phosphorus in sewage sludge needs to be recovered, as it is a major phosphorus-source. However, all sludge is not suitable for direct recycling on agricultural land, e.g. when the content of heavy metals is too high. To achieve an increased recycling of phosphorus from sewage sludge there is a need of research and development of alternative methods to return the phosphorus from sewage sludge to agricultural land.The aim of the project is to show that sewage sludge can be co-combusted with demolition wood in existing boilers, and that the ash can be processed for extraction of phosphorus, together with valuable by-products from the process. Further effects of the project will be the development of new knowledge about combustion with a high sludge to demolition wood ratio in a grate boiler (up to 45 % sludge with respect to wet mixture), which has not been studied in full-scale combustion earlier. The project's goal is to demonstrate mixing and combustion of fuel mixtures of sludge and demolition wood, and subsequent extraction of phosphorus from ash. The target groups for this work are energy companies, suppliers of grate boilers, municipalities, wastewater treatment plants and authorities.The project involves the mixing of sewage sludge and demolition wood, combustion-tests of the fuel mixtures and laboratory experiments on bottom ash and fly ash for phosphorus extraction using EasyMining Sweden's method for phosphorus extraction from ash. Extensive analyses have been carried out on fuel, bottom ash and fly ash, as well as thermodynamic equilibrium calculations on the formed compounds containing phosphorus.The experience of preparing sludge fuel mixtures shows that the mixtures should be prepared in the near future to when they are to be combusted, to avoid a composting process in the fuel. The project shows that it is possible to combust sludge fuel mixtures with an admixture of up to 45 % sludge relative wet fuel, in an existing grate boiler during one day. However, to combust sludge fuel mixtures over a longer period of time and at a higher load, modifications of the de-ashing system and the flue gas cleaning system are needed. The results indicate a reduced tendency of slagging on the fuel bed at the combustion of sludge mixtures. The analyses of the fly ash showed a trend towards less corrosive ash at combustion of sludge mixtures. The phosphorus content in the ash in this work was 3-4 %. For process economics and from the phosphorus extraction point, as high phosphorus content as possible in the ash is preferable. Higher phosphorus content can be accomplished by mixing sludge with a fuel with lower ash content than demolition wood, co-combustion with a fuel with higher phosphorus content than demolition wood, or by increasing the percentage of sewage sludge in the fuel mixture. Still, a higher proportion of sludge in the mixture would require a higher dry matter content of the sludge in order to get proper combustion conditions. It is primarily bottom ash that is suitable for phosphorus extraction using Easy Mining Sweden's method. If fly ash are to be used for phosphorus extraction, an optimization of the dissolution conditions is required, which was not included in this project. In this project, phosphorus is extracted as ammonium phosphate. The purity of ammonium phosphate is very high, which means that unwanted substances and heavy metals in sewage sludge will not be returned to contaminate fields.
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| 15. |
- Calcagnile, Olga, et al.
(författare)
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S100B levels are affected by older age but not by alcohol intoxication following mild traumatic brain injury
- 2013
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Biomarkers of brain damage and head injury are potentially useful tools in the management of afflicted patients. Particularly S100B has received much attention and has been adapted into clinical guidelines. Alcohol intoxication and higher age (65 years and over) have been used as risk factors for serious complications following head injury. The effect of these factors on S100B levels has not been fully established in a relevant patient cohort. Methods: We prospectively included 621 adult patients with mild traumatic brain injury (TBI) and S100B sampling. Mild TBI was defined as Glasgow Come Scale 14-15 with loss of consciousness and/or amnesia, but without high-risk factors for intracranial complications. These patients would normally require CT scanning according to local and most international guidelines. S100B was sampled within 3 hours following trauma. Results: 280 patients (45%) were intoxicated by alcohol. Alcohol intoxication had no effect on S100B levels (p = 0.65) and the performance of S100B remained unchanged in these patients. 115 patients (22%) were 65 years or older with elevated S100B levels being more common in this group compared to patients under 65 (p = 0.029). Although the sensitivity of S100B was unchanged in older patients, the specificity was poorer. Conclusion: S100B can be used reliably in mild TBI patients with alcohol intoxication. The clinically utility of S100B in older patients may be limited by very poor specificity leading to only a small decrease in CT scanning.
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| 16. |
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| 17. |
- Egeskog, Andrea, 1981, et al.
(författare)
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Actions and opinions of Brazilian farmers who shift to sugarcane : an interview-based assessment with discussion of implications for land-use change
- 2016
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Ingår i: Land use policy. - Kidlington : Elsevier. - 0264-8377 .- 1873-5754. ; 57, s. 594-604
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Tidskriftsartikel (refereegranskat)abstract
- Sugarcane ethanol systems can deliver large greenhouse gas emissions savings if emissions associated with land-use change are kept low. This qualitative study documents and analyzes actions and opinions among Brazilian farmers who shift to sugarcane production. Semi-structured interviews were held with 28 actors associated with sugarcane production in three different regions: one traditional sugarcane region and two regions where sugarcane is currently expanding. Most farmers considered sugarcane a land diversification option with relatively low economic risk, although higher risk than their previous land use. Beef production was considered a low-risk option, but less profitable than sugarcane. In conjunction with converting part of their land to sugarcane, most farmers maintained and further intensified their previous agricultural activity, often beef production. Several farmers invested in expanded production in other regions with relatively low land prices. Very few farmers in the expansion regions shifted all their land from the former, less profitable, use to sugarcane. Very few farmers in this study had deforested any land in connection with changes made when shifting to sugarcane. The respondents understand "environmental friendliness" as compliance with the relevant legislation, especially the Brazilian Forest Act, which is also a requirement for delivering sugarcane to the mills. Indirect land-use change is not a concern for the interviewed farmers, and conversion of forests and other native vegetation into sugarcane plantations is uncontroversial if legal. We derive hypotheses regarding farmers' actions and opinions from our results. These hypotheses aim to contribute to better understanding of what takes place in conjunction with expansion of sugarcane and can, when tested further, be of use in developing, e.g., policies for iLUC-free biofuel production.
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| 18. |
- Engdahl, Johan, 1968, et al.
(författare)
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Geographic and socio-demographic differences in uptake of population-based screening for atrial fibrillation: The STROKESTOP I study
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 222, s. 430-435
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The rationale behind screening for atrial fibrillation (AF) is to prevent ischemic stroke. Socio-demographic differences are expected to affect screening uptake. Geographic differences may provide further insights leading to targeted interventions for improved uptake. The objective of this study was to evaluate geographic and socio-demographic differences in uptake of AF screening in the population-based study STROKESTOP I. METHODS: STROKESTOP was carried out in two Swedish counties with a total population of 2.3 million inhabitants. Half of the residents aged 75-76years were randomized to the screening arm: invitation to clinical examination followed by ambulant ECG recording. Information on each invited person's residential parish (n=157) was used. On parish-level, aggregated data for the participants and non-participants, respectively, were obtained with respect to socioeconomic variables: educational level, disposable income, immigrant and marital status. Geo-maps displaying participation ratios were estimated by hierarchical Bayes methods. RESULTS: The overall participation rate was similar in men and women but lower in Stockholm, 47.6% (5665/11,903) than in Halland, 61.2% (1495/2443). Participation was clearly associated with the socioeconomic variables. Participation not taking into account socioeconomy varied more markedly across the parishes in the Stockholm county (range: 0.65-1.26) than in the Halland county (0.94-1.27). After adjustment for socioeconomic variables, a geographic variation remained in Stockholm, but not in Halland. CONCLUSION: Participation in AF screening varied according to socioeconomic conditions. Geographic variation in participation was marked in the Stockholm county, with only one screening clinic. Geo-mapping of participation yielded useful information needed to intervene for improved screening uptake.
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| 19. |
- Engdahl, Johan, et al.
(författare)
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Uptake of atrial fibrillation screening aiming at stroke prevention: geo-mapping of target population and non-participation
- 2013
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 35, s. 163-164
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a screening study for silent atrial fibrillation (AF), which is a frequent source of cardiac emboli with ischemic stroke, the proportion of non-participants was considerable and their clinical profile differed from the participants' profile. We intended to geo-map the target population and non-participation in an attempt to understand factors related to screening uptake and, thereby, obtain useful information needed to intervene for improved uptake. Method: In the municipality of Halmstad, Sweden, all residents born in 1934-1935 were invited to the screening study during April 2010 to February 2012. The total study group included 848 participants and 367 non-participants from 12 parishes. Geo-maps displaying participation, along with target-population-based geo-maps displaying proportion of immigrants and ischemic stroke incidence, were used. Results: Smoothed non-participation ratios (SmNPR) varied from 0.81 to 1.24 across different parishes (SmNRP = 1 corresponds to the expected participation based on the total study group). Among high risk individuals, the geographical variation was more pronounced (SmNPR range 0.75-1.51). Two parishes with higher share of immigrants and elevated population-based ischemic stroke incidence showed markedly lower participation, particularly among high-risk individuals. Conclusion: AF screening uptake varied evidently between parishes, particularly among high-risk individuals. Geo-mapping of target population and non-participation yielded useful information needed to intervene for improved screening uptake.
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| 20. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 21. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 22. |
- Gustavsson, Eva, et al.
(författare)
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Visioner och praktik : om examensarbetet i professionslärosätet
- 2010
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Ingår i: PUH - Pedagogiska utvecklingsprojekt i högskolan 2010. - : Högskolan i Borås. ; , s. 15-25
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrunden till denna uppsats är en diskussion mellan oss författare vid ett litteraturseminarium vid Högskolan i Borås (HB). Diskussionen handlade om vår pedagogiska verksamhet och att ta hänsyn till motstridiga krav. Utbildning ska vara flexibel men samtidigt standardiserad, utbildning ska förbereda studenterna för specifika yrken men samtidigt ”lära studenterna för livet”. Vi har observerat att liknande resonemang kommer till uttryck också i andra sammanhang. Ett exempel är propositionerna ”Fokus på kunskap i den högre utbildningen”1 och ”En akademi i tiden - ökad frihet för universitet och högskolor”2. Ett annat är den seminarieserie – Från HB till Humboldt: Perspektiv på universitetsidén under 200 år – som genomförs nu i vår vid HB. Vi kan konstatera att de motsägelsefulla krav vi upplever i vår roll som pedagoger hänger samman med en mer övergripande utveckling inom den högre utbildningen. De ideal som typiskt förknippats med högre utbildning har på senare tid kommit att ställas mot mer politiskt orienterade modeller. Vad betyder denna utveckling för vår praktik? Vi tar utgångspunkt i centrala utvecklingstendenser inom den högre utbildningen i Europa. Detta för att visa på förekomsten av alternativa tolkningar och anpassningar till ”Bologna” som utgör den rådande styrmodellen för högre utbildning i Europa. Vi förflyttar oss därefter till HB och dess utbildning av civilekonomer. Genom exempel visar vi hur den svenska tolkningen av den högre utbildningens styrmodell påverkar vårt pedagogiska utvecklingsarbete. Syftet är att problematisera och ifrågasätta den ”svenska tolkningen” genom att lyfta fram dess för praktiken motsägelsefulla konsekvenser.
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| 23. |
- Gustavsson, Eva, 1960, et al.
(författare)
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Visioner och praktik - om examensarbetet i professionslärosätet
- 2010
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Ingår i: Peter Sigrén (red.) PUH - Pedagogiska utvecklingsprojekt i högskolan 2010, Rapport från Västra Götalands högskolor. - Borås : Högskolan i Borås. ; , s. 15-25
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 24. |
- Haitina, Tatjana, et al.
(författare)
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Further evidence for ancient role of ACTH peptides at melanocortin (MC) receptors; pharmacology of dogfish and lamprey peptides at dogfish MC receptors
- 2007
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 28:4, s. 798-805
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Tidskriftsartikel (refereegranskat)abstract
- The cloning of melanocortin (MC) receptors in distant species has provided us tools to get insight in how the ligand–receptors interactions in the MC system have evolved. We have however lacked studies on pharmacology of native ancient melanocortin peptides at the ancient MC receptors. In this paper we synthesized melanocortin peptides from both the sea lamprey (Petromyzon marinus) and spiny dogfish (Squalus acanthias) and tested them on the MC3 and MC4 receptors from spiny dogfish. The results show that both the dogfish and lamprey ACTH peptides have similar or higher affinity than the dogfish α-, β- and γ-MSH peptides to the dogfish MC3 and MC4 receptors. Moreover, both the dogfish and lamprey ACTH peptides have more than 10-fold higher affinity than α-MSH to the dogfish MC4 receptor. We also show that dogfish δ-MSH is able to bind to MC receptors and its potency is higher than of dogfish β-MSH, which is considered to be its precursor. Our results provide the first evidence that native ACTH ligands from dogfish and lamprey have a preference above native MSH peptides to ancient version of the MC3 and MC4 receptors. This further strengthens the hypotheses that the ligand contributing to the first version of the melanocortin ligand-receptor system resembled ACTH.
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| 25. |
- Hansson, Karl, 1985, et al.
(författare)
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Expanding the cerebrospinal fluid endopeptidome
- 2017
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Ingår i: Proteomics. - : Wiley. - 1615-9853. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- Biomarkers of neurodegenerative disorders are needed to assist in diagnosis, to monitor disease progression and therapeutic interventions, and to provide insight into disease mechanisms. One route to identify such biomarkers is by proteomic and peptidomic analysis of cerebrospinal fluid (CSF). In the current study, we performed an in-depth analysis of the human CSF endopeptidome to establish an inventory thatmay serve as a basis for future targeted biomarker studies. High-pH RP HPLC was employed for off-line sample prefractionation followed by low-pH nano-LC-MS analysis. Different software programs and scoring algorithms for peptide identification were employed and compared. A total of 18 031 endogenous peptides were identified at a FDR of 1%, increasing the number of known endogenous CSF peptides 10fold compared to previous studies. The peptides were derived from 2 053 proteins of which more than 60 have been linked to neurodegeneration. Notably, among the findings were six peptides derived from microtubule-associated protein tau, three of which span the diagnostically interesting threonine-181 (Tau-F isoform). Also, 213 peptides from amyloid precursor protein were identified, 58 of which were partially or completely within the sequence of amyloid beta 1-40/42, as well as 109 peptides from apolipoprotein E, spanning sequences that discriminate between the E2/E3/E4 isoforms of the protein.
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