| 1. |
- Hertz, Hans M., et al.
(författare)
-
Propagation-based phase-contrast imaging with laboratory sources
- 2016
-
Ingår i: Optics InfoBase Conference Papers. - Washington, D.C. : OSA - The Optical Society. - 9781943580095
-
Konferensbidrag (refereegranskat)abstract
- We demonstrate that propagation-based phase-contrast x-ray imaging with state-of-the art laboratory microfocus sources allows imaging of thick biomedical objects with very high spatial resolution.
|
|
| 2. |
- Larsson, Jakob C., et al.
(författare)
-
High-spatial-resolution nanoparticle X-ray fluorescence tomography
- 2016
-
Ingår i: MEDICAL IMAGING 2016. - : SPIE. - 9781510600188
-
Konferensbidrag (refereegranskat)abstract
- X-ray fluorescence tomography (XFCT) has potential for high-resolution 3D molecular x-ray bio-imaging. In this technique the fluorescence signal from targeted nanoparticles (NPs) is measured, providing information about the spatial distribution and concentration of the NPs inside the object. However, present laboratory XFCT systems typically have limited spatial resolution (>1 mm) and suffer from long scan times and high radiation dose even at high NP concentrations, mainly due to low efficiency and poor signal-to-noise ratio. We have developed a laboratory XFCT system with high spatial resolution (sub-100 mu m), low NP concentration and vastly decreased scan times and dose, opening up the possibilities for in-vivo small-animal imaging research. The system consists of a high-brightness liquid-metal-jet microfocus x-ray source, x-ray focusing optics and an energy-resolving photon-counting detector. By using the source's characteristic 24 keV line-emission together with carefully matched molybdenum nanoparticles the Compton background is greatly reduced, increasing the SNR. Each measurement provides information about the spatial distribution and concentration of the Mo nanoparticles. A filtered back-projection method is used to produce the final XFCT image.
|
|
| 3. |
|
|
| 4. |
- Lozano, Rafael, et al.
(författare)
-
Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
- 2018
-
Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
|
|
| 5. |
- Middeldorp, Christel M., et al.
(författare)
-
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
-
Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
|
|
| 6. |
- Sawcer, Stephen, et al.
(författare)
-
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
|
|
| 7. |
- Wang, Haidong, et al.
(författare)
-
Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
- 2016
-
Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
|
|
| 8. |
- Wang, Haidong, et al.
(författare)
-
Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
|
|
| 9. |
- Ahlkvist, Johan, et al.
(författare)
-
One-pot catalytic conversion of Nordic pulp media into green platform chemicals
- 2013
-
Ingår i: Applied Catalysis A. - : Elsevier. - 0926-860X .- 1873-3875. ; 454, s. 21-29
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, both sulphite and sulphate (Kraft) cellulose from Nordic pulp mills were used as raw materials in the catalytic one-pot synthesis of green platform chemicals, levulinic and formic acids, respectively. The catalyst of choice was a macro-porous, cationic ion-exchange resin, Amberlyst 70. The optimal reaction conditions were determined and the influence of various gas atmospheres was investigated. The maximum yields of 53% formic acid and 57% of levulinic acid were separately obtained in a straight-forward conversion system only containing cellulose, water and the heterogeneous catalyst. The concept introduces a one-pot procedure providing a feasible route to green platform chemicals obtained via conversion of coniferous soft wood pulp to levulinic and formic acids, respectively.
|
|
| 10. |
- Ahlkvist, Johan, et al.
(författare)
-
Reaction Network upon One-pot Catalytic Conversion of Pulp
- 2013
-
Konferensbidrag (refereegranskat)abstract
- Nordic sulphite and sulphate (Kraft) cellulose originating from Nordic pulp mills were used as raw materials in the catalytic synthesis of green platform chemicals, levulinic and formic acids, respectively. The catalyst of choice used in this study was a macro-porous, cationic ion-exchange resin Amberlyst 70 for which the optimal reaction conditions leading to best yields were determined. For this system, maximum yields of 53 mol-% and 57 mol-% were obtained for formic and levulinic acid, respectively. The reaction network of the various chemical species involved was investigated and a simple mechanistic approach involving first order reaction kinetics was developed. The prototype model was able to describe the behaviour of the system in a satisfactory manner.
|
|
| 11. |
|
|
| 12. |
- Ajaikumar, Samikannu, et al.
(författare)
-
Oxidation of α-pinene over gold containing bimetallic nanoparticles supported on reducible TiO2 by DPU method
- 2011
-
Ingår i: Applied Catalysis A. - Amsterdam : Elsevier. - 0926-860X .- 1873-3875. ; 392:1-2, s. 11-18
-
Tidskriftsartikel (refereegranskat)abstract
- A series of bimetallic catalysts Au–M (where M = Cu, Co and Ru) were supported on a reducible TiO2 oxide via deposition-precipitation (DP) method with a slow decomposition of urea as the precipitating agent. The characteristic structural features of the prepared materials were characterized by various physico-chemical techniques such as X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). XPS results indicated the formation of alloyed bimetallic particles on the TiO2 support. TEM results confirmed the fine dispersion of metal nanoparticles on the support with an average particle size in the range of 3–5 nm. An industrially important process, oxy-functionalization of α-pinene was carried out over the prepared bimetallic heterogeneous catalysts under liquid phase conditions. Reaction parameters such as the reaction time, temperature, and the effect of solvent were studied for optimal conversion of α-pinene into verbenone. The major products obtained were verbenone, verbenol, α-pinene oxide and alkyl-pinene peroxide. The activity of the catalysts followed the order; AuCu/TiO2 > AuCo/TiO2 > Cu/TiO2 > Au/TiO2 > AuRu/TiO2. Upon comparison of the various catalysts, AuCu/TiO2 was found to be an active and selective catalyst towards the formation of verbenone. The temperature, nature of the catalysts and the choice of solvents greatly influenced the reaction rate.
|
|
| 13. |
|
|
| 14. |
- Allentoft, Morten E., et al.
(författare)
-
Population genomics of post-glacial western Eurasia
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
-
Tidskriftsartikel (refereegranskat)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
|
|
| 15. |
|
|
| 16. |
- Aronsson, Carin Andrén, et al.
(författare)
-
Dietary Intake and Body Mass Index Influence the Risk of Islet Autoimmunity in Genetically At-Risk Children : A Mediation Analysis Using the TEDDY Cohort
- 2023
-
Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 2023
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Objective: Growth and obesity have been associated with increased risk of islet autoimmunity (IA) and progression to type 1 diabetes. We aimed to estimate the effect of energy-yielding macronutrient intake on the development of IA through BMI. Research Design and Methods: Genetically at-risk children (n = 5,084) in Finland, Germany, Sweden, and the USA, who were autoantibody negative at 2 years of age, were followed to the age of 8 years, with anthropometric measurements and 3-day food records collected biannually. Of these, 495 (9.7%) children developed IA. Mediation analysis for time-varying covariates (BMI z-score) and exposure (energy intake) was conducted. Cox proportional hazard method was used in sensitivity analysis. Results: We found an indirect effect of total energy intake (estimates: indirect effect 0.13 [0.05, 0.21]) and energy from protein (estimates: indirect effect 0.06 [0.02, 0.11]), fat (estimates: indirect effect 0.03 [0.01, 0.05]), and carbohydrates (estimates: indirect effect 0.02 [0.00, 0.04]) (kcal/day) on the development of IA. A direct effect was found for protein, expressed both as kcal/day (estimates: direct effect 1.09 [0.35, 1.56]) and energy percentage (estimates: direct effect 72.8 [3.0, 98.0]) and the development of GAD autoantibodies (GADA). In the sensitivity analysis, energy from protein (kcal/day) was associated with increased risk for GADA, hazard ratio 1.24 (95% CI: 1.09, 1.53), p = 0.042. Conclusions: This study confirms that higher total energy intake is associated with higher BMI, which leads to higher risk of the development of IA. A diet with larger proportion of energy from protein has a direct effect on the development of GADA.
|
|
| 17. |
- Beecham, Ashley H, et al.
(författare)
-
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
-
Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
|
|
| 18. |
|
|
| 19. |
- Berndtsson, Ronny, et al.
(författare)
-
Dagvatten från Växjö tätort. Kvantiteter och kvaliteter samt olika belastningar på olika recipienter.
- 1989
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Föreliggande rapport har genomförts för att kvantifiera föroreningstransporterna med dagvatten från Växjö tätort till de olika recipienterna i kommunen, på månads- och årsbasis. Avbördningen av dagvatten och föroreningstransporter för kväve, fosfor, kemisk syreförbrukning, koppar, zink och bly, har bestämts för 52 olika delområden. Den totala årliga dagvattenvolymen som avrinner från Växjö tätort, till intilliggande recipienter uppgår till 2,94 miljoner m3. De största dagvattenvolymerna förekommer under sommar- och höstmånaderna. Det dagvatten som årligen avrinner från Växjö tätort till de 8 recipienterna innehåller stora kvantiteter föroreningar; 6.300 kg kväve, 330 kg fosfor, 205 ton kemisk syreförbrukning (COD), 107 kg koppar, 298 kg zink och 26 kg bly. Växjösjön är den recipient som mottar den största belastningen av alla recipienterna, Växjösjön är också den till ytan minsta av recipienterna. De i utredningen beräknade belastningarna har inte ställts i relation till andra utsläppskällor. För Växjösjöns del har dock tidigare rapporter behandlat helhetsbilden.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Birkheim, K., et al.
(författare)
-
The Role of Psychological Capital in Perception of Safety Climate Among Air Traffic Controllers
- 2013
-
Ingår i: Journal of leadership & organizational studies. - : SAGE Publications. - 1548-0518 .- 1939-7089. ; 20:2, s. 232-241
-
Tidskriftsartikel (refereegranskat)abstract
- Previous research has shown that psychological capital (PsyCap) is associated with desired employee behavioral and performance outcomes. Extending previous research, we examine, in two studies, if the PsyCap of Norwegian air traffic controllers is related to their perceptions of safety climate. Based on bootstrapping procedures, results from Study 1 (N = 77) and Study 2 (N = 38) revealed that PsyCap was positively correlated with safety climate. In Study 1, PsyCap explained 31% of the variance in safety climate. Controlling for mediating effects of positive and negative emotions in Study 2, PsyCap explained 15.5% of the variance. These results provide first-time empirical evidence linking PsyCap to safety climate in safety critical organizations.
|
|
| 23. |
|
|
| 24. |
- Bjureland, William, et al.
(författare)
-
Challenges in applying fixed partial factors to rock engineering design
- 2017
-
Ingår i: Geotechnical Special Publication. - Reston : American Society of Civil Engineers (ASCE). - 0895-0563. ; :283, s. 384-393
-
Tidskriftsartikel (refereegranskat)abstract
- The Swedish national guidelines for design of the main structural support system in road and railway rock tunnels have been adjusted to cohere with Eurocode 7. In the design guidelines, the limit states that the designer should consider are specified. The main method to account for uncertainties in the Swedish guidelines is similar to the method preferred in Eurocode 7: the partial factor method. For each limit state, fixed partial factors retrieved from different sections of the Eurocodes are specified. However, fixed partial factors may not correspond to the same structural reliability for all design situations. In this paper, we show for a common design situation in rock engineering design how partial factors in theory should vary with design geometries and uncertainties. The derived partial factors are compared to the Eurocodes’ fixed values. We find that using fixed partial factors to ensure structural safety in these limit states might not be suitable. The implications are discussed along with suggestions of other more suitable methods to account for uncertainties in rock engineering design.
|
|
| 25. |
- Bjureland, William, 1987-, et al.
(författare)
-
Dimensionering av sprutbetongförstärkning för lösa block med sannolikhetsbaserade metoder
- 2020
-
Konferensbidrag (populärvet., debatt m.m.)abstract
- Användning av sannolikhetsbaserade metoder för dimensionering av bergförstärkning är ett tillvägagångssätt som är accepterat i Eurokoderna. Vid dimensionering med dessa metoder beaktas osäkerheter stringent genom att ansätta sannolikhetsfördelningar för relevanta parametrar. Konstruktionens säkerhet säkerställs genom att verifiera att sannolikheten att överskrida bärförmågan är lägre än den i Eurokoderna kravställda brottsannolikheten. För tillämpning av sannolikhetsbaserade metoder för dimensionering av sprutbetongförstärkning för lösa block har ett problem varit att data saknats för att kunna beskriva relevanta parametrar med representativa sannolikhetsfördelningar. Dessutom samverkar de olika brottmoderna och måste därför betraktas ur ett systemperspektiv, vilket inte beaktats i tidigare studier. I denna artikel presenteras resultatet av ett doktorandprojekt med finansiering av SBUF, BeFo, SVC och SKB. Baserat på ovanstående aspekter presenteras en metodik för dimensionering av sprutbetongförstärkning för lösa block med sannolikhetsbaserade metoder. Inledningsvis presenteras sannolikhetsfördelningar för sprutbetongens parametrar baserat på en stor mängd analyserade data från Citybanan. Därefter presenteras den utvecklade dimensioneringsmetodiken, vilken bygger på att en initial dimensionering av sprutbetongen utförs innan tunneldrivningen påbörjas och att den applicerade sprutbetongens bärförmåga därefter verifieras med hjälp av kontrollmätningar från fält och Bayesiansk statistik.
|
|
| 26. |
|
|
| 27. |
- Bjureland, William, 1987-, et al.
(författare)
-
Influence of spatially varying thickness on load-bearing capacity of shotcrete
- 2020
-
Ingår i: Tunnelling and Underground Space Technology. - : Elsevier. - 0886-7798 .- 1878-4364. ; 98
-
Tidskriftsartikel (refereegranskat)abstract
- A common approach to verify a shotcrete layer's ability to secure blocks that can exist between rockbolts in a tunnel is to use analytical calculations. For this situation, an attractive approach to account for variability in the shotcrete parameters is to use reliability-based methods. Variability can then be accounted for by assigning suitable probability distributions to all relevant input parameters. Structural safety can be ensured by verifying that the probability of limit exceedance is smaller than an acceptable target probability of failure. However, even though analytical calculations and reliability-based methods can be used to design shotcrete support, one of the commonly made basic assumptions is that the load-bearing capacity of the shotcrete is governed by the spatial average of the input parameters. Thus, the spatial variability of the parameters are neglected. As a result, if the capacity is governed by the lowest value of a certain parameter, this assumption is non-conservative. In this paper, we present a novel approach in which the minimum of either the spatial average of a shotcrete slab of varying thickness, or the spatial average along the periphery of a loose block of that same slab, is used to estimate the load-bearing capacity of the shotcrete in a tunnel. The approach is based on results from numerical simulations of a shotcrete slab that we perform to investigate the effect that a spatially varying thickness has on the flexural load-bearing capacity of the slab. The results from the simulations show that the shotcrete's flexural load-bearing capacity might be overestimated when using the spatial average of shotcrete thickness between four rockbolts in design. Using the presented approach, the spatial variability of shotcrete thickness can be accounted for in practical design of tunnels without complex and time-consuming numerical simulations.
|
|
| 28. |
- Bjureland, William
(författare)
-
On reliability-based design of rock tunnel support
- 2017
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tunneling involves large uncertainties. Since 2009, design of rock tunnels in European countries should be performed in accordance with the Eurocodes. The main principle in the Eurocodes is that it must be shown in all design situations that no relevant limit state is exceeded. This can be achieved with a number of different methods, where the most common one is design by calculation. To account for uncertainties in design, the Eurocode states that design by calculation should primarily be performed using limit state design methods, i.e. the partial factor method or reliability-based methods. The basic principle of the former is that it shall be assured that a structure’s resisting capacity is larger than the load acting on the structure, with high enough probability. Even if this might seem straightforward, the practical application of limit state design to rock tunnel support has only been studied to a limited extent.The aim of this licentiate thesis is to provide a review of the practical applicability of using reliability-based methods and the partial factor method in design of rock tunnel support. The review and the following discussion are based on findings from the cases studied in the appended papers. The discussion focuses on the challenges of applying fixed partial factors, as suggested by Eurocode, in design of rock tunnel support and some of the practical difficulties the engineer is faced with when applying reliability-based methods to design rock tunnel support.The main conclusions are that the partial factor method (as defined in Eurocode) is not suitable to use in design of rock tunnel support, but that reliability-based methods have the potential to account for uncertainties present in design, especially when used within the framework of the observational method. However, gathering of data for statistical quantification of input variables along with clarification of the necessary reliability levels and definition of “failure” are needed.
|
|
| 29. |
- Bjureland, William, et al.
(författare)
-
Probability distributions of shotcrete parameters for reliability-based analyses of rock tunnel support
- 2019
-
Ingår i: Tunnelling and Underground Space Technology. - : Elsevier. - 0886-7798 .- 1878-4364. ; 87, s. 15-26
-
Tidskriftsartikel (refereegranskat)abstract
- A common support measure for underground excavations in jointed rock masses to support loose blocks is to apply a thin shotcrete layer to the periphery of the excavation and systematically install rockbolts into the surrounding rock mass. In this support system, large blocks are carried by the rockbolts and small blocks are carried by the thin shotcrete layer. To verify the shotcrete layer's load-bearing capacity and to stringently account for the large uncertainties incorporated in the variables involved in determining its capacity, analytical calculations in combination with reliability-based methods can be used. However, a lack of knowledge exists regarding the magnitude and uncertainty of shotcrete characteristics (thickness, adhesion, flexural tensile strength, residual flexural tensile strength, and compressive strength), making it difficult to apply reliability-based methods. A statistical quantification of these characteristics is therefore important to facilitate reliability-based methods in design and verification of shotcrete support. In this paper, we illustrate how shotcrete support against small loose blocks can be viewed as a correlated conditional structural system and how this system can be analyzed using reliability-based methods. In addition, we present a unique amount of data for the aforementioned variables, which are all incorporated in the design and verification of a shotcrete layer's ability to sustain loads from small loose blocks. Based on the presented data, we statistically quantify and propose suitable probability distributions for each variable. Lastly, we illustrate how the proposed probability distributions can be used in the design process to calculate the probability of exceeding the shotcrete's load-bearing capacity. Both the probabilistic quantification and the defined correlated conditional structural system along with the illustrative calculation example are followed by a discussion of their implications.
|
|
| 30. |
|
|
| 31. |
- Bjureland, William, et al.
(författare)
-
Reliability aspects of rock tunnel design with the observational method
- 2017
-
Ingår i: International Journal of Rock Mechanics And Mining Sciences. - : PERGAMON-ELSEVIER SCIENCE LTD. - 1365-1609 .- 1873-4545. ; 98, s. 102-110
-
Tidskriftsartikel (refereegranskat)abstract
- According to Eurocode 7, two accepted approaches for managing uncertainty in tunnel design are reliability based methods and the observational method. Reliability-based methods account for uncertainty by acknowledging the random variation of the input parameters; the observational method does this by verifying the expected behavior from an initial design during the course of construction. However, in the framework of the observational method, as defined in Eurocode 7, no guidance is given on the selection of suitable parameters for observation and how they can be linked to the limits of acceptable behavior and, at a sufficiently early stage, the decision for implementing contingency actions. Furthermore, no guidance is given on how to verify that the structure fulfills society's required safety level. In this paper, we present a design procedure for shotcrete-supported rock tunnels that combines reliability-based methods with the observational method. The design procedure applies a deformation-based limit state function for the shotcrete support that is based on the convergence confinement method. We suggest how the requirements in the observational method, as defined in Eurocode 7, may be satisfied for this application. In particular, we focus on the structural reliability aspects. The structural reliability of the preliminary design is assessed with Monte Carlo simulations by calculating the expected deformations of the tunnel. The appropriateness of the preliminary design is then verified by observing the actual deformations during the course of construction. The observed deformations are used to predict the future behavior of the tunnel and to update the assessed probability of unsatisfactory behavior. If the defined deformation-based alarm limit regarding the structural reliability is exceeded, predefined contingency actions are put into operation. The procedure is illustrated with a shotcrete-lined circular rock tunnel and practical aspects in satisfying the reliability requirements with the observational method are discussed.
|
|
| 32. |
- Bjureland, William
(författare)
-
Reliability-based design of rock tunnel support
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since 2009, design of rock tunnels can be performed in accordance with the Eurocodes, which allows that different design methodologies are applied, such as design by calculation or design using the observational method. To account for uncertainties in design, the Eurocode states that design by calculation should primarily be performed using the partial factor method or reliability-based methods. The basic principle of both of these methods is that it shall be assured that a structure’s resisting capacity is larger than the load acting on the structure, with sufficiently high probability. Even if this might seem straightforward, the practical application of limit state design to rock tunnel support has only been studied to a limited extent.The overall aim of this project has been to develop reliability-based methods for environmental and economic optimization of rock tunnel support, with a special focus on shotcrete support. To achieve this, this thesis aims to: (1) assess the applicability of the partial factor method and reliability-based methods for design of shotcrete support, exclusively or in combination with the observational method, (2) quantify the magnitude and uncertainty of the shotcrete’s input parameters, and (3) assess the influence from spatial variability on shotcrete’s load-bearing capacity and judge the correctness of the assumption that the load-bearing capacity of the support is governed by the mean values of its input parameters.The thesis shows that the partial factor method is not suitable, and in some cases not applicable, to use in design of rock tunnel support. Instead, the thesis presents a reliability-based design methodology for shotcrete in rock tunnels with respect to loose blocks between rockbolts and a design methodology for shotcrete lining based on a combination of the observational method and reliability-based methods. The presented design methodologies enable optimization of the shotcrete support and shotcrete lining by stringently accounting for uncertainties related to input data throughout the design process. The thesis also discusses the limited knowledge that we as an industry sometimes have in our calculation models and the clarifications that should be made in future revisions of the Eurocode related to target reliability and the definition of failure.
|
|
| 33. |
|
|
| 34. |
- Björnfot, Cecilia, et al.
(författare)
-
Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults : a 4D flow MRI study
- 2024
-
Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : Sage Publications. - 0271-678X .- 1559-7016.
-
Tidskriftsartikel (refereegranskat)abstract
- White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66–85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV’s stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.
|
|
| 35. |
- Bodén, Ida, 1977-, et al.
(författare)
-
In vivo skin measurements with a novel probe head for simultaneous skin impedance and near-infrared spectroscopy
- 2011
-
Ingår i: Skin research and technology. - : Wiley. - 0909-752X .- 1600-0846. ; 17:4, s. 494-504
-
Tidskriftsartikel (refereegranskat)abstract
- Background/purpose: Near-infrared (NIR) spectroscopy and skin impedance (IMP) measurements are useful techniques for objective diagnostics of various skin diseases. Here, we present a combined probe head for simultaneous, time-saving NIR spectroscopy and skin impedance measurements. The probe also ensures that both measurements are performed under equal conditions and at the same skin location.Methods: Finite element method simulations were performed for evaluation of the impedance. In vivo skin measurements were performed and combined NIR and impedance spectra were analysed by means of multivariate methods with respect to body location, age and gender. The classification rate was determined by a planar discriminant analysis. Reproducibility was investigated by calculation of scatter values and statistical significance between overlapping groups was assessed by the calculation of intra-model distances, q.Results: The novel probe yielded rapid reproducible results and was easy to manage. Significant differences between skin locations and to a lesser extent age groups and gender were demonstrated.Conclusion: With the novel probe, statistically significant differences between overlapping classes in score plots can be confirmed by calculating intra-model distances. The influence of molecular differences in the skin at different body locations is larger than the influence of gender or age and therefore relevant reference measurements are discussed.
|
|
| 36. |
- Bukhanko, Natalia, et al.
(författare)
-
Continuous gas phase synthesis of 1-ethyl chloride from ethyl alcohol and hydrochloric acid over Al2O3-based catalysts: the ‘green’ route
- 2013
-
Ingår i: ACS Sustainable Chemistry and Engineering. - : American Chemical Society (ACS). - 2168-0485. ; 1:8, s. 883-893
-
Tidskriftsartikel (refereegranskat)abstract
- The synthesis of 1-ethyl chloride in the gas-phase mixture of ethanol and hydrochloric acid over ZnCl2/Al2O3 catalysts was studied in a continuous reactor using both commercial and tailor-made supports. The catalytic materials were characterized by the means of structural (XPS, TEM, XRD, and BET) and catalytic activity (selectivity and conversion) measurements. The reaction parameters such as temperature, pressure, and feedstock flow rates were optimized for the conversion of ethanol to ethyl chloride. The new tailor-made highly porous Al2O3-based catalyst outperformed its commercial counterpart by exhibiting high conversion and selectivity (98%) at the temperature of 325 °C. Long-term stability tests (240 h) confirmed the excellent durability of the tailor-made alumina catalysts. The process demonstrated here poses an efficient and economic “green” large-scale on-site synthesis of this industrially important reactant in industry, where bioethanol is produced and 1-ethyl chloride is necessary, e.g., for ethylation of cellulose and synthetic polymer products. On-site in situ production of ethyl chloride avoids the problems associated with the transportation and storage of toxic and flammable 1-ethyl chloride.
|
|
| 37. |
- Bukhanko, Natalia, et al.
(författare)
-
Gas phase synthesis of 'green' ethyl chloride
- 2012
-
Konferensbidrag (refereegranskat)abstract
- Various xZnCl2/Al2O3 (x = 0-2 wt %) catalysts, and the effect of the type of alumina in the gas phase synthesis of ethyl chloride from ethyl alcohol and HCl were studied. The influence of temperature, pressure, and feed composition was investigated. The nature of catalytic material significantly influenced the performance of the system. The tailor-made high-porous Al2O3 was the optimal catalyst that showed high conversion and selectivity. At 325°C, the conversion obtained was 94-96% and selectivity remained at a constant level of 98% throughout the experiment. This is an abstract of a paper presented at the CHISA 2012 - 20th International Congress of Chemical and Process Engineering and PRES 2012 - 15th Conference PRES (Prague, Czech Republic 8/25-29/2012).
|
|
| 38. |
- Bukhanko, Natalia, et al.
(författare)
-
Gas phase synthesis of isopropyl chloride from isopropanol and HCl over alumina catalysts
- 2014
-
Ingår i: 21st International Congress of Chemical and Process Engineering, CHISA 2014 and 17th Conference on Process Integration, Modelling and Optimisation for Energy Saving and Pollution Reduction, PRES 2014. - : Czech Society of Chemical Engineering. - 9781510828131 ; , s. 72-73
-
Konferensbidrag (refereegranskat)
|
|
| 39. |
- Curman, Philip, et al.
(författare)
-
Darier disease is associated with neurodegenerative disorders and epilepsy
- 2024
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Darier disease (DD) is a rare monogenetic skin disorder with limited data on its potential association with neurological disorders. This study aimed to investigate the association between DD and neurological disorders, specifically Parkinson's disease, dementias, and epilepsy. Using Swedish national registers in a period spanning between 1977 and 2013, 935 individuals with DD were compared with up to 100 comparison individuals each, randomly selected from the general population based on birth year, sex, and county of residence at the time of the first diagnosis of DD. Individuals with DD had increased risks of being diagnosed with Parkinson's disease (RR 2.1, CI 1.1; 4.4), vascular dementia (RR 2.1, CI 1.0; 4.2), and epilepsy, (RR 2.5, CI 1.8; 3.5). No association of DD with other dementias were detected. This study demonstrates a new association between DD and neurodegenerative disorders and epilepsy, underlining the need for increased awareness, interdisciplinary collaboration, and further research to understand the underlying mechanisms. Early identification and management of neurological complications in DD patients could improve treatment strategies and patient outcomes. The findings also highlight the role of SERCA2 in the pathophysiology of neurological disorders, offering new targets for future research and potentials for novel treatments.
|
|
| 40. |
- Curman, Philip, et al.
(författare)
-
Hailey-Hailey Disease is Associated with Diabetes : A Population-based Cohort Study, Clinical Cohort Study, and Pedigree Analysis
- 2023
-
Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden. - 0001-5555 .- 1651-2057. ; 103
-
Tidskriftsartikel (refereegranskat)abstract
- Hailey-Hailey disease is a rare hereditary skin disease caused by mutations in the ATP2C1 gene encoding the secretory pathway Ca2+/Mn2+-ATPase 1 (SPCA1) protein. Extracutaneous manifestations of Hailey-Hailey disease are plausible but still largely unknown. The aim of this study was to explore the association between Hailey-Hailey disease and diabetes. A population-based cohort study of 347 individuals with Hailey-Hailey disease was performed to assess the risks of type 1 diabetes and type 2 diabetes, using Swedish nationwide registries. Pedigrees from 2 Swedish families with Hailey-Hailey disease were also investigated: 1 with concurrent type 1 diabetes and HLA-DQ3, the other with type 2 diabetes. Lastly, a clinical cohort with 23 individuals with Hailey-Hailey disease and matched healthy controls was evaluated regarding diabetes. In the register data males with Hailey-Hailey disease had a 70% elevated risk of type 2 diabetes, whereas no excess risk among women could be confirmed. In both pedigrees an unusually high inheritance for diabetes was observed. In the clinical cohort, individuals with Hailey-Hailey disease displayed a metabolic phenotype indicative of type 2 diabetes. Hailey-Hailey disease seems to act as a synergistic risk factor for diabetes. This study indicates, for the first time, an association between Hailey-Hailey disease and diabetes and represents human evidence that SPCA1 and the Golgi apparatus may be implicated in diabetes pathophysiology.
|
|
| 41. |
- Curman, Philip, et al.
(författare)
-
Increased risk of depression and anxiety in individuals with Darier disease
- 2024
-
Ingår i: British Journal of Dermatology. - : Wiley-Blackwell Publishing Inc.. - 0007-0963 .- 1365-2133.
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with Darier disease have an increased risk of depression and anxiety, which agrees with patterns of increased prescription of antidepressants and anxiolytics in people with the disease.
|
|
| 42. |
-
Dehydroisomerization of α-pinene over metal supported Si-SBA-15 mesoporous molecular sieves
- 2013
-
Proceedings (redaktörskap) (refereegranskat)abstract
- The effective dispersion of active metal species on mesoporous Si-SBA-15 is acquired by means of deposition-precipitation method. In order to achieve this, the surface of Si-SBA-15 was first modified with TiO2 via grafting method, followed by deposition-precipitation method (DP) to obtain a fine dispersion of metallic nanoparticles over TiO2 modified Si-SBA-15. The structural features of the synthesized materials were characterized by means of X-ray diffraction (XRD), nitrogen sorption (BET), XPS and HR-TEM. A valuable platform chemical, p-cymene, was produced over the prepared catalyst by dehydroisomerization of α-pinene under vapour-phase conditions. A stable catalyst for one-spot synthesis of renewable p-cymene from α-pinene was developed.
|
|
| 43. |
- Elding Larsson, Helena, et al.
(författare)
-
Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children
- 2018
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:1, s. 193-202
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: During the A/H1N1 2009 (A/California/04/2009) pandemic, mass vaccination with a squalene-containing vaccine, Pandemrix®, was performed in Sweden and Finland. The vaccination was found to cause narcolepsy in children and young adults with the HLA-DQ 6.2 haplotype. The aim of this study was to investigate if exposure to Pandemrix® similarly increased the risk of islet autoimmunity or type 1 diabetes. Methods: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, children are followed prospectively for the development of islet autoimmunity and type 1 diabetes. In October 2009, when the mass vaccination began, 3401 children at risk for islet autoimmunity and type 1 diabetes were followed in Sweden and Finland. Vaccinations were recorded and autoantibodies against insulin, GAD65 and insulinoma-associated protein 2 were ascertained quarterly before the age of 4 years and semi-annually thereafter. Results: By 5 August 2010, 2413 of the 3401 (71%) children observed as at risk for an islet autoantibody or type 1 diabetes on 1 October 2009 had been vaccinated with Pandemrix®. By 31 July 2016, 232 children had at least one islet autoantibody before 10 years of age, 148 had multiple islet autoantibodies and 96 had developed type 1 diabetes. The risk of islet autoimmunity was not increased among vaccinated children. The HR (95% CI) for the appearance of at least one islet autoantibody was 0.75 (0.55, 1.03), at least two autoantibodies was 0.85 (0.57, 1.26) and type 1 diabetes was 0.67 (0.42, 1.07). In Finland, but not in Sweden, vaccinated children had a lower risk of islet autoimmunity (0.47 [0.29, 0.75]), multiple autoantibodies (0.50 [0.28, 0.90]) and type 1 diabetes (0.38 [0.20, 0.72]) compared with those who did not receive Pandemrix®. The analyses were adjusted for confounding factors. Conclusions/interpretation: Children with an increased genetic risk for type 1 diabetes who received the Pandemrix® vaccine during the A/H1N1 2009 pandemic had no increased risk of islet autoimmunity, multiple islet autoantibodies or type 1 diabetes. In Finland, the vaccine was associated with a reduced risk of islet autoimmunity and type 1 diabetes.
|
|
| 44. |
- Ellegård, Rada, 1985-
(författare)
-
Effects of Complement Opsonization of HIV on Dendritic Cells : and Implications for the Immune Response
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dendritic cells are key players during HIV pathogenesis, and shape both the immediate immune response at the site of infection as well as directing the adaptive immune response against the virus. HIV has developed a plethora of immune evasion mechanisms that hijack dendritic cell functions, suppressing their ability to mount an accurate immune response and exploiting them for efficient viral transfer to target T cells.To achieve successful replication within dendritic cells without triggering danger signaling, HIV accomplishes a delicate balance where only a low level of transcription can be sustained without triggering antiviral responses that would harm the virus. Here, we describe how the presence of HSV2 coinfection, which is very common in geographic areas with a high HIV prevalence and almost triples the risk of HIV acquisition, alters dendritic cell state to support much higher levels of HIV infection. We found this effect to be mediated by the STING pathway, which is involved in the sensing of DNA in the cell cytosol. STING activation led to an upregulation of factors such as IRF3 and NFkB that can be used for HIV transcription and a degradation of factors that restrict HIV replication.In addition, we describe how HIV exploits the human complement system, a group of proteins that usually help the human body to identify dangerous pathogens while avoiding reaction towards self. HIV can coat itself, i.e. become opsonized, in complement fragments that are typically only present on the body’s own cells, allowing it to activate signaling pathways that are associated with tolerance. Dendritic cells that come into contact with complement opsonized HIV do not mount danger responses, despite the fact that HIV-derived single stranded RNA triggers the pathogen recognition receptor TLR8. The suppression of danger responses is mediated by activation of complement receptor 3, and leads to an increased infection of the dendritic cell and affects its interactions with other immune cells. There is a lack of recruitment of NK cells to the site of infection, and an inhibition of NK cell killing, which plays an important role in the destruction of HIV-infected cells in vivo. T cells primed by dendritic cells exposed to complement opsonized HIV have a lower ability to develop towards effector phenotype, and have an increased expression of the markers PD1, TIM3 and LAG3 which are associated with T cell dysfunction and exhaustion. In addition, T cells primed by these dendritic cells in the presence of NK cells upregulate markers CD38, CXCR3 and CCR4, which have been linked to an increased susceptibility to HIV infection.In summary, we add to the current knowledge on HIV immune evasion mechanisms that allow the virus to establish infection, as well as describing mechanisms that govern whether dendritic cells mount danger signaling and an immune response or not.
|
|
| 45. |
- English, William, et al.
(författare)
-
Quality and mass transport properties of sugar beet roots under short duration, high airflow post-harvest storage
- 2023
-
Ingår i: Journal of Stored Products Research. - 0022-474X .- 1879-1212. ; 104
-
Tidskriftsartikel (refereegranskat)abstract
- Active ventilation of stored sugar beet roots is used to control system temperature and slow the loss of quality that occurs with plant respiration and the growth of pathogens. Ventilation can at the same time increase rates of dehydration and dehydration related stresses of the stored sugar beet roots. Recent research into the use of forced ventilation to modify temperature in in-field sugar beet root stores has suggested that a controlled dehydration of roots could lead to improvements in quality. This work aimed to investigate the impacts to sugar beet root quality from short-term, high volume airflow during post-harvest storage. A modified environment experimental setup was developed. The experiment tested four airflow rates over three levels of ventilation duration, with the longest duration being seven days. Air temperature and relative humidity was constant within each seven day run, but varied between runs. Results showed that a mean weight loss of 11.7% with a corresponding increase in sucrose content of 13.2% was achieved at the highest airflow rate and ventilation duration. These changes in quality were a result of the transfer of water from the sugar beet roots. No reduction in total sucrose or other quality parameters was observed. The dependence of the rate of water transfer from the roots on airflow rate was quantified as the convective mass transfer coefficient. Estimates are given and cross-validated using dimensional analysis.
|
|
| 46. |
- Fernandez-Rozadilla, Ceres, et al.
(författare)
-
Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
-
Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
- Gaze, William H, et al.
(författare)
-
Influence of humans on evolution and mobilization of environmental antibiotic resistome.
- 2013
-
Ingår i: Emerging infectious diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6059 .- 1080-6040. ; 19:7
-
Forskningsöversikt (refereegranskat)abstract
- The clinical failure of antimicrobial drugs that were previously effective in controlling infectious disease is a tragedy of increasing magnitude that gravely affects human health. This resistance by pathogens is often the endpoint of an evolutionary process that began billions of years ago in non-disease-causing microorganisms. This environmental resistome, its mobilization, and the conditions that facilitate its entry into human pathogens are at the heart of the current public health crisis in antibiotic resistance. Understanding the origins, evolution, and mechanisms of transfer of resistance elements is vital to our ability to adequately address this public health issue.
|
|
| 50. |
- Ghalwash, Mohamed, et al.
(författare)
-
Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood : a prospective cohort study
- 2023
-
Ingår i: The Lancet Child and Adolescent Health. - 2352-4642. ; 7:4, s. 261-268
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Screening for islet autoantibodies in children and adolescents identifies individuals who will later develop type 1 diabetes, allowing patient and family education to prevent diabetic ketoacidosis at onset and to enable consideration of preventive therapies. We aimed to assess whether islet autoantibody screening is effective for predicting type 1 diabetes in adolescents aged 10−18 years with an increased risk of developing type 1 diabetes. Methods: Data were harmonised from prospective studies from Finland (the Diabetes Prediction and Prevention study), Germany (the BABYDIAB study), and the USA (Diabetes Autoimmunity Study in the Young and the Diabetes Evaluation in Washington study). Autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured at each follow-up visit. Children who were lost to follow-up or diagnosed with type 1 diabetes before 10 years of age were excluded. Inverse probability censoring weighting was used to include data from remaining participants. Sensitivity and the positive predictive value of these autoantibodies, tested at one or two ages, to predict type 1 diabetes by the age of 18 years were the main outcomes. Findings: Of 20 303 children with an increased type 1 diabetes risk, 8682 were included for the analysis with inverse probability censoring weighting. 1890 were followed up to 18 years of age or developed type 1 diabetes between the ages of 10 years and 18 years, and their median follow-up was 18·3 years (IQR 14·5–20·3). 442 (23·4%) of 1890 adolescents were positive for at least one islet autoantibody, and 262 (13·9%) developed type 1 diabetes. Time from seroconversion to diabetes diagnosis increased by 0·64 years (95% CI 0·34–0·95) for each 1-year increment of diagnosis age (Pearson's correlation coefficient 0·88, 95% CI 0·50–0·97, p=0·0020). The median interval between the last prediagnostic sample and diagnosis was 0·3 years (IQR 0·1–1·3) in the 227 participants who were autoantibody positive and 6·8 years (1·6–9·9) for the 35 who were autoantibody negative. Single screening at the age of 10 years was 90% (95% CI 86–95) sensitive, with a positive predictive value of 66% (60–72) for clinical diabetes. Screening at two ages (10 years and 14 years) increased sensitivity to 93% (95% CI 89–97) but lowered the positive predictive value to 55% (49–60). Interpretation: Screening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials. Funding: JDRF International.
|
|
