| 1. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 2. |
- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 3. |
- Johnson, Randi K., et al.
(författare)
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Metabolite-related dietary patterns and the development of islet autoimmunity
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s).
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| 4. |
- Krischer, Jeffrey P, et al.
(författare)
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Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
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| 5. |
- Smith, Laura B., et al.
(författare)
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Psychological manifestations of celiac disease autoimmunity in young children
- 2017
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 139:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Psychological symptoms can be associated with celiac disease; abstract however, this association has not been studied prospectively in a pediatric cohort. We examined mother report of psychological functioning in children persistently positive for tissue transglutaminase autoantibodies (tTGA), defined as celiac disease autoimmunity (CDA), compared with children without CDA in a screening population of genetically at-risk children. We also investigated differences in psychological symptoms based on mothers' awareness of their child's CDA status. METHODS: The Environmental Determinants of Diabetes in the Young study followed 8676 children to identify triggers of type 1 diabetes and celiac disease. Children were tested for tTGA beginning at 2 years of age. The Achenbach Child Behavior Checklist assessed child psychological functioning at 3.5 and 4.5 years of age. RESULTS: At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA (all Ps ≤ .03). Unaware-CDA mothers also reported more child anxiety and depression, withdrawn behavior, aggressive behavior, and sleep problems than 440 mothers aware of their child's CDA status (all Ps ≤.04). At 4.5 years, there were no differences. CONCLUSIONS: In 3.5-year-old children, CDA is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child's CDA status. Mothers' knowledge of their child's CDA status is associated with fewer reports of psychological symptoms, suggesting that awareness of the child's tTGA test results affects reporting of symptoms.
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| 6. |
- Törn, Carina, et al.
(författare)
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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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| 7. |
- Ask, Maria, et al.
(författare)
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A hydraulic stress measurement system for deep borehole investigations
- 2017
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Ingår i: Geophysical Research Abstracts. - : European Geosciences Union (EGU). - 1029-7006 .- 1607-7962. ; 19
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Lulea University of Technology (LTU) is developing and building a wire-line system for hydraulic rock stress measurements, with funding from the Swedish Research Council and Lulea University of Technology. In this project, LTU is collaborating with University of Strasbourg and Geosigma AB. The stress state influences drilling and drillability, as well as rock mass stability and permeability. Therefore, knowledge about the state of in-situ stress (stress magnitudes, and orientations) and its spatial variation with depth is essential for many underground rock engineering projects, for example for underground storage of hazardous material (e.g. nuclear waste, carbon dioxide), deep geothermal exploration, and underground infrastructure (e.g. tunneling, hydropower dams). The system is designed to conduct hydraulic stress testing in slim boreholes. There are three types of test methods: (1) hydraulic fracturing, (2) sleeve fracturing and (3) hydraulic testing of pre-existing fractures. These are robust methods for determining in situ stresses from boreholes. Integration of the three methods allows determination of the three-dimensional stress tensor and its spatial variation with depth in a scientific unambiguously way. The stress system is composed of a downhole and a surface unit. The downhole unit consists of hydraulic fracturing equipment (straddle packers and downhole imaging tool) and their associated data acquisition systems. The testing system is state of the art in several aspects including: (1) Large depth range (3 km), (2) Ability to test three borehole dimensions (N=76 mm, H=96 mm, and P=122 mm), (3) Resistivity imager maps the orientation of tested fracture; (4) Highly stiff and resistive to corrosion downhole testing equipment; and (5) Very detailed control on the injection flow rate and cumulative volume is obtained by a hydraulic injection pump with variable piston rate, and a highly sensitive flow-meter. At EGU General Assembly 2017, we would like to present this new and unique stress measurement system and some initial test results from a 1200 m long borehole in crystalline rock
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| 8. |
- Ask, Maria, et al.
(författare)
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Exploration for deep enhanced geothermal systems with Riksriggen and the LTU downhole stress measurement system
- 2017
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Ingår i: 4th Sustainable Earth Sciences Conference and Exhibition 2017, Held at Near Surface Geoscience Conference and Exhibition 2017. - : European Association of Geoscientists and Engineers. - 9781510850811 ; , s. 21-25
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Konferensbidrag (refereegranskat)abstract
- Recent developments in drilling technology have resulted in about five to ten times faster penetration rates compared to penetration rates of conventional diamond drilling. The increased penetration rates open up for affordable drilling of deep boreholes in regions with cold crust, such as in Scandinavia, allowing for geothermal energy generation in enhanced geothermal systems. We present two infrastructures for downhole sampling and testing, Riksriggen and the LTU downhole stress measurement system. Riksriggen produces a borehole that allows in-situ sampling and testing to 2.5 km depth. Furthermore, highly relevant data for geothermal energy production is produced, for example fracture geometries and frequencies, as well as depth of zones with elevated transmissivity zones and their in-situ hydraulic conductivities. The LTU downhole stress measurement system allows determination of the three-dimensional stress tensor and its spatial variation with depth in a scientific unambiguously way. Thus, Riksriggen and the LTU downhole stress measurement system provide data needed for planning most stable borehole trajectory with depth and to determine optimal pattern of production and injection wells (e.g. hydraulic stimulation by fraccing), as well as for assessing the risk of induced seismicity.
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| 9. |
- Ask, Maria V. S., et al.
(författare)
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Stress Analysis in Boreholes Drag Bh and Leknes Bh, Nordland, North Norway
- 2015
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Ingår i: Rock Mechanics and Rock Engineering. - : Springer Science and Business Media LLC. - 0723-2632 .- 1434-453X. ; 48:4, s. 1475-1484
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Tidskriftsartikel (refereegranskat)abstract
- Nordland in northern Norway is characterized by enhanced seismicity and uplift that makes it the most tectonically active area in Norway. This study is part of a project entitled Neotectonics in Norway—Implications for Petroleum Exploration, which aims at enhancing the understanding of regional-scale stress and strain dynamics in Nordland, and to impact risk and hazard assessment and petroleum exploration. This paper attempts to constrain the orientation of in situ horizontal stress using high-resolution acoustic televiewer logging data. The Geological Survey of Norway has drilled two 0.8 km deep near-vertical boreholes on opposite sides of the Vestfjord in Nordland, the open bight of sea that separates the Lofoten archipelago from the Norwegian mainland. Both boreholes are drilled just North of 68_ N, with borehole Leknes Bh located near the geographic center of the Lofoten archipelago, and borehole Drag Bh located on approximate equal distance from the shore, on the Norwegian mainland. The results of this study are in most practical aspects inconclusive, mainly due to poor data quality. The data analysis has revealed erroneously high-borehole diameter, and several artifacts such as eccentric logging tool, rugose borehole wall, spiral hole, tool sticking and missing data. Four intervals with passive in situ stress indicators (borehole breakout and drilling-induced fractures) were found in travel time and amplitude images of the Drag Bh, suggesting approximately N–S orientation of maximum horizontal stress. However, these intervals are not found in cross-plots. Either result yields the lowest World Stress Map ranking quality (E).
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| 10. |
- Ahmadi, Omid, et al.
(författare)
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Revealing the deeper structure of the end-glacial Pärvie fault system in northern Sweden by seismic reflection profiling
- 2015
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Ingår i: Solid Earth Discussions. - : Copernicus GmbH. - 1869-9537 .- 1869-9529 .- 1869-9510. ; 6:2, s. 537-563
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Tidskriftsartikel (refereegranskat)abstract
- Fault scarps that extend up to 155 km and have offsets of tens of meters at the surface are present in the northern parts of Finland, Norway and Sweden. These fault scarps are inferred to have formed during earthquakes with magnitudes up to 8 at the time of the last deglaciation. The Pärvie fault system represents the largest earthquake so far documented in northern Scandinavia, both in terms of its length and its calculated magnitude. It is also the longest known glacially induced fault in the world. Present-day microearthquakes occur along the length of the fault scarp on the eastern side of the scarp, in general agreement with an east dipping main fault. In the central section of the fault, where there is a number of subsidiary faults east of the main fault, it has been unclear how the earthquakes relate to the faults mapped at the surface. A seismic profile across the Pärvie Fault system acquired in 2007, with a mechanical hammer as a source, showed a good correlation between the surface mapped faults and moderate to steeply dipping reflectors. The most pronounced reflector could be mapped to about 3 km depth. In an attempt to map the fault system to deeper levels, a new 22 km long 2-D seismic profile which followed the 2007 line was acquired in June 2014. For deeper penetration an explosive source with a maximum charge size of 8.34 kg in 20 m deep shot holes was used. Reflectors can now be traced to deeper levels with the main 65◦ east dipping fault interpreted as a weakly reflective structure. As in the previous profile, there is a pronounced strongly reflective 60◦ west dipping structure present to the east of the main fault that can now be mapped to about 8 km depth. Extrapolations of the main and subsidiary faults converge at a depth of about 11.5 km where current earthquake activity is concentrated, suggesting their intersection has created favorable conditions for seismic stress release. Based on the present and previous seismic reflection data, potential locations for future boreholes for drilling into the fault system are proposed.
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