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- Rewers, Marian, et al.
(författare)
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The Environmental Determinants of Diabetes in the Young (TEDDY) Study
- 2008
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1150, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The etiology of type 1 diabetes (T1D) remains unknown, but a growing body of evidence points to infectious agents and/or components of early childhood diet. The National Institutes of Health has established the TEDDY Study consortium of six clinical centers in the United States and Europe and a data coordinating center to identify environmental factors predisposing to, or protective against, islet autoimmunity and T1D. From 2004-2009, TEDDY will screen more than 360,000 newborns from both the general population and families already affected by T1D to identify an estimated 17,804 children with high-risk HLA-DR,DQ genotypes. Of those, 7,801 (788 first-degree relatives and 7,013 newborns with no family history of T1D) will be enrolled in prospective follow-up beginning before the age of 4.5 months. As of May 2008, TEDDY has screened more than 250,000 newborns and enrolled nearly 5,000 infants--approximately 70% of the final cohort. Participants are seen every 3 months up to 4 years of age, with subsequent visits every 6 months until the subject is 15 years of age. Blood samples are collected at each visit for detection of candidate infectious agents and nutritional biomarkers; monthly stool samples are collected for infectious agents. These samples are saved in a central repository. Primary endpoints include (1) appearance of one or more islet autoantibodies (to insulin, GAD65 or IA-2) confirmed at two consecutive visits; (2) development of T1D. By age 15, an estimated 800 children will develop islet autoimmunity and 400 will progress to T1D; 67 and 27 children have already reached these endpoints.
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| 2. |
- TEDDY study group, The, et al.
(författare)
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The environmental determinants of diabetes in the young (TEDDY) study: Study design
- 2007
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 8:5, s. 286-298
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Tidskriftsartikel (refereegranskat)abstract
- The primary objective of this multicenter, multinational, epidemiological study is the identification of infectious agents, dietary factors, or other environmental exposures that are associated with increased risk of autoimmunity and type 1 diabetes mellitus (T1DM). Factors affecting specific phenotypic manifestations such as early age of onset or rate of progression or with protection from the development of T1DM will also be identified. The Environmental Determinants of Diabetes in the Young (TEDDY) is an observational cohort study in which newborns who are younger than 4 months and have high-risk human leukocyte antigen alleles in the general population or are first-degree relatives (FDRs) of patients affected with T1DM will be enrolled. Six clinical centers in the USA and Europe will screen 361 588 newborns, of which it is anticipated that 17 804 will be eligible for enrollment with just over 7800 followed. Recruitment will occur over 5 yr, with children being followed to the age of 15 yr. Identification of such factors will lead to a better understanding of disease pathogenesis and result in new strategies to prevent, delay, or reverse T1DM.
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| 3. |
- Alrutz, Marie, et al.
(författare)
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Projektledning
- 2013
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Bok (populärvet., debatt m.m.)abstract
- Projektledning är ett yrke med egen certifiering. Det pågår en spännande utveckling inom området och det blir allt viktigare att hålla sig ajour med utvecklingen.Det övergripande målet med den här handboken är att vara en ständigt aktuell heltäckande bok om projektarbete. Innehållsmässigt täcker den både frågor som har med struktur och styrning att göra och frågor om ledning av människor och mänskliga processer i grupp. Kompetens inom projekt byggs av både kunskap och erfarenhet. Vi följer kontinuerligt aktuell forskning inom dessa områden och bjuder in intressanta forskare att medverka som författare. Vi skildrar verkliga projekt och låter erfarenheterna få plats, både de bästa erfarenheterna och de utmaningar som man tagit sig igenom.Handboken är levande och det innebär att artiklar tas bort för att ge plats för nya, i takt med att den uppdateras fortlöpande.
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| 4. |
- Borgfeldt, Christer, et al.
(författare)
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Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1)
- 2001
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 92:4, s. 497-502
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Tidskriftsartikel (refereegranskat)abstract
- The plasminogen activating system is involved in tumor growth and metastasis by degradation of extracellular matrix, and modulation of cell adhesion and migration. Benign and well-differentiated malignant ovarian tumors present as cystic lesions with preserved glandular morphology, whereas poorly differentiated tumors and metastases are solid with characteristic absence of glandular morphology. We analyzed the mRNAs for urokinase plasminogen activator (uPA), its receptor (uPAR), and inhibitor (PAI-1) in serous ovarian tumors by in situ hybridization and by densitometric scanning of Northern blots prepared from tissue extracts. The mRNA expressing cells in the in situ hybridization sections were evaluated and counted by two different observers. The number of mRNA expressing cells for uPA, uPAR and PAI-1 were all significantly increased in solid as compared with cystic malignant tumors. The increased expression of all three mRNA species was mainly located in the stroma of poorly differentiated tumors and metastases. Apart from being expressed in the stroma of these tumors, uPAR mRNA was also expressed by tumor cells located along the stromal/epithelial boarder. In addition, the tumor tissue content of uPA, uPAR and PAI-1 mRNAs as measured by Northern blots were higher in the solid as compared with the cystic tumors. Increased expression of uPA, uPAR and PAI-1 genes in the solid tumors suggest a correlation with a more aggressive phenotype.
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| 5. |
- Borgfeldt, Christer, et al.
(författare)
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High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancer
- 2003
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 107:4, s. 658-665
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Tidskriftsartikel (refereegranskat)abstract
- volved in tumor growth and metastasis. We assayed the components of the uPA system in homogenates of 64 primary epithelial ovarian tumors and 5 metastases and evaluated the association of these parameters to prognosis in the 51 malignant cases. The levels of uPA, PAI-2 and the uPA: PAI-I complex increased with progressive loss of histological differentiation (P-trend <0.001, <0.05 and <0.001). The level of PAI-I was higher in poorly than in well/moderately differentiated tumors (p = 0.03). The content of uPAR was lower in benign tumors as compared to borderline malignancies (p = 0.002), invasive primary tumors (p < 0.001), and metastases (p = 0.002). Surprisingly, the level of uPAR was lower in poorly differentiated as compared to both borderline (p = 0.01) and well differentiated malignant tumors (p = 0.005). Also, the level of uPAR was lower in advanced as compared to early stages of the disease (P-trend = 0.002). The median follow-up time for patients was 5.8 years. High tumor tissue levels of uPAR were associated with longer postoperative survival (HR = 0.4, 95% CI = 0.2-0.8, p = 0.01). In contrast, shorter survival was evident in patients with high tumor levels of uPA from 2 years on after operation (HR = 4.6, 95% CI = 1.2-17, p = 0.02). High tPA levels tended to be associated with shorter overall survival after 2 years (HR = 2.9, 95% 95% Cl = 0.9-9.8, p = 0.08). Although high tumor tissue content of uPAR was associated with a less aggressive phenotype characterized by well differentiated histology and longer survival, low content of uPAR in the poorly differentiated tumors and metastases presumably results from increased elimination of uPAR. (C) 2003 Wiley-Liss, Inc.
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| 9. |
- 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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