| 1. |
- Andersen, Niels S., et al.
(författare)
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Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma
- 2009
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 27:26, s. 4365-4370
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.
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| 2. |
- Benzinou, Michael, et al.
(författare)
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Common nonsynonymous variants in PCSK1 confer risk of obesity.
- 2008
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:8, s. 943-5
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D, and rs6234-rs6235, encoding the Q665E-S690T pair, were consistently associated with obesity in adults and children (P = 7.27 x 10(-8) and P = 2.31 x 10(-12), respectively). Functional analysis showed a significant impairment of the N221D-mutant PC1/3 protein catalytic activity.
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| 3. |
- Bonefeld-Jorgensen, Eva C, et al.
(författare)
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Xenoestrogenic activity in blood of European and Inuit populations
- 2006
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Ingår i: Environmental Health. - 1476-069X. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human exposure to persistent organic pollutants (POPs) is ubiquitous and found in all individuals. Studies have documented endocrine disrupting effects and impact on reproduction. The aim of the present study was to compare the level of xenoestrogenic activity in serum of groups with varying POP exposure, and to evaluate correlations to the POP biomarkers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 358 men: Greenlandic Inuit's, Swedish fishermen, and Warsaw (Poland) and Kharkiv (Ukraine) inhabitants. Xenoestrogenicity of serum extracts alone (XER) and XER competitive (XERcomp) effect on 17beta-estradiol induced estrogen receptor (ER) transactivity were assessed in the hormone free, lipophilic serum fraction containing the POPs using the MVLN human breast cancer cell line. RESULTS: No agonistic XER activity was exhibited for Inuit serum samples, while 12 - 24% of the European samples had detectable agonistic XER activity. On the contrary, 71% of Inuit serum samples antagonized XERcomp compared to 7 - 30 % in the other regions. XER and XERcomp were not or weakly correlated to the two POP markers. XER activity of Inuit samples was negatively associated to levels of CB-153 and p,p'-DDE. For the Warsaw group a positive and negative correlation between XER and p,p'-DDE and estradiol equivalence level and CB-153 levels was found. CONCLUSION: No strong consistent association between xenoestrogenic net activity and the two POP markers was found. The results showed that the selected POP markers alone can not predict the integrated xenoestrogenic serum activity. Correlations to the POP markers were found at the extreme edge; the Inuit's and Warsaw study groups eliciting high frequency of samples with ER antagonistic and agonistic activity, respectively. We suggest that the variation in xenoestrogenic serum activity reflects differences in POP exposure mixture, genetic factors and/or life style factors.
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| 4. |
- Bunikis, Ignas, 1981-, et al.
(författare)
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An RND-type efflux system in Borrelia burgdorferi is involved in virulence and resistance to antimicrobial compounds
- 2008
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Ingår i: PLoS Pathogenicity. - 1553-7374. ; 4:2, s. e1000009-
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Tidskriftsartikel (refereegranskat)abstract
- Borrelia burgdorferi is remarkable for its ability to thrive in widely different environments due to its ability to infect various organisms. In comparison to enteric Gram-negative bacteria, these spirochetes have only a few transmembrane proteins some of which are thought to play a role in solute and nutrient uptake and excretion of toxic substances. Here, we have identified an outer membrane protein, BesC, which is part of a putative export system comprising the components BesA, BesB and BesC. We show that BesC, a TolC homolog, forms channels in planar lipid bilayers and is involved in antibiotic resistance. A besC knockout was unable to establish infection in mice, signifying the importance of this outer membrane channel in the mammalian host. The biophysical properties of BesC could be explained by a model based on the channel-tunnel structure. We have also generated a structural model of the efflux apparatus showing the putative spatial orientation of BesC with respect to the AcrAB homologs BesAB. We believe that our findings will be helpful in unraveling the pathogenic mechanisms of borreliae as well as in developing novel therapeutic agents aiming to block the function of this secretion apparatus.
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| 5. |
- Dehlendorff, Christian, et al.
(författare)
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Designing simulation experiments with controllable and uncontrollable factors
- 2008
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Ingår i: 2008 Winter Simuation Conference. - Piscataway, NJ : IEEE Communications Society. - 9781424427079 ; , s. 2909-2915
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Konferensbidrag (refereegranskat)abstract
- In this study we propose a new method for designing computer experiments inspired by the split plot designs used in physical experimentation. The basic layout is that each set of controllable factor settings corresponds to a whole plot for which a number of subplots, each corresponding to one combination of settings of the uncontrollable factors, is employed. The caveat is a desire that the subplots within each whole plot cover the design space uniformly. A further desire is that in the combined design, where all experimental runs are considered at once, the uniformity of the design space coverage should be guaranteed. Our proposed method allows for a large number of uncontrollable and controllable settings to be run in a limited number of runs while uniformly covering the design space for the uncontrollable factors
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| 6. |
- Dencker, Magnus, et al.
(författare)
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BMI and objectively measured body fat and body fat distribution in prepubertal children.
- 2007
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 27:1, s. 12-16
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Tidskriftsartikel (refereegranskat)abstract
- Background Body Mass Index (BMI) is often used as a surrogate estimate of body fat in epidemiological studies. This study explores the association between BMI, body fat and body fat distribution assessed by Dual-Energy X-Ray Absorptiometry (DXA) in younger children. Methods Cross-sectional study of 246 children (138 boys and 108 girls) aged 8-11 years. DXA was used to quantify abdominal fat mass (AFM), total body fat (TBF) and also total body fat as percentage of total body mass (BF%). Body fat distribution was calculated as AFM/TBF. Results We found close correlations between BMI vs. TBF, BF% and AFM (r = 0.94, r = 0.92 and r = 0.93) for boys and (r = 0.95, r = 0.92 and r = 0.95) for girls, respectively (P < 0.05 for all r-values). However, significantly lower correlation (P < 0.001 for difference between the r-values) existed for body fat distribution (r = 0.64 for boys and 0.73 for girls). Conclusion Percentage body fat, TBF and AFM were all closely associated with BMI, suggesting that BMI serves as a good surrogate marker for obesity in population studies. However, a significantly lower correlation existed for BMI vs. body fat distribution, which may be a limitation when BMI is used to study cardiovascular risk factors in epidemiological studies.
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| 7. |
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| 8. |
- Dencker, Magnus, et al.
(författare)
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Body fat related to daily physical activity and insulin concentrations in non-diabetic children.
- 2008
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Ingår i: Clinical Physiology and Functional Imaging. - 1475-0961. ; 28, s. 211-215
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Tidskriftsartikel (refereegranskat)abstract
- This study explored the associations between body fat versus daily physical activity and insulin concentrations in non-diabetic young children in a cross-sectional study of 172 children (93 boys and 79 girls) aged 8-11 years. Blood samples were analysed for serum insulin and daily physical activity was measured by accelerometers. Time spent performing vigorous activity was estimated from accelerometer data by using established cut-off points. Dual-energy x-ray absorptiometry (DXA) was used to quantify abdominal fat mass (AFM) and total body fat (TBF), also calculated as percentage of body weight (BF%). Body fat distribution was calculated as AFM/TBF. Body fat distribution was independently linked to both insulin concentrations and physical activity. In contrast, TBF, AFM, and BF% were linked to physical activity only and not to insulin concentrations. In conclusion in this population of non-diabetic children, body fat distribution was independently associated with increased concentrations of insulin and deceased amount of vigorous activity per day. Also, AFM, TBF, and BF% were independently related to minutes of vigorous activity per day.
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| 9. |
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| 10. |
- Dencker, Magnus, et al.
(författare)
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Daily physical activity and its relation to aerobic fitness in children aged 8-11 years.
- 2006
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 96:5, s. 587-592
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Tidskriftsartikel (refereegranskat)abstract
- A positive relationship between daily physical activity and aerobic fitness exists in adults. Studies in children have given conflicting results, possibly because of differences in methods used to assess daily physical activity and fitness. No study regarding daily physical activity and fitness in children has been published, where fitness has been assessed by direct measurement of maximum oxygen uptake and related to daily physical activity intensities by accelerometers. We examined 248 children (140 boys and 108 girls), aged 7.9-11.1 years. Maximum workload and maximal oxygen uptake (VO2PEAK) by indirect calorimetry were measured during a maximum bicycle ergometer exercise test. Exercise capacity was adjusted for body mass and (body mass)(2/3). Daily physical activity was evaluated by accelerometers, worn around the waist for 4 days. Mean accelerometer counts and time spent in vigorous physical activity were calculated. VO2PEAK was correlated with mean accelerometer counts (r=0.23 for boys and r=0.23 for girls, both P < 0.05), but somewhat better with time spent in vigorous activity (r=0.32 for boys, r=0.30 for girls, both P < 0.05). All results remained virtually the same regardless of the method used to adjust for differences in body size.
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| 11. |
- Dencker, Magnus, et al.
(författare)
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Daily physical activity related to body fat in children aged 8-11 years
- 2006
-
Ingår i: Journal of Pediatrics. - : Elsevier BV. - 1097-6833 .- 0022-3476. ; 149:1, s. 38-42
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the association between objectively measured daily Study design Cross-sectional, observational, study of 248 children aged 7.9 to 11.1 years. Abdominal fat mass and total body fat mass were measured by dual-energy X-ray absorptiometry. Daily physical activity was assessed by accelerometers for 4 days. Results Total body fat expressed as a percentage of body mass was inversely related to minutes of vigorous physical activity per day, for all children r = -0.38 (P < .05). Children, both boys and girls, in the highest quartile of body fat performed on average 12 minutes less vigorous activity per day compared with their counterparts in the lowest quartile. Multiple regression analysis revealed that independent factors for body fat were number of minutes of vigorous activity per day and sex. Conclusion Low physical activity can be a contributing factor in childhood obesity. Only longitudinal studies, however, can give more definitive information about the relation between daily physical activity and obesity.
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| 12. |
- Dencker, Magnus, et al.
(författare)
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Gender differences and determinants of aerobic fitness in children aged 8-11 years.
- 2007
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 99, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of gender differences in maximum oxygen uptake have come to different conclusions. Limited data exists where the determinants of maximum oxygen uptake have been evaluated in a comprehensive manner. Thus, we examined 248 children (140 boys and 108 girls), aged 7.9-11.1 years. Body composition was determined by dual-energy X-ray absorptiometry, measured variables were total body fat (TBF) and lean body mass (LBM). Maximal oxygen uptake (VO2peak) was measured by indirect calorimetry during a maximal cycle exercise test. Daily physical activity was assessed by accelerometers and duration of vigorous activity per day (VPA) was calculated. Left ventricular inner diastolic diameter (LVDD) was measured by echocardiography. Lung function was evaluated with spirometric testing and whole body plethysmography. Boys had between 8 and 18% higher values than girls for VO2peak, dependent upon whether VO2peak was expressed in absolute values or scaled to body mass, LBM or if allometric scaling was used. In multiple regression analysis absolute values of aerobic fitness were independently related to LBM, maximal heart rate (Max HR), gender, LVDD, and VPA. Furthermore, when VO2peak was scaled to body mass it was independently related to In TBF, Max HR, gender, VPA, and LVDD. Lung function had no relation to VO2peak. Our study concludes that body composition is the main predictor for VO2peak, in children aged 8-11 years, whereas VPA or LVDD has only a modest impact. Existing gender differences in VO2peak cannot be explained only by differences in body composition, physical activity, or heart size.
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| 13. |
- Dencker, Magnus, et al.
(författare)
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Maximal oxygen uptake versus maximal power output in children
- 2008
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Ingår i: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 26:13, s. 1397-1402
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Tidskriftsartikel (refereegranskat)abstract
- Maximal oxygen uptake ([Vdot]O2max) is considered the optimal method to assess aerobic fitness. The measurement of [Vdot]O2max, however, requires special equipment and training. Maximal exercise testing with determination of maximal power output offers a more simple approach. This study explores the relationship between [Vdot]O2max and maximal power output in 247 children (139 boys and 108 girls) aged 7.9-11.1 years. Maximal oxygen uptake was measured by indirect calorimetry during a maximal ergometer exercise test with an initial workload of 30W and 15Wmin-1 increments. Maximal power output was also measured. A sample (n=124) was used to calculate reference equations, which were then validated using another sample (n=123). The linear reference equation for both sexes combined was: [Vdot]O2max (mlmin-1)=96 + 10.6maximal power + 3.5body mass. Using this reference equation, estimated [Vdot]O2max per unit of body mass (mlmin-1kg-1) calculated from maximal power correlated closely with the direct measurement of [Vdot]O2max (r=0.91, P0.001). Bland-Altman analysis gave a mean limits of agreement of 0.22.9 (mlmin-1kg-1) (1s). Our results suggest that maximal power output serves as a good surrogate measurement for [Vdot]O2max in population studies of children aged 8-11 years.
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| 14. |
- Dencker, Magnus, et al.
(författare)
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Objectively measured daily physical activity related to cardiac size in young children.
- 2009
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Ingår i: Scandinavian Journal of Medicine & Science in Sports. - : Wiley. - 1600-0838 .- 0905-7188. ; Aug 5, s. 664-668
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Tidskriftsartikel (refereegranskat)abstract
- Training studies in children have suggested that endurance training can give enlargement of cardiac dimensions. This relationship has not been studied on a population-based level in young children with objective methods. A cross-sectional study was made of 248 children (140 boys and 108 girls), aged 8-11 years, from a population-based cohort. Left ventricular end-diastolic diameter (LVDD) and left atrial end-systolic diameter (LA) were measured with echocardiography and indexed for body surface area (BSA). Physical activity was assessed by accelerometry, and the duration of vigorous physical activity per day (VPA) was calculated. Acceptable accelerometer and echocardiography measurements were obtained in 228 children (boys=127, girls=101). Univariate correlations between VPA and LVDD were indexed for BSA in boys (r=0.27, P<0.05) and in girls (r=0.10, NS). Multiple regression analysis showed that independent factors for LVDD, indexed for BSA for boys, were age and VPA. LA indexed for BSA was not related to physical activity variables in either gender. No clear relationship exists between cardiac size and daily physical activity in children aged 8-11 years. This suggests that significant cardiac remodelling due to volume exposure secondary to a high amount of physical activity begins later in life.
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| 15. |
- Engelke, Fredric, et al.
(författare)
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Inventering av provtagningsstrategier för jord, grundvatten och porgas
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Inom ramen för Naturvårdsverkets kunskapsprogram Hållbar Sanering har ett projekt om strategier för provtagning av förorenad jord, grundvatten och porgas genomförts. Syftet med projektet har varit att inventera vilka befintliga metoder och vägledningar som finns för att effektivisera provtagning av olika medier. Projektet redovisas i föreliggande syntesrapport samt i fem delrapporter. En delrapport finns för respektive jord, grundvatten och porgas. Dessa finns i sin helhet i kapitel 9, 10 och 11. Delrapporterna ger en överblick av vilka strategier som finns tillgängliga, men ingen av rapporterna har haft som målsättning att ta fram en vägledning för hur provtagning bör utföras. Övriga två delrapporter redovisar hur undersökningar har utförts i Sverige och Danmark. I delrapporten avseende provtagningsstrategier för jord redovisas en sammanfattning av flera olika provtagningsstrategier, inklusive deras för- och nackdelar samt under vilka förutsättningar olika strategier fungerar bäst. Två förhållandevis nya strategier presenteras: rankbaserad strategi och anpassad klusterprovtagning. Strategierna baseras främst på amerikanska vägledningar framtagna på uppdrag av US Environmental Protection Agency, USEPA. I delrapporten avseende provtagningsstrategier för grundvatten beskrivs olika strategier beroende på syftet med provtagningen. Några mjukvaruprogram för visualisering av undersökningsresultat i två och tre dimensioner har inventerats och beskrivs med för- och nackdelar. Delrapporten, som är skriven på danska, beskriver olika strategier principiellt och för detaljerade anvisningar och råd avseende t.ex. borrmetodik och provtagningsmetoder hänvisas till olika danska och svenska handböcker inom området. Provtagning av porgas är en modernare teknik än både jord- och grundvattenprovtagning. Inventeringen visar att det finns vägledningar kring hur och med vilka metoder porgasmätningar bör utföras, men att det saknas till stor del rekommendationer kring provtagningsstrategier som är inriktade mot mätning av porgas, eller så är vägledningarna generellt utformade. Övriga två delrapporter är en inventering av hur undersökningar har utförts inom ramen för olika undersökningsprojekt i Sverige och Danmark.
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| 16. |
- Ewert, Frank, et al.
(författare)
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A methodology for enhanced flexibility of integrated assessment in agriculture
- 2009
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Ingår i: Environmental Science and Policy. - : Elsevier BV. - 1462-9011. ; 12:5, s. 546-561
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Tidskriftsartikel (refereegranskat)abstract
- Agriculture is interrelated with the socio-economic and natural environment and faces increasingly the problem of managing its multiple functions in a sustainable way. Growing emphasis is on adequate policies that can support both agriculture and sustainable development. Integrated Assessment and Modelling (IAM) can provide insight into the potential impacts of policy changes. An increasing number of Integrated Assessment (IA) models are being developed, but these are mainly monolithic and are targeted to answer specific problems. Approaches that allow flexible IA for a range of issues and functions are scarce. Recently, a methodology for policy support in agriculture has been developed that attempts to overcome some of the limitations of earlier IA models. The proposed framework (SEAMLESS-IF) integrates relationships and processes across disciplines and scales and combines quantitative analysis with qualitative judgments and experiences. It builds on the concept of systems analysis and attempts to enable flexible coupling of models and tools. The present paper aims to describe progress in improving flexibility of IAM achieved with the methodology developed for SEAMLESS-IF. A brief literature review identifying limitations in the flexibility of IAM is followed by a description of the progress achieved with SEAMLESS-IF. Two example applications are used to illustrate relevant capabilities of SEAMLESS-IF. The examples refer to (i) the impacts on European agriculture of changes in world trade regulations and (ii) regional impacts of the EU Nitrates Directive in combination with agro-management changes. We show that improving the flexibility of IAM requires flexibility in model linking but also a generic set up of all IA steps. This includes problem and scenario definition, the selection and specification of indicators and the indicator framework, the structuring of the database, and the visualization of results. Very important is the flexibility to integrate, select and link models, data and indicators depending on the application. Technical coupling and reusability of model components is greatly improved through adequate software architecture (SEAMLESS-IF uses OpenMI). The use of ontology strongly supports conceptual consistency of model linkages. However, the scientific basis for linking models across disciplines and scales is still weak and requires specific attention in future research. We conclude that the proposed framework significantly advances flexibility in IAM and that it is a good basis to further improve integrated modelling for policy impact assessment in agriculture. (C) 2009 Elsevier Ltd. All rights reserved.
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| 17. |
- Geisler, Christian H., et al.
(författare)
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Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue : a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 112:7, s. 2687-93
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.
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| 18. |
- Gilbert, M. Thomas P., et al.
(författare)
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Paleo-Eskimo mtDNA genome reveals matrilineal discontinuity in Greenland
- 2008
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 320:5884, s. 1787-1789
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Tidskriftsartikel (refereegranskat)abstract
- The Paleo- Eskimo Saqqaq and Independence I cultures, documented from archaeological remains in Northern Canada and Greenland, represent the earliest human expansion into the New World's northern extremes. However, their origin and genetic relationship to later cultures are unknown. We sequenced a mitochondrial genome from a Paleo- Eskimo human by using 3400- to 4500- year- old frozen hair excavated from an early Greenlandic Saqqaq settlement. The sample is distinct from modern Native Americans and Neo- Eskimos, falling within haplogroup D2a1, a group previously observed among modern Aleuts and Siberian Sireniki Yuit. This result suggests that the earliest migrants into the New World's northern extremes derived from populations in the Bering Sea area and were not directly related to Native Americans or the later Neo- Eskimos that replaced them.
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| 19. |
- Gorokhova, Elena, et al.
(författare)
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Stable isotopes show food web changes after invasion by the predatory cladoceran Cercopagis pengoi in a Baltic Sea bay
- 2005
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Ingår i: Oecologia. - : Springer Science and Business Media LLC. - 0029-8549 .- 1432-1939. ; 143:2, s. 251-259
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Tidskriftsartikel (refereegranskat)abstract
- Cercopagis pengoi, a recent invader to the Baltic Sea and the Laurentian Great Lakes, is a potential competitor with fish for zooplankton prey. We used stable C and N isotope ratios to elucidate trophic relationships between C. pengoi, zooplankton (microzooplankton, 90–200 m, mostly copepod nauplii and rotifers; mesozooplankton, >200 m, mostly copepods), and zooplanktivorous fish (herring, size range 5–15 cm and sprat, 9–11 cm) in a coastal area of the northern Baltic Sea. The isotope ratios in C. pengoi and fish were much higher than those of zooplankton, showing general trends of enrichment with trophic level. Young-of-the-year (YOY) herring had a significantly higher 15N/14N ratio than C. pengoi, suggesting of a trophic linkage between the two species. To evaluate the possible relative importance of different food sources for C. pengoi and YOY herring, two-source isotope-mixing models for N were used, with micro- and mesozooplankton as prey for C. pengoi and mesozooplankton and C. pengoi as prey for YOY herring. These models indicate that mesozooplankton was the major food source of both species. However, microzooplankton may be important prey for young stages of C. pengoi. Comparative analyses of the herring trophic position before and after the invasion by C. pengoi showed a trophic level shift from 2.6 to 3.4, indicating substantial alterations in the food web structure. Our findings contribute to a growing body of evidence, showing that C. pengoi can modify food webs and trophic interactions in invaded ecosystems.
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| 20. |
- Hansen, Lone, et al.
(författare)
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Anatomy and biomechanics of the back muscles in the lumbar spine with reference to biomechanical modeling
- 2006
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Ingår i: Spine. - 0362-2436. ; 31:17, s. 1888-1899
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Forskningsöversikt (refereegranskat)abstract
- Study Design. This article describes the development of a musculoskeletal model of the human lumbar spine with focus on back muscles. It includes data from literature in a structured form. Objective. To review the anatomy and biomechanics of the back muscles related to the lumbar spine with relevance for biomechanical modeling. Summary of Background Data. To reduce complexity, muscle units have been incorporated in an abridged manner, reducing their actions more or less to a single force equivalent. In early models of the lumbar spine, this may have been a necessary step to reduce complexity and, thereby, calculation time. The muscles of the spine are well described in the literature, but mainly qualitatively. Most of the literature provides a description of the structures without precise data of fiber length, muscle length, cross-sectional areas, moment arms, forces, etc. The predicted output of musculoskeletal models is very much dependent on the input parameters. The information needed to improve models consists of better approximations of the attachments to the vertebrae, and more precise data. Method. Review of literature. Results. The predicted output of musculoskeletal models is very much dependent on the input parameters. Moderate changes in the assumed muscle line-of-action (i.e., moment arm) could substantially alter the magnitudes of predicted muscle and spinal forces, while the choice of optimization formulation is less sensitive. Conclusions. Input parameters, moment arms, as well as physiologic cross-sectional areas have a profound effect on the predicted muscle forces. Therefore, it is important to choose the values for moment arm and physiologic cross-sectional area carefully because they are essential input parameters to biomechanical models.
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| 21. |
- Kadi, Fawzi, et al.
(författare)
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The behaviour of satellite cells in response to exercise : what have we learned from human studies?
- 2005
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Ingår i: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 451:2, s. 319-327
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the complex role played by satellite cells in the adaptive response to exercise in human skeletal muscle has just begun. The development of reliable markers for the identification of satellite cell status (quiescence/activation/proliferation) is an important step towards the understanding of satellite cell behaviour in exercised human muscles. It is hypothesised currently that exercise in humans can induce (1) the activation of satellite cells without proliferation, (2) proliferation and withdrawal from differentiation, (3) proliferation and differentiation to provide myonuclei and (4) proliferation and differentiation to generate new muscle fibres or to repair segmental fibre injuries. In humans, the satellite cell pool can increase as early as 4 days following a single bout of exercise and is maintained at higher level following several weeks of training. Cessation of training is associated with a gradual reduction of the previously enhanced satellite cell pool. In the elderly, training counteracts the normal decline in satellite cell number seen with ageing. When the transcriptional activity of existing myonuclei reaches its maximum, daughter cells generated by satellite cell proliferation are involved in protein synthesis by enhancing the number of nuclear domains. Clearly, delineating the events and the mechanisms behind the activation of satellite cells both under physiological and pathological conditions in human skeletal muscles remains an important challenge.
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| 22. |
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| 23. |
- Lindberg, Olof, et al.
(författare)
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Cortical morphometric subclassification of frontotemporal lobar degeneration
- 2009
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Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 30:6, s. 1233-1239
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration (FTLD) is a primary neurodegenerative disease comprising 3 clinical subtypes: frontotemporal dementia (FTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). The subdivision is primarily based on the characteristic clinical symptoms displayed by each subtype. We hypothesized that these symptoms would be correlated to characteristic patterns of brain atrophy, which could be indentified and used for subclassification of subjects with FTLD. MATERIALS AND METHODS: Volumes of 9 cortical regions were manually parcellated and measured on both hemispheres on 27 controls, 12 patients with FTD, 9 patients with PNFA, and 13 patients with SD. The volumetric data were analyzed by traditional t tests and by a multivariate discriminant analysis (partial least squares discriminant analysis). RESULTS: The ensemble or pattern of atrophy was a good discriminator in pair-wise comparison between the subtypes: FTD compared with SD (sensitivity 100% [12/12], specificity 100% [13/13]); FTD compared with PNFA (sensitivity 92% [11/12], specificity 89% [8/9]); and SD compared with PNFA (sensitivity 86% [11/13], specificity 100% [9/9]). Temporal-versus-frontal atrophy was the most important pattern for discriminating SD from the other 2 subtypes. Right-sided versus left-sided atrophy was the most important pattern for discriminating between subjects with FTD and PNFA. CONCLUSIONS: FTLD subtypes generally display a characteristic pattern of atrophy, which may be considered in diagnosing patients with FTLD.
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| 24. |
- Lindqvist, Charlotte, et al.
(författare)
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The Laptev Sea walrus Odobenus rosmarus laptevi: an enigma revisited
- 2009
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Ingår i: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 38:2, s. 113-127
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Tidskriftsartikel (refereegranskat)abstract
- The walrus (Odobenus rosmarus) is in some current systematic schemes divided into three subspecies: O. r. rosmarus in the North Atlantic, O. r. divergens in the North Pacific and O. r. laptevi in the Laptev Sea. These three subspecies have been described as differing in body size, but the taxonomic status of O. r. laptevi is disputed. The current study applies molecular and morphometric methods to assess the taxonomic status of O. r. laptevi and to analyse the systematic and phylogeographic relationships between the three purported walrus subspecies. Tusk length and tusk circumference were measured from the few skulls available of O. r. laptevi, and the obtained values were within the ranges reported for Pacific walruses. Thus, morphologically, subspecies status for O. r. laptevi is not supported according to the Amadon Mayr '75% rule'. Phylogenetic analyses and haplotype networks based on mitochondrial nucleotide sequence data of NADH dehydrogenase 1, 16S rRNA, cytochrome oxidase I and the D-loop of the control region of the historic O. r. laptevi bone material and contemporary O. r. rosmarus and O. r. divergens showed that the Laptev Sea walrus groups with individuals from the North Pacific. Thus, the mitochondrial sequence data do not support the recognition of three walrus subspecies as reciprocally monophyletic evolutionary units with independent evolutionary histories. Only O. r. rosmarus and O. r. divergens meet this criterion with the present sampling. Accordingly, we recommend that Odobenus r. laptevi be abandoned and the Laptev walrus instead be recognized as the westernmost population of the Pacific walrus, Odobenus r. divergens. However, further research is recommended to assess whether the Laptev walrus could be considered as a significant unit in terms of conservation and management, since it is unique in several ecological parameters.
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| 25. |
- Long, Manhai, et al.
(författare)
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Dioxin-like activities in serum across European and Inuit populations
- 2006
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Ingår i: Environmental Health. - 1476-069X. ; 5:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay. RESULTS: The European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group. CONCLUSION: No consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors.
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| 26. |
- Looi Chee Leong, Jeffrey, et al.
(författare)
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Caudate nucleus volumes in frontotemporal lobar degeneration : differential atrophy in subtypes
- 2008
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Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 29:8, s. 1537-1543
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Frontostriatal circuits involving the caudate nucleus have been implicated in frontotemporal lobar degeneration (FTLD). We assessed caudate nucleus volumetrics in FTLD and subtypes: frontotemporal dementia (FTD, n = 12), semantic dementia (SD, n = 13), and progressive nonfluent aphasia (PNFA, n = 9) in comparison with healthy controls (n = 27) and subjects with Alzheimer disease (AD, n = 19). MATERIALS AND METHODS: Diagnoses were based on accepted clinical criteria. Manual volume measurement of the head and body of the caudate, excluding the tail, was conducted on T1-weighted brain MR imaging scans, using a published protocol, by a single analyst blinded to the diagnosis. RESULTS: Paired t tests (P < .05) showed that the right caudate nucleus volume was significantly larger than the left in controls and PNFA. No hemispheric asymmetry was found in AD, ETD, and SD. Across the groups, there was a positive partial correlation between the left caudate nucleus volume and Mini-Mental State Examination (MMSE) scores (r = 0.393, n = 76, P = .001) with higher left caudate volumes associated with higher MMSE scores. Multivariate analysis of covariance was used to assess the statistical significance between the subject groups (AD, ETD, SD, PNFA, and controls) as independent variables and raw right/left caudate volumes at the within-subject level (covariates: age and intracranial volume; P < .05). Control volume was largest, followed by AD (93% of control volume), SD (92%), PNFA (79%), and ETD (75%). CONCLUSIONS: Volume of the head and body of the caudate nucleus differs in subtypes of FTLD, due to differential frontostriatal dysfunction in subtypes being reflected in structural change in the caudate, and is correlated with cognition
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| 27. |
- Malmström, Helena, et al.
(författare)
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Ancient DNA Reveals Lack of Continuitybetween Neolithic Hunter-Gatherersand Contemporary Scandinavians
- 2009
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 19:20, s. 1758-1762
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Tidskriftsartikel (refereegranskat)abstract
- The driving force behind the transition from a foraging to a farming lifestyle in prehistoric Europe (Neolithization) has been debated for more than a century [1–3]. Of particular interest is whether population replacement or cultural exchange was responsible [3–5]. Scandinavia holds a unique place in this debate, for it maintained one of the last major hunter-gatherer complexes in Neolithic Europe, the Pitted Ware culture [6]. Intriguingly, these late hunter-gatherers existed in parallel to early farmers for more than a millennium before they vanished some 4,000 years ago [7, 8]. The prolonged coexistence of the two cultures in Scandinavia has been cited as an argument against population replacement between the Mesolithic and the present [7, 8]. Through analysis of DNA extracted from ancient Scandinavian human remains, we show that people of the Pitted Ware culture were not the direct ancestors of modern Scandinavians (including the Saami people of northern Scandinavia) but are more closely related to contemporary populations of the eastern Baltic region. Our findings support hypotheses arising from archaeological analyses that propose a Neolithic or post-Neolithic population replacement in Scandinavia [7]. Furthermore, our data are consistent with the view that the eastern Baltic represents a genetic refugia for some of the European hunter-gatherer populations.
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| 28. |
- Persson, Christian, 1960-, et al.
(författare)
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New Business Forms in e-Business and Media “e-Media”
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In a preliminary study a Nordic network for e-Business has been established between the media industry, vendors, service providers and scientists. This network has performed this project with the scope to develop new new innovative service forms and products for this new business area called ”e-Media”, and to identify the value chains and new business models needed for this area.The study first analyses the strucrural changes in the media and allied industries, i.e. content creation and advertising. Thereafter, a framework for innovations in e-Media is built together with a variety of business models. The framework is then used to identify new innovative service embryos for e-Media. Finally eight new services are exploited in industrial case studies.The outcome of the project is an extensive description of innovation methods, business models, more than sixty innovation embryos for exploitation and eight examples of more or less successfully exploited e-Media pilot cases. The project also elucidates the huge business potential of e-Media.
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| 29. |
- Persson, Christian, 1960-, et al.
(författare)
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New Business Forms in e-Business and Media – e-Media
- 2009
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Ingår i: Iarigai 2009.
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Konferensbidrag (refereegranskat)abstract
- It has been the scope of this study to create new service forms and business models for the border area between e-Business and Media (e-Media). The project was carried out by a Nordic consortium consisting of five research organisations and eight companies with financial support from the Nordic Innovation Centre (NICe). The study first analyses the structural changes in the media and allied industries, i.e. content creation and advertising. Thereafter, a framework for innovations in e-Media is built up, together with a variety of business models. The framework is used to identify new, innovative service embryos for the e-Media sector. Finally eight new services are developed in industrial case studies. The project has been carried out by a consortium consisting of five Nordic research organisations, which have relations to e-Business and the media sector, together with eight industrial partners from the media sector, software companies, and service providers. The outcome of the project is an extensive description of innovation methods and business models for Nordic companies working in the media or e-Business sector or offering services over the net. The report also gives eight examples of more or less successfully exploited e-Media pilot cases.
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| 30. |
- Rokling-Andersen, Merethe H, et al.
(författare)
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Effects of long-term exercise and diet intervention on plasma adipokine concentrations.
- 2007
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Ingår i: The American journal of clinical nutrition. - 0002-9165. ; 86:5, s. 1293-301
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In a randomized, controlled, 2 x 2 factorial trial on the effect of long-term changes in diet and exercise, a significant reduction in body weight and fat mass was observed. Alterations in leptin and plasminogen activator inhibitor-1 concentrations were previously reported from this study. OBJECTIVE: We examined the separate and combined effects of a 1-y exercise and diet intervention on several adipokines; adiponectin, interleukin-6 and -8, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, hepatocyte growth factor, nerve growth factor, C-reactive protein, and resistin. DESIGN: One hundred eighty-eight men with several risk factors for diabetes and cardiovascular disease were randomly allocated to 4 groups: diet, exercise, combined diet and exercise, and control. RESULTS: Plasma adiponectin concentrations remained unchanged, whereas body mass index and fat mass decreased after dietary changes and an increase in physical activity. In the control group, adiponectin concentrations were reduced. Analyzed according to the factorial design, only diet intervention had a significant (P = 0.03) positive effect on plasma adiponectin relative to control, and this effect was largely explained by changes in fat mass. After adjustment for change in percentage body fat, there were significant positive effects on tumor necrosis factor-alpha in all 3 intervention groups (P = 0.01 for the diet group, 0.03 for the exercise group, and 0.05 for the combined diet and exercise group). Minor changes were observed for the other adipokines. Neither baseline concentrations of nor changes in adiponectin and plasminogen activator inhibitor-1 were significantly correlated to the other adipokines, whereas concentrations of and changes in the other adipokines were significantly correlated. CONCLUSION: Diet intervention had a significant positive effect on adiponectin concentrations, which is largely explained by a reduction in fat mass.
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| 31. |
- Sloth Andersen, Ebbe, et al.
(författare)
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The tmRDB and SRPDB resources.
- 2006
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 34:Database issue
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Tidskriftsartikel (refereegranskat)abstract
- Maintained at the University of Texas Health Science Center at Tyler, Texas, the tmRNA database (tmRDB) is accessible at the URL http://psyche.uthct.edu/dbs/tmRDB/tmRDB.html with mirror sites located at Auburn University, Auburn, Alabama (http://www.ag.auburn.edu/mirror/tmRDB/) and the Royal Veterinary and Agricultural University, Denmark (http://tmrdb.kvl.dk/). The signal recognition particle database (SRPDB) at http://psyche.uthct.edu/dbs/SRPDB/SRPDB.html is mirrored at http://srpdb.kvl.dk/ and the University of Goteborg (http://bio.lundberg.gu.se/dbs/SRPDB/SRPDB.html). The databases assist in investigations of the tmRNP (a ribonucleoprotein complex which liberates stalled bacterial ribosomes) and the SRP (a particle which recognizes signal sequences and directs secretory proteins to cell membranes). The curated tmRNA and SRP RNA alignments consider base pairs supported by comparative sequence analysis. Also shown are alignments of the tmRNA-associated proteins SmpB, ribosomal protein S1, alanyl-tRNA synthetase and Elongation Factor Tu, as well as the SRP proteins SRP9, SRP14, SRP19, SRP21, SRP54 (Ffh), SRP68, SRP72, cpSRP43, Flhf, SRP receptor (alpha) and SRP receptor (beta). All alignments can be easily examined using a new exploratory browser. The databases provide links to high-resolution structures and serve as depositories for structures obtained by molecular modeling.
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| 32. |
- Tidemand-Lichtenberg, Peter, et al.
(författare)
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Nonlinear cavity dumping of a high finesse frequency mixing module
- 2007
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Ingår i: Optics Express. - 1094-4087. ; 15:15, s. 9799-9803
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Tidskriftsartikel (refereegranskat)abstract
- We present a novel generic approach for pulsed light generation in the visible spectrum. We demonstrate how the circulating field of a high finesse laser can be efficiently cavity dumped through sum- frequency mixing with externally injected high peak power single pass pulses. Periodically poled KTP is used as the nonlinear medium to minimize the peak power requirement of the injected beam. The experimental setup consists of a high finesse 1342 nm Nd:YVO4 laser cavity and a passively Q-switched Nd:YAG laser. Yellow pulses at 593 nm are generated.
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| 33. |
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| 34. |
- Wejse, Christian, et al.
(författare)
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Serum 25-hydroxyvitamin D in a West African population of tuberculosis patients and unmatched healthy controls
- 2007
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Ingår i: American Journal of Clinical Nutrition. - 1938-3207. ; 86:5, s. 1376-1383
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known regarding vitamin D deficiency (VDD) in African populations and in tuberculosis (TB) patients. VDD has been shown to be associated with TB. Objective: We aimed to compare the degree of vitamin D insufficiency (VDI) and VDD in TB patients and healthy adult controls in a West African population. Design: An unmatched case-control study was performed at a Demographic Surveillance Site in Guinea-Bissau. Serum 25-hydroxyvitamin D-3 [25(OH)D-3] concentrations were measured in 362 TB patients and in 494 controls. Results: Hypovitammosis D [25(OH)D-3 <= 75 nmol/L] was more common in TB patients, but VDD [25(OH)D-3 <= 50 nmol/L] was more common and more severe in controls. We observed hypovitaminosis D in 467o (167/362) of the TB patients and in 39% (193/494) of the controls: the relative risk (RR) of hypovitaminosis D was 1.18 (95% Cl: 1.01. 1.38). VDD was observed in 8.5% (31/362) of the TB patients and in 13.2% (65/494) of the controls. The RR was 0.65 (95% Cl: 0.43,0.98), mainly because severe VDD [25(OH)D-3 <= 25 nmol/L] was observed in only I of 362 TB patients (0.2%) and in 24 of 494 controls (4.9%). After adjustment for background factors, hypovitaminosis D was not more frequent in TB patients than in healthy controls, but the mean serum 25(OH)D3 concentration remained lower. Conclusions: Hypovitammosis D was highly prevalent in TB patients and in healthy controls living at 12 degrees N; severe VDD was rare in TB patients. The finding indicates that the serum 25(OH)D3 concentration is associated with TB infection, but whether this role is a symptom or is causal was not established.
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| 35. |
- Wejse, Christian, et al.
(författare)
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Vitamin D as Supplementary Treatment for Tuberculosis A Double-blind, Randomized, Placebo-controlled Trial
- 2009
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 179:9, s. 843-850
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Tidskriftsartikel (refereegranskat)abstract
- Rationale Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis. Objectives: To test whether vitamin D supplementation of patients with tuberculosis (TB) improved clinical outcome and reduced mortality. Methods: We conducted a randomized, double-blind, place-bocontrolled trial in TB clinics at a demographic surveillance site in Guinea-Bissau. We included 365 adult patients with TB starting antituberculosis treatment; 281 completed the 12-month follow-up. The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment. Measurements and Main Results: The primary outcome was reduction in a clinical severity score (TBscore) for all patients with pulmonary TB. The secondary outcome was 12-month mortality. No serious adverse effects were reported; mild hypercalcemia was rare and present in both arms. Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo. Overall mortality was 15% (54 of 365) at I year of follow-up and similar in both arms (30 of 187 for vitamin D treated and 24 of 178 for placebo; relative risk, 1.19 [0.58-1.95]). HIV infection was seen in 36% (131 of 359): 21% (76 of 359) HIV-1, 10% (36 of 359) HIV-2, and 5% (19 of 357) HIV-1+2. Conclusions: Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB; it is possible that the dose used was insufficient. Clinical trial registered with www.controlled-trials.com/isrctn (ISRCTN35212132).
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| 36. |
- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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