| 1. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
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| 3. |
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| 4. |
- Weigelt, G., et al.
(author)
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VLTI-MATISSE chromatic aperture-synthesis imaging of eta Carinae's stellar wind across the Br alpha line Periastron passage observations in February 2020
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 652
-
Journal article (peer-reviewed)abstract
- Context. Eta Carinae is a highly eccentric, massive binary system (semimajor axis similar to 15.5 au) with powerful stellar winds and a phase-dependent wind-wind collision (WWC) zone. The primary star, eta Car A, is a luminous blue variable (LBV); the secondary, eta Car B, is a Wolf-Rayet or O star with a faster but less dense wind. Aperture-synthesis imaging allows us to study the mass loss from the enigmatic LBV eta Car. Understanding LBVs is a crucial step toward improving our knowledge about massive stars and their evolution. Aims. Our aim is to study the intensity distribution and kinematics of eta Car's WWC zone. Methods. Using the VLTI-MATISSE mid-infrared interferometry instrument, we perform Br alpha imaging of eta Car's distorted wind. Results. We present the first VLTI-MATISSE aperture-synthesis images of eta Car A's stellar windin several spectral channels distributed across the Br alpha 4.052 mu m line (spectral resolving power R similar to 960). Our observations were performed close to periastron passage in February 2020 (orbital phase similar to 14.0022). The reconstructed iso-velocity images show the dependence of the primary stellar wind on wavelength or line-of-sight (LOS) velocity with a spatial resolution of 6 mas (similar to 14 au). The radius of the faintest outer wind regions is similar to 26 mas (similar to 60 au). At several negative LOS velocities, the primary stellar wind is less extended to the northwest than in other directions. This asymmetry is most likely caused by the WWC. Therefore, we see both the velocity field of the undisturbed primary wind and the WWC cavity. In continuum spectral channels, the primary star wind is more compact than in line channels. A fit of the observed continuum visibilities with the visibilities of a stellar wind CMFGEN model (CMFGEN is an atmosphere code developed to model the spectra of a variety of objects) provides a full width at half maximum fit diameter of the primary stellar wind of 2.84 +/- 0.06 mas (6.54 +/- 0.14 au). We comparethe derived intensity distributions with the CMFGEN stellar wind model and hydrodynamic WWC models.
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| 5. |
- Bearden, IG, et al.
(author)
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Particle production in central Pb+Pb collisions at 158A GeV/c
- 2002
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 66:4
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Journal article (peer-reviewed)abstract
- The NA44 experiment has measured single-particle inclusive spectra for charged pions, kaons, and protons as a function of transverse mass near midrapidity in 158A GeV/c Pb+Pb collisions. From the particle mass dependence of the observed m(T) distributions, we are able to deduce a value of about 120 MeV for the temperature at thermal freeze-out. From the observed ratios of the rapidity densities, we find values of the chemical potentials for light and strange quarks and a chemical freeze-out temperature of approximately 140 MeV.
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| 6. |
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| 7. |
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| 8. |
- Gerkin, RC, et al.
(author)
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The best COVID-19 predictor is recent smell loss: a cross-sectional study
- 2020
-
In: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
-
Journal article (other academic/artistic)abstract
- BackgroundCOVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19.MethodsThis preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery.ResultsBoth C19+ and C19-groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ∼50% of participants and was best predicted by time since illness onset.ConclusionsAs smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4<OR<10), which can be deployed when viral lab tests are impractical or unavailable.
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| 9. |
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| 10. |
- Demichev, Vadim, et al.
(author)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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In: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Journal article (peer-reviewed)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 11. |
- Langerak, A. W., et al.
(author)
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EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations
- 2012
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 26:10, s. 2159-2171
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Research review (peer-reviewed)abstract
- PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
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| 12. |
- Bearden, IG, et al.
(author)
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Deuteron and triton production with high energy sulphur and lead beams
- 2002
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 23:2, s. 237-247
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Journal article (peer-reviewed)abstract
- Proton and deuteron production has been observed in S+S and S+Pb collisions at 200 A-GeV and in Pb+Pb reactions at 158 A-GeV at the CERN SPS accelerator. For Pb+Pb triton production was also measured. The p and d spectra as well as the p and t spectra were observed in similar rapidity ranges and over similar ranges of transverse momenta per nucleon, making it possible to interpret the cross sections of the composite particles in terms of coalescence mechanisms. Volumes of homogeneity were extracted and compared to pion-pair HBT interferometry results. Special attention is given to the dependence on transverse mass, centrality and rapidity.
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| 13. |
- Pervjakova, Natalia, et al.
(author)
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Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
- 2022
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 31:19, s. 3377-3391
-
Journal article (peer-reviewed)abstract
- Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy (GenDIP) Consortium assembled genome-wide association studies (GWAS) of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (p < 5x10-8) with GDM, mapping to/near MTNR1B (p = 4.3x10-54), TCF7L2 (p = 4.0x10-16), CDKAL1 (p = 1.6 × 10-14), CDKN2A-CDKN2B (p = 4.1x10-9) and HKDC1 (p = 2.9x10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D; and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomisation analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Islar, Mine, et al.
(author)
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Diverse values of nature for sustainability
- 2022
-
In: Nature. - 0028-0836 .- 1476-4687. ; 620, s. 813-823
-
Journal article (peer-reviewed)abstract
- Twenty-five years since foundational publications on valuing ecosystem services for human well-being1,2, addressing the global biodiversity crisis3 still implies confronting barriers to incorporating nature’s diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever4. Notwithstanding agreements to incorporate nature’s values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)5 and the UN Sustainable Development Goals6, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature7. Arguably, a ‘values crisis’ underpins the intertwined crises of biodiversity loss and climate change8, pandemic emergence9 and socio-environmental injustices10. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature’s diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions7,11. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.
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| 18. |
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| 19. |
- Andrén Aronsson, Carin, et al.
(author)
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Age at Gluten Introduction and Risk of Celiac Disease.
- 2015
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In: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 135:2, s. 239-245
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Journal article (peer-reviewed)abstract
- The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children.
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| 20. |
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| 21. |
- Beyerlein, Andreas, et al.
(author)
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Intake of Energy and Protein is Associated with Overweight Risk at Age 5.5 Years : Results from the Prospective TEDDY Study
- 2017
-
In: Obesity. - : Wiley. - 1930-7381. ; 25:8, s. 1435-1441
-
Journal article (peer-reviewed)abstract
- Objective: The associations of energy, protein, carbohydrate, and fat intake with weight status up to the age of 5.5 years were prospectively assessed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Methods: Food record data (over 3 days) and BMI measurements between 0.25 and 5.5 years were available from 5,563 children with an increased genetic risk for type 1 diabetes followed from shortly after birth. Odds ratios (ORs) were calculated for overweight and obesity by previous intake of energy, protein, carbohydrate, and fat with adjustment for potential confounders. Results: Having overweight or obesity at the age of 5.5 years was positively associated with mean energy intake in previous age intervals (e.g., adjusted OR [95% CI] for overweight: 1.06 [1.04-1.09] per 100 kcal intake at the age of 4.5-5.0 years) and with protein intake after the age of 3.5 and 4.5 years, respectively (e.g., adjusted OR for overweight: 1.06 [1.03-1.09] per 1% of energy intake at the age of 4.5-5.0 years). The respective associations with carbohydrate and fat intake were less consistent. Conclusions: These findings indicate that energy and protein intake are positively associated with increased risk for overweight in childhood but yield no evidence for potential programming effects of protein intake in infancy.
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| 22. |
- Haghighi, Mona, et al.
(author)
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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
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Journal article (peer-reviewed)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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| 23. |
- Mathas, S, et al.
(author)
-
Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma
- 2006
-
In: Nature Immunology. - : Nature Publishing Group. - 1529-2908 .- 1529-2916. ; 7:2, s. 207-215
-
Journal article (peer-reviewed)abstract
- B cell differentiation is controlled by a complex network of lineage-restricted transcription factors. How perturbations to this network alter B cell fate remains poorly understood. Here we show that classical Hodgkin lymphoma tumor cells, which originate from mature B cells, have lost the B cell phenotype as a result of aberrant expression of transcriptional regulators. The B cell-specific transcription factor program was disrupted by overexpression of the helix-loop-helix proteins ABF-1 and Id2. Both factors antagonized the function of the B cell-determining transcription factor E2A. As a result, expression of genes specific to B cells was lost and expression of genes not normally associated with the B lineage was upregulated. These data demonstrate the plasticity of mature human lymphoid cells and offer an explanation for the unique classical Hodgkin lymphoma phenotype.
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| 24. |
- Mramba, Lazarus K., et al.
(author)
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Detecting potential outliers in longitudinal data with time-dependent covariates
-
In: European Journal of Clinical Nutrition. - 0954-3007.
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Journal article (peer-reviewed)abstract
- Background: Outliers can influence regression model parameters and change the direction of the estimated effect, over-estimating or under-estimating the strength of the association between a response variable and an exposure of interest. Identifying visit-level outliers from longitudinal data with continuous time-dependent covariates is important when the distribution of such variable is highly skewed. Objectives: The primary objective was to identify potential outliers at follow-up visits using interquartile range (IQR) statistic and assess their influence on estimated Cox regression parameters. Methods: Study was motivated by a large TEDDY dietary longitudinal and time-to-event data with a continuous time-varying vitamin B12 intake as the exposure of interest and development of Islet Autoimmunity (IA) as the response variable. An IQR algorithm was applied to the TEDDY dataset to detect potential outliers at each visit. To assess the impact of detected outliers, data were analyzed using the extended time-dependent Cox model with robust sandwich estimator. Partial residual diagnostic plots were examined for highly influential outliers. Results: Extreme vitamin B12 observations that were cases of IA had a stronger influence on the Cox regression model than non-cases. Identified outliers changed the direction of hazard ratios, standard errors, or the strength of association with the risk of developing IA. Conclusion: At the exploratory data analysis stage, the IQR algorithm can be used as a data quality control tool to identify potential outliers at the visit level, which can be further investigated.
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| 25. |
- Niinistö, Sari, et al.
(author)
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Children's erythrocyte fatty acids are associated with the risk of islet autoimmunity
- 2021
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
-
Journal article (peer-reviewed)abstract
- Our aim was to investigate the associations between erythrocyte fatty acids and the risk of islet autoimmunity in children. The Environmental Determinants of Diabetes in the Young Study (TEDDY) is a longitudinal cohort study of children at high genetic risk for type 1 diabetes (n = 8676) born between 2004 and 2010 in the U.S., Finland, Sweden, and Germany. A nested case-control design comprised 398 cases with islet autoimmunity and 1178 sero-negative controls matched for clinical site, family history, and gender. Fatty acids composition was measured in erythrocytes collected at the age of 3, 6, and 12 months and then annually up to 6 years of age. Conditional logistic regression models were adjusted for HLA risk genotype, ancestry, and weight z-score. Higher eicosapentaenoic and docosapentaenoic acid (n - 3 polyunsaturated fatty acids) levels during infancy and conjugated linoleic acid after infancy were associated with a lower risk of islet autoimmunity. Furthermore, higher levels of some even-chain saturated (SFA) and monounsaturated fatty acids (MUFA) were associated with increased risk. Fatty acid status in early life may signal the risk for islet autoimmunity, especially n - 3 fatty acids may be protective, while increased levels of some SFAs and MUFAs may precede islet autoimmunity.
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| 26. |
- Parma, Valentina, et al.
(author)
-
More Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis
- 2020
-
In: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 45:7, s. 609-622
-
Journal article (peer-reviewed)abstract
- Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19–79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (−79.7 ± 28.7, mean ± standard deviation), taste (−69.0 ± 32.6), and chemesthetic (−37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.
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| 27. |
- Pilotto, Francesca, et al.
(author)
-
Meta-analysis of multidecadal biodiversity trends in Europe
- 2020
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
-
Journal article (peer-reviewed)abstract
- Local biodiversity trends over time are likely to be decoupled from global trends, as local processes may compensate or counteract global change. We analyze 161 long-term biological time series (15-91 years) collected across Europe, using a comprehensive dataset comprising ~6,200 marine, freshwater and terrestrial taxa. We test whether (i) local long-term biodiversity trends are consistent among biogeoregions, realms and taxonomic groups, and (ii) changes in biodiversity correlate with regional climate and local conditions. Our results reveal that local trends of abundance, richness and diversity differ among biogeoregions, realms and taxonomic groups, demonstrating that biodiversity changes at local scale are often complex and cannot be easily generalized. However, we find increases in richness and abundance with increasing temperature and naturalness as well as a clear spatial pattern in changes in community composition (i.e. temporal taxonomic turnover) in most biogeoregions of Northern and Eastern Europe. The global biodiversity decline might conceal complex local and group-specific trends. Here the authors report a quantitative synthesis of longterm biodiversity trends across Europe, showing how, despite overall increase in biodiversity metric and stability in abundance, trends differ between regions, ecosystem types, and taxa.
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| 28. |
- Pitchika, Anitha, et al.
(author)
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Associations of Maternal Diabetes During Pregnancy with Overweight in Offspring : Results from the Prospective TEDDY Study
- 2018
-
In: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 26:9, s. 1457-1466
-
Journal article (peer-reviewed)abstract
- Objective: This study aimed to determine the relationship between different forms of, and potential pathways between, maternal diabetes and childhood obesity at different ages. Methods: Prospective cohort data from The Environmental Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324 children examined from 0.25 to 6 years of age, were analyzed. Cross-sectional and longitudinal analyses taking into account potential confounders and effect modifiers such as maternal prepregnancy BMI and birth weight z scores were performed. Results: Offspring of mothers with gestational diabetes mellitus (GDM) or type 1 diabetes mellitus (T1DM) showed a higher BMI standard deviation score and increased risk for overweight and obesity at 5.5 years of age than offspring of mothers without diabetes. While these associations could be substantially explained by maternal prepregnancy BMI in offspring of mothers with GDM, significant associations disappeared after adjustment for birth weight z scores in offspring of T1DM mothers. Furthermore, overweight risk became stronger with increasing age in offspring of mothers with diabetes compared with offspring of mothers without diabetes. Conclusions: Maternal diabetes is associated with increased risk of offspring overweight, and the association appears to get stronger as children grow older. Indeed, intrauterine exposure to maternal T1DM may predispose children to later obesity through increased birth weight, while maternal BMI is more important in children exposed to GDM.
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| 29. |
- Silva, M., et al.
(author)
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EMB3Rs: A game-changer tool to support waste heat recovery and reuse
- 2024
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In: Energy Conversion and Management. - : Elsevier BV. - 0196-8904 .- 1879-2227. ; 309
-
Journal article (peer-reviewed)abstract
- At a time when European countries try to cope with escalating energy prices while decarbonizing their economies, waste heat recovery and reuse arises as part of the solution for sustainable energy transitions. The lack of appropriate assessment tools has been pointed out as one of the main barriers to the wider deployment of waste heat recovery projects and as a reason why its potential remains largely untapped. The EMB3Rs platform emerges as an online, open-source, comprehensive and novel tool that provides an integrated assessment of different types of waste heat recovery solutions, (e.g. internal or external) and comprises several analysis dimensions (e.g. physical, geographical, technical, market, and business models). It has been developed together with stakeholders, and tested in a number of representative contexts, covering both industrial and heat network applications. This has demonstrated the enormous potential of the tool in dealing with complex simulations, while delivering accurate results within a significantly lower time-frame than traditional analysis. The EMB3Rs tool removes important barriers such as analysis costs, time and complexity for the user, and aims at supporting a wider investment in waste heat recovery and reuse by providing an integrated estimation of the costs and benefits of such projects. This paper describes the tool and illustrates how it can be applied to help unlock the potential of waste heat recovery across European countries.
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| 30. |
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| 31. |
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| 32. |
- Yang, Jimin, et al.
(author)
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Factors associated with longitudinal food record compliance in a paediatric cohort study.
- 2015
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In: Public Health Nutrition. - 1475-2727. ; :Jun 19, s. 1-10
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Journal article (peer-reviewed)abstract
- Non-compliance with food record submission can induce bias in nutritional epidemiological analysis and make it difficult to draw inference from study findings. We examined the impact of demographic, lifestyle and psychosocial factors on such non-compliance during the first 3 years of participation in a multidisciplinary prospective paediatric study.
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| 33. |
- Andrén Aronsson, Carin, et al.
(author)
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Age at first introduction to complementary foods is associated with sociodemographic factors in children with increased genetic risk of developing type 1 diabetes.
- 2015
-
In: Maternal and Child Nutrition. - : Wiley. - 1740-8709 .- 1740-8695. ; 11:4, s. 803-814
-
Journal article (peer-reviewed)abstract
- Infant's age at introduction to certain complementary foods (CF) has in previous studies been associated with islet autoimmunity, which is an early marker for type 1 diabetes (T1D). Various maternal sociodemographic factors have been found to be associated with early introduction to CF. The aims of this study were to describe early infant feeding and identify sociodemographic factors associated with early introduction to CF in a multinational cohort of infants with an increased genetic risk for T1D. The Environmental Determinants of Diabetes in the Young study is a prospective longitudinal birth cohort study. Infants (N = 6404) screened for T1D high risk human leucocyte antigen-DQ genotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4, DR4/1, DR4/13, DR4/9 and DR3/9) were followed for 2 years at six clinical research centres: three in the United States (Colorado, Georgia/Florida, Washington) and three in Europe (Sweden, Finland, Germany). Age at first introduction to any food was reported at clinical visits every third month from the age of 3 months. Maternal sociodemographic data were self-reported through questionnaires. Age at first introduction to CF was primarily associated with country of residence. Root vegetables and fruits were usually the first CF introduced in Finland and Sweden and cereals were usually the first CF introduced in the United States. Between 15% and 20% of the infants were introduced to solid foods before the age of 4 months. Young maternal age (<25 years), low educational level (<12 years) and smoking during pregnancy were significant predictors of early introduction to CF in this cohort. Infants with a relative with T1D were more likely to be introduced to CF later.
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| 34. |
- Bessani, A., et al.
(author)
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BiobankCloud : A platform for the secure storage, sharing, and processing of large biomedical data sets
- 2016
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In: 1st International Workshop on Data Management and Analytics for Medicine and Healthcare, DMAH 2015 and Workshop on Big-Graphs Online Querying, Big-O(Q) 2015 held in conjunction with 41st International Conference on Very Large Data Bases, VLDB 2015. - Cham : Springer. - 9783319415758 - 9783319415765 ; , s. 89-105
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Conference paper (peer-reviewed)abstract
- Biobanks store and catalog human biological material that is increasingly being digitized using next-generation sequencing (NGS). There is, however, a computational bottleneck, as existing software systems are not scalable and secure enough to store and process the incoming wave of genomic data from NGS machines. In the BiobankCloud project, we are building a Hadoop-based platform for the secure storage, sharing, and parallel processing of genomic data. We extended Hadoop to include support for multi-tenant studies, reduced storage requirements with erasure coding, and added support for extensible and consistent metadata. On top of Hadoop, we built a scalable scientific workflow engine featuring a proper workflow definition language focusing on simple integration and chaining of existing tools, adaptive scheduling on Apache Yarn, and support for iterative dataflows. Our platform also supports the secure sharing of data across different, distributed Hadoop clusters. The software is easily installed and comes with a user-friendly web interface for running, managing, and accessing data sets behind a secure 2-factor authentication. Initial tests have shown that the engine scales well to dozens of nodes. The entire system is open-source and includes pre-defined workflows for popular tasks in biomedical data analysis, such as variant identification, differential transcriptome analysis using RNA-Seq, and analysis of miRNA-Seq and ChIP-Seq data.
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| 38. |
- Croy, Ilona, et al.
(author)
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Human olfactory lateralization requires trigeminal activation
- 2014
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In: Neuroimage. - : Elsevier BV. - 1053-8119. ; 98, s. 289-295
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Journal article (peer-reviewed)abstract
- Rats are able to lateralize odors. This ability involves specialized neurons in the orbitofrontal cortex which are able to process the left, right and bilateral presentation of stimuli. However, it is not clear whether this function is preserved in humans. Humans are in general not able to differentiate whether a selective olfactory stimulant has been applied to the left or right nostril; however exceptions have been reported. Following a screening of 152 individuals with an olfactory lateralization test, we identified 19 who could lateralize odors above chance level. 15 of these lateralizers" underwent olfactory fMRI scanning in a block design and were compared to 15 controls matched for age and sex distribution. As a result both groups showed comparable activation of olfactory eloquent brain areas. However, subjects with lateralization ability had a significantly enhanced activation of cerebral trigeminal processing areas (somatosensory cortex, intraparietal sulcus). In contrast to controls, lateralizers furthermore exhibited no suppression in the area of the trigeminal principal sensory nucleus. An exploratory study with an olfactory change detection paradigm furthermore showed that lateralizers oriented faster towards changes in the olfactory environment. Taken together, our study suggests that the trigeminal system is activated to a higher degree by the odorous stimuli in the group of lateralizers". We conclude that humans are not able to lateralize odors based on the olfactory input alone, but vary in the degree to which the trigeminal system is recruited. (C) 2014 Elsevier Inc All rights reserved.
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| 39. |
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| 40. |
- Flohr, E. L. R., et al.
(author)
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THE FATE OF THE INNER NOSE : ODOR IMAGERY IN PATIENTS WITH OLFACTORY LOSS
- 2014
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In: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 268, s. 118-127
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Journal article (peer-reviewed)abstract
- Cerebral activations during olfactory mental imagery are fairly well investigated in healthy participants but little attention has been given to olfactory imagery in patients with olfactory loss. To explore whether olfactory loss leads to deficits in olfactory imagery, neural responses using functional magnetic resonance imaging (fMRI) and self-report measures were investigated in 16 participants with acquired olfactory loss and 19 control participants. Participants imagined both pleasant and unpleasant odors and their visual representations. Patients reported less vivid olfactory but not visual images than controls. Results from neuroimaging revealed that activation patterns differed between patients and controls. While the control group showed stronger activation in olfactory brain regions for unpleasant compared to pleasant odors, the patient group did not. Also, activation in critical areas for olfactory imagery was correlated with the duration of olfactory dysfunction, indicating that the longer the duration of dysfunction, the more the attentional resources were employed. This indicates that participants with olfactory loss have difficulties to perform olfactory imagery in the conventional way. Regular exposure to olfactory information may be necessary to maintain an olfactory imagery capacity.
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| 41. |
- Gerkin, Richard C., et al.
(author)
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Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms
- 2021
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In: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 46
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Journal article (peer-reviewed)abstract
- In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0–100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19−; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19− groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: −82.5 ± 27.2 points; C19−: −59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0–10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
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| 42. |
- Hakola, Leena, et al.
(author)
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Intake of B vitamins and the risk of developing islet autoimmunity and type 1 diabetes in the TEDDY study
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In: European Journal of Nutrition. - 1436-6215.
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Journal article (peer-reviewed)abstract
- PURPOSE: The aim was to study the association between dietary intake of B vitamins in childhood and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D) by the age of 10 years.METHODS: We followed 8500 T1D-susceptible children born in the U.S., Finland, Sweden, and Germany in 2004 -2010 from the Environmental Determinants of Diabetes in the Young (TEDDY) study, which is a prospective observational birth cohort. Dietary intake of seven B vitamins was calculated from foods and dietary supplements based on 24-h recall at 3 months and 3-day food records collected regularly from 6 months to 10 years of age. Cox proportional hazard models were adjusted for energy, HLA-genotype, first-degree relative with T1D, sex, and country.RESULTS: A total of 778 (9.2) children developed at least one autoantibody (any IA), and 335 (3.9%) developed multiple autoantibodies. 280 (3.3%) children had IAA and 319 (3.8%) GADA as the first autoantibody. 344 (44%) children with IA progressed to T1D. We observed that higher intake of niacin was associated with a decreased risk of developing multiple autoantibodies (HR 0.95; 95% CI 0.92, 0.98) per 1 mg/1000 kcal in niacin intake. Higher intake of pyridoxine (HR 0.66; 95% CI 0.46, 0.96) and vitamin B12 (HR 0.87; 95% CI 0.77, 0.97) was associated with a decreased risk of IAA-first autoimmunity. Higher intake of riboflavin (HR 1.38; 95% CI 1.05, 1.80) was associated with an increased risk of GADA-first autoimmunity. There were no associations between any of the B vitamins and the outcomes "any IA" and progression from IA to T1D. CONCLUSION: In this multinational, prospective birth cohort of children with genetic susceptibility to T1D, we observed some direct and inverse associations between different B vitamins and risk of IA.
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| 44. |
- Hummel, Sandra, et al.
(author)
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Associations of breastfeeding with childhood autoimmunity, allergies, and overweight : The Environmental Determinants of Diabetes in the Young (TEDDY) study
- 2021
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In: The American journal of clinical nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 114:1, s. 134-142
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Journal article (peer-reviewed)abstract
- BACKGROUND: Breastfeeding has beneficial effects on numerous health outcomes.OBJECTIVES: We investigated whether breastfeeding duration is associated with the development of early childhood autoimmunity, allergies, or obesity in a multinational prospective birth cohort.METHODS: Infants with genetic susceptibility for type 1 diabetes (n = 8676) were followed for the development of autoantibodies to islet autoantigens or transglutaminase, allergies, and for anthropometric measurements to a median age of 8.3 y (IQR: 2.8-10.2 y). Information on breastfeeding was collected at 3 mo of age and prospectively thereafter. A propensity score for longer breastfeeding was calculated from the variables that were likely to influence any or exclusive breastfeeding. The risks of developing autoimmunity or allergy were assessed using Cox proportional hazards models, and the risk of obesity at 5.5 y of age was assessed using logistic regression with adjustment by the propensity score.RESULTS: Breastfeeding duration was not associated with a lower risk of either islet or transglutaminase autoimmunity (any breastfeeding >6 mo, adjusted HR: 1.07; 95% CI: 0.96, 1.19; exclusive breastfeeding >3 mo, adjusted HR: 1.03; 95% CI: 0.92, 1.15). Exclusive breastfeeding >3 mo was associated with a decreased risk of seasonal allergic rhinitis (adjusted HR: 0.70; 95% CI: 0.53, 0.92; P < 0.01). Any breastfeeding >6 mo and exclusive breastfeeding >3 mo were associated with decreased risk of obesity (adjusted OR: 0.62; 95% CI: 0.47, 0.81; P < 0.001; and adjusted OR: 0.68; 95% CI: 0.47, 0.95; P < 0.05, respectively).CONCLUSIONS: Longer breastfeeding was not associated with a lower risk of childhood (islet or transglutaminase) autoimmunity in genetically at-risk children but was associated with decreased risk of seasonal allergic rhinitis and obesity at 5.5 y of age.
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| 45. |
- Hummel, Sandra, et al.
(author)
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First infant formula type and risk of islet autoimmunity in the environmental determinants of diabetes in the young (TEDDY) study
- 2017
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:3, s. 398-404
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Journal article (peer-reviewed)abstract
- OBJECTIVE Studies on the introduction of infant formulas and its effect on the risk of islet autoimmunity and type 1 diabetes (T1D) have yielded inconsistent results. We investigated whether the introduction of formula based on hydrolyzed cow'smilk as the first formula is associated with reduced islet autoimmunity risk in a large prospective cohort. RESEARCH DESIGN AND METHODS The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively monitors 8,676 children at increased genetic risk for T1D. Autoantibodies to insulin, GAD65, and IA2 were measured regularly to define islet autoimmunity. Information on formula feeding was collected by questionnaires at 3 months of age. RESULTS In survival analyses, after adjustment for family history with T1D, HLA genotype, sex, country, delivery mode, breast-feeding 3 months, and seasonality of birth, we observed no significant association with islet autoimmunity in infants who received extensively hydrolyzed compared with nonhydrolyzed cow'smilk-based formula as the first formula during the first 3 months (adjusted hazard ratio 1.38 [95% CI 0.95; 2.01]), and a significantly increased risk for extensively hydrolyzed formula introduced during the first 7 days (adjusted hazard ratio 1.57 [1.04; 2.38]). Using a partially hydrolyzed or other formula as the first formula, or no formula, was not associated with islet autoimmunity risk. CONCLUSIONS These results add to the existing evidence that islet autoimmunity risk is not reduced, and may be increased, by using hydrolyzed compared with nonhydrolyzed cow's milk-based infant formula as the first formula in infants at increased genetic risk for T1D .
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)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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| 50. |
- Mattila, Markus, et al.
(author)
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Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes : the TEDDY study
- 2020
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63:2, s. 278-286
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: We studied the association of plasma ascorbic acid with the risk of developing islet autoimmunity and type 1 diabetes and examined whether SNPs in vitamin C transport genes modify these associations. Furthermore, we aimed to determine whether the SNPs themselves are associated with the risk of islet autoimmunity or type 1 diabetes. Methods: We used a risk set sampled nested case–control design within an ongoing international multicentre observational study: The Environmental Determinants of Diabetes in the Young (TEDDY). The TEDDY study followed children with increased genetic risk from birth to endpoints of islet autoantibodies (350 cases, 974 controls) and type 1 diabetes (102 cases, 282 controls) in six clinical centres. Control participants were matched for family history of type 1 diabetes, clinical centre and sex. Plasma ascorbic acid concentration was measured at ages 6 and 12 months and then annually up to age 6 years. SNPs in vitamin C transport genes were genotyped using the ImmunoChip custom microarray. Comparisons were adjusted for HLA genotypes and for background population stratification. Results: Childhood plasma ascorbic acid (mean ± SD 10.76 ± 3.54 mg/l in controls) was inversely associated with islet autoimmunity risk (adjusted OR 0.96 [95% CI 0.92, 0.99] per +1 mg/l), particularly islet autoimmunity, starting with insulin autoantibodies (OR 0.94 [95% CI 0.88, 0.99]), but not with type 1 diabetes risk (OR 0.93 [95% Cl 0.86, 1.02]). The SLC2A2 rs5400 SNP was associated with increased risk of type 1 diabetes (OR 1.77 [95% CI 1.12, 2.80]), independent of plasma ascorbic acid (OR 0.92 [95% CI 0.84, 1.00]). Conclusions/interpretation: Higher plasma ascorbic acid levels may protect against islet autoimmunity in children genetically at risk for type 1 diabetes. Further studies are warranted to confirm these findings. Data availability: The datasets generated and analysed during the current study will be made available in the NIDDK Central Repository at https://www.niddkrepository.org/studies/teddy.
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