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| 14. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 15. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 16. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 19. |
- Hallett, Lauren M., et al.
(författare)
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Restoration ecology through the lens of
- 2023
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Ingår i: Trends in Ecology & Evolution. - : CELL PRESS. - 0169-5347 .- 1872-8383. ; 38:11, s. 1085-1096
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Forskningsöversikt (refereegranskat)abstract
- Advances in restoration ecology are needed to guide ecological restoration in a variable and changing world. Coexistence theory provides a framework for how variability in environmental conditions and species interactions affects species success. Here, we conceptually link coexistence theory and restoration ecology. First, including low-density growth rates (LDGRs), a classic metric of coexistence, can improve abundance-based restoration goals, because abundances are sensitive to initial treatments and ongoing variability. Second, growth-rate partitioning, developed to identify coexistence mechanisms, can improve restoration practice by informing site selection and indicating necessary interventions (e.g., site amelioration or competitor removal). Finally, coexistence methods can improve restoration assessment, because initial growth rates indicate trajectories, average growth rates measure success, and growth partitioning highlights interventions needed in future.
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| 20. |
- Li, W, et al.
(författare)
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Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL
- 2020
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Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 6:1, s. 63-
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Tidskriftsartikel (refereegranskat)abstract
- Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.
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| 22. |
- Neff, A, et al.
(författare)
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The ESTMJS (European Society of Temporomandibular Joint Surgeons) Consensus and Evidence-Based Recommendations on Management of Condylar Dislocation
- 2021
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:21
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Tidskriftsartikel (refereegranskat)abstract
- Although condylar dislocation is not uncommon, terminology, diagnostics, and treatment concepts vary considerably worldwide. This study aims to present a consensus recommendation based on systematically reviewed literature and approved by the European Society of TMJ Surgeons (ESTMJS). Based on the template of the evidence-based German guideline (register # 007-063) the ESTMJS members voted on 30 draft recommendations regarding terminology, diagnostics, and treatment initially via a blinded modified Delphi procedure. After unblinding, a discussion and voting followed, using a structured consensus process in 2019. An independent moderator documented and evaluated voting results and alterations from the original draft. Although the results of the preliminary voting were very heterogenous and differed significantly from the German S3 guideline (p < 0.0005), a strong consensus was achieved in the final voting on terminology, diagnostics, and treatment. In this voting, multiple alterations, including adding and discarding recommendations, led to 24 final recommendations on assessment and management of TMJ dislocation. To our knowledge, the ESTMJS condylar dislocation recommendations are the first both evidence and consensus-based international recommendations in the field of TMJ surgery. We recommend they form the basis for clinical practice guidelines for the management of dislocations of the mandibular condyle.
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| 23. |
- Sutton, M. A., et al.
(författare)
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Dynamics of ammonia exchange with cut grassland : Strategy and implementation of the GRAMINAE Integrated Experiment
- 2009
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Ingår i: Biogeosciences. - : Copernicus Publications (on behalf of the European Geosciences Union). - 1726-4170 .- 1726-4189. ; 6:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- A major international experiment on ammonia (NH3) biosphere-atmosphere exchange was conducted over intensively managed grassland at Braunschweig, Germany. The experimental strategy was developed to allow an integrated analysis of different features of NH3 exchange including: a) quantification of nearby emissions and advection effects, b) estimation of net NH3 fluxes with the canopy by a range of micrometeorological measurements, c) analysis of the sources and sinks of NH3 within the plant canopy, including soils and bioassay measurements, d) comparison of the effects of grassland management options on NH3 fluxes and e) assessment of the interactions of NH3 fluxes with aerosol exchange processes. Additional technical objectives included the inter-comparison of different estimates of sensible and latent heat fluxes, as well as continuous-gradient and Relaxed Eddy Accumulation (REA) systems for NH3 fluxes. The prior analysis established the spatial and temporal design of the experiment, allowing significant synergy between these objectives. The measurements were made at 7 measurement locations, thereby quantifying horizontal and vertical profiles, and covered three phases: a) tall grass canopy prior to cutting (7 days), b) short grass after cutting (7 days) and c) re-growing sward following fertilization with ammonium nitrate (10 days). The sequential management treatments allowed comparison of sources-sinks, advection and aerosol interactions under a wide range of NH3 fluxes. This paper describes the experimental strategy and reports the grassland management history, soils, environmental conditions and air chemistry during the experiment, finally summarizing how the results are coordinated in the accompanying series of papers.
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| 25. |
- Weiss-Lehman, Christopher P., et al.
(författare)
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Disentangling key species interactions in diverse and heterogeneous communities : A Bayesian sparse modelling approach
- 2022
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:5, s. 1263-1276
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Tidskriftsartikel (refereegranskat)abstract
- Modelling species interactions in diverse communities traditionally requires a prohibitively large number of species-interaction coefficients, especially when considering environmental dependence of parameters. We implemented Bayesian variable selection via sparsity-inducing priors on non-linear species abundance models to determine which species interactions should be retained and which can be represented as an average heterospecific interaction term, reducing the number of model parameters. We evaluated model performance using simulated communities, computing out-of-sample predictive accuracy and parameter recovery across different input sample sizes. We applied our method to a diverse empirical community, allowing us to disentangle the direct role of environmental gradients on species intrinsic growth rates from indirect effects via competitive interactions. We also identified a few neighbouring species from the diverse community that had non-generic interactions with our focal species. This sparse modelling approach facilitates exploration of species interactions in diverse communities while maintaining a manageable number of parameters.
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| 27. |
- Harris, M., et al.
(författare)
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Chronostratigraphic correlation of the volcanic 1.21 Ga Barby and Haiber Flats Formations in the Sinclair Supergroup of Namibia
- 2021
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Ingår i: Journal of African Earth Sciences. - : Elsevier BV. - 1464-343X. ; 178
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Tidskriftsartikel (refereegranskat)abstract
- This work investigates Mesoproterozoic volcanic rocks of the Haiber Flats, Barby, Welverdiend and Kairab Formations, and associated intrusive rocks in the Konkiep Terrane. Various correlations have been made in the past and recent dating work yields contrasting ages. U–Pb dating of zircons is applied in combination with Sm–Nd and Lu–Hf isotopes to determine the age, assess correlation and ascertain the much-debated tectonic setting. Ion probe U–Pb zircon dating yields ages of 1218 ± 5 Ma, 1212 ± 4 Ma and 1212 ± 5 Ma (all errors 2σ) for three samples of the Haiber Flats Formation and 1219 ± 13 Ma, 1215 ± 19 Ma for the Barby Formation. The ages obtained for the Barby Formation agree with the 1217 ± 2 Ma and 1214 ± 5 Ma ages reported from previous investigations. Rocks mapped as the supposedly older Kairab rhyolite and felsic tuff gave younger ages of 1220 ± 4 Ma and 1222 ± 10 Ma, respectively, which are coeval with the Barby and Haiber Flats Formations. Two Gorab Gabbro samples, previously mapped as Kairab Formation, yield ages of 1341 ± 8 Ma and 1336 ± 8 Ma. These older ages are within error of two Welverdiend Formation samples which gave ages of 1344 ± 6 Ma and 1337 ± 9 Ma, and the formation was previously dated in the type area at 1327 ± 10 Ma. These ages confirm the reassignment of rocks originally mapped as tholeiitic Barby Formation into the Welverdiend Formation, north of a newly identified stratigraphic hiatus corresponding to the geophysically defined Wêreldend Lineament. Sm–Nd and Lu–Hf isotopic signatures for the Barby, Haiber Flats and coeval Kairab samples indicate that they are co-magmatic and derived from partly depleted mantle contaminated by older crust. TDM model ages of these samples range from 2.5 to 1.5 Ga with a major 2.2 to 1.8 Ga group. This suggests that the older crustal component was Paleoproterozoic but included some Archean material. The Welverdiend Formation and Gorab Gabbros show similarity in age, Sm–Nd and Lu–Hf characteristics and were probably derived from partially depleted mantle, or from a well-homogenised mixture of depleted mantle and older crust. REE diagrams indicate enrichment in LREE (La–Gd) and a flat HREE pattern (Tb to Lu). On spidergrams, most samples are characterised by negative Nb–Ta anomalies and positive K and Pb anomalies which indicate a subduction-related setting (with positive Sr anomaly) or a reworked crustal origin. The similarity in ages, isotopic signatures and geochemistry confirms the correlation of the Barby and Haiber Flats Formation. © 2021 Elsevier Ltd
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| 28. |
- Lehman, Joel, et al.
(författare)
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The Surprising Creativity of Digital Evolution: A Collection of Anecdotes from the Evolutionary Computation and Artificial Life Research Communities
- 2020
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Ingår i: Artificial Life. - : MIT Press - Journals. - 1530-9185 .- 1064-5462. ; 26:2, s. 274-306
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Tidskriftsartikel (refereegranskat)abstract
- Evolution provides a creative fount of complex and subtle adaptations that often surprise the scientists who discover them. However, the creativity of evolution is not limited to the natural world: Artificial organisms evolving in computational environments have also elicited surprise and wonder from the researchers studying them. The process of evolution is an algorithmic process that transcends the substrate in which it occurs. Indeed, many researchers in the field of digital evolution can provide examples of how their evolving algorithms and organisms have creatively subverted their expectations or intentions, exposed unrecognized bugs in their code, produced unexpectedly adaptations, or engaged in behaviors and outcomes, uncannily convergent with ones found in nature. Such stories routinely reveal surprise and creativity by evolution in these digital worlds, but they rarely fit into the standard scientific narrative. Instead they are often treated as mere obstacles to be overcome, rather than results that warrant study in their own right. Bugs are fixed, experiments are refocused, and one-off surprises are collapsed into a single data point. The stories themselves are traded among researchers through oral tradition, but that mode of information transmission is inefficient and prone to error and outright loss. Moreover, the fact that these stories tend to be shared only among practitioners means that many natural scientists do not realize how interesting and lifelike digital organisms are and how natural their evolution can be. To our knowledge, no collection of such anecdotes has been published before. This article is the crowd-sourced product of researchers in the fields of artificial life and evolutionary computation who have provided first-hand accounts of such cases. It thus serves as a written, fact-checked collection of scientifically important and even entertaining stories. In doing so we also present here substantial evidence that the existence and importance of evolutionary surprises extends beyond the natural world, and may indeed be a universal property of all complex evolving systems.
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| 33. |
- Dainotti, Maria Giovanna, et al.
(författare)
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Inferring the Redshift of More than 150 GRBs with a Machine-learning Ensemble Model
- 2024
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Ingår i: Astrophysical Journal, Supplement Series. - 0067-0049. ; 271:1
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-ray bursts (GRBs), due to their high luminosities, are detected up to a redshift of 10, and thus have the potential to be vital cosmological probes of early processes in the Universe. Fulfilling this potential requires a large sample of GRBs with known redshifts, but due to observational limitations, only 11% have known redshifts (z). There have been numerous attempts to estimate redshifts via correlation studies, most of which have led to inaccurate predictions. To overcome this, we estimated GRB redshift via an ensemble-supervised machine-learning (ML) model that uses X-ray afterglows of long-duration GRBs observed by the Neil Gehrels Swift Observatory. The estimated redshifts are strongly correlated (a Pearson coefficient of 0.93) and have an rms error, namely, the square root of the average squared error <Δz2>, of 0.46 with the observed redshifts showing the reliability of this method. The addition of GRB afterglow parameters improves the predictions considerably by 63% compared to previous results in peer-reviewed literature. Finally, we use our ML model to infer the redshifts of 154 GRBs, which increase the known redshifts of long GRBs with plateaus by 94%, a significant milestone for enhancing GRB population studies that require large samples with redshift.
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| 36. |
- Escaned, Javier, et al.
(författare)
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Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes
- 2018
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Ingår i: JACC. - : Elsevier. - 1936-8798 .- 1876-7605. ; 11:15, s. 1437-1449
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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| 37. |
- Foeldvari, Ivan, et al.
(författare)
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Gender differences in juvenile systemic sclerosis patients : Results from the international juvenile scleroderma inception cohort
- 2023
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Ingår i: Journal of Scleroderma and Related Disorders. - : Sage Publications. - 2397-1983 .- 2397-1991. ; 8:2, s. 120-130
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis.Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months.Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement.Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.
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| 38. |
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| 39. |
- Kennedy, J., et al.
(författare)
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Learning and reusing dialog for repeated interactions with a situated social agent
- 2017
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Ingår i: 17th International Conference on Intelligent Virtual Agents, IVA 2017. - Cham : Springer. - 9783319674001 ; , s. 192-204
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Konferensbidrag (refereegranskat)abstract
- Content authoring for conversations is a limiting factor in creating verbal interactions with intelligent virtual agents. Building on techniques utilizing semi-situated learning in an incremental crowdworking pipeline, this paper introduces an embodied agent that self-authors its own dialog for social chat. In particular, the autonomous use of crowdworkers is supplemented with a generalization method that borrows and assesses the validity of dialog across conversational states. We argue that the approach offers a community-focused tailoring of dialog responses that is not available in approaches that rely solely on statistical methods across big data. We demonstrate the advantages that this can bring to interactions through data collected from 486 conversations between a situated social agent and 22 users during a 3 week long evaluation period.
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| 40. |
- Lehman, S E, et al.
(författare)
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Biocompliant Composite Au/pHEMA Plasmonic Scaffolds for 3D Cell Culture and Noninvasive Sensing of Cellular Metabolites
- 2020
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Ingår i: Advanced Healthcare Materials. - : Wiley-VCH Verlag. - 2192-2640 .- 2192-2659.
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Tidskriftsartikel (refereegranskat)abstract
- The field of 3D printing is an area of active research, with a substantial focus given to the design and construction of customized tools for applications in technology. There exists a particular need in these developing areas of opportunity for new multi-functional soft materials that are biologically compatible for the growth and directed culturing of cells. Herein, a composite material consisting of gold nanoparticles with useful plasmonic properties embedded within a highly hydrophilic poly-2-hydroxyethylmethacrylate matrix is described and characterized. This composite material serves dual functions as both host framework scaffold for cell lines such as pre-osteoblasts as well as a plasmonic biosensor for in situ measurements of living cells. The plasmonic properties of this system are characterized as a function of the material properties and related to compositional features of the material through a proposed light-directed mechanism. This chemistry provides a tunable, 3D printable plasmonic composite material of encapsulated gold nanoparticles in a biologically-compliant, acrylate-based hydrogel matrix. Surface-enhanced Raman scattering studies of 3D-microcultures supported by the scaffolds are carried out and the strong influence of perm-selective molecular diffusion in its analytical responses is established. Most notably, specific, largely hydrophilic, cellular metabolites are detected within the supported live cultures.
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| 41. |
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| 42. |
- Lum, P Y, et al.
(författare)
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Extracting insights from the shape of complex data using topology
- 2013
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- This paper applies topological methods to study complex high dimensional data sets by extracting shapes (patterns) and obtaining insights about them. Our method combines the best features of existing standard methodologies such as principal component and cluster analyses to provide a geometric representation of complex data sets. Through this hybrid method, we often find subgroups in data sets that traditional methodologies fail to find. Our method also permits the analysis of individual data sets as well as the analysis of relationships between related data sets. We illustrate the use of our method by applying it to three very different kinds of data, namely gene expression from breast tumors, voting data from the United States House of Representatives and player performance data from the NBA, in each case finding stratifications of the data which are more refined than those produced by standard methods.
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| 43. |
- Lustenhouwer, Nicky, et al.
(författare)
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Experimental evolution of dispersal : Unifying theory, experiments and natural systems
- 2023
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Ingår i: Journal of Animal Ecology. - : John Wiley & Sons. - 0021-8790 .- 1365-2656. ; 92:6, s. 1113-1123
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Tidskriftsartikel (refereegranskat)abstract
- Dispersal is a central life history trait that affects the ecological and evolutionary dynamics of populations and communities. The recent use of experimental evolution for the study of dispersal is a promising avenue for demonstrating valuable proofs of concept, bringing insight into alternative dispersal strategies and trade-offs, and testing the repeatability of evolutionary outcomes. Practical constraints restrict experimental evolution studies of dispersal to a set of typically small, short-lived organisms reared in artificial laboratory conditions. Here, we argue that despite these restrictions, inferences from these studies can reinforce links between theoretical predictions and empirical observations and advance our understanding of the eco-evolutionary consequences of dispersal. We illustrate how applying an integrative framework of theory, experimental evolution and natural systems can improve our understanding of dispersal evolution under more complex and realistic biological scenarios, such as the role of biotic interactions and complex dispersal syndromes.
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| 46. |
- Niewold, T, et al.
(författare)
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SKIN PROTEOME INVESTIGATION IN CUTANEOUS LUPUS ERYTHEMATOSUS (CLE) REVEALS NOVEL UNIQUE DISEASE PATHWAYS
- 2020
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 335-335
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Cutaneous lupus erythematosus (CLE) is an autoimmune disease. It can be limited to the skin or be one of manifestations of systemic LE (SLE). The typical histopathologic pattern in CLE/SLE is interface dermatitis, which can also be observed in dermatomyositis (DM). While LE may affect any organ system, DM most commonly affect muscles and skin.Objectives:The aim of this study was to investigate the whole proteome of skin inflammatory foci in the cohort of CLE and DM patients in a comparatory, hypothesis-free manner and identify disease-unique molecular mechanisms.Methods:CLE (n=6), DM (n=5) patients and controls (n=6) were recruited at diagnosis or disease exacerbation. Skin biopsies were acquired, examined by a pathologist and selected inflammatory foci were laser micro-dissected. The total protein content was analyzed by mass-spectrometry, further analysis was performed by string-db.org platform. Certain proteomic findings were confirmed by immunohistochemistry (IHC).Results:CLE infiltrates were more protein rich in comparison to DM lesions. There ratio of 5x upregulated proteins in LE/DM was 60, while ratio for DM/LE was 13. Our results confirmed high abundance of (IFN)-regulated proteins both in CLE and DM, including: IFIT, MX and OAS families. Proteins expressed differentially in CLE covered complement proteins (C1b), including membrane attack complex (MAC) (C5, C6, C7, C8A and B) and complement regulators (CFHR1, CFHR2, CFHR5), as well as regulators of coagulation: thrombospondin 2 (THBS2), thrombin (F2), fibrinogen (F12) and annexin A3 (ANXA3). Importantly, we identified interleukin (IL) -16 as the only detectable and highly abundant cytokine in the CLE lesions and confirmed this finding by IHC.Conclusion:ConclusionsOur data confirm evidence on IFN-regulated processes in CLE/SLE. Importantly, we identified IL-16 as a novel cytokine most strongly upregulated locally in the skin lesions. Moreover, we identified activation of MAC, complement regulating proteins as well as involvement of coagulation/fibrinolysis system. The study brings information on novel pathways involved in the inflammatory foci of the skin lesions in CLE patients. Our findings are of interest in further search of new therapeutic targets.Disclosure of Interests: :Timothy Niewold: None declared, Karin Popovic-Silwerfeldt: None declared, Julia Lehman: None declared, Alexander Meves: None declared, Cristine Charlesworth: None declared, Benjamin Madden: None declared, Aliisa Hayry: None declared, Aleksandra Antovic: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Marie Wahren-Herlenius: None declared, Elisabet Svenungsson: None declared, Vilija Oke: None declared
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| 47. |
- Potter, Maggie M., et al.
(författare)
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Autonomous Light Management in Flexible Photoelectrochromic Films Integrating High Performance Silicon Solar Microcells
- 2020
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Ingår i: ACS Applied Energy Materials. - : AMER CHEMICAL SOC. - 2574-0962. ; 3:2, s. 1540-1551
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Tidskriftsartikel (refereegranskat)abstract
- Commercial smart window technologies for dynamic light and heat management in building and automotive environments traditionally rely on electrochromic (EC) materials powered by an external source. This design complicates building-scale installation requirements and substantially increases costs for applications in retrofit construction. Self-powered photoelectrochromic (PEC) windows are an intuitive alternative wherein a photovoltaic (PV) material is used to power the EC device, which modulates the transmission of the incident solar flux. The PV component in this application must be sufficiently transparent and produce enough power to efficiently modulate the EC device transmission. Here, we propose Si solar microcells (mu-cells) that are (i) small enough to be visually transparent to the eye and (ii) thin enough to enable flexible PEC devices. Visual transparency is achieved when Si mu-cells are arranged in high pitch (i.e., low-integration density) form factors while maintaining the advantages of a single-crystalline PV material (i.e., long lifetime and high performance). Additionally, the thin dimensions of these Si mu-cells enable fabrication on flexible substrates to realize flexible PEC devices. The current work demonstrates this concept using WO3 as the EC material and V2O5 as the ion storage layer, where each component is fabricated via sol-gel methods that afford improved prospects for scalability and tunability in comparison to thermal evaporation methods. The EC devices display fast switching times, as low as 8 s, with a modulation in transmission as high as 33%. Integration with two Si mu-cells in series (affording a 1.12 V output) demonstrates an integrated PEC module design with switching times of less than 3 min and a modulation in transmission of 32% with an unprecedented EC:PV areal ratio.
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| 48. |
- Qayed, Muna, et al.
(författare)
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Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia : Implications for Prophylaxis
- 2018
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 24:3, s. 521-528
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Tidskriftsartikel (refereegranskat)abstract
- Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR], .42; 95% confidence interval [CI], .26 to .70; P = .0008), grade II-IV aGVHD (HR, .24; 95% CI, .10 to .56; P = .001), and cGVHD (HR, .32; 95% CI, .19 to .54; P < .001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .36; 95% CI, .20 to .65; P = .0007) and in 2009-2013 (HR, .24; 95% CI. .11 to .53; P = .0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .23; 95% CI, .08 to .65; P = .0056) and 2009-2013 (HR, .16; 95% CI, .04 to .67; P = .0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis.
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| 49. |
- Ren, Hongzu, et al.
(författare)
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Evidence for the involvement of xenobiotic-responsive nuclear receptors in transcriptional effects upon perfluoroalkyl acid exposure in diverse species
- 2009
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Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 27:3-4, s. 266-277
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Tidskriftsartikel (refereegranskat)abstract
- Humans and ecological species have been found to have detectable body burdens of a number of perfluorinated alkyl acids (PFAA) including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). In mouse and rat liver these compounds elicit transcriptional and phenotypic effects similar to peroxisome proliferator chemicals (PPC) that work through the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARα). Recent studies indicate that along with PPARα other nuclear receptors are required for transcriptional changes in the mouse liver after PFOA exposure including the constitutive activated receptor (CAR) and pregnane X receptor (PXR) that regulate xenobiotic metabolizing enzymes (XME). To determine the potential role of CAR/PXR in mediating effects of PFAAs in rat liver, we performed a meta-analysis of transcript profiles from published studies in which rats were exposed to PFOA or PFOS. We compared the profiles to those produced by exposure to prototypical activators of CAR, (phenobarbital (PB)), PXR (pregnenolone 16 alpha-carbonitrile (PCN)), or PPARα (WY-14,643 (WY)). As expected, PFOA and PFOS elicited transcript profile signatures that included many known PPARα target genes. Numerous XME genes were also altered by PFOA and PFOS but not WY. These genes exhibited expression changes shared with PB or PCN. Reexamination of the transcript profiles from the livers of chicken or fish exposed to PFAAs indicated that PPARα, CAR, and PXR orthologs were not activated. Our results indicate that PFAAs under these experimental conditions activate PPARα, CAR, and PXR in rats but not chicken and fish. Lastly, we discuss evidence that human populations with greater CAR expression have lower body burdens of PFAAs.
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