| 1. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 2. |
- Bauer, Michael, et al.
(författare)
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Association between solar insolation and a history of suicide attempts in bipolar I disorder.
- 2019
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Ingår i: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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| 3. |
- Elbert, Philipp, et al.
(författare)
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Engine On/Off Control for the Energy Management of a Serial Hybrid Electric Bus via Convex Optimization
- 2014
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Ingår i: IEEE Transactions on Vehicular Technology. - 0018-9545 .- 1939-9359. ; 63:8, s. 3549-3559
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Tidskriftsartikel (refereegranskat)abstract
- Convex optimization has recently been suggested for solving the optimal energy management problem of hybrid electric vehicles. Compared to dynamic programming, this approach can significantly reduce the computational time, but the price to pay are additional model approximations and heuristics for discrete decision variables such as engine on/off control. In this paper, the globally optimal engine on/off conditions are derived analytically. It is demonstrated that the optimal engine on/off strategy is to switch the engine on if and only if the requested power exceeds a certain non-constant threshold. By iteratively computing the threshold and the power split using convex optimization, the optimal solution to the energy management problem is found. The effectiveness of the presented approach is demonstrated in two sizing case studies. The first case study deals with high energy capacity batteries, while the second case study deals with supercapacitors that have much lower energy capacity. In both cases, the proposed algorithm yields optimal results much faster than the dynamic programming algorithm.
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| 4. |
- Heck, Philipp R., et al.
(författare)
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Unusual sources of fossil micrometeorites deduced from relict chromite in the small size fraction in ~467 Ma old limestone
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Ingår i: Meteoritics and Planetary Science. - 1086-9379.
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Tidskriftsartikel (refereegranskat)abstract
- Extraterrestrial chrome spinel and chromite extracted from the sedimentary rock record are relicts from coarse micrometeorites and rarely meteorites. They are studied to reconstruct the paleoflux of meteorites to the Earth and the collisional history of the asteroid belt. Minor element concentrations of Ti and V, and oxygen isotopic compositions of these relict minerals were used to classify the meteorite type they stem from, and thus to determine the relative meteorite group abundances through time. While coarse sediment-dispersed extraterrestrial chrome-spinel (SEC) grains from ordinary chondrites dominate through the studied time windows in the Phanerozoic, there are exceptions: We have shown that ~467 Ma ago, 1 Ma before the breakup of the L chondrite parent body (LCPB), more than half of the largest (>63 μm diameter) grains were achondritic and originated from differentiated asteroids in contrast to ordinary chondrites which dominated the meteorite flux throughout most of the past 500 Ma. Here, we present a new data set of oxygen isotopic compositions and elemental compositions of 136 grains of a smaller size fraction (32–63 μm) in ~467 Ma old pre-LCPB limestone from the Lynna River section in western Russia, that was previously studied by elemental analysis. Our study constitutes the most comprehensive oxygen isotopic data set of sediment-dispersed extraterrestrial chrome spinel to date. We also introduce a Raman spectroscopy-based method to identify SEC grains and distinguish them from terrestrial chrome spinel with ~97% reliability. We calibrated the Raman method with the established approach using titanium and vanadium concentrations and oxygen isotopic compositions. We find that ordinary chondrites are approximately three times more abundant in the 32–63 μm fraction than achondrites. While abundances of achondrites compared to ordinary chondrites are lower in the 32–63 μm size fraction than in the >63 μm one, achondrites are approximately three times more abundant in the 32–62 μm fraction than they are in the present flux. We find that the sources of SEC grains vary for different grain sizes, mainly as a result of parent body thermal metamorphism. We conclude that the meteorite flux composition ~467 Ma ago ~1 Ma before the breakup of the LCPB was fundamentally different from today and from other time windows studied in the Phanerozoic, but that in contrast to the large size fraction ordinary chondrites dominated the flux in the small size fraction. The high abundance of ordinary chondrites in the studied samples is consistent with the findings based on coarse extraterrestrial chrome-spinel from other time windows.
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| 5. |
- Kessing, Lars Vedel, et al.
(författare)
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DSM-5 and ICD-11 criteria for bipolar disorder: Implications for the prevalence of bipolar disorder and validity of the diagnosis - A narrative review from the ECNP bipolar disorders network.
- 2021
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Ingår i: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. - : Elsevier BV. - 1873-7862. ; 47, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- This narrative review summarizes and discusses the implications of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and the upcoming International Classification of Diseases (ICD)-11 classification systems on the prevalence of bipolar disorder and on the validity of the DSM-5 diagnosis of bipolar disorder according to the Robin and Guze criteria of diagnostic validity. Here we review and discuss current data on the prevalence of bipolar disorder diagnosed according to DSM-5 versus DSM-IV, and data on characteristics of bipolar disorder in the two diagnostic systems in relation to extended Robin and Guze criteria: 1) clinical presentation, 2) associations with para-clinical data such as brain imaging and blood-based biomarkers, 3) delimitation from other disorders, 4) associations with family history / genetics, 5) prognosis and long-term follow-up, and 6) treatment effects. The review highlights that few studies have investigated consequences for the prevalence of the diagnosis of bipolar disorder and for the validity of the diagnosis. Findings from these studies suggest a substantial decrease in the point prevalence of a diagnosis of bipolar with DSM-5 compared with DSM-IV, ranging from 30-50%, but a smaller decrease in the prevalence during lifetime, corresponding to a 6% reduction. It is concluded that it is likely that the use of DSM-5 and ICD-11 will result in diagnostic delay and delayed early intervention in bipolar disorder. Finally, we recommend areas for future research.
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| 6. |
- Müller Bicca, Marcos, et al.
(författare)
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Permian-Early Triassic tectonics and stratigraphy of the Karoo Supergroup in northwestern Mozambique
- 2017
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Ingår i: Journal of African Earth Sciences. - : Elsevier. - 1464-343X .- 1879-1956. ; 130, s. 8-27
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Tidskriftsartikel (refereegranskat)abstract
- The Gondwana continent was the base of great basin inception, sedimentation and magmatism throughout the Cambrian to Middle Jurassic periods. The northwestern Mozambique igneous and metamorphic basement assemblages host the NW-trending Moatize Minjova Basin, which has great economic potential for coal and gas mining. This rift basin was activated by an S-SW stress field during the Early Permian period, as constrained by regional and field scale structural data. Tectonically induced subsidence in the basin, from the reactivation of NW-SE and NNE-SSW regional structures is well recorded by faults, folds and synsedimentary fractures within the Early Late Permian Moatize Formation. NW-SE, N-S and NE-SW field structures consist of post-Karoo reactivation patterns related to a NNE-SSW extension produced by the Pangea breakup and early inception stages of the Great East African Rift System. The Early Late Permian sequences of the Moatize-Minjova Basin are composed of fluvial meandering, coal-bearing beds of the Moatize Formation, which comprises mostly floodplain, crevasse splay and fluvial channel lithofacies associations, deposited in a cyclic pattern. This sequence was overlapped by a multiple-story, braided fluvial plain sequence of the Matinde Formation (Late Permian – Early Triassic). Lithofacies associations in the Matinde Formation and its internal relationships suggest deposition of poorly channelized braided alluvial plain in which downstream and probably lateral accretion macroforms alternate with gravity flow deposits. NW paleoflow measurements suggest that Permian fluvial headwaters were located somewhere southeast of the study area, possibly between the African and Antarctic Precambrian highlands.
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| 7. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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