| 1. |
- Vogels, Thomas, et al.
(författare)
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Propagation of Tau Pathology : Integrating Insights From Postmortem and In Vivo Studies
- 2020
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 87:9, s. 808-818
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Forskningsöversikt (refereegranskat)abstract
- Cellular accumulation of aggregated forms of the protein tau is a defining feature of so-called tauopathies such as Alzheimer's disease, progressive supranuclear palsy, and chronic traumatic encephalopathy. A growing body of literature suggests that conformational characteristics of tau filaments, along with regional vulnerability to tau pathology, account for the distinct histopathological morphologies, biochemical composition, and affected cell types seen across these disorders. In this review, we describe and discuss recent evidence from human postmortem and clinical biomarker studies addressing the differential vulnerability of brain areas to tau pathology, its cell-to-cell transmission, and characteristics of the different strains that tau aggregates can adopt. Cellular biosensor assays are increasingly used in human tissue to detect the earliest forms of tau pathology, before overt histopathological lesions (i.e., neurofibrillary tangles) are apparent. Animal models with localized tau expression are used to uncover the mechanisms that influence spreading of tau aggregates. Further, studies of human postmortem-derived tau filaments from different tauopathies injected in rodents have led to striking findings that recapitulate neuropathology-based staging of tau. Furthermore, the recent advent of tau positron emission tomography and novel fluid-based biomarkers render it possible to study the temporal progression of tau pathology in vivo. Ultimately, evidence from these approaches must be integrated to better understand the onset and progression of tau pathology across tauopathies. This will lead to improved methods for the detection and monitoring of disease progression and, hopefully, to the development and refinement of tau-based therapeutics.
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| 2. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 3. |
- Amare, Azmeraw, 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: Research square. - : Research Square Platform LLC.
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder 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=2,367) 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<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 4. |
- 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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| 5. |
- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 6. |
- Anderson, John B, et al.
(författare)
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New Trellis source codes based on linear congruential recursions
- 2003
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Ingår i: Proc., 2003 IEEE International Symposium on Information Theory, Yokohama. - 0780377281 ; , s. 170-170
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Konferensbidrag (refereegranskat)abstract
- We evaluate a new class of rate-distortion codes based on simple linear congruential recursions. Codes are demonstrated for the uniform and Gaussian sources, whose performance exceeds that so far reported in the literature, including that reported for TCQ codes. The results also point to a new correlation relationship that apparently must exist for trellis codes.
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| 7. |
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| 8. |
- Coombes, Brandon J, et al.
(författare)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
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Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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| 9. |
- Eriksson, Tomas, et al.
(författare)
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Good trellis source codes at fractional rates
- 2004
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Ingår i: Proceedings. 2004 IEEE International Symposium on Information Theory. - 0780382803 ; , s. 496-496
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Konferensbidrag (refereegranskat)abstract
- Two new kinds of fractional-rate trellis source codes based on linear congruential recursions are evaluated. Properties of good codes are given. Square error distortion is similar to or better than competing schemes
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| 10. |
- Eriksson, Tomas, et al.
(författare)
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Image coding with the MAP criterion
- 2002
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Ingår i: Proceedings, IEEE 2002 Data Compression Conference. - 0769514774 ; , s. 453-453
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Konferensbidrag (refereegranskat)abstract
- BCJR based source coding of image residuals is investigated. From a trellis representation of the residual, a joint source-channel coding system is formed. Then the BCJR algorithm is applied to find the MAP encoding. MAP and minimized squared error encoding are compared. The novelty of this work is the use of the BCJR algorithm and the MAP criterion in the source coding procedure. The source encoding system described preserves more features than an MSE based encoder. Also, blocking artifacts are reduced.
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| 11. |
- Eriksson, Tomas, et al.
(författare)
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MAP criterion image coding using the BCJR algorithm
- 2002
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Ingår i: Proceedings 2002 IEEE International Symposium on Information Theory (Cat. No.02CH37371). - 0780375017 ; , s. 291-291
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Konferensbidrag (refereegranskat)abstract
- BCJR based source coding of image residuals is explored. From a trellis representation of the residual, a joint source-channel coding system is formed. The use of the BCJR algorithm is possible due to a procedure which transforms the residuals to a representation with independent identically distributed components having unit variance
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| 12. |
- Eriksson, Tomas, et al.
(författare)
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MAP criterion trellis source coding for short data sequences
- 2003
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Ingår i: Proc., IEEE Data Compression Conf., Snowbird, UT. - 0769518966 ; , s. 43-52
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Konferensbidrag (refereegranskat)abstract
- New trellis constructions for compression of short data sequences are presented. Traditional low rate trellis source coding suffers from having a too small a reproduction alphabet. Governed by alphabet-constrained rate-distortion theory we propose a simple method which for a source coding rate of 1 bit per sample allows 2n reconstruction values for a trellis with 2n states. The proposed method is based on the maximum a posteriori probability criterion distortion measure and it employs tailbiting. Simulation results are compared to TCQ-like methods.
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| 13. |
- Eriksson, Tomas, et al.
(författare)
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New methods for trellis source coding at rates above and below one
- 2004
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Ingår i: Proceedings. DCC 2004. Data Compression Conference. - 0769520820 ; , s. 537-537
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Konferensbidrag (refereegranskat)abstract
- This paper presents new methods trellis source coding at rates above and below one. The new schemes have in common a code design based on branch correlation, a large reproducer alphabet, and an encoder based on either the Viterbi algorithm or a tailbiting MAP technique. The methods are easily adapted to various bit rates, but here only the results for R = 2 and R = 1/2 bits per source sample are presented. Results, demonstrated for the memoryless Gaussian source, show similar or better performances than previous methods with similar coding complexity
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| 14. |
- Eriksson, Tomas, et al.
(författare)
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On the block size of trellis quantizers
- 2005
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Ingår i: Proceedings. DCC 2005. Data Compression Conference. - 0769523099 ; , s. 457-457
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Konferensbidrag (refereegranskat)abstract
- Summary form only given. In this paper, we examine the effect of block size on the performance of trellis based quantization. In particular, the Viterbi and tailbiting BCJR algorithms are compared. It is shown that for short blocks of data, the T-BCJR algorithm achieves a superior performance over the Viterbi algorithm (VA). One approach is to use the maximum a posteriori probability (MAP) heuristic and the T-BCJR algorithm. If the MAP-encoder does not produce a tailbiting state sequence, the path is modified for a number of stages at the beginning and end of the block such that it tailbites. The enclosed figure shows MSE as a function of block size and sample position, respectively, for a rate R=1 bit per sample, 32-state trellis quantizer and an IID Gaussian source. The effects of start-up are clearly visible. For the T-BCJR algorithm, the distortion is evenly distributed across the whole block. The performance decrease for short blocks stems from the increase in the number of tailbiting violations for short blocks and the suboptimal modification to ensure tailbiting. The results presented here hold for a large class of trellis constructions, such as TCQ
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| 15. |
- Eriksson, Tomas, et al.
(författare)
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Short-block variable-length trellis quantization
- 2005
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Ingår i: Proc., 2005 IEEE Data Compression Conf., Snowbird. - 1068-0314. - 0769523099 ; , s. 251-260
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Konferensbidrag (refereegranskat)abstract
- We present two methods for variable-rate trellis quantization. Both methods utilize trellis codes based on linear congruential (LC) recursions. LC code trellises have good pseudo-random properties and are easily adapted to serve reconstruction alphabets of different sizes. The first method finds an entropy-constrained code only by optimizing over a scale factor. The scale factor modifies an initial reproducer alphabet in order to skew the associated set of codeword lengths. Using a Lagrangian formulation and the maximum a posteriori (MAP) heuristic, we also develop an entropy-constrained trellis quantizer suitable for short blocks of data. Here the tailbiting BCJR algorithm is used to find the MAP path in the trellis. Simulation results for the Gaussian and Laplacian distributions show that the proposed method is competitive with the best in the literature.
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| 16. |
- Eriksson, Tomas, et al.
(författare)
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Trellis based variable rate residual image coding over noisy channels
- 2006
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Ingår i: Proceedings. DCC 2006. Data Compression Conference. - 1068-0314. - 0769525458 ; , s. 252-261
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Konferensbidrag (refereegranskat)abstract
- We consider the lossy image compression problem and propose a model-residual approach. Polynomial basis images encode the model image and powerful new trellis codes quantize the residual part. A simple bit allocation scheme determines the residual bit rates and a variety of rates are attainable without entropy coding. The trellis structure is also used to form a joint source and channel coding scheme for the residual components. Results are shown for the 0.4-1.6 bits per pixel region. Comparisons are made to several state-of-the-art techniques and show that the proposed scheme is very competitive
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| 17. |
- Giuliani, Federica, et al.
(författare)
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NLITED - New Level of Integrated Techniques for Daylighting Education: preliminary data on the use of an e-learning platform
- 2022
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Ingår i: LUX Europa 2022 : Proceedings of the 14th European Lighting Conference - Proceedings of the 14th European Lighting Conference. - 9788011022693 - 9788011022693 ; , s. 138-146
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Konferensbidrag (refereegranskat)abstract
- Project NLITED – New Level of Integrated Techniques for Daylighting Education - is an educational project for students and professionals. The project's objective is to create and develop an online eLearning platform with 32 eModules dedicated to daylight knowledge. The project also offers e-learners two summer school training where the theoryis put into practice. The platform was launched on January 31, 2022. The paper analyses the participation during the first four months of online activity until May 31, 2022. It discusses which eModules have received the highest participation rate and which have the lowest. These data are compared to the preferences on modules expressed by different panels of experts. The experts expressed their recommendations for specific educational content during workshops conducted in 2021, which led to the definition of the curriculum. Furthermore, participants also fill out an evaluation test on the quality and the usability of the eModule(s) they have taken. This information leads to the amendments of the ePlatform which are in the scope of action for the final year of the NLTED project.
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| 18. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 19. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
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| 20. |
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| 21. |
- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 22. |
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| 23. |
- Jasinski, Michal, et al.
(författare)
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Operation and Planning of Energy Hubs Under Uncertainty - a Review of Mathematical Optimization Approaches
- 2023
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Ingår i: IEEE Access. - 2169-3536 .- 2169-3536. ; 11, s. 7208-7228
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Tidskriftsartikel (refereegranskat)abstract
- Co-designing energy systems across multiple energy carriers is increasingly attracting attention of researchers and policy makers, since it is a prominent means of increasing the overall efficiency of the energy sector. Special attention is attributed to the so-called energy hubs, i.e., clusters of energy communities featuring electricity, gas, heat, hydrogen, and also water generation and consumption facilities. Managing an energy hub entails dealing with multiple sources of uncertainty, such as renewable generation, energy demands, wholesale market prices, etc. Such uncertainties call for sophisticated decision-making techniques, with mathematical optimization being the predominant family of decision-making methods proposed in the literature of recent years. In this paper, we summarize, review, and categorize research studies that have applied mathematical optimization approaches towards making operational and planning decisions for energy hubs. Relevant methods include robust optimization, information gap decision theory, stochastic programming, and chance-constrained optimization. The results of the review indicate the increasing adoption of robust and, more recently, hybrid methods to deal with the multi-dimensional uncertainties of energy hubs.
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| 24. |
- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 25. |
- Karnkowska, Anna, et al.
(författare)
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The Oxymonad Genome Displays Canonical Eukaryotic Complexity in the Absence of a Mitochondrion
- 2019
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Ingår i: Molecular biology and evolution. - : OXFORD UNIV PRESS. - 0737-4038 .- 1537-1719. ; 36:10, s. 2292-2312
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Tidskriftsartikel (refereegranskat)abstract
- The discovery that the protist Monocercomonoides exilis completely lacks mitochondria demonstrates that these organelles are not absolutely essential to eukaryotic cells. However, the degree to which the metabolism and cellular systems of this organism have adapted to the loss of mitochondria is unknown. Here, we report an extensive analysis of the M. exilis genome to address this question. Unexpectedly, we find that M. exilis genome structure and content is similar in complexity to other eukaryotes and less "reduced" than genomes of some other protists from the Metamonada group to which it belongs. Furthermore, the predicted cytoskeletal systems, the organization of endomembrane systems, and biosynthetic pathways also display canonical eukaryotic complexity. The only apparent preadaptation that permitted the loss of mitochondria was the acquisition of the SUF system for Fe-S cluster assembly and the loss of glycine cleavage system. Changes in other systems, including in amino acid metabolism and oxidative stress response, were coincident with the loss of mitochondria but are likely adaptations to the microaerophilic and endobiotic niche rather than the mitochondrial loss per se. Apart from the lack of mitochondria and peroxisomes, we show that M. exilis is a fully elaborated eukaryotic cell that is a promising model system in which eukaryotic cell biology can be investigated in the absence of mitochondria.
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