| 61. |
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| 62. |
- Laisk, Triin, et al.
(författare)
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The genetic architecture of sporadic and multiple consecutive miscarriage.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Miscarriage is a common, complex trait affecting ~15% of clinically confirmed pregnancies. Here we present the results of large-scale genetic association analyses with 69,054 cases from five different ancestries for sporadic miscarriage, 750 cases of European ancestry for multiple (≥3) consecutive miscarriage, and up to 359,469 female controls. We identify one genome-wide significant association (rs146350366, minor allele frequency (MAF) 1.2%, P = 3.2 × 10-8, odds ratio (OR) = 1.4) for sporadic miscarriage in our European ancestry meta-analysis and three genome-wide significant associations for multiple consecutive miscarriage (rs7859844, MAF = 6.4%, P = 1.3 × 10-8, OR = 1.7; rs143445068, MAF = 0.8%, P = 5.2 × 10-9, OR = 3.4; rs183453668, MAF = 0.5%, P = 2.8 × 10-8, OR = 3.8). We further investigate the genetic architecture of miscarriage with biobank-scale Mendelian randomization, heritability, and genetic correlation analyses. Our results show that miscarriage etiopathogenesis is partly driven by genetic variation potentially related to placental biology, and illustrate the utility of large-scale biobank data for understanding this pregnancy complication.
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| 63. |
- Licht, Rasmus W., et al.
(författare)
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Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG-6)
- 2010
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Ingår i: Bipolar Disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 12:5, s. 483-493
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: In industry-generated pivotal studies, lamotrigine has been found to be superior to placebo and comparable to lithium in the maintenance treatment of bipolar I disorder. Here, we directly compared lamotrigine to lithium under conditions similar to clinical routine conditions. Methods: Adult bipolar I disorder patients with at least two episodes within the last five years and an index episode requiring treatment were randomized to lithium (n = 78; doses adjusted to obtain serum levels of 0.5-1.0 mmol/L) or to lamotrigine (n = 77; up-titrated to 400 mg/day) as maintenance treatments. Randomization took place when clinically appropriate, and comedication was allowed within the first six months after randomization. The patients were enrolled from March 2001 to December 2005, and observations were censored December 2006, allowing a subgroup of patients to be followed for more than five years. The primary outcome measure was time to predefined endpoints indicating insufficient maintenance treatment, and the major secondary outcome measure was time to any study endpoint. Data were analyzed primarily by Cox proportional regression models. Results: For the primary outcome measure, the crude Hazard Rate Ratio (HRR) (lamotrigine relative to lithium) was 0.92 [95% confidence interval (CI): 0.60-1.40]. When the primary endpoints were broken down by polarity, the HRRs (lamotrigine relative to lithium) for mania and depression were, respectively, 1.91 (95% CI: 0.73-5.04) and 0.69 (95% CI: 0.41-1.22). There was no between-group difference in terms of staying in study [HRR: 0.85 (95% CI: 0.61-1.19)]. Most treatment failures occurred within the first 1.5 years of treatment, and, among patients followed for at least five years, practically no patients were maintained successfully on monotherapy with either of the drugs. The lithium-treated patients reported diarrhea, tremor, polyuria, and thirst more frequently. Two cases, probably lamotrigine-related, of benign rash occurred. Conclusions: No differences in maintenance effectiveness between lithium and lamotrigine could be demonstrated. Lamotrigine was better tolerated than lithium, but apparently this did not influence the outcome.
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| 64. |
- Liu, Liming, 1976, et al.
(författare)
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Use of genome-scale metabolic models for understanding microbial physiology
- 2010
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Ingår i: FEBS Letters. - : Wiley. - 1873-3468 .- 0014-5793. ; 584:12, s. 2556-2564
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Tidskriftsartikel (refereegranskat)abstract
- The exploitation of microorganisms in industrial, medical, food and environmental biotechnology requires a comprehensive understanding of their physiology. The availability of genome sequences and accumulation of high-throughput data allows gaining understanding of microbial physiology at the systems level, and genome-scale metabolic models represent a valuable framework for integrative analysis of metabolism of microorganisms. Genome-scale metabolic models are reconstructed based on a combination of genome sequence information and detailed biochemical information, and these reconstructed models can be used for analyzing and simulating the operation of metabolism in response to different stimuli. Here we discuss the requirement for having detailed physiological insight in order to exploit microorganisms for production of fuels, chemicals and pharmaceuticals. We further describe the reconstruction process of genome-scale metabolic models and different algorithms that can be used to apply these models to gain improved insight into microbial physiology. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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| 65. |
- Liu, Shiping, et al.
(författare)
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Population Genomics Reveal Recent Speciation and Rapid Evolutionary Adaptation in Polar Bears
- 2014
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 157:4, s. 785-794
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Tidskriftsartikel (refereegranskat)abstract
- Polar bears are uniquely adapted to life in the High Arctic and have undergone drastic physiological changes in response to Arctic climates and a hyper-lipid diet of primarily marine mammal prey. We analyzed 89 complete genomes of polar bear and brown bear using population genomic modeling and show that the species diverged only 479-343 thousand years BP. We find that genes on the polar bear lineage have been under stronger positive selection than in brown bears; nine of the top 16 genes under strong positive selection are associated with cardiomyopathy and vascular disease, implying important reorganization of the cardiovascular system. One of the genes showing the strongest evidence of selection, APOB, encodes the primary lipoprotein component of low-density lipoprotein (LDL); functional mutations in APOB may explain how polar bears are able to cope with life-long elevated LDL levels that are associated with high risk of heart disease in humans.
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| 66. |
- Lorenzen, Eline D., et al.
(författare)
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Species-specific responses of Late Quaternary megafauna to climate and humans
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 479:7373, s. 359-364
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.
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| 67. |
- Lucani, Daniel E., et al.
(författare)
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Secure generalized deduplication via multi-key revealing encryption
- 2020
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Ingår i: Security and Cryptography for Networks - 12th International Conference, SCN 2020, Proceedings. - Cham : Springer International Publishing. - 1611-3349 .- 0302-9743. - 9783030579890 ; 12238 LNCS, s. 298-318
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Konferensbidrag (refereegranskat)abstract
- Cloud Storage Providers (CSPs) offer solutions to relieve users from locally storing vast amounts of data, including personal and sensitive ones. While users may desire to retain some privacy on the data they outsource, CSPs are interested in reducing the total storage space by employing compression techniques such as deduplication. We propose a new cryptographic primitive that simultaneously realizes both requirements: Multi-Key Revealing Encryption (MKRE). The goal of MKRE is to disclose the result of a pre-defined function over multiple ciphertexts, even if the ciphertexts were generated using different keys, while revealing nothing else about the data. We present a formal model and a security definition for MKRE and provide a construction of MKRE for generalized deduplication that only uses symmetric key primitives in a black-box way. Our construction allows (a) cloud providers to reduce the storage space by using generalized deduplication to compress encrypted data across users, and (b) each user to maintain a certain privacy level for the outsourced information. Our scheme can be proven secure in the random oracle model (and we argue that this is a necessary evil). We develop a proof-of-concept implementation of our solution. For a test data set, our MKRE construction achieves secure generalized deduplication with a compression ratio of 87% for 1 KB file chunks and 82.2% for 8 KB chunks. Finally, our experiments show that, compared to generalized deduplication setup with un-encrypted files, adding privacy via MKRE introduces a compression overhead of less than $$3\%$$ and reduces the storage throughput by at most $$6.9\%$$.
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| 68. |
- Lützhøft, Ditte Olsen, et al.
(författare)
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Marked gut microbiota dysbiosis and increased imidazole propionate are associated with a NASH Göttingen Minipig model
- 2022
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Ingår i: BMC Microbiology. - : BioMed Central (BMC). - 1471-2180. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gut microbiota dysbiosis is associated with the development of non-alcoholic steatohepatitis (NASH) through modulation of gut barrier, inflammation, lipid metabolism, bile acid signaling and short-chain fatty acid production. The aim of this study was to describe the impact of a choline-deficient amino acid defined high fat diet (CDAHFD) on the gut microbiota in a male Göttingen Minipig model and on selected pathways implicated in the development of NASH.RESULTS: Eight weeks of CDAHFD resulted in a significantly altered colon microbiota mainly driven by the bacterial families Lachnospiraceae and Enterobacteriaceae, being decreased and increased in relative abundance, respectively. Metabolomics analysis revealed that CDAHFD decreased colon content of short-chain fatty acid and increased colonic pH. In addition, serum levels of the microbially produced metabolite imidazole propionate were significantly elevated as a consequence of CDAHFD feeding. Hepatic gene expression analysis showed upregulation of mechanistic target of rapamycin (mTOR) and Ras Homolog, MTORC1 binding in addition to downregulation of insulin receptor substrate 1, insulin receptor substrate 2 and the glucagon receptor in CDAHFD fed minipigs. Further, the consequences of CDAHFD feeding were associated with increased levels of circulating cholesterol, bile acids, and glucagon but not total amino acids.CONCLUSIONS: Our results indicate imidazole propionate as a new potentially relevant factor in relation to NASH and discuss the possible implication of gut microbiota dysbiosis in the development of NASH. In addition, the study emphasizes the need for considering the gut microbiota and its products when developing translational animal models for NASH.
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| 69. |
- Lyth, Johan, et al.
(författare)
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Population-based prognostic instrument (SweMR 2.0) for melanoma- specific survival- An ideal tool for individualised treatment decisions for Swedish patients
- 2023
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Ingår i: European Journal of Surgical Oncology. - : ELSEVIER SCI LTD. - 0748-7983 .- 1532-2157. ; 49:10
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The prognosis for patients with melanoma has improved due to better treatments in recent years and updated tools to accurately predict an individual's risk are warranted. This study aims to describe a prognostic instrument for patients with cutaneous melanoma and its potential as a clinical device for treatment decisions.Methods: Patients with localised invasive cutaneous melanoma diagnosed in 1990-2021 with data on tumour thickness were identified from the population-based Swedish Melanoma Registry. The parametric Royston-Parmar (RP) method was used to estimate melanoma-specific survival (MSS) probabilities. Separate models were constructed for patients (<= 1 mm) and (>1 mm) and prognostic groups were created based on all combinations of age, sex, tumour site, tumour thickness, absence/presence of ulceration, histopathologic type, Clark's level of invasion, mitoses and sentinel lymph node (SLN) status.Results: In total, 72 616 patients were identified, 41 764 with melanoma <= 1 mm and 30 852 with melanoma >1 mm. The most important variable was tumour thickness for both (<= 1 mm) and (>1 mm), that explained more than 50% of the survival. The second most important variables were mitoses (<= 1 mm) and SLN status (>1 mm). The prognostic instrument successfully created probabilities for >30 000 prognostic groups.Conclusions: The Swedish updated population-based prognostic instrument, predicts MSS survival up to 10 years after diagnosis. The prognostic instrument gives more representative and up-to-date prognostic information for Swedish patients with primary melanoma than the present AJCC staging. Additional to clinical use and the adjuvant setting, the information retrieved could be used to plan future studies.
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| 70. |
- Marchowski, Dominik, et al.
(författare)
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Effectiveness of the European Natura 2000 network to sustain a specialist wintering waterbird population in the face of climate change
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Analysis of coordinated Greater Scaup (Aythya marila) count data from the last 30 years showed a 38.1% decrease in wintering numbers in North-West Europe, from 309,000 during 1988–1991 to c.192,300 individuals during 2015–2018. Annual trends in wintering numbers differed throughout the range. Numbers decreased in the UK, Ireland, and in the Netherlands, while numbers were stable in Denmark. Germany, Poland, Sweden, and Estonia showed increasing numbers, suggesting a shift in the distribution of the species within its wintering grounds towards the east and north. Higher temperatures in northern and eastern areas were correlated with the range shift of the wintering distribution. Deaths from bycatch drowning of Scaup in fishing gear have significantly decreased in recent decades in the Netherlands, where currently the greatest threat is considered the deterioration of food resources. The increasing concentration of wintering Scaup in coastal Poland and Germany (where lack of effective implementation of conservation measures fail to protect the species from the impacts of bycatch and declining food quality) pose major threats to the entire population.
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