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- Johansson, Håkan, 1972-, et al.
(författare)
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Characterization of Campylobacter spp. isolated from wild birds in the Antarctic and Sub-Antarctic
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:11
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Tidskriftsartikel (refereegranskat)abstract
- A lack of knowledge of naturally occurring pathogens is limiting our ability to use the Antarctic to study the impact human-mediated introduction of infectious microorganisms have on this relatively uncontaminated environment. As no large-scale coordinated effort to remedy this lack of knowledge has taken place, we rely on smaller targeted efforts to both study present microorganisms and monitor the environment for introductions. In one such effort, we isolated Campylobacter species from fecal samples collected from wild birds in the Antarctic Peninsula and the sub-Antarctic island of South Georgia. Indeed, in South Georgia, we found Campylobacter lari and the closely related Campylobacter peloridis, but also distantly related human-associated multilocus sequence types of Campylobacter jejuni. In contrast, in the Antarctic Peninsula, we found C. tart and two closely related species, Campylobacter subantarcticus and Campylobacter volucris, but no signs of human introduction. In fact, our finding of human-associated sequence types of C. jejuni in South Georgia, but not in the Antarctic Peninsula, suggests that efforts to limit the spread of infectious microorganisms to the Antarctic have so far been successful in preventing the introduction of C. jejuni. However, we do not know how it came to South Georgia and whether the same mode of introduction could spread it from there to the Antarctic Peninsula.
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- Balk, Lennart, et al.
(författare)
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Widespread episodic thiamine deficiency in Northern Hemisphere wildlife
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B-1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiaminedependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.
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- Barth, Julia M.I., et al.
(författare)
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Genome architecture enables local adaptation of Atlantic cod despite high connectivity
- 2017
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 26:17, s. 4452-4466
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Tidskriftsartikel (refereegranskat)abstract
- Adaptation to local conditions is a fundamental process in evolution; however, mechanisms maintaining local adaptation despite high gene flow are still poorly understood. Marine ecosystems provide a wide array of diverse habitats that frequently promote ecological adaptation even in species characterized by strong levels of gene flow. As one example, populations of the marine fish Atlantic cod (Gadus morhua) are highly connected due to immense dispersal capabilities but nevertheless show local adaptation in several key traits. By combining population genomic analyses based on 12K single nucleotide polymorphisms with larval dispersal patterns inferred using a biophysical ocean model, we show that Atlantic cod individuals residing in sheltered estuarine habitats of Scandinavian fjords mainly belong to offshore oceanic populations with considerable connectivity between these diverse ecosystems. Nevertheless, we also find evidence for discrete fjord populations that are genetically differentiated from offshore populations, indicative of local adaptation, the degree of which appears to be influenced by connectivity. Analyses of the genomic architecture reveal a significant overrepresentation of a large ~5 Mb chromosomal rearrangement in fjord cod, previously proposed to comprise genes critical for the survival at low salinities. This suggests that despite considerable connectivity with offshore populations, local adaptation to fjord environments may be enabled by suppression of recombination in the rearranged region. Our study provides new insights into the potential of local adaptation in high gene flow species within fine geographical scales and highlights the importance of genome architecture in analyses of ecological adaptation.
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- Benatar, Michael, et al.
(författare)
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Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 2024
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
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- Berg, Hanna, et al.
(författare)
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A Semi-supervised Approach for De-identification of Swedish Clinical Text
- 2020
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Ingår i: Proceedings of the 12th Conference on Language Resources and Evaluation (LREC 2020). - : European Language Resources Association. - 9791095546344 ; , s. 4444-4450
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Konferensbidrag (refereegranskat)abstract
- An abundance of electronic health records (EHR) is produced every day within healthcare. The records possess valuable information for research and future improvement of healthcare. Multiple efforts have been done to protect the integrity of patients while making electronic health records usable for research by removing personally identifiable information in patient records. Supervised machine learning approaches for de-identification of EHRs need annotated data for training, annotations that are costly in time and human resources. The annotation costs for clinical text is even more costly as the process must be carried out in a protected environment with a limited number of annotators who must have signed confidentiality agreements. In this paper is therefore, a semi-supervised method proposed, for automatically creating high-quality training data. The study shows that the method can be used to improve recall from 84.75% to 89.20% without sacrificing precision to the same extent, dropping from 95.73% to 94.20%. The model’s recall is arguably more important for de-identification than precision.
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