| 1. |
- Larsson, Kjell, et al.
(författare)
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Effects of an extensive Prymnesium polylepis bloom on breeding eiders in the Baltic Sea
- 2014
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Ingår i: Journal of Sea Research. - : Elsevier. - 1385-1101 .- 1873-1414. ; 88, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- The effects of an extensive bloom of the potentially toxic Prymnesium polylepis (Haptophyta) on breeding eiders (Somateria mollissima) in the Baltic Sea were analysed. Increasing abundances of the alternate stage P. polylepis was detected by a marine monitoring programme in the autumn 2007. The bloom peaked between March and May 2008 in the southern, central and northwestern Baltic Proper and abundances of up to 5 x 106 cells l- 1 were recorded. At several sites P. polylepis constituted between 30 and 90% of the total phytoplankton biovolume. The flagellate was only recorded in low numbers in the northeastern Baltic Proper and Gulf of Finland. The abundances were low in 2007, 2009 and 2010. In 28 eider colonies situated in the southern and central Baltic Proper, sharp and synchronous declines in the number of nesting eiders were observed from 2007 to 2008. In colonies on Gotland in the central Baltic Proper, a 76% decrease, from 6650 nests to 1620 nests, was followed by increases in 2009 and 2010, although not up to numbers observed in 2007. At Utklippan and Ertholmene in the southern Baltic Proper, the observed decreases of 55%, from 144 to 65 nests, and 36%, from 1660 to 1060 nests, respectively, between 2007 and 2008, were followed by increases in 2009 and 2010 up to the level observed in 2007. By contrast, no general decline of the number of nesting eiders was observed from 2007 to 2008 in 75 colonies in the northeastern Baltic Proper and Gulf of Finland. Hence, the spatial distribution of the P. polylepis bloom in 2008 closely matched the observed distribution of extensive non-breeding of female eiders. We suggest that the intensive spring bloom of P. polylepis, either through a toxic or non-toxic pathway, affected the main benthic food of eiders, i.e. blue mussels (Mytilus trossulus x Mytilus edulis), at pre-breeding foraging sites close to the breeding sites, and, subsequently, the body condition of adult female eiders and their breeding propensity.
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| 2. |
- Stranneheim, Henrik, et al.
(författare)
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Rapid pulsed whole genome sequencing for comprehensive acute diagnostics of inborn errors of metabolism
- 2014
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15, s. 1090-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Massively parallel DNA sequencing (MPS) has the potential to revolutionize diagnostics, in particular for monogenic disorders. Inborn errors of metabolism (IEM) constitute a large group of monogenic disorders with highly variable clinical presentation, often with acute, nonspecific initial symptoms. In many cases irreversible damage can be reduced by initiation of specific treatment, provided that a correct molecular diagnosis can be rapidly obtained. MPS thus has the potential to significantly improve both diagnostics and outcome for affected patients in this highly specialized area of medicine. Results: We have developed a conceptually novel approach for acute MPS, by analysing pulsed whole genome sequence data in real time, using automated analysis combined with data reduction and parallelization. We applied this novel methodology to an in-house developed customized work flow enabling clinical-grade analysis of all IEM with a known genetic basis, represented by a database containing 474 disease genes which is continuously updated. As proof-of-concept, two patients were retrospectively analysed in whom diagnostics had previously been performed by conventional methods. The correct disease-causing mutations were identified and presented to the clinical team after 15 and 18 hours from start of sequencing, respectively. With this information available, correct treatment would have been possible significantly sooner, likely improving outcome. Conclusions: We have adapted MPS to fit into the dynamic, multidisciplinary work-flow of acute metabolic medicine. As the extent of irreversible damage in patients with IEM often correlates with timing and accuracy of management in early, critical disease stages, our novel methodology is predicted to improve patient outcome. All procedures have been designed such that they can be implemented in any technical setting and to any genetic disease area. The strategy conforms to international guidelines for clinical MPS, as only validated disease genes are investigated and as clinical specialists take responsibility for translation of results. As follow-up in patients without any known IEM, filters can be lifted and the full genome investigated, after genetic counselling and informed consent.
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| 3. |
- Ekström, Ingrid, et al.
(författare)
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Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion
- 2017
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Ingår i: Journal of The American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 65:6, s. 1238-1243
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period.DesignProspective cohort study.SettingBetula Study, Umeå, Sweden.ParticipantsA population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774).MeasurementsOlfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade.ResultsWithin the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction.ConclusionPoor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.
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| 4. |
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| 5. |
- Ghilagaber, Gebrenegus, 1958-, et al.
(författare)
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Adjustment of Anticipatory Covariates in Retrospective Surveys : An Expected Likelihood Approach
- 2023
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Ingår i: Stats. - : MDPI. - 2571-905X. ; 6:4, s. 1179-1197
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Tidskriftsartikel (refereegranskat)abstract
- We address an inference issue where the value of a covariate is measured at the date of the survey but is used to explain behavior that has occurred long before the survey. This causes bias because the value of the covariate does not follow the temporal order of events. We propose an expected likelihood approach to adjust for such bias and illustrate it with data on the effects of educational level achieved by the time of marriage on risks of divorce. For individuals with anticipatory educational level (whose reported educational level was completed after marriage), conditional probabilities of having attained the reported level before marriage are computed. These are then used as weights in the expected likelihood to obtain adjusted estimates of relative risks. For our illustrative data set, the adjusted estimates of relative risks of divorce did not differ significantly from those obtained from anticipatory analysis that ignores the temporal order of events. Our results are slightly different from those in two other studies that analyzed the same data set in a Bayesian framework, though the studies are not fully comparable to each other.
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| 6. |
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| 7. |
- Ghilagaber, Gebrenegus, et al.
(författare)
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Maximum Likelihood Adjustment of Anticipatory Covariates in the Analysis of Retrospective Data
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- A multiplicative hazard model in the presence of anticipatory covariates is estimated by maximum likelihood. The case study concerns the e§ects of educational level on risks of divorce. For individuals with anticipatory educational levels, conditional probabilities of having attained the reported level before marriage are used as weights in the likelihood. The adjusted estimates of relative risks do not di§er signiÖcantly from those from anticipatory analysis.
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| 8. |
- Josefsson, Maria, et al.
(författare)
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APOE-epsilon 4 effects on longitudinal decline in olfactory and non-olfactory cognitive abilities in middle-aged and old adults
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Characterizing aging-related decline trajectories in mental abilities, and relationships of the epsilon 4 allele of the Apolipoprotein gene, helps to identify individuals at high risk for dementia. However, longitudinal changes in olfactory and non-olfactory cognitive abilities have not been investigated in relation to the epsilon 4 allele. In the present study, participants from a large population-based study (657 middle-aged and 556 old) were tested over 10 years on their performance on an odor identification task and three non-olfactory cognitive tasks; MMSE, episodic memory, and semantic memory. Our key finding is that in middle-aged participants, odor identification declined twice as fast for epsilon 4/4 homozygotes, compared to non-carriers. However, in old participants, the epsilon 4/4 homozygotes showed an impaired odor identification ability, but they declined at a similar rate as the non-carriers. Furthermore, in old participants all assessments displayed aging-related declines, but exaggerated declines in epsilon 4-carriers were found only in MMSE and episodic memory assessments. In sum, we present evidence that odor identification ability starts to decline already in middle-aged, and that carriers of epsilon 4/4, who are at highest risk of developing dementia, decline twice as fast. Our results may have implications for use of odor identification assessment in detection of early-stage dementia.
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| 9. |
- Larsson, Karl-Magnus, et al.
(författare)
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Structural mechanism of allosteric substrate specificity regulation in a ribonucleotide reductase
- 2004
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 11:11, s. 1142-1149
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Tidskriftsartikel (refereegranskat)abstract
- Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides into deoxyribonucleotides, which constitute the precursor pools used for DNA synthesis and repair. Imbalances in these pools increase mutational rates and are detrimental to the cell. Balanced precursor pools are maintained primarily through the regulation of the RNR substrate specificity. Here, the molecular mechanism of the allosteric substrate specificity regulation is revealed through the structures of a dimeric coenzyme B12-dependent RNR from Thermotoga maritima, both in complexes with four effector-substrate nucleotide pairs and in three complexes with only effector. The mechanism is based on the flexibility of loop 2, a key structural element, which forms a bridge between the specificity effector and substrate nucleotides. Substrate specificity is achieved as different effectors and their cognate substrates stabilize specific discrete loop 2 conformations. The mechanism of substrate specificity regulation is probably general for most class I and class II RNRs.
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| 10. |
- Larsson, Maria, et al.
(författare)
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Loss of Olfactory Function Predicts Mortality Irrespective of Dementia Conversion : 10-year follow-up of an age-varied sample
- 2016
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Ingår i: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 41:9, s. e111-e288
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to examine the association between performance in odor identification and future mortality in a community cohort of adults aged between 40 and 90 years. We assessed olfactory performance with a 13-item-version of the Scandinavian Odor Identification Test (SOIT). The results showed that during follow-up (mean=9.4 years, standard deviation=2.23), 411 of 1774 (23.2%) participants died. In a Cox model, the association between higher SOIT score and mortality was highly significant (hazard ratio [HR]=0.74, per point interval, 95% confidence interval [CI]=0.71–0.77, p<0.001). The effect was attenuated, but remained significant after controlling for age, sex, education, and health and cognitive variables that were also associated with an increased risk of mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Controlling for dementia conversion prior to death did not attenuate the association between SOIT score and mortality (HR=0.92, 95% CI=0.87–0.97, p=0.001). Similar results were obtained for olfactory sensitivity as assessed by self-report. Overall, the present findings show that poor odor identification performance is associated with an increased likelihood of future mortality in middle-aged and older adults, after controlling for social, cognitive, and medical risk factors. Most importantly, controlling for the development of dementia did not attenuate the association between odor identification and mortality, suggesting that olfactory decline might mark deteriorating health also irrespective of dementia.
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