| 38991. |
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| 38992. |
- Hedenström, Mattias, et al.
(författare)
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Visualization and interpretation of OPLS models based on 2D NMR Data
- 2008
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Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier. - 0169-7439 .- 1873-3239. ; 92:2, s. 110-117
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Tidskriftsartikel (refereegranskat)abstract
- Multivariate analysis on spectroscopic 1H NMR data is well established in metabolomics and other fields where the composition of complex samples is studied. However, biomarker identification can be hampered by overlapping resonances. 2D NMR data provides a more detailed “fingerprint” of the chemical structure and composition of the sample with greatly improved spectral resolution compared to 1H NMR data. In this report, we demonstrate a procedure for the construction of multivariate models based on frequency domain 2D NMR data where the loadings can be visualized as highly informative 2D loading spectra. This method is based on the analysis of raw spectral data without any need for peak picking or integration prior to analysis. Spectral features such as line widths and peak positions are thus retained. Hence, the loadings can be visualized and interpreted on a molecular level as pseudo 2D spectra in order to identify potential biomarkers. To demonstrate this strategy we have analyzed HSQC spectra acquired from populus phloem plant extracts originating from a set of designed experiments with OPLS regression.
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| 38993. |
- Hedenus, Michael, 1945-
(författare)
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Clinical impact of epoetins in the treatment of anemia with special emphasis on patients with lymphoid malignancies. : dosing, iron supplementation and safety
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to determine the relevant dose of arbepoetin-alfa (DA) in patients with lymphoproliferative diseases (LPD) and chemotherapy induced anemia (CIA), to study the clinical impact of intravenous (IV) iron supplementation combined with epoetin beta treatment, to identify factors that might predict hemoglobin (Hb) response to treatment with epoetins and to investigate safety of DA.A dose-finding phase II study was able to assess a reasonable DA dose of 2.25 μg/kg once weekly for the treatment of CIA in patients with LPD. Dose-response trends were observed for the different dose cohorts although not statistically significant for any of the endpoints. However a significantly higher proportion of patients achieved Hb response (increase ≥2 g/dL) in the combined DA groups than in placebo (P<0.001).A larger pivotal phase II trial was performed in a similar setting o confirm that the dose 2.25μg/kg once weekly was appropriate and safe. The proportion of patients achieving Hb response was significantly higher in the DA group (60%) than in the placebo group (18%) (P<0,001) and resulted in higher mean changes in Hb than placebo from baseline, 2.66 g/dl versus 0.69 /dl. Also a significantly lower proportion of patients in the DA group (31%) received RBC tranfusions than in the placebo group (48%). The short-term safety of DA with the tested dose was confirmed. The efficacy of DA was consistent for all end points independent of malignancy type or baseline endogenous erythropoietin serum levels.The correction of moderate anemia in truly iron repleted patients with clinically stable LPD not receiving hemotherapy or RBC transfusions with epoetin beta treatment, with or without IV iron treatment was studied in an open label randomized trial. Also the impact on iron kinetics was assessed. The mean change in Hb concentration from baseline to end of treatment (EOT ) was 2.91 versus 1.50 g/dL respectively (P<0.0001). There was a significant (P<0.0001) difference in mean Hb at EOT between the iron and no-iron groups (13.0 g/dL versus 11.8 g/dL). Hb response was achieved by significantly more patients in the iron group (P=0.0012)than in the no-iron group (93% versus 53%) and the median time to achieve a Hb response was 6 weeks in the iron group compared with 12 weeks in the no-iron group. The mean weekly epoetin dose per patient was statistically significant lower in the iron group at week 13 (P =0.029) and at least 25% lower at EOT.To investigate the long-term safety of DA in cancer patients with CIA four previously published double blind, randomized placebo-controlled phase II -III studies were analysed (n = 1.129). Median durations of progression-free survival and overall survival was comparable between DA and placebo for lung cancer (median follow up 15.8 months), for LPD (median follow up 32.6 months) and in the pooled population (follow up 4 months).
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| 38994. |
- Hedenus, Michael, et al.
(författare)
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Darbepoetin alfa for the treatment of chemotherapy-induced anemia: disease progression and survival analysis from four randomized, double-blind, placebo-controlled trials
- 2005
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 23:28, s. 6941-6948
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Tidskriftsartikel (refereegranskat)abstract
- To determine the effect of darbepoetin alfa (DA) on progression-free survival (PFS) and overall survival (OS) in patients with chemotherapy-induced anemia (CIA). Patients and Methods Two 16-week randomized, double-blind, placebo-controlled phase III studies of weekly DA in anemic patients with lung cancer (n = 314) or lymphoproliferative malignancies (LPMs; n = 344) undergoing chemotherapy were analyzed with prospectively defined long-term PFS and OS end points. Short-term effects of DA on PFS and OS were analyzed by including two additional 16-week dose-finding, double-blind, placebo-controlled studies in anemic patients with multiple tumor types (n = 405) and LPMs (n = 66). Results Median follow-up is 15.8 months (lung cancer) and 32.6 months (LPM). Median duration of PFS was comparable between DA and placebo: 5.1 months (95% CI, 4.1 to 6.9 months) versus 4.4 months (95% CI, 3.7 to 5.3 months) for lung cancer and 14.2 months (95% CI, 12.2 to 17.5 months) versus 15.9 months (95% CI, 13.1 to 19.0 months) for LPMs. The estimated hazard ratio (HR) of death related to DA use for lung cancer was 0.77 (95% CI, 0.59 to 1.01) and 1.26 (95% CI, 0.92 to 1.71) for LPMs. In the pooled analyses of all four studies (n = 1,129), no differences in PFS or OS were observed between DA and placebo (HR = 0.92; 95% CI, 0.78 to 1.07; and HR = 0.95; 95% CI, 0.78 to 1.16, respectively). Conclusion Treatment with DA does not seem to influence PFS or OS in patients with CIA. Prospective, randomized clinical trials will provide additional insights into the effects of DA on PFS and OS in specific tumor types.
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| 38995. |
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| 38996. |
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| 38997. |
- Hedenås, Henrik, et al.
(författare)
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Conservation of epiphytic lichens : Significance of remnant aspen (Populus tremula) trees in clear-cuts
- 2007
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Ingår i: Biological Conservation. - Barking : Applied Science Publishers. - 0006-3207 .- 1873-2917. ; 135:3, s. 388-395
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Tidskriftsartikel (refereegranskat)abstract
- In the boreal forest landscape, aspen has been effectively selected against in favour of conifers. The decrease in aspen is of particular concern since it has more host-specific species associated with it than any other boreal tree species. Recently forest management systems have begun to include green-tree retention in order to maintain structural diversity. We initiated this study in order to investigate whether retained aspen trees provide suitable habitats for epiphytic lichens and, if so, whether this varies according to species characteristics, such as morphology and photobiont. We chose to investigate the abundance and vitality of five species: three foliose cyanobacterial lichens (Collema curtisporum, Collema furfuraceum and Leptogium saturninum) and two crustose green-algal lichens (Biatora epixanthoides and Mycobilimbia carneoalbida). These lichens were examined on aspen within forest stands and on remnant aspen in clear-cuts at eight localities, in northern Sweden. Our results show that the response to exposure following clear-felling differs between species according to their morphology. The two crustose lichens were more abundant in the forest stands compared to the clear-cuts. In the clear-cuts, they mainly occurred on the northern sides of the trunks. Even 24 years after cutting, the three cyanolichens were equally or even more abundant on trees in the clear-cuts than in the forest stands. However, they were mainly found on the northern sides of the remnant aspen. We suggest that remnant aspen trees may function as suitable substrate and as stepping stones for colonisation of new stands, at least for the cyanolichens studied here.
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| 38998. |
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| 38999. |
- Hedenås, Henrik, et al.
(författare)
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Significance of old aspen (Populus tremula) trees for the occurrence of lichen photobionts
- 2007
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 135:3, s. 380-387
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Tidskriftsartikel (refereegranskat)abstract
- In the boreal forest landscape, aspen has been effectively selected against in favour of conifers. The decrease in aspen is of particular concern, since it has more host-specific species associated with it than any other boreal tree species. Recently, forest management systems have begun to include green-tree retention in order to maintain structural diversity. Earlier studies have focused on the importance of remnant aspen trees for lichen species prevalence. We have focused on the occurrence of free-living photobionts, i.e. cyanobacteria and green-algae, since a successful establishment of sexually dispersed lichens will depend upon the presence of the photobiont. Our study shows that the abundances of Gloeocystis, Nostoc, Scytonema and Trentepohlia increased with stand age, while the abundance of Trebouxia decreased. The response to clear-felling differed between genera. The two cyanobacterial genera were able to persist in clear-cuts, although they were more abundant on the northern side of the remnant trees. The green-algae showed no consistent pattern, Trentepohlia was affected while Trebouxia was unaffected. Our study indicates that the prerequisites for new-establishment for spore dispersed lichen species, on remnant aspen, may be fulfilled in terms of availability of free-living photobionts on the northern side of the trunks. In support of this interpretation we found that the occurrence of cyanolichens was positively correlated with the occurrence of free-living cyanobacteria in the clear-cuts. We conclude that tree retention is likely to provide a useful tool for increasing biodiversity in managed forest landscapes provided that source populations still exist in the surrounding landscape.
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| 39000. |
- Hedenås, Henrik, et al.
(författare)
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Species occurrences at stand level cannot be understood without considering the landscape context: Cyanolichens on aspen in boreal Sweden
- 2008
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Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 141, s. 710-718
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in conservation biology is to understand species’ responses to habitat loss. In Fennoscandia, the ongoing decline in aspen in forests is of particular concern, since aspen is the boreal forest tree species that supports the most host-specific species of cryptogams and invertebrates. In order to predict the potential effects of aspen decline we compared the occurrence of three epiphytic cyanolichens in old-growth stands of the same habitat quality, in four aspen-rich and four aspen-poor landscapes. Collema curtisporum and Collema furfuraceum were, on average, five and six times more frequent, respectively, in the aspen-rich than in the aspen-poor landscapes. Leptogium saturninum was not affected by the abundance of aspen stands at the landscape level. Our data suggests that lichen species with poor dispersal abilities may be more sensitive to habitat loss than more easily dispersed species and that species with broader habitat amplitude may be less sensitive to habitat loss than more specialized species, even if they have inferior dispersal ability. We conclude that (i) predictions of species occurrences at the stand level have to take account of the amount of suitable habitat at the landscape level, and (ii) predicting the responses of individual species based on life-history traits can be crucial, but cannot be based on single traits. Thus our study shows that biological value cannot be assessed on the basis of habitat quality alone and that a landscape perspective is needed for the sustainable management of specialist species.
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