| 1. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 2. |
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| 3. |
- Akselsson, Cecilia, et al.
(författare)
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Nutrient and carbon budgets in forest soils as decision support in sustainable forest management
- 2007
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 1872-7042 .- 0378-1127. ; 238:1-3, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about the nutrient and carbon budgets in forest soils is essential to maintain sustainable production, but also in several environmental issues, such as acidification, eutrophication and climate change. The budgets are strongly influenced by atmospheric deposition as well as forestry. This study demonstrates how budget calculations for nitrogen (N), carbon (C) and base cations (BC) can be used as a basis for policy decisions on a regional level in Sweden. The study was based on existing nutrient and C budget calculations on a regional scale in Sweden. The nutrient budgets have been calculated for each square in a national 5 km x 5 km net by means of mass balances including deposition, harvest losses, leaching, weathering (BC) and fixation (N). Scenarios with different deposition and forestry intensity have been run and illustrated on maps. A simplified C budget has been estimated by multiplying the N accumulation with the C/N ratio in the organic layer, based on the assumption that the C/N ratio in the accumulating organic matter is equal to the ratio in the soil organic matter pool. The budget approaches differ from earlier budget studies since they involve regional high resolution data, combine deposition and forestry scenarios and integrate different environmental aspects. The results indicate that whole-tree harvesting will cause net losses of N and base cations in large parts of Sweden, which means that forestry will not be sustainable unless nutrients are added through compensatory fertilization. To prevent net losses following whole-tree harvesting, compensatory fertilization of base cations would be required in almost the whole country, whereas N fertilization would be needed mainly in the northern half of Sweden. The results further suggest that today's recommendations for N fertilization should be revised in southern Sweden by applying the southwest-northeast gradient of the N budget calculations. The C and N accumulation calculations show that C sequestration in Swedish forest soils is not an effective or sustainable way to decrease the net carbon dioxide emissions. A better way is to apply whole-tree harvesting and use the branches, tops and needles as biofuel replacing fossil fuels. This could reduce the present carbon dioxide emissions from fossil fuels substantially. The study shows that high resolution budget calculations that illuminate different aspects of sustainability in forest ecosystems are important tools for identifying problem areas, investigating different alternatives through scenario analyses and developing new policies. Cooperation with stakeholders increases the probability that the research will be useful. (c) 2006 Elsevier B.V. All fights reserved.
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| 4. |
- Berg, Björn, et al.
(författare)
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Sequestration of carbon in the humus layer of Swedish forests - direct measurements
- 2009
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Ingår i: Canadian Journal of Forest Research. - 0045-5067 .- 1208-6037. ; 39:5, s. 962-975
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Tidskriftsartikel (refereegranskat)abstract
- To determine sequestration rates of carbon dioxide (CO2) we calculated the carbon (C) storage rate in humus layers of Swedish forests with Podsolic soils, which account for 14.2 x 106 ha of the 22.7 x 106 ha of forested land in Sweden. Our data set covered 41 years of humus inventories and mean humus layer thickness in 82513 plots. We analysed three forest types: (i) all combinations of tree species, (ii) forests dominated (>70%) by Norway spruce (Picea abies (L.) Karst.), and (Ui) forests dominated (>70%) by Scots pine (Pinus sylvestris L.). To relate changes in humus layer thickness to land area we used the intersections in 25 km x 25 km grids and used kriging interpolation, permitting calculations for each forest type. For each intersection mean humus thickness for each year was calculated and regressed against time to obtain the rate of change. This rate, humus bulk density, and humus C concentration were used, to calculate sequestration rates. The mean sequestration rate was 251 kg C-ha-1'year1, which is higher than theoretical values. The sequestration rate was positively related to temperature sum, albeit including effects of forest management. The pine-dominated forest type had a mean rate of 283 kgCha⁁year-1, and. the spruce-dominated had a mean rate of 239 kg Cha-1-year1. Under similar site conditions, pine sequestered more C than spruce (difference of 71 kg Cha-1'year-1; p < 0.0001), showing the importance of this type of ecosystem for C sequestration.
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| 5. |
- Gundersen, Per Ole M., et al.
(författare)
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Metabolite Profiling of Ortho-, Meta- and Para-Fluorofentanyl by Hepatocytes and High-Resolution Mass Spectrometry
- 2020
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 44:2, s. 140-148
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Tidskriftsartikel (refereegranskat)abstract
- New psychoactive substances are emerging on the illegal drug market. Synthetic opioids including fentanyl analogues are of special concern due to their high potency. This indicates the possibility of low drug concentrations in vivo and calls for sensitive analytical methods and identification of the most appropriate analytical targets. In this study the in vitro metabolism of ortho-, meta- and para-fluorofentanyl, three fluorinated derivatives of fentanyl, has been investigated using human hepatocytes and compared to the results from an authentic human urine sample. Based on knowledge on the metabolism of similar fentanyl analogues N-dealkylation and hydroxylation was hypothesized to be the most central pathways. The three fluorofentanyl isomers were incubated with pooled human hepatocytes at 1, 3 and 5 h. Liquid chromatography quadrupole time of flight mass spectrometry operating in data-dependent mode was used to analyse the hepatocyte samples, as well as the hydrolysed and non-hydrolysed authentic urine sample. Data were analysed by a targeted approach with a database of potential metabolites. The major metabolite formed in vitro was the N-dealkylation product norfluorofentanyl. In addition various hydroxylated metabolites, a N-oxide, dihydrodiol metabolites and a hydroxymethoxy metabolite were found. In total, 14 different metabolites were identified for each fluorofentanyl isomer. In the authentic urine sample, three metabolites were detected in addition to the ortho-fluorofentanyl parent compound, with hydroxymethoxy metabolite having the highest abundance followed by norfluorofentanyl and a metabolite hydroxylated on the ethylphenyl ring. This in vitro study showed that the metabolic pattern for ortho-, meta-, and para-fluorofentanyl was close to those previously reported for other fentanyl analogues. We suggest that the hydroxymethoxy metabolite and the metabolite hydroxylated on the ethylphenyl ring should be the metabolites primarily investigated in further studies to determine the most appropriate marker for intake of fluorofentanyl derivatives in urine drug screening for human subjects.
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| 6. |
- Gundersen, Per Ole M., et al.
(författare)
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Retrospective screening of synthetic cannabinoids, synthetic opioids and designer benzodiazepines in data files from forensic post mortem samples analysed by UHPLC-QTOF-MS from 2014 to 2018
- 2020
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Ingår i: Forensic Science International. - : ELSEVIER IRELAND LTD. - 0379-0738 .- 1872-6283. ; 311
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of new psychoactive substances (NPS) on the illicit drug market has led to major challenges for the analytical laboratories. Keeping screening methods up to date with all relevant drugs is hard to achieve and the risk of missing important findings in biological samples is a matter of concern. Aiming for an extended retrospective data analysis, diagnostic fragment ions from synthetic cannabinoids (n = 251), synthetic opioids (n = 88) and designer benzodiazepines (n = 26) not included in our original analytical method were obtained from the crowdsourced database HighResNPS.com and converted to a personalized library in a format compatible with the analytical instrumentation. Data files from the analysis of 1314 forensic post mortem samples with an Agilent 6540 ultra high pressure liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) performed in our laboratory from January 2014 to December 2018 were retrieved and retrospectively processed with the new personalized library. Potentially positive findings were grouped in two: The most confident findings contained MS/MS data for library match (category 1) whereas the less confident findings lacked such data (category 2). Five new category 1 findings were identified: Flubromazepam in two data files from 2015 and 2016, respectively, phenibut (4-amino-3-phenylbutyric acid) in one data file from 2015, fluorofentanyl in one data file from 2016 and cyclopropylfentanyl in one data file from 2018. Retention time matches with reference standards further strengthened these findings. A list of 35 presumably positive category 2 findings was generated. Of these, only one finding of phenibut was considered plausible after checking retention times and signal-to-noise ratios. This study shows that new compounds can be detected retrospectively in data files from QTOF-MS using an updated library containing diagnostic fragment ions. Automatic screening procedures can be useful, but a manual re-evaluation of positive findings will always be necessary. (C) 2020 The Author(s). Published by Elsevier B.V.
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| 7. |
- Gundersen, Per Ole M., et al.
(författare)
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Screening, quantification, and confirmation of synthetic cannabinoid metabolites in urine by UHPLC-QTOF-MS
- 2019
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Ingår i: Drug Testing and Analysis. - : WILEY. - 1942-7603 .- 1942-7611. ; 11:1, s. 51-67
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic cannabinoids are one of the most significant groups within the category new psychoactive substances (NPS) and in recent years new compounds have continuously been introduced to the market of recreational drugs. A sensitive and quantitative screening method in urine with metabolites of frequently seized compounds in Norway (AB-FUBINACA, AB-PINACA, AB-CHMINACA, AM-2201, AKB48, 5F-AKB48, BB-22, JWH-018, JWH-073, JWH-081, JWH-122, JWH-203, JWH-250, PB-22, 5F-PB-22, RCS-4, THJ-2201, and UR-144) using ultra-high pressure liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS) has been developed. The samples were treated with ss-glucuronidase prior to extraction and solid-phase extraction was used. Liquid handling was automated using a robot. Chromatographic separation was achieved using a C18-column and a gradient of water and acetonitrile, both with 0.1% formic acid. Each sample was initially screened for identification and quantification followed by a second injection for confirmation. The concentrations by which the compounds could be confirmed varied between 0.1 and 12 ng/mL. Overall the validation showed that the method fulfilled the set criteria and requirements for matrix effect, extraction recovery, linearity, precision, accuracy, specificity, and stability. One thousand urine samples from subjects in drug withdrawal programs were analyzed using the presented method. The metabolite AB-FUBINACA M3, hydroxylated metabolite of 5F-AKB48, hydroxylated metabolite of AKB48, AKB48 N-pentanoic acid, 5F-PB-22 3-carboxyindole, BB-22 3-carboxyindole, JWH-018 N-(5-hydroxypentyl), JWH-018 N-pentanoic acid, and JWH-073 N-butanoic acid were quantified and confirmed in 2.3% of the samples. The method was proven to be sensitive, selective and robust for routine use for the investigated metabolites.
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| 8. |
- Gundersen, P., et al.
(författare)
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The response of methane and nitrous oxide fluxes to forest change in Europe
- 2012
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 9:10, s. 3999-4012
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Tidskriftsartikel (refereegranskat)abstract
- Forests in Europe are changing due to interactions between climate change, nitrogen (N) deposition and new forest management practices. The concurrent impact on the forest greenhouse gas (GHG) balance is at present difficult to predict due to a lack of knowledge on controlling factors of GHG fluxes and response to changes in these factors. To improve the mechanistic understanding of the ongoing changes, we studied the response of soil–atmosphere exchange of nitrous oxide (N2O) and methane (CH4) at twelve experimental or natural gradient forest sites, representing anticipated future forest change. The experimental manipulations, one or more per site, included N addition (4 sites), changes of climate (temperature, 1 site; precipitation, 2 sites), soil hydrology (3 sites), harvest intensity (1 site), wood ash fertilisation (1 site), pH gradient in organic soil (1 site) and afforestation of cropland (1 site). On average, N2O emissions increased by 0.06 ± 0.03 (range 0–0.3) g N2O-N m−2 yr−1 across all treatments on mineral soils, but the increase was up to 10 times higher in an acidic organic soil. Soil moisture together with mineral soil C / N ratio and pH were found to significantly influence N2O emissions across all treatments. Emissions were increased by elevated N deposition, especially in interaction with increased soil moisture. High pH reduced the formation of N2O, even under otherwise favourable soil conditions. Oxidation (uptake) of CH4 was on average reduced from 0.16 ± 0.02 to 0.04 ± 0.05 g CH4-C m−2 yr−1 by the investigated treatments. The CH4 exchange was significantly influenced by soil moisture and soil C / N ratio across all treatments, and CH4 emissions occurred only in wet or water-saturated conditions. For most of the investigated forest manipulations or natural gradients, the response of both N2O and CH4 fluxes was towards reducing the overall GHG forest sink. The most resilient forests were dry Mediterranean forests, as well as forests with high soil C / N ratio or high soil pH. Mitigation strategies may focus on (i) sustainable management of wet forest areas and forested peatlands, (ii) continuous forest cover management, (iii) reducing atmospheric N input and, thus, N availability, and (iv) improving neutralisation capacity of acid soils (e.g. wood ash application).
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| 9. |
- Heděnec, Petr, et al.
(författare)
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Mycorrhizal association of common European tree species shapes biomass and metabolic activity of bacterial and fungal communities in soil
- 2020
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Ingår i: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717. ; 149
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have revealed effects of various tree species on soil physical and chemical properties. However, effects of various tree species on composition and activity of soil microbiota and the relevant controls remain poorly understood. We evaluated the influence of tree species associated with two different mycorrhizal types, ectomycorrhiza (EcM) and arbuscular mycorrhiza (AM), on growth, biomass and metabolic activity of soil fungal and bacterial communities using common garden tree species experiments throughout Denmark. The soil microbial communities differed between six European tree species as well as between EcM (beech, lime, oak and spruce) and AM (ash and maple) tree species. The EcM tree species had higher fungal biomass, fungal growth and bacterial biomass, while AM species showed higher bacterial growth. The results indicated that microbial community composition and functioning differed between groups of tree species with distinct litter qualities that generate soil C/N ratio and soil pH differences. The mycorrhizal association only partly explained litter quality and soil microbial species differences since lime was more similar to AM tree species. In addition, our results indicated that tree species-mediated soil pH and C/N ratio were the most important variables shaping microbial communities with a positive effect on bacterial and a negative effect on fungal growth rates. The results suggest that tree species-mediated microbial community composition and activity may be important drivers of the different vertical soil C distribution previously observed in AM and EcM tree species.
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| 10. |
- Klemedtsson, Leif, 1953, et al.
(författare)
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Soil CN ratio as a scalar parameter to predict nitrous oxide emissions
- 2005
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 11:7, s. 1142-1147
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Tidskriftsartikel (refereegranskat)abstract
- Forested histosols have been found in some cases to be major, and in other cases minor, sources of the greenhouse gas nitrous oxide (N2O). In order to estimate the total national or global emissions of N2O from histosols, scaling or mapping parameters that can separate low- and high-emitting sites are needed, and should be included in soil databases. Based on interannual measurements of N2O emissions from drained forested histosols in Sweden, we found a strong negative relationship between N2O emissions and soil CN ratios (r(adj)(2)=0.96, mean annual N2O emission=ae((-b CN ratio))). The same equation could be used to estimate the N2O emissions from Finnish and German sites based on CN ratios in published data. We envisage that the correlation between N2O emissions and CN ratios could be used to scale N2O emissions from histosols determined at sampled sites to national levels. However, at low CN ratios (i.e. below 15-20) other parameters such as climate, pH and groundwater tables increase in importance as regulating factors affecting N2O emissions.
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