1. |
- Lindberg, Margaretha, et al.
(författare)
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Postoperative pain after colorectal surgery
- 2020
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 35:7, s. 1265-1272
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Postoperative pain is a keystone in perioperative programs, as pain negatively impacts recovery. This study aimed to evaluate pain after elective colorectal surgery and to identify risk factors for postoperative pain.Methods: This prospective cohort study comprised consecutive patients undergoing elective colorectal surgery within the Enhanced Recovery after Surgery (ERAS) perioperative program between March 2013 and April 2017. The numeric rating scale (NRS) was used to estimate maximum pain. Logistic regression was used to model associations with the type of surgery, age, gender, and comorbidities.Results: The cohort comprised 434 of 459 eligible patients. On the day of surgery to postoperative day 3, 50-64% of patients reported moderate to severe pain (NRS 4-10). Postoperative pain was similar for open and minimally invasive rectal surgery, while patients undergoing minimally invasive colonic surgery experienced more pain on the day of surgery and less pain on postoperative days 2 and 3 vs. open colonic surgery. Younger age was associated with more pain every postoperative day and by 0.7 NRS/10 years (95% CI 0.5-0.9, P < 0.001) on the day of surgery, while having diabetes type 2 was associated with less postoperative pain by - 1.3 NRS (95% CI - 2.4 to - 0.2) on the day of surgery.Conclusions: The majority, and young patients in particular, experience moderate to severe pain after open and minimally invasive colorectal surgery, despite following ERAS perioperative program. There is a need for effective and individualized analgesia after colorectal surgery, since the individual pain response to surgery is difficult to predict.
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2. |
- Molnár, Adrienne, et al.
(författare)
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Portomesenteric venous contact ≤180° and overall survival in resectable head and body pancreatic adenocarcinoma treated with upfront surgery
- 2023
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 49:11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Upfront surgery is the standard of care for resectable pancreatic cancer, defined as the absence of or ≤180° tumour contact with the portal/superior mesenteric vein. We hypothesized that portomesenteric venous contact is prognostically unfavourable and aimed to assess whether it is associated with poorer outcomes compared with no venous contact in resectable head and body pancreatic cancer.Methods: This single-centre retrospective study included patients undergoing upfront surgery for resectable head and body pancreatic cancer in 2010–2020 at Umeå University Hospital, Sweden. No venous contact was compared with portomesenteric venous contact of ≤180° based on preoperative imaging. Survival on an intention-to-treat basis was compared with Kaplan-Meier curves, a log-rank test and Cox proportional hazards models.Results: The final study cohort included 39 patients with portomesenteric venous contact and 144 patients without venous contact. Patients with portomesenteric tumour contact had a median overall survival of 15.3 months compared to 23.0 months (log rank P = 0.059). Portomesenteric venous contact was an independent negative prognostic factor for survival in the multivariable Cox model (HR 1.68; 95% CI 1.11–2.55, P = 0.014) and was associated with higher rates of microscopically non-radical resections (R1) (50% vs 26.1%, P = 0.012) and pathological lymph node metastasis (76.7% vs 56.8%, P = 0.012). There was no difference in adjuvant chemotherapy receipt or postoperative complications between the groups.Conclusions: Portomesenteric venous contact is associated with poorer overall survival and higher rates of R1 resections and lymph node metastasis in patients with resectable head and body pancreatic cancer treated with upfront surgery.
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3. |
- Bodin, Per, et al.
(författare)
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Efficient modeling of sun/shade canopy radiation dynamics explicitly accounting for scattering
- 2012
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 5:2, s. 535-541
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedThe separation of global radiation (Rg) into its direct (Rb) and diffuse constituents (Rg) is important when modeling plant photosynthesis because a high Rd:Rg ratio has been shown to enhance Gross Primary Production (GPP). To include this effect in vegetation models, the plant canopy must be separated into sunlit and shaded leaves. However, because such models are often too intractable and computationally expensive for theoretical or large scale studies, simpler sun-shade approaches are often preferred. A widely used and computationally efficient sun-shade model was developed by Goudriaan (1977) (GOU). However, compared to more complex models, this model's realism is limited by its lack of explicit treatment of radiation scattering.Here we present a new model based on the GOU model, but which in contrast explicitly simulates radiation scattering by sunlit leaves and the absorption of this radiation by the canopy layers above and below (2-stream approach). Compared to the GOU model our model predicts significantly different profiles of scattered radiation that are in better agreement with measured profiles of downwelling diffuse radiation. With respect to these data our model's performance is equal to a more complex and much slower iterative radiation model while maintaining the simplicity and computational efficiency of the GOU model.
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4. |
- Bonner, Mark TL., et al.
(författare)
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Those who can don't want to, and those who want to can't: An eco-evolutionary mechanism of soil carbon persistence
- 2022
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Ingår i: Soil Biology and Biochemistry. - : Elsevier. - 0038-0717 .- 1879-3428. ; 174
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Tidskriftsartikel (refereegranskat)abstract
- Reliable manipulation of soil organic matter (SOM) – a necessity for optimal land management – is constrained by our limited mechanistic understanding of SOM formation. Here we propose a novel mechanistic element that may contribute to SOM dynamics, supplementing existing frameworks, based on evolutionary-ecological rather than chemical or physical limitations to decomposition. We argue that decomposition of some substrates may be constrained by spatial competition from opportunists. We describe and test a mathematical model based on our framework, providing a proof-of-concept that substrate can, in principle, be spared decomposition and accumulate even when it is physically and chemically accessible. Our framework can help explain a variety of SOM dynamics, including priming and the suppression of decomposition by nitrogen addition, as well as the typical composition of SOM. An augmented mechanistic framework for understanding SOM dynamics can help guide targeted empirical study, which in turn can contribute to more optimised land management.
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5. |
- Borgmästars, Emmy, et al.
(författare)
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Circulating tissue polypeptide-specific antigen in pre-diagnostic pancreatic cancer samples
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:21
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Tidskriftsartikel (refereegranskat)abstract
- Early detection of pancreatic ductal adenocarcinoma (PDAC) is challenging, and late diagnosis partly explains the low 5-year survival. Novel and sensitive biomarkers are needed to enable early PDAC detection and improve patient outcomes. Tissue polypeptide specific antigen (TPS) has been studied as a biomarker in PDAC diagnostics, and it has previously been shown to reflect clinical status better than the ‘golden standard’ biomarker carbohydrate antigen 19-9 (CA 19-9) that is most widely used in the clinical setting. In this cross-sectional case-control study using pre-diagnostic plasma samples, we aim to evaluate the potential of TPS as a biomarker for early PDAC detection. Furthermore, in a subset of individuals with multiple samples available at different time points before diagnosis, a longitudinal analysis was used. We assessed plasma TPS levels using enzyme-linked immunosorbent assay (ELISA) in 267 pre-diagnostic PDAC plasma samples taken up to 18.8 years before clinical PDAC diagnosis and in 320 matched healthy controls. TPS levels were also assessed in 25 samples at PDAC diagnosis. Circulating TPS levels were low both in pre-diagnostic samples of future PDAC patients and in healthy controls, whereas TPS levels at PDAC diagnosis were significantly increased (odds ratio 1.03; 95% confidence interval: 1.01–1.05) in a logistic regression model adjusted for age. In conclusion, TPS levels increase late in PDAC progression and hold no potential as a biomarker for early detection.
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6. |
- Borgmästars, Emmy, 1990-
(författare)
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In search of early biomarkers in pancreatic ductal adenocarcinoma using multi-omics and bioinformatics
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive malignancy with a 5-year survival of 10 %. Surgery is the only curative treatment. Unfortunately, few patients are eligible for surgery due to late detection. Thus, we need ways to detect the disease at an earlier stage and for that good screening biomarkers could be used. Previous studies have analyzed circulating analytes in prospective studies to identify early PDAC signals. One such class is microRNAs (miRNAs). MicroRNAs are non-coding RNAs of around 22 nucleotides that act as post- transcriptional regulators by interaction with messenger RNAs (mRNAs). The function of a miRNA can be elucidated by target prediction, to identify its potential targets, followed by enrichment analysis of the predicted targets. Challenges with this approach includes a lot of false positives being generated and that miRNAs can perform their role in a tissue- or disease-specific manner. Other classes of analytes that have previously been studied in prospective PDAC cohorts are metabolites and proteins. Aims: This thesis has three aims. First, to build a miRNA functional analysis pipeline with correlation support between miRNA and its predicted target genes. Second, to identify potential circulating biomarkers for early detection of PDAC using multi-omics. Third, to identify potential prognostic metabolites in a prospective PDAC cohort.Methods: We used publicly available data from the cancer genome atlas-pancreatic adenocarcinoma (TCGA-PAAD) and pre-diagnostic plasma samples from the Northern Sweden Health and Disease Study. We built a pipeline in R including miRNA, mRNA, and protein expression data from TCGA-PAAD for in silico miRNA functional analysis. Pre- diagnostic plasma samples from future PDAC patients as well as matched healthy controls were analyzed using multi- omics. Tissue polypeptide specific antigen (TPS) was analyzed by enzyme linked immunosorbent assay in 267 future PDAC samples and 320 healthy controls. Metabolomics and clinical biomarkers (carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), and CA 15-3) were profiled in 100 future PDAC samples and 100 healthy controls using liquid chromatography-mass spectrometry (MS), gas chromatography-MS, and multi-plex technology. Of these, a subset of 39 future PDAC patients and 39 healthy controls were profiled for 2083 microRNAs using targeted sequencing and 644 proteins using proximity extension assays. Circulating levels of multi-omics analytes were analyzed using conditional or unconditional logistic regression. Least absolute shrinkage and selection operator (LASSO) in combination with 500 bootstrap iterations identified the most informative variables. The prognostic value of metabolites was assessed using cox regression. Multi-omics factor analysis (MOFA) and data integration analysis for biomarker discovery using latent components (DIABLO) were used for multi-omics integration analyses.Results: An automated pipeline was built consisting of 1) miRNA target prediction, 2) correlation analyses between miRNA and its targets on mRNA and protein expression levels, and 3) functional enrichment of correlated targets to identify enriched Kyoto encyclopedia of genes and genomes (KEGG) pathways and gene ontology (GO) terms for a specific miRNA. The pipeline was run for all microRNAs (~700) detected in the TCGA-PAAD cohort. These results can be downloaded from a shiny app (https://emmbor.shinyapps.io/mirfa/). TPS was not altered in pre-diagnostic PDAC patients up to 24 years prior to diagnosis, but increased at diagnosis (OR = 1.03, 95 % CI: 1.01-1.05). Internal area under curves of 0.74, 0.80, and 0.88 were achieved for five metabolites, two proteins, and two miRNAs that were selected by LASSO and bootstrap iterations, in combination with CA 19-9. Neither MOFA nor DIABLO separated well between future PDAC cases and healthy controls. Conclusions: Our bioinformatics pipeline for in silico functional analysis of microRNAs successfully identifies enriched KEGG pathways and GO terms for miRNA isoforms. The investigated plasma samples are heterogeneous, but among the analyzed variables, we identified five metabolites, two proteins, and two microRNAs with highest potential for early PDAC detection. CA 19-9 levels increased closer to diagnosis. We identified five fatty acids that could be studied in a diagnostic PDAC cohort as prognostic biomarkers.
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7. |
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8. |
- Borgmästars, Emmy, et al.
(författare)
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Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
- 2024
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Ingår i: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 15:2, s. 755-767
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.
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9. |
- Borgmästars, Emmy, et al.
(författare)
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Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank
- 2024
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Ingår i: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 15:2, s. 755-767
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.Methods: We performed metabolomics by liquid and gas chromatography-mass spectrometry in plasma samples from 82 future pancreatic cancer patients and 82 matched healthy controls within the Northern Sweden Health and Disease Study (NSHDS). Logistic regression was used to assess univariate associations between metabolites and pancreatic cancer risk. Least absolute shrinkage and selection operator (LASSO) logistic regression was used to design a metabolite-based risk score. We used receiver operating characteristic (ROC) analyses to assess the discriminative performance of the metabolite-based risk score.Results: Among twelve risk-associated metabolites with a nominal P value <0.05, we defined a risk score of three metabolites [indoleacetate, 3-hydroxydecanoate (10:0-OH), and retention index (RI): 2,745.4] using LASSO. A logistic regression model containing these three metabolites, age, sex, body mass index (BMI), smoking status, sample date, fasting status, and carbohydrate antigen 19-9 (CA 19-9) yielded an internal area under curve (AUC) of 0.784 [95% confidence interval (CI): 0.714–0.854] compared to 0.681 (95% CI: 0.597–0.764) for a model without these metabolites (P value =0.007). Seventeen metabolites were significantly associated with pancreatic cancer survival [false discovery rate (FDR) <0.1].Conclusions: Indoleacetate, 3-hydroxydecanoate (10:0-OH), and RI: 2,745.4 were identified as the top candidate biomarkers for early detection. However, continued efforts are warranted to determine the usefulness of these metabolites as early pancreatic cancer biomarkers.
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10. |
- Borgmästars, Emmy, et al.
(författare)
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Multi-omics profiling to identify early plasma biomarkers in pre-diagnostic pancreatic ductal adenocarcinoma : a nested case-control study
- 2024
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Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor survival. Novel biomarkers are urgently needed to improve the outcome through early detection. Here, we aimed to discover novel biomarkers for early PDAC detection using multi-omics profiling in pre-diagnostic plasma samples biobanked after routine health examinations.A nested case-control study within the Northern Sweden Health and Disease Study was designed. Pre-diagnostic plasma samples from 37 future PDAC patients collected within 2.3 years before diagnosis and 37 matched healthy controls were included. We analyzed metabolites using liquid chromatography mass spectrometry and gas chromatography mass spectrometry, microRNAs by HTG edgeseq, proteins by multiplex proximity extension assays, as well as three clinical biomarkers using milliplex technology. Supervised and unsupervised multi-omics integration were performed as well as univariate analyses for the different omics types and clinical biomarkers. Multiple hypothesis testing was corrected using Benjamini-Hochberg's method and a false discovery rate (FDR) below 0.1 was considered statistically significant.Carbohydrate antigen (CA) 19-9 was associated with PDAC risk (OR [95 % CI] = 3.09 [1.31–7.29], FDR = 0.03) and increased closer to PDAC diagnosis. Supervised multi-omics models resulted in poor discrimination between future PDAC cases and healthy controls with obtained accuracies between 0.429–0.500. No single metabolite, microRNA, or protein was differentially altered (FDR < 0.1) between future PDAC cases and healthy controls.CA 19-9 levels increase up to two years prior to PDAC diagnosis but extensive multi-omics analysis including metabolomics, microRNAomics and proteomics in this cohort did not identify novel early biomarkers for PDAC.
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12. |
- Cayssials, Valerie, et al.
(författare)
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Inflammatory potential of diet and pancreatic cancer risk in the EPIC study
- 2022
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Ingår i: European Journal of Nutrition. - : Springer Nature. - 1436-6207 .- 1436-6215. ; 61, s. 2313-2320
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: There is existing evidence on the potential role of chronic inflammation in the pathogenesis of pancreatic cancer (PC) and on how risk may be modulated by dietary factors. Pro-inflammatory diets are suggested to be associated with increased risk of PC but, so far, evidence remains not conclusive. We examined the association between the dietary inflammatory potential and PC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which includes 450,112 participants.Methods: After a 14-year follow-up, a total of 1239 incident PC cases were included in this study. The inflammatory potential of the diet was estimated using an Inflammatory Score of the Diet (ISD). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between the ISD and PC were estimated using multivariable Cox regression models, adjusted for known risk factors for PC.Results: Participants with higher ISDs had a higher risk of developing PCs. In the fully adjusted multivariate model, the risk of PC increased by 11% (HR 1.11, 95% CI 1.02–1.22) for 1 point each standard deviation increase in the ISD score. Neither obesity nor any other known risk factor for PC showed statistically significant interactions.Conclusion: To the best of our knowledge, this is the first prospective study reporting a positive relationship between the inflammatory potential of diet and PC. Since early diagnosis and treatment of pancreatic cancer might be challenging, prevention remains the major hope for reducing the burden of this disease.
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14. |
- Franklin, Oskar, et al.
(författare)
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A simulation-based approach to a near-optimal thinning strategy: allowing harvesting times to be determined for individual trees
- 2020
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Ingår i: Canadian Journal of Forest Research. - : Canadian Science Publishing. - 0045-5067 .- 1208-6037. ; 50, s. 320-331
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Tidskriftsartikel (refereegranskat)abstract
- As various methods for precision inventories, including light detection and ranging (LiDAR), are becoming increasingly common in forestry, planning at the individual-tree level is becoming more viable. In this study, we present a method for finding the optimal thinning times for individual trees from an economic perspective. The method utilizes a forest growth model based on individual trees that has been fitted to Norway spruce (Picea abies (L.) Karst.) stands in northern Sweden. We find that the optimal management strategy is to thin from above (i.e., harvesting trees that are larger than average). We compare our optimal strategy with a conventional management strategy and find that the optimal strategy results in approximately 20% higher land expectation value. Furthermore, we find that for the optimal strategy, increasing the discount rate will reduce the final harvest age and increase the basal area reduction. Decreasing the cost to initiate a thinning (e.g., machinery-related transportation costs) increases the number of thinnings and delays the first thinning.
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15. |
- Franklin, Oskar, 1985-, et al.
(författare)
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Adjuvant chemotherapy with or without radiotherapy for resected pancreatic cancer after multiagent neoadjuvant chemotherapy
- 2024
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Ingår i: Annals of Surgical Oncology. - : Springer Nature. - 1068-9265 .- 1534-4681. ; 31:8, s. 4966-4975
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting.Methods: This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45–50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup.Results: Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61–0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37–0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44–0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors.Conclusion: After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.
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18. |
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19. |
- Franklin, Oskar, et al.
(författare)
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Combining conventional and stroma-derived tumour markers in pancreatic ductal adenocarcinoma
- 2015
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Ingår i: Cancer Biomarkers. - : IOS Press. - 1574-0153. ; 15:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A lack of disease-specific symptoms and good tumour markers makes early detection and diagnosis of pancreatic ductal adenocarcinoma (PDAC) challenging. OBJECTIVE: To analyse the tissue expression and circulating levels of four stroma-derived substances (type IV collagen, endostatin/type XVIII collagen, osteopontin and tenascin C) and four conventional tumour markers (CA 19-9, TPS, CEA and Ca 125) in a PDAC cohort.METHODS: Tissue expression of markers in normal pancreas and PDAC tissue was analysed with immunofluorescence. Plasma concentrations of markers were measured before and after surgery. Patients with non-malignant disorders served as controls.RESULTS: The conventional and stromal substances were expressed in the cancer cell compartment and the stroma, respectively. Although most patients had increased levels of many markers before surgery, 2/12 (17%) of patients had normal levels of Ca 19-9 at this stage. High preoperative endostatin/type XVIII collagen, and postoperative type IV collagen was associated with short survival. Neither the pre-nor postoperative levels of TPS, Ca 125 or CA 19-9 were associated to survival.CONCLUSIONS: PDAC is characterized by an abundant stroma. These initial observations indicate that the stroma can be a source of PDAC tumour markers that are found in different compartments of the cancer, thus reflecting different aspects of tumour biology.
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20. |
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21. |
- Franklin, Oskar
(författare)
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KEYLINK: towards a more integrative soil representation for inclusion in ecosystem scale models. I. review and model concept
- 2020
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Ingår i: PeerJ. - : PeerJ. - 2167-8359. ; 8
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Forskningsöversikt (refereegranskat)abstract
- The relatively poor simulation of the below-ground processes is a severe drawback for many ecosystem models, especially when predicting responses to climate change and management. For a meaningful estimation of ecosystem production and the cycling of water, energy, nutrients and carbon, the integration of soil processes and the exchanges at the surface is crucial. It is increasingly recognized that soil biota play an important role in soil organic carbon and nutrient cycling, shaping soil structure and hydrological properties through their activity, and in water and nutrient uptake by plants through mycorrhizal processes. In this article, we review the main soil biological actors (microbiota, fauna and roots) and their effects on soil functioning. We review to what extent they have been included in soil models and propose which of them could be included in ecosystem models. We show that the model representation of the soil food web, the impact of soil ecosystem engineers on soil structure and the related effects on hydrology and soil organic matter (SOM) stabilization are key issues in improving ecosystem-scale soil representation in models. Finally, we describe a new core model concept (KEYLINK) that integrates insights from SOM models, structural models and food web models to simulate the living soil at an ecosystem scale.
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22. |
- Franklin, Oskar, et al.
(författare)
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Modeling carbon allocation in trees : a search for principles
- 2012
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Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 0829-318X .- 1758-4469. ; 32:6, s. 648-666
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Forskningsöversikt (refereegranskat)abstract
- We review approaches to predicting carbon and nitrogen allocation in forest models in terms of their underlying assumptions and their resulting strengths and limitations. Empirical and allometric methods are easily developed and computationally efficient, but lack the power of evolution-based approaches to explain and predict multifaceted effects of environmental variability and climate change. In evolution-based methods, allocation is usually determined by maximization of a fitness proxy, either in a fixed environment, which we call optimal response (OR) models, or including the feedback of an individual's strategy on its environment (game-theoretical optimization, GTO). Optimal response models can predict allocation in single trees and stands when there is significant competition only for one resource. Game-theoretical optimization can be used to account for additional dimensions of competition, e.g., when strong root competition boosts root allocation at the expense of wood production. However, we demonstrate that an OR model predicts similar allocation to a GTO model under the root-competitive conditions reported in free-air carbon dioxide enrichment (FACE) experiments. The most evolutionarily realistic approach is adaptive dynamics (AD) where the allocation strategy arises from eco-evolutionary dynamics of populations instead of a fitness proxy. We also discuss emerging entropy-based approaches that offer an alternative thermodynamic perspective on allocation, in which fitness proxies are replaced by entropy or entropy production. To help develop allocation models further, the value of wide-ranging datasets, such as FLUXNET, could be greatly enhanced by ancillary measurements of driving variables, such as water and soil nitrogen availability.
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23. |
- Franklin, Oskar, 1985-, et al.
(författare)
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Novel prognostic markers within the CD44-stromal ligand network in pancreatic cancer
- 2019
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Ingår i: Journal of Pathology. - : John Wiley & Sons. - 0022-3417 .- 1096-9896. ; 5:2, s. 130-141
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Tidskriftsartikel (refereegranskat)abstract
- The dense stroma in pancreatic cancer tumours is rich in secreted extracellular matrix proteins and proteoglycans. Secreted hyaluronan, osteopontin and type IV collagen sustain oncogenic signalling by interactions with CD44s and its variant isoform CD44v6 on cancer cell membranes. Although well established in animal and in vitro models, this oncogenic CD44-stromal ligand network is less explored in human cancer. Here, we use a pancreatic cancer tissue microarray from 69 primary tumours and 37 metastatic lymph nodes and demonstrate that high tumour cell expression of CD44s and, surprisingly, low stromal deposition of osteopontin correlate with poor survival independent of established prognostic factors for pancreatic cancer. High stromal expression of hyaluronan was a universal trait of both primary tumours and metastatic lymph nodes. However, hyaluronan species of different molecular mass are known to function differently in pancreatic cancer biology and immunohistochemistry cannot distinguish between them. Using gas-phase electrophoretic molecular mobility analysis, we uncover a shift towards high molecular mass hyaluronan in pancreatic cancer tissue compared to normal pancreas and at a transcriptional level, we find that hyaluronan synthesising HAS2 correlates positively with CD44. The resulting prediction that high molecular mass hyaluronan would then correlate with poor survival in pancreatic cancer was confirmed in serum samples, where we demonstrate that hyaluronan >27 kDa measured before surgery is an independent predictor of postoperative survival. Our findings confirm the prognostic value of CD44 tissue expression and highlight osteopontin tissue expression and serum high molecular mass hyaluronan as novel prognostic markers in pancreatic cancer.
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24. |
- Franklin, Oskar, et al.
(författare)
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Organizing principles for vegetation dynamics
- 2020
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Ingår i: Nature plants. - : Springer Science and Business Media LLC. - 2055-026X .- 2055-0278. ; 6:5, s. 444-453
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Tidskriftsartikel (refereegranskat)abstract
- Plants and vegetation play a critical-but largely unpredictable-role in global environmental changes due to the multitude of contributing processes at widely different spatial and temporal scales. In this Perspective, we explore approaches to master this complexity and improve our ability to predict vegetation dynamics by explicitly taking account of principles that constrain plant and ecosystem behaviour: natural selection, self-organization and entropy maximization. These ideas are increasingly being used in vegetation models, but we argue that their full potential has yet to be realized. We demonstrate the power of natural selection-based optimality principles to predict photosynthetic and carbon allocation responses to multiple environmental drivers, as well as how individual plasticity leads to the predictable self-organization of forest canopies. We show how models of natural selection acting on a few key traits can generate realistic plant communities and how entropy maximization can identify the most probable outcomes of community dynamics in space- and time-varying environments. Finally, we present a roadmap indicating how these principles could be combined in a new generation of models with stronger theoretical foundations and an improved capacity to predict complex vegetation responses to environmental change. Integrating natural selection and other organizing principles into next-generation vegetation models could render them more theoretically sound and useful for earth system applications and modelling climate impacts.
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25. |
- Franklin, Oskar, et al.
(författare)
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Pine forest floor carbon accumulation in response to N and PK additions : Bomb C-14 modelling and respiration studies
- 2003
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Ingår i: Ecosystems (New York. Print). - : Springer Science and Business Media LLC. - 1432-9840 .- 1435-0629. ; 6:7, s. 644-658
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Tidskriftsartikel (refereegranskat)abstract
- The addition of nitrogen via deposition alters the carbon balance of temperate forest ecosystems by affecting both production and decomposition rates. The effects of 20 years of nitrogen (N) and phosphorus and potassium (PK) additions were studied in a 40-year-old pine stand in northern Sweden. Carbon fluxes of the forest floor were reconstructed using a combination of data on soil 14C, tree growth, and litter decomposition. N-only additions caused an increase in needle litterfall, whereas both N and PK additions reduced long-term decomposition rates. Soil respiration measurements showed a 40% reduction in soil respiration for treated compared to control plots. The average age of forest floor carbon was 17 years. Predictions of future soil carbon storage indicate an increase of around 100% in the next 100 years for the N plots and 200% for the NPK plots. As much as 70% of the increase in soil carbon was attributed to the decreased decomposition rate, whereas only 20% was attributable to increased litter production. A reduction in decomposition was observed at a rate of N addition of 30 kg C ha−1 y−1, which is not an uncommon rate of N deposition in central Europe. A model based on the continuous-quality decomposition theory was applied to interpret decomposer and substrate parameters. The most likely explanations for the decreased decomposition rate were a fertilizer-induced increase in decomposer efficiency (production-to-assimilation ratio), a more rapid rate of decrease in litter quality, and a decrease in decomposer basic growth rate.
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26. |
- Franklin, Oskar, et al.
(författare)
-
Plasma micro-RNA alterations appear late in pancreatic cancer
- 2018
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 267:4, s. 775-781
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this research was to study whether plasma microRNAs (miRNA) can be used for early detection of pancreatic cancer (PC) by analyzing prediagnostic plasma samples collected before a PC diagnosis. Background: PC has a poor prognosis due to late presenting symptoms and early metastasis. Circulating miRNAs are altered in PC at diagnosis but have not been evaluated in a prediagnostic setting. Methods: We first performed an initial screen using a panel of 372 miRNAs in a retrospective case-control cohort that included early-stage PC patients and healthy controls. Significantly altered miRNAs at diagnosis were then measured in an early detection case-control cohort wherein plasma samples in the cases are collected before a PC diagnosis. Carbohydrate antigen 19–9 (Ca 19–9) levels were measured in all samples for comparison. Results: Our initial screen, including 23 stage I-II PC cases and 22 controls, revealed 15 candidate miRNAs that were differentially expressed in plasma samples at PC diagnosis. We combined all 15 miRNAs into a multivariate statistical model, which outperformed Ca 19–9 in receiver-operating characteristics analysis. However, none of the candidate miRNAs, individually or in combination, were significantly altered in prediagnostic plasma samples from 67 future PC patients compared with 132 matched controls. In comparison, Ca 19–9 levels were significantly higher in the cases at <5 years before diagnosis. Conclusion: Plasma miRNAs are altered in PC patients at diagnosis, but the candidate miRNAs found in this study appear late in the course of the disease and cannot be used for early detection of the disease.
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27. |
- Franklin, Oskar
(författare)
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Response to Comment on "Mycorrhizal association as a primary control of the CO2 fertilization effect"
- 2017
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Ingår i: ScienceDirect. - : American Association for the Advancement of Science (AAAS). ; 355, s. 358-
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Annan publikation (refereegranskat)abstract
- Norby et al. center their critique on the design of the data set and the response variable used. We address these criticisms and reinforce the conclusion that plants that associate with ectomycorrhizal fungi exhibit larger biomass and growth responses to elevated CO2 compared with plants that associate with arbuscular mycorrhizae.
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28. |
- Franklin, Oskar
(författare)
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Social dynamics within decomposer communities lead to nitrogen retention and organic matter build-up in soils
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- The chemical structure of organic matter has been shown to be only marginally important for its decomposability by microorganisms. The question of why organic matter does accumulate in the face of powerful microbial degraders is thus key for understanding terrestrial carbon and nitrogen cycling. Here we demonstrate, based on an individual-based microbial community model, that social dynamics among microbes producing extracellular enzymes ('decomposers') and microbes exploiting the catalytic activities of others ('cheaters') regulate organic matter turnover. We show that the presence of cheaters increases nitrogen retention and organic matter build-up by downregulating the ratio of extracellular enzymes to total microbial biomass, allowing nitrogen-rich microbial necromass to accumulate. Moreover, increasing catalytic efficiencies of enzymes are outbalanced by a strong negative feedback on enzyme producers, leading to less enzymes being produced at the community level. Our results thus reveal a possible control mechanism that may buffer soil CO2 emissions in a future climate.
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29. |
- Franklin, Oskar, 1985-
(författare)
-
Stromal components and micro-RNAs as biomarkers in pancreatic cancer
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Pancreatic ductal adenocarcinoma (PDAC) patients have the poorest 5-year survival rates of all cancer forms. It is difficult to diagnose at early disease stages, tumour relapse after surgery is common, and current chemotherapies are ineffective. Carbohydrate antigen 19-9 (Ca 19-9), the only clinically implemented PDAC biomarker, is insufficient for diagnostic and screening purposes.PDAC tumours are characterised by a voluminous stroma that is rich in extracellular matrix (ECM) molecules such as collagens, hyaluronan (HA) and matricellular proteins. These stromal components have been suggested to promote PDAC cell migration, proliferation, evasion of apoptosis and chemotherapy resistance. Those events are mediated via interactions with adhesion receptors, such as integrins and CD44 receptors expressed on cancer cell surfaces.Micro-RNAs (miRNA) post-transcriptionally regulate gene expression in health and disease. At the time of PDAC diagnosis, miRNA levels are altered both in plasma and tumour tissue. Before PDAC diagnosis, tissue miRNA levels are altered in precursor lesions, raising the possibility that plasma miRNAs might aid in early detection.In this thesis, it is hypothesised that stromal components and miRNAs can serve as tissue or blood based biomarkers in PDAC. The aims are: (1) to characterise the expression of stromal components and their receptors in normal and cancerous tissue; (2) to find potential stroma-associated tissue and blood-based biomarkers for diagnosis and prognosis estimates; (3) to determine the cellular effects of type IV collagen (Col IV) in PDAC; (4) to determine if plasma miRNAs that are altered in manifest PDAC can be used to diagnose PDAC earlier.Methods The expression patterns of Col IV, Col IV-binding integrin subunits (α1, α2, β1), Endostatin, Osteopontin (OPN) and Tenascin C (TNC) were analysed in frozen PDAC and normal pancreatic tissue. A tissue microarray (TMA) was constructed using formalin-fixed, paraffin-embedded primary tumours and lymph node metastases. The TMA was used to study the expression levels and associations with survival of the standard CD44 receptor (CD44s), its variant isoform 6 (CD44v6), HA, OPN and Col IV. Circulating levels of HA, Col IV, Endostatin, OPN and TNC were measured in PDAC patients and healthy individuals, and compared with conventional tumour markers (Ca 19-9, CEA, Ca 125 and TPS). The functional roles of Col IV were studied in PDAC cell lines by: (1) growth on different matrices (2) blocking Col IV binding integrin subunits, (3) blocking the Col IV domains 7s, CB3 and NC1, and (4) by down regulation of PDAC cell synthesis of Col IV using siRNA transfection. Plasma miRNAs alterations were screened for in samples from patients with manifest disease, using real-time quantitative PCR (RT-qPCR). To find early miRNA alterations, levels of those miRNAs that were altered at diagnosis were measured in prediagnostic plasma samples.Results High tissue expression of both the standard CD44 receptor (CD44s) and its variant isoform CD44v6 as well as low expression of stromal OPN were associated with poor survival. In addition, high CD44s and low OPN predicted poor survival independent of established prognostic factors.Circulating Col IV, Endostatin, OPN, TNC and HA were increased in preoperative samples from PDAC patients. Preoperatively, higher levels of serum-HA and plasma-Endostatin were associated with shorter survival. Postoperatively, higher levels of Col IV, Endostatin and OPN were associated with shorter survival. On the contrary, only one of the conventional tumour markers was associated with survival (Ca 125).Col IV stimulated PDAC cell proliferation and migration and inhibited apoptosis in vitro, dependent on the collagenous domain (CB3) of Col IV and the Col IV binding integrin subunit β1. Reduced endogenous Col IV synthesis inhibited these effects, suggesting that PDAC cells synthesise Col IV to stimulate tumour-promoting events via a newly discovered autocrine loop.15 miRNAs were altered in early stage PDAC patients and the combination of these markers outperformed Ca 19-9 in discriminating patients from healthy individuals. However, none of the miRNAs were altered in prediagnostic samples, suggesting that plasma miRNA alterations appear late in the disease course.Conclusions Up regulated stromal components in PDAC tumours are detectable in blood samples and are potential diagnostic and prognostic biomarkers in PDAC. High circulating levels of Col IV, Endostatin, OPN and HA predict poor survival, as well as high expression of CD44s and CD44v6 and low expression of OPN in tumour tissue. PDAC cells synthesise Col IV, which forms BM-like structures close to cancer cells and promote tumour progression in vitro via an autocrine loop. Several plasma-miRNAs are altered in PDAC, but are not useful for early discovery.
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30. |
- Franklin, Oskar
(författare)
-
Synergistic effects of diffusion and microbial physiology reproduce the Birch effect in a micro-scale model
- 2016
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Ingår i: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 93, s. 28-37
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Tidskriftsartikel (refereegranskat)abstract
- Large rainfall events following drought cause pulses of CO2 flux that are higher than models predict. This phenomenon, named the "Birch effect" after its discoverer, has been observed for decades, and will influence carbon-climate feedbacks as drying-rewetting (DRW) cycles become more common under intensified climates. Yet, the many interacting factors that determine how soil DRW cycles affect C balance have been difficult to separate empirically. Here we use a spatially explicit biogeochemical-microbial model to examine the mechanisms underlying CO2 dynamics under DRW. We independently model physiological activity and diffusion based on how they vary with (constant) moisture levels in nature, and subject the model to DRW to test the importance of different mechanisms in models with one or two microbial functional groups (cheaters and producers). Our model reproduces respiration patterns similar to empirical observations of the Birch effect when we include mechanisms that link water content to microbial growth and to diffusion rate, whereas inclusion of either mechanism alone produces significantly lower pulses upon rewetting. Diffusion limitation under drought increases substrate availability under rewetting, a process mediated by biogeochemical hotspots and continued enzyme activity under drought. At the same time, high microbial growth under rewetting is needed to replenish enzyme pools and to sustain the biomass required to generate respiration pulses under repeated DRW. Inclusion of cheaters in the model dampens the size of the rewetting pulse and the cumulative amount of CO2 release, as cheaters outcompete producers and reduce overall biomass. Our results provide several novel hypotheses regarding the microbial, biogeochemical, and spatial processes that mediate the Birch effect, which will contribute to a better mechanistic understanding of this important deviation from model predictions. (C) 2015 Elsevier Ltd. All rights reserved.
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31. |
- Franklin, Oskar, et al.
(författare)
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The carbon bonus of organic nitrogen enhances nitrogen use efficiency of plants
- 2017
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Ingår i: Plant, Cell and Environment. - : Wiley. - 0140-7791 .- 1365-3040. ; 40, s. 25-35
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Tidskriftsartikel (refereegranskat)abstract
- The importance of organic nitrogen (N) for plant nutrition and productivity is increasingly being recognized. Here we show that it is not only the availability in the soil that matters, but also the effects on plant growth. The chemical form of N taken up, whether inorganic (such as nitrate) or organic (such as amino acids), may significantly influence plant shoot and root growth, and nitrogen use efficiency (NUE). We analysed these effects by synthesizing results from multiple laboratory experiments on small seedlings (Arabidopsis, poplar, pine and spruce) based on a tractable plant growth model. A key point is that the carbon cost of assimilating organic N into proteins is lower than that of inorganic N, mainly because of its carbon content. This carbon bonus makes it more beneficial for plants to take up organic than inorganic N, even when its availability to the roots is much lower - up to 70% lower for Arabidopsis seedlings. At equal growth rate, root:shoot ratio was up to three times higher and nitrogen productivity up to 20% higher for organic than inorganic N, which both are factors that may contribute to higher NUE in crop production.
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32. |
- Fransson, Peter, 1988-, et al.
(författare)
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A simulation-based approach to a near optimal thinning strategy : allowing for individual harvesting times for individual trees
- 2020
-
Ingår i: Canadian Journal of Forest Research. - : Canadian Science Publishing. - 0045-5067 .- 1208-6037. ; 50:3, s. 320-331
-
Tidskriftsartikel (refereegranskat)abstract
- As various methods for precision inventories, such as LiDAR, are becoming increasingly common in forestry, individual-tree level planning is becoming more viable. Here, we present a method for finding the optimal thinning times for individual trees from an economic perspective. The method utilizes an individual tree-based forest growth model that has been fitted to Norway spruce (Picea abies (L.) Karst.) stands in northern Sweden. We find that the optimal management strategy is to thin from above, i.e. harvesting trees that are larger than average. We compare our optimal strategy with a conventional management strategy and find that it results in approximately 20% higher land expectation value. Furthermore, we find that increasing the discount rate will, for the optimal strategy, reduce the final harvest age and increase the basal area reduction. Decreasing the cost to initiate a thinning (e.g., machinery-related transportation costs) increases the number of thinnings and delays the first thinning.
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33. |
- Fransson, Peter, 1988-, et al.
(författare)
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A tree’s quest for light : optimal height and diameter growth under a shading canopy
- 2021
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Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 0829-318X .- 1758-4469. ; 41:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- For trees in forests, striving for light is matter of life and death, either by growing taller toward brighter conditions or by expanding the crown to capture more of the available light. Here, we present a mechanistic model for the development path of stem height and crown size, accounting for light capture and growth, as well as mortality risk. We determine the optimal growth path among all possible trajectories using dynamic programming. The optimal growth path follows a sequence of distinct phases: (i) initial crown size expansion, (ii) stem height growth toward the canopy, (iii) final expansion of the crown in the canopy and (iv) seed production without further increase in size. The transition points between these phases can be optimized by maximizing fitness, defined as expected lifetime reproductive production. The results imply that to reach the canopy in an optimal way, trees must consider the full profile of expected increasing light levels toward the canopy. A shortsighted maximization of growth based on initial light conditions can result in arrested height growth, preventing the tree from reaching the canopy. The previous result can explain canopy stratification, and why canopy species often get stuck at a certain size under a shading canopy. The model explains why trees with lower wood density have a larger diameter at a given tree height and grow taller than trees with higher wood density. The model can be used to implement plasticity in height versus diameter growth in individual-based vegetation and forestry models.
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34. |
- Fransson, Peter, 1988-, et al.
(författare)
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Comparing distance-independent and distance-dependent competition indices for Picea abies
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Competition between individual trees is important for forest growth. Modeling the underlying interactions is difficult and sometimes not possible. Consequently, simplified competition indices are often used as a proxy. Several studies have shown that including competition indices into growth models will improve accuracy. However, there is no consensus on which or what type of indices work well. Here, we compare several indices of two qualitatively different types: distance-independent and distance-dependent indices. These indices are incorporated into a log-linear growth model and tested against 5-year diameter growth data collected from three Norway spruce plots that each have different fertilization treatments. We find that although distance-dependent indices performed better, distance-independent indices can also perform well; R2adj = 0.66 vs. 0.62 for the best indices in each category. We find that Bella’s index to be the best distance-dependent index (the index depends on distance between competitors and their diameters) and Reineke’s index to be the best distance-independent index (this index depends on the mean quadratic diameter and density in the stand). We also find that the performance ranking of indices is consistent across three different fertilization treatments.
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35. |
- Fransson, Peter, 1988-, et al.
(författare)
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Model-based investigation on the effects of spatial evenness, and size selection in thinning of Picea abies stands
- 2019
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Ingår i: Scandinavian Journal of Forest Research. - : Taylor & Francis. - 0282-7581 .- 1651-1891. ; 34:3, s. 189-199
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Tidskriftsartikel (refereegranskat)abstract
- Size and spatial distribution of trees are important for forest stand growth, but the extent to which itmatters in thinning operations, in terms of wood production and stand economy, has rarely beendocumented. Here we investigate how the choice of spatial evenness and tree-size distribution ofresidual trees impacts wood production and stand economy. A spatially explicit individual-basedgrowth model was used, in conjunction with empirical cost functions for harvesting andforwarding, to calculate net production and net present value for different thinning operations inNorway spruce stands in Northern Sweden. The in silico thinning operations were defined by threevariables: (1) spatial evenness after thinning, (2) tree size preference for harvesting, and (3) basalarea reduction. We found that thinning that increases spatial evenness increases net productionand net present value by around 2.0%, compared to the worst case. When changing the spatialevenness in conjunction with size preference we could observe an improvement of the netproduction and net present value up to 8.0%. The magnitude of impact differed greatly betweenthe stands (from 1.7% to 8.0%) and was highest in the stand with the lowest stem density.
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36. |
- Fransson, Peter, 1988-
(författare)
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Optimal thinning : a theoretical investigation on individual-tree level
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Paper I: In paper I, we asked how a tree should optimally allocate its resources to maximize its fitness. We let a subject tree grow in an environment shaded by nearby competing trees. The competitors were assumed to have reached maturity and had stopped growing, thus creating a static light environment for the subject tree to grow in. The light environment was modeled as a logistic function. For the growth model we used the pipe model as a foundation, linking tree width and leaf mass. This allowed us to construct a dynamic tree-growth model where the tree can allocate biomass from photosynthesis (net productivity) to either stem-height growth, crown-size growth, or reproduction (seed production). Using Pontryagin's maximum principle we derived necessary conditions for optimal biomass allocation, and on that built a heuristic allocation model. The heuristic model states that the tree should first invest into crown-size and then switch to tree height-growth, and lastly invest into crown-size before the growth investments stop and all investments are allocated to reproduction. To test our heuristic method, we used it to determine the growth in several different light environments. The results were then compared to the optimal growth trajectories. The optimal growth was determined by applying dynamic programming. Our less computationally demanding heuristic performed very well in comparison. We also found there exist a critical crown-size: if the subject tree possessed a larger crown-size, the tree would be unable to reach up to the canopy height.Paper II: One of the most important aspects of modelling forest growth, and modelling growth of individual trees in general, is the competition between trees. A high level of competition pressure has a negative impact on the growth of individual trees. There are many ways of modelling competition, the most common one is by using a competition index. In this paper we tested 16 competition indices, in conjunction with a log-linear growth model, in terms of the mean squared error and the coefficient of determination. 5 competition indices are distance-independent (i.e. distance between the competitors are not taken into consideration) and 11 are distance-dependent. The data we used to fit our growth model, with accompanying competition index, was taken from an experimental site, in northern Sweden, of Norway spruce. The growth data for the Norway spruce comes from stands which were treated with one of two treatments, solid fertilization, liquid fertilization, or no treatment (control stand). We found that the distance-dependent indices perform better than the distance-independent. However, both the best distance-dependent and independent index performed overall well. We also found that the ranking of the indices was unaffected by the stand treatment, i.e. indices that work well for one treatment will work well for the others.Paper III: In this paper we studied how spatial distribution and size selection affect the residual trees, after a thinning operation, in terms of merchantable wood production and stand economy. We constructed a spatially explicit individual-based forest-growth model and fitted and validated the model against empirical data for Norway spruce stands in northern Sweden. To determine the cost for the forest operation we employed empirical cost functions for harvesting and forwarding. The income from the harvested timber is calculated from volume-price lists. The thinnings were determined by three parameters: the spatial evenness of residual trees, the size selection of removed trees, and the basal area reduction. In order to find tree selections fulfilling these constraints we used the metropolis algorithm. We varied these three constrains and applied them for thinning of different initial configurations of Norway spruce stands. The initial configurations for the stands where collected from empirical data. We found that changing the spatial evenness and size selection improved the net wood production and net present value of the stand up to 8%. However, the magnitude of improvement was dependent on the initial configuration (the magnitude of improvement varied between 1.7%—8%).Paper IV: With new technology and methods from remote sensing, such as LIDAR, becoming more prevalent in forestry, the ability to assess information on a detailed scale has become more available. Measurements for each individual tree can be more easily gathered on a larger scale. This type of data opens up for using individual-based model for practical precision forestry planning. In paper IV we used the individual-based model constructed in paper III to find the optimal harvesting time for each individual tree, such that the land expectation value is maximized. We employed a genetic algorithm to find a near optimal solution to our optimization. We optimized a number of initial Norway spruce stands (data obtained from field measurements). The optimal management strategy was to apply thinning from above. We also found that increasing the discount rate will decrease the time for final felling and increase basal area reduction for the optimal strategy. Decreasing relocation costs (the cost to bring machines to the stand) led to an increase in the number of optimal thinnings and postponed the first thinning. Our strategy was superior to both the unthinned strategy and a conventional thinning strategy, both in terms of land expectation value (>20% higher) and merchantable wood production.
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37. |
- Hahn, Max, et al.
(författare)
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Mesoscopic 3D imaging of pancreatic cancer and Langerhans islets based on tissue autofluorescence
- 2020
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Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- The possibility to assess pancreatic anatomy with microscopic resolution in three dimensions (3D) would significantly add to pathological analyses of disease processes. Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis with over 90% of the patients dying within 5 years after diagnosis. Cure can be achieved by surgical resection, but the efficiency remains drearily low. Here we demonstrate a method that without prior immunohistochemical labelling provides insight into the 3D microenvironment and spread of PDAC and premalignant cysts in intact surgical biopsies. The method is based solely on the autofluorescent properties of the investigated tissues using optical projection tomography and/or light-sheet fluorescence microscopy. It does not interfere with subsequent histopathological analysis and may facilitate identification of tumor-free resection margins within hours. We further demonstrate how the developed approach can be used to assess individual volumes and numbers of the islets of Langerhans in unprecedently large biopsies of human pancreatic tissue, thus providing a new means by which remaining islet mass may be assessed in settings of diabetes. Generally, the method may provide a fast approach to provide new anatomical insight into pancreatic pathophysiology.
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38. |
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39. |
- Hall, Marianne, 1976, et al.
(författare)
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Which are the most important parameters for modelling carbon assimilation in boreal Norway spruce under elevated [CO2] and temperature conditions?
- 2013
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Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 0829-318X .- 1758-4469. ; 33:11, s. 1156-1176
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Tidskriftsartikel (refereegranskat)abstract
- Photosynthesis is highly responsive to environmental and physiological variables, including phenology, foliage nitrogen (N) content, atmospheric CO2 concentration ([CO2]), irradiation (Q), air temperature (T) and vapour pressure deficit (D). Each of these responses is likely to be modified by long-term changes in climatic conditions such as rising air temperature and [CO2]. When modelling photosynthesis under climatic changes, which parameters are then most important to calibrate for future conditions? To assess this, we used measurements of shoot carbon assimilation rates and microclimate conditions collected at Flakaliden, northern Sweden. Twelve 40-year-old Norway spruce trees were enclosed in whole-tree chambers and exposed to elevated [CO2] and elevated air temperature, separately and in combination. The treatments imposed were elevated temperature, +2.8°C in July/August and +5.6°C in December above ambient, and [CO2] (ambient CO2 ∼370μmolmol−1, elevated CO2 ∼700μmolmol−1). The relative importance of parameterization of Q, T and D responses for effects on the photosynthetic rate, expressed on a projected needle area, and the annual shoot carbon uptake was quantified using an empirical shoot photosynthesis model, which was developed and fitted to the measurements. The functional form of the response curves was established using an artificial neural network. The [CO2] treatment increased annual shoot carbon (C) uptake by 50%. Most important was effects on the light response curve, with a 67% increase in light-saturated photosynthetic rate, and a 52% increase in the initial slope of the light response curve. An interactive effect of light saturated photosynthetic rate was found with foliage N status, but no interactive effect for high temperature and high CO2. The air temperature treatment increased the annual shoot C uptake by 44%. The most important parameter was the seasonality, with an elongation of the growing season by almost 4 weeks. The temperature response curve was almost flat over much of the temperature range. A shift in temperature optimum had thus an insignificant effect on modelled annual shoot C uptake. The combined temperature and [CO2] treatment resulted in a 74% increase in annual shoot C uptake compared with ambient conditions, with no clear interactive effects on parameter values.
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40. |
- Harrison, Sandy P., et al.
(författare)
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Eco-evolutionary optimality as a means to improve vegetation and land-surface models
- 2021
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 231:6, s. 2125-2141
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Forskningsöversikt (refereegranskat)abstract
- Global vegetation and land-surface models embody interdisciplinary scientific understanding of the behaviour of plants and ecosystems, and are indispensable to project the impacts of environmental change on vegetation and the interactions between vegetation and climate. However, systematic errors and persistently large differences among carbon and water cycle projections by different models highlight the limitations of current process formulations. In this review, focusing on core plant functions in the terrestrial carbon and water cycles, we show how unifying hypotheses derived from eco-evolutionary optimality (EEO) principles can provide novel, parameter-sparse representations of plant and vegetation processes. We present case studies that demonstrate how EEO generates parsimonious representations of core, leaf-level processes that are individually testable and supported by evidence. EEO approaches to photosynthesis and primary production, dark respiration and stomatal behaviour are ripe for implementation in global models. EEO approaches to other important traits, including the leaf economics spectrum and applications of EEO at the community level are active research areas. Independently tested modules emerging from EEO studies could profitably be integrated into modelling frameworks that account for the multiple time scales on which plants and plant communities adjust to environmental change.
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41. |
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42. |
- Hemmingsson, Oskar, 1975-, et al.
(författare)
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Excision and suture in the midline versus Karydakis flap surgery for pilonidal sinus : randomized clinical trial
- 2022
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Ingår i: BJS Open. - : Oxford University Press. - 2474-9842. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are several surgical options for the management of pilonidal disease, including midline and off midline closure, but prospective studies are rare. The study hypothesis was that Karydakis flap surgery would result in shorter wound healing and fewer recurrences than excision of pilonidal sinus and suture in the midline.METHODS: A randomized clinical trial was conducted in two hospitals in Sweden between 2006 and 2015 to compare excision and suture in the midline with Karydakis flap surgery. Adult patients with a chronic pilonidal sinus disease were randomized 1:1 at the outpatient clinic without blinding. Power calculation based on recurrence of 2 per cent for Karydakis flap and 10 per cent for excision and primary closure in the midline required 400 patients with 90 per cent statistical power at 5 per cent significance assuming 10 per cent loss during follow-up. Participants were followed up until complete wound healing; late follow-up after 6-13 years was performed by telephone by two blinded assessors. The two co-primary outcomes were time to complete wound healing and recurrence rate.RESULTS: The study was terminated early at a planned interim analysis due slow recruitment and a significant difference in primary outcome. In total, 125 patients were randomized, of whom 116 were available for the present analysis. Median wound healing time was 49 days (95 per cent confidence interval (c.i.) 32 to 66) for excision with suture in the midline and 14 days (95 per cent c.i. 12 to 20) for Karydakis flap surgery (P < 0.001). There were five recurrences in each group, after a median follow-up of 11 years (P = 0.753).CONCLUSION: Karydakis flap surgery for pilonidal sinus disease led to a shorter wound healing time than excision and suture in the midline but no difference in recurrence rates.Registration number: NCT00412659 (http://www.clinicaltrials.gov).
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43. |
- Henriksson, Nils, et al.
(författare)
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The mycorrhizal tragedy of the commons
- 2021
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 24:6, s. 1215-1224
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Tidskriftsartikel (refereegranskat)abstract
- Trees receive growth-limiting nitrogen from their ectomycorrhizal symbionts, but supplying the fungi with carbon can also cause nitrogen immobilization, which hampers tree growth. We present results from field and greenhouse experiments combined with mathematical modelling, showing that these are not conflicting outcomes. Mycorrhizal networks connect multiple trees, and we modulated C provision by strangling subsets of Pinus sylvestris trees, assuming that carbon supply to fungi was reduced proportionally to the strangled fraction. We conclude that trees gain additional nitrogen at the expense of their neighbours by supplying more carbon to the fungi. But this additional carbon supply aggravates nitrogen limitation via immobilization of the shared fungal biomass. We illustrate the evolutionary underpinnings of this situation by drawing on the analogous tragedy of the commons, where the shared mycorrhizal network is the commons, and explain how rising atmospheric CO2 may lead to greater nitrogen immobilization in the future.
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44. |
- Henriksson, Nils, et al.
(författare)
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Tree water uptake enhances nitrogen acquisition in a fertilized boreal forest - but not under nitrogen-poor conditions
- 2021
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 232, s. 113-122
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Tidskriftsartikel (refereegranskat)abstract
- Understanding how plant water uptake interacts with acquisition of soil nitrogen (N) and other nutrients is fundamental for predicting plant responses to a changing environment, but it is an area where models disagree. We present a novel isotopic labelling approach which reveals spatial patterns of water and N uptake, and their interaction, by trees. The stable isotopes N-15 and H-2 were applied to a small area of the forest floor in stands with high and low soil N availability. Uptake by surrounding trees was measured. The sensitivity of N acquisition to water uptake was quantified by statistical modelling. Trees in the high-N stand acquired twice as much N-15 as in the low-N stand and around half of their N uptake was dependent on water uptake (H-2 enrichment). By contrast, in the low-N stand there was no positive effect of water uptake on N uptake. We conclude that tree N acquisition was only marginally dependent on water flux toward the root surface under low-N conditions whereas under high-N conditions, the water-associated N uptake was substantial. The results suggest a fundamental shift in N acquisition strategy under high-N conditions.
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45. |
- Hofhansl, Florian, et al.
(författare)
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Mechanisms driving plant functional trait variation in a tropical forest
- 2021
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 11:9, s. 3856-3870
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Tidskriftsartikel (refereegranskat)abstract
- Plant functional trait variation in tropical forests results from taxonomic differences in phylogeny and associated genetic differences, as well as, phenotypic plastic responses to the environment. Accounting for the underlying mechanisms driving plant functional trait variation is important for understanding the potential rate of change of ecosystems since trait acclimation via phenotypic plasticity is very fast compared to shifts in community composition and genetic adaptation. We here applied a statistical technique to decompose the relative roles of phenotypic plasticity, genetic adaptation, and phylogenetic constraints. We examined typically obtained plant functional traits, such as wood density, plant height, specific leaf area, leaf area, leaf thickness, leaf dry mass content, leaf nitrogen content, and leaf phosphorus content. We assumed that genetic differences in plant functional traits between species and genotypes increase with environmental heterogeneity and geographic distance, whereas trait variation due to plastic acclimation to the local environment is independent of spatial distance between sampling sites. Results suggest that most of the observed trait variation could not be explained by the measured environmental variables, thus indicating a limited potential to predict individual plant traits from commonly assessed parameters. However, we found a difference in the response of plant functional traits, such that leaf traits varied in response to canopy-light regime and nutrient availability, whereas wood traits were related to topoedaphic factors and water availability. Our analysis furthermore revealed differences in the functional response of coexisting neotropical tree species, which suggests that endemic species with conservative ecological strategies might be especially prone to competitive exclusion under projected climate change.
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46. |
- Högberg, Peter, et al.
(författare)
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Tamm review: on the nature of the nitrogen limitation to plant growth in Fennoscandian boreal forests.
- 2017
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 403, s. 161-185
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Forskningsöversikt (refereegranskat)abstract
- The supply of nitrogen commonly limits plant production in boreal forests and also affects species composition and ecosystem functions other than plant growth. These interrelations vary across the landscapes, with the highest N availability, plant growth and plant species richness in ground-water discharge areas (GDAs), typically in toe-slope positions, which receive solutes leaching from the much larger groundwater recharge areas (GRAs) uphill. Plant N sources include not only inorganic N, but, as heightened more recently, also organic N species. In general, also the ratio inorganic N over organic N sources increase down hillslopes. Here, we review recent evidence about the nature of the N limitation and its variations in Fennoscandian boreal forests and discuss its implications for forest ecology and management.The rate of litter decomposition has traditionally been seen as the determinant of the rate of N supply. However, while N-rich litter decomposes faster than N-poor litter initially, N-rich litter then decomposes more slowly, which means that the relation between N % of litter and its decomposability is complex. Moreover, in the lower part of themor-layer, where the most superficial mycorrhizal roots first appear, and N availability matters for plants, the ratio of microbial N over total soil N is remarkably constant over the wide range in litter and soil C/N ratios of between 15 and 40 for N-rich and N-poor sites, respectively. Nitrogen-rich and-poor sites thus differ in the sizes of the total N pool and the microbial N pool, but not in the ratio between them. A more important difference is that the soil microbial N pool turns over faster in N -rich systems because the microbes are more limited by C, while microbes in N-poor systems are a stronger sink for available N.Furthermore, litter decomposition in the most superficial soil horizon (as studied by the so-called litter-bag method) is associated with a dominance of saprotrophic fungi, and absence of mycorrhizal fungi. The focal zone in the context of plant N supply in N-limited forests is further down the soil profile, whereectomycorrhizal (ECM) roots become abundant. Molecular evidence and stable isotope data indicate that in the typical N-poor boreal forests, nitrogen is retained in saprotrophic fungi, likely until they run out of energy (available C-compounds). Then, as heightened by recent research, ECM fungi, which are supplied by photosynthate from the trees, become the superior competitors for N.In N-poor boreal soils strong N retention by microorganisms keeps levels of available N very low. This is exacerbated by an increase in tree C allocation to mycorrhizal fungi (TCAM) relative to net primary production (NPP) with decreasing soil N supply, which causes ECM fungi to retain much of the available soil N for their own growth and transfer little to their tree hosts. The transfer of N through the ECM fungi, and not the rate of litter decomposition, is likely limiting the rate of tree N supply under such conditions. All but a few stress-tolerant less N-demanding plant species, like the ECM trees themselves and ericaceous dwarf shrubs, are excluded.With increasing N supply, a weakening of ECM symbiosis caused by the relative decline in TCAM contributes to shifts in soil microbial community composition from fungal dominance to bacterial dominance. Thus, bacteria, which are less C-demanding, but more likely to release N than fungi, take over. This, and the relatively high pH in GDA, allow autotrophic nitrifying bacteria to compete successfully for the NH4+ released by C-limited organisms and causes the N cycle to open up with leaching of nitrate (NO) and gaseous N losses through denitrification. These N-rich conditions allow species-rich communities of N-demanding plant species. Meanwhile, ECM fungi have a smaller biomass, are supplied with N in excess of their demand and will export more N to their host trees. Hence, the gradient from low to high N supply is characterized by profound variations in plant and soil microbial physiologies, especially their relations to the C-to-N supply ratio. We propose how interactions among functional groups can be understood and modelled (the plant-microbe carbon-nitrogen model).With regard to forest management these perspectives explain why the creation of larger tree-free gaps favors the regeneration of tree seedlings under N-limited conditions through reduced belowground competition for N, and why such gaps are less important under high N supply (but when light might be limiting). We also discuss perspectives on the relations between N supply, biodiversity, and eutrophication of boreal forests from N deposition or forest fertilization. (C) 2017 The Authors. Published by Elsevier B.V.
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47. |
- Jacobson, Sara, et al.
(författare)
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Hyperglycemia as a risk factor in pancreatic cancer : A nested case-control study using prediagnostic blood glucose levels
- 2021
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 21:6, s. 1112-1118
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples.METHODS: Prospective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t-test and log rank test.RESULTS: The unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05-1.60, P = .015). Impaired fasting glucose (≥6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05-2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26-12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08-8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04-2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival.CONCLUSIONS: High fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer.
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48. |
- John, Juliane, et al.
(författare)
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Redox-controlled reorganization and flavin strain within the ribonucleotide reductase R2b–NrdI complex monitored by serial femtosecond crystallography
- 2022
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Ingår i: eLIFE. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Redox reactions are central to biochemistry and are both controlled by and induce protein structural changes. Here, we describe structural rearrangements and crosstalk within the Bacillus cereus ribonucleotide reductase R2b–NrdI complex, a di-metal carboxylate-flavoprotein system, as part of the mechanism generating the essential catalytic free radical of the enzyme. Femtosecond crystallography at an X-ray free electron laser was utilized to obtain structures at room temperature in defined redox states without suffering photoreduction. Together with density functional theory calculations, we show that the flavin is under steric strain in the R2b–NrdI protein complex, likely tuning its redox properties to promote superoxide generation. Moreover, a binding site in close vicinity to the expected flavin O2 interaction site is observed to be controlled by the redox state of the flavin and linked to the channel proposed to funnel the produced superoxide species from NrdI to the di-manganese site in protein R2b. These specific features are coupled to further structural changes around the R2b–NrdI interaction surface. The mechanistic implications for the control of reactive oxygen species and radical generation in protein R2b are discussed.
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49. |
- John, Juliane, et al.
(författare)
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Redox-controlled reorganization and flavin strain within the ribonucleotide reductase R2b–NrdI complex monitored by serial femtosecond crystallography
- 2022
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Redox reactions are central to biochemistry and are both controlled by and induce protein structural changes. Here, we describe structural rearrangements and crosstalk within the Bacillus cereus ribonucleotide reductase R2b–NrdI complex, a di-metal carboxylate-flavoprotein system, as part of the mechanism generating the essential catalytic free radical of the enzyme. Femtosecond crystallography at an X-ray free electron laser was utilized to obtain structures at room temperature in defined redox states without suffering photoreduction. Together with density functional theory calculations, we show that the flavin is under steric strain in the R2b–NrdI protein complex, likely tuning its redox properties to promote superoxide generation. Moreover, a binding site in close vicinity to the expected flavin O2 interaction site is observed to be controlled by the redox state of the flavin and linked to the channel proposed to funnel the produced superoxide species from NrdI to the di-manganese site in protein R2b. These specific features are coupled to further structural changes around the R2b–NrdI interaction surface. The mechanistic implications for the control of reactive oxygen species and radical generation in protein R2b are discussed.
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50. |
- Jonas, Matthias, et al.
(författare)
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Sustaining ecosystem services : overcoming the dilemma posed by local actions and planetary boundaries
- 2014
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Ingår i: Earth's Future. - 2328-4277. ; 2:8, s. 407-420
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Tidskriftsartikel (refereegranskat)abstract
- Resolving challenges related to the sustainability of natural capital and ecosystem services is an urgent issue. No roadmap on reaching sustainability exists; and the kind of sustainable land use required in a world that acknowledges both multiple environmental boundaries and local human well-being presents a quandary. In this commentary, we argue that a new globally consistent and expandable systems-analytical framework is needed to guide and facilitate decision making on sustainability from the planetary to the local level, and vice versa. This framework would strive to link a multitude of Earth system processes and targets; it would give preference to systemic insight over data complexity through being highly explicit in spatiotemporal terms. Its strength would lie in its ability to help scientists uncover and explore potential, and even unexpected, interactions between Earth’s subsystems with planetary environmental boundaries and socioeconomic constraints coming into play. Equally importantly, such a framework would allow countries such as Brazil, a case study in this commentary, to understand domestic or even local sustainability measures within a global perspective and to optimize them accordingly.
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