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| 2. |
- Cashin, Peter H., et al.
(author)
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Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases : A randomised trial
- 2016
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In: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 53, s. 155-162
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Journal article (peer-reviewed)abstract
- Background: First-line treatment of isolated resectable colorectal peritoneal metastases remains unclear. This study (the Swedish peritoneal study) compares cytoreductive surgery and intraperitoneal chemotherapy (surgery arm) with systemic chemotherapy (chemotherapy arm). Methods: Patients deemed resectable preoperatively were randomised to surgery and intraperitoneal 5-fluorouracil 550 mg/m(2) /d for 6 d with repeated courses every month or to systemic oxaliplatin and 5-fluorouracil regimen every second week. Both treatments continued for 6 months. Primary end-point was overall survival (OS) and secondary end-points were progression-free survival (PFS), and morbidity. Results: The study terminated prematurely when 48 eligible patients (24/arm) were included due to recruitment difficulties. Two-year OS was 54% in the surgery arm and 38% in the chemotherapy arm (p = 0.04). After 5 years, 8 versus 1 patient were alive, respectively (p = 0.02). Median OS was 25 months versus 18 months, respectively, hazard ratio 0.51 (95% confidence interval: 0.27-0.96, p = 0.04). PFS in the surgery arm was 12 months versus 11 months in the chemotherapy arm (p = 0.16) with 17% versus 0% 5-year PFS. Grade III-IV morbidity was seen in 42% and 50% of the patients, respectively. No mortalities. Conclusions: Cytoreductive surgery with intraperitoneal chemotherapy may be superior to systemic oxaliplatin-based treatment of colorectal cancer with resectable isolated peritoneal metastases.(ClinicalTrials. gov nr: NCT01524094).
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| 3. |
- Cashin, Peter, 1984-, et al.
(author)
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Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases
- 2018
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In: European Journal of Surgical Oncology. - : ELSEVIER SCI LTD. - 0748-7983 .- 1532-2157. ; 44:7, s. 983-990
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Journal article (peer-reviewed)abstract
- Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.
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| 4. |
- Corvigno, Sara, et al.
(author)
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Multi-parametric profiling of renal cell, colorectal, and ovarian cancer identifies tumour-type-specific stroma phenotypes and a novel vascular biomarker
- 2017
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In: The journal of pathology. Clinical research. - : WILEY. - 2056-4538. ; 3:3, s. 214-224
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Journal article (peer-reviewed)abstract
- A novel set of integrated procedures for quantification of fibroblast-rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well-annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression. Second, analyses of the cohorts have been used to explore the prognostic significance of a novel vascular metric, 'vessel distance inter-quartile range (IQR)' that describes intra-case heterogeneity regarding vessel distribution. The comparisons between the three tumour types demonstrated a set of significant differences. Vessel density of renal cell cancer was statistically significantly higher than in colorectal and ovarian cancer. Vessel diameter was statistically significantly higher in ovarian cancer. Concerning perivascular status, colorectal cancer displayed significantly higher levels of perivascular PDGFR-beta expression than the other two tumour types. Intra-case heterogeneity of perivascular PDGFR-beta expression was also higher in colorectal cancer. Notably, these fibroblast-dominated stroma phenotypes matched previously described experimental tumour stroma characteristics, which have been linked to differential sensitivity to anti-VEGF drugs. High 'vessel distance IQR' was significantly associated with poor survival in both renal cell cancer and colorectal cancer. In renal cell cancer, this characteristic also acted as an independent prognostic marker according to multivariate analyses including standard clinico-pathological characteristics. Explorative subset analyses indicated particularly strong prognostic significance of 'vessel distance IQR' in T stage 4 of this cancer type. Together, these analyses identified tumour-type-specific vascular-stroma phenotypes of possible functional significance, and suggest 'vessel distance IQR' as a novel prognostic biomarker.
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| 5. |
- Erlinge, Sam, et al.
(author)
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Lemming-Food Plant Interactions, Density Effects, and Cyclic Dynamics on the Siberian Tundra
- 2011
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In: Arctic. - 0004-0843. ; 64:4, s. 421-428
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Journal article (peer-reviewed)abstract
- Theory predicts that trophic interactions can produce cyclic dynamics of microtine rodents, but that in addition, social interactions are necessary to create the cyclicity. We tested the induced defence hypothesis as a component driving multiannual cycles by analyzing data on Siberian lemming (Lemmus sibiricus Kerr) populations and the levels of trypsin inhibitors (TI) and free proteins (SPP) in their food plants. We collected data at 12 sites along the Palaearctic tundra coast in 1994 and correlated these measures with lemming density and cycle phase. A negative correlation between lemming density and TI/SPP in Carex was found at the 12 sites. Cycle phase tended to correlate significantly with TI/SPP, and plants being grazed by lemmings respond with some delay. Mass of pancreas, the organ producing proteolytic enzymes, co-varied negatively with TI/SPP. These findings are in accord with predictions from the induced defence hypothesis. En contrast, reproductive effort did not conform to the predictions but co-varied strongly with density. Data are in accord with theory predicting that, in addition to trophic interactions, some self-regulation is necessary to create cyclic dynamics. Our data show that the plant defence hypothesis alone is not a sufficient explanation for the cyclicity. Several factors interact, including predation, food quality (including induced defence chemicals), and intra-specific competition.
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| 6. |
- Erlinge, Sam, et al.
(author)
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Reproductive behaviour of female Siberian lemmings during the increase and peak phase of the lemming cycle
- 2000
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In: Oecologia. - : Springer Science and Business Media LLC. - 1432-1939 .- 0029-8549. ; 123:2, s. 200-207
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Journal article (peer-reviewed)abstract
- The reproduction of female Siberian lemmings in the increase and peak phases of the lemming cycle was investigated in connection with a ship-borne expedition along the Siberian arctic tundra. The cycle phase of each studied lemming population was determined using demographic analyses, i.e. current density indices (captured lemmings per 100 traps per 24 h), information on previous density (frequency of old lemming faeces and runways), and information from dendrochronological analyses revealing the most recent winters with a high intensity of willow-stem scarring caused by lemmings. The cycle phase determination was corroborated with data on the age profiles of the populations. The reproductive behaviour of female lemmings differed markedly in relation to cycle phase. In increase-phase populations, all captured females (including young and winter born) were reproducing (had embryos or were lactating), and females started to reproduce early in life, i.e. when <2 months old. By contrast, in peak-phase populations, only 6% of the young females and 63% of the winter-born ones were reproducing, and females did not start to reproduce until they were 5-6 months old. The average number of embryos per reproducing female was significantly higher in increase-phase populations than in peak-phase ones. It is concluded that the rapid population growth in lemmings during the increase phase can largely be explained by the early (young age) reproductive start and, consequently, the shorter generation time, the high proportion of females taking part in reproduction, and the large litters produced. Similarly, a delay in the start of reproduction, a lower proportion of reproducing females, and smaller litter sizes produced by peak-phase lemming populations can contribute substantially to the deceleration in the population increase and possibly lead to a decline.
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| 7. |
- Frodin, Peter
(author)
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Species interactions and community structure
- 2002
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Doctoral thesis (other academic/artistic)abstract
- In this theses I have focused on how the mechanisms of species interactions affect community structure. It is well known that certain species may have a particularly strong influence on the structure of a community. What is not fully understood is how to characterize these species that have such a strong impact on community structure. In my work, I have work tried to find out what makes such species "keystones". This has been done both with models of small interacting units, but also with help of field data. I have attempted to estimate how direct as well as indirect effects among interacting species affect both the species abundance and the dynamics of the community. The analyse then implies that the effects of both direct as well as indirect interactions on species are of fundamental interest. Another issue I have focused on is how additional energy (enrichment) affects species interactions, stability, and particularly local stability properties of the ecological system. It is not fully understood how additional energy enters a system, neither how the additional resources are allocated among the producers. I have modeled a few scenarios with different allocation possibilities, and have shown that stability is crucially dependent on how the additional energy is spent by the producer level in the system. The local stability properties of a system is also very model dependent. The same model, but with different assumptions about how the enrichment is entering show very different dynamic outcomes. Finally, I have looked at how spatial structure increases stability in a community of interacting species. However, the opposite also seems to be true, i.e., that fragmented environments can have a negative effect on community persistence, when the number of patches is exceeding a certain threshold, a subsecuent loss of stability do occur.
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| 8. |
- Omstedt, Anders, 1949, et al.
(author)
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Future changes in the Baltic Sea acid-base (pH) and oxygen balances
- 2012
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In: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 64
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Journal article (peer-reviewed)abstract
- Possible future changes in Baltic Sea acid–base (pH) and oxygen balances were studied using a catchment–sea coupled model system and numerical experiments based on meteorological and hydrological forcing datasets and scenarios. By using objective statistical methods, climate runs for present climate conditions were examined and evaluated using Baltic Sea modelling. The results indicate that increased nutrient loads will not inhibit future Baltic Sea acidification; instead, the seasonal pH cycle will be amplified by increased biological production and mineralization. All examined scenarios indicate future acidification of the whole Baltic Sea that is insensitive to the chosen global climate model. The main factor controlling the direction and magnitude of future pH changes is atmospheric CO2 concentration (i.e. emissions). Climate change and land-derived changes (e.g. nutrient loads) affect acidification mainly by altering the seasonal cycle and deep-water conditions. Apart from decreasing pH, we also project a decreased saturation state of calcium carbonate, decreased respiration index, and increasing hypoxic area – all factors that will threaten the marine ecosystem. We demonstrate that substantial reductions in fossil-fuel burning are needed to minimize the coming pH decrease and substantial reductions in nutrient loads are needed to reduce the coming increase in hypoxic and anoxic waters.
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