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- Labori, Knut Jørgen, et al.
(författare)
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Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1) : a multicentre, randomised, phase 2 trial
- 2024
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Ingår i: The Lancet Gastroenterology & Hepatology. - : The Lancet Group. - 2468-1253. ; 9:3, s. 205-217
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn patients undergoing resection for pancreatic cancer, adjuvant modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improves overall survival compared with alternative chemotherapy regimens. We aimed to compare the efficacy and safety of neoadjuvant FOLFIRINOX with the standard strategy of upfront surgery in patients with resectable pancreatic ductal adenocarcinoma.MethodsNORPACT-1 was a multicentre, randomised, phase 2 trial done in 12 hospitals in Denmark, Finland, Norway, and Sweden. Eligible patients were aged 18 years or older, with a WHO performance status of 0 or 1, and had a resectable tumour of the pancreatic head radiologically strongly suspected to be pancreatic adenocarcinoma. Participants were randomly assigned (3:2 before October, 2018, and 1:1 after) to the neoadjuvant FOLFIRINOX group or upfront surgery group. Patients in the neoadjuvant FOLFIRINOX group received four neoadjuvant cycles of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, leucovorin 400 mg/m2, and fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h on day 1 of each 14-day cycle), followed by surgery and adjuvant chemotherapy. Patients in the upfront surgery group underwent surgery and then received adjuvant chemotherapy. Initially, adjuvant chemotherapy was gemcitabine plus capecitabine (gemcitabine 1000 mg/m2 over 30 min on days 1, 8, and 15 of each 28-day cycle and capecitabine 830 mg/m2 twice daily for 3 weeks with 1 week of rest in each 28-day cycle; four cycles in the neoadjuvant FOLFIRINOX group, six cycles in the upfront surgery group). A protocol amendment was subsequently made to permit use of adjuvant modified FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2 over 46 h on day 1 of each 14-day cycle; eight cycles in the neoadjuvant FOLFIRINOX group, 12 cycles in the upfront surgery group). Randomisation was performed with a computerised algorithm that stratified for each participating centre and used a concealed block size of two to six. Patients, investigators, and study team members were not masked to treatment allocation. The primary endpoint was overall survival at 18 months. Analyses were done in the intention-to-treat (ITT) and per-protocol populations. Safety was assessed in all patients who were randomly assigned and received at least one cycle of neoadjuvant or adjuvant therapy. This trial is registered with ClinicalTrials.gov, NCT02919787, and EudraCT, 2015-001635-21, and is ongoing.FindingsBetween Feb 8, 2017, and April 21, 2021, 77 patients were randomly assigned to receive neoadjuvant FOLFIRINOX and 63 to undergo upfront surgery. All patients were included in the ITT analysis. For the per-protocol analysis, 17 (22%) patients were excluded from the neoadjuvant FOLFIRINOX group (ten did not receive neoadjuvant therapy, four did not have pancreatic ductal adenocarcinoma, and three received another neoadjuvant regimen), and eight (13%) were excluded from the upfront surgery group (seven did not have pancreatic ductal adenocarcinoma and one did not undergo surgical exploration). 61 (79%) of 77 patients in the neoadjuvant FOLFIRINOX group received neoadjuvant therapy. The proportion of patients alive at 18 months by ITT was 60% (95% CI 49–71) in the neoadjuvant FOLFIRINOX group versus 73% (62–84) in the upfront surgery group (p=0·032), and median overall survival by ITT was 25·1 months (95% CI 17·2–34·9) versus 38·5 months (27·6–not reached; hazard ratio [HR] 1·52 [95% CI 1·00–2·33], log-rank p=0·050). The proportion of patients alive at 18 months in per-protocol analysis was 57% (95% CI 46–67) in the neoadjuvant FOLFIRINOX group versus 70% (55–83) in the upfront surgery group (p=0·14), and median overall survival in per-protocol population was 23·0 months (95% CI 16·2–34·9) versus 34·4 months (19·4–not reached; HR 1·46 [95% CI 0·99–2·17], log-rank p=0·058). In the safety population, 42 (58%) of 73 patients in the neoadjuvant FOLFIRINOX group and 19 (40%) of 47 patients in the upfront surgery group had at least one grade 3 or worse adverse event. 63 (82%) of 77 patients in the neoadjuvant group and 56 (89%) of 63 patients in the upfront surgery group had resection (p=0·24). One sudden death of unknown cause and one COVID-19-related death occurred after the first cycle of neoadjuvant FOLFIRINOX. Adjuvant chemotherapy was initiated in 51 (86%) of 59 patients with resected pancreatic ductal adenocarcinoma in the neoadjuvant FOLFIRINOX group and 44 (90%) of 49 patients with resected pancreatic ductal adenocarcinoma in the upfront surgery group (p=0·56). Adjuvant modified FOLFIRINOX was given to 13 (25%) patients in the neoadjuvant FOLFIRINOX group and 19 (43%) patients in the upfront surgery group. During adjuvant chemotherapy, neutropenia (11 [22%] patients in the neoadjuvant FOLFIRINOX group and five [11%] in the upfront surgery group) was the most common grade 3 or worse adverse event.InterpretationThis phase 2 trial did not show a survival benefit from neoadjuvant FOLFIRINOX in resectable pancreatic ductal adenocarcinoma compared with upfront surgery. Implementation of neoadjuvant FOLFIRINOX was challenging. Future trials on treatment sequencing in resectable pancreatic ductal adenocarcinoma should be biomarker driven.
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| 4. |
- Mellqvist Glenn Persson, Johan, et al.
(författare)
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Sol FTIR mätningar vid Harestua solobservatorium under 2010
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Mätningar av den atmosfäriska kolumnen av väteklorid, ozon och ersättningfreonet HCFC22har, tillsammans med flera andra ämnen, genomförts under 53 dagar år 2010 från Harestuasolobservatorium (60 oN, 11oO). Mätningarna är en del i det Svenska naturvårdsverketsprogram:Skyddande ozonskikt och görs inom ramen för det globala nätverket NDACC. FörHarestua mätstation finns sedan 1994 cirka 800 mätdagar lagrade i en databas, vilketmöjliggör att studera trender av ovan nämnda ämnen. En analys av trenden för ozon indikerar en svag positiv trend på 0.25%/år. För HCl, i vilket merparten av atmosfären klor finns lagrat, erhålls en signifikant negativ trend på 0.90%/år och för HCFC 22 en positiv trend på 4.3%/år.
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| 5. |
- Alami, Jones, et al.
(författare)
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Phase tailoring of Ta thin films by highly ionized pulsed magnetron sputtering
- 2007
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Ingår i: Thin Solid Films. - : Elsevier. - 0040-6090 .- 1879-2731. ; 515:7-8, s. 3434-3438
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Tidskriftsartikel (refereegranskat)abstract
- Ta thin films were grown on Si substrates at different inclination angles with respect to the sputter source using high power impulse magnetron sputtering (HIPIMS), an ionized physical vapor deposition technique. The ionization allowed for better control of the energy and directionality of the sputtered species, and consequently for improved properties of the deposited films. Depositions were made on Si substrates with the native oxide intact. The structure of the as deposited films was investigated using X-ray diffraction, while a four-point probe setup was used to measure the resistivity. A substrate bias process-window for growth of bcc-Ta was observed. However, the process-window position changed with changing inclination angles of the substrate. The formation of this low-resistivity bcc-phase could be understood in light of the high ion flux from the HIPIMS discharge.
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| 7. |
- Bergerson, Emma, et al.
(författare)
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Superior Outcome of Early ACL Reconstruction versus Initial Non-reconstructive Treatment With Late Crossover to Surgery A Study From the Swedish National Knee Ligament Registry
- 2022
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Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 50:4, s. 896-903
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although comparable clinical and functional outcomes have been reported after nonsurgical and surgical anterior cruciate ligament (ACL) treatment, few studies have investigated the effects of early versus late ACL reconstruction with initial rehabilitation. Purpose: To determine patient-reported knee function in patients who initially undergo nonreconstructive treatment after an ACL injury but who later choose to undergo ACL reconstruction as compared with (1) patients undergoing ACL reconstruction close to the index injury and (2) patients treated nonreconstructively at 1 to 10 years of follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: Results from the Knee injury and Osteoarthritis Outcome Score (KOOS) were extracted from the Swedish National Knee Ligament Registry for patients treated with nonreconstruction, early ACL reconstruction, and initial nonreconstruction but subsequent ACL reconstruction (crossover group). The KOOS4 (a mean of 4 KOOS subscales) was analyzed cross-sectionally at baseline and at the 1-, 2-, 5-, and 10-year follow-ups. Additionally, the Patient Acceptable Symptom State (PASS) was applied to all KOOS subscales from baseline to the 10-year follow-up. Results: A total of 1,074 crossover, 484 nonreconstruction, and 20,352 early ACL reconstruction cases were included. The crossover group reported lower KOOS4 values than the group undergoing early ACL reconstruction at baseline and at all follow-ups (mean difference [95% CI]): baseline, -6.5 (-8.0 to -5.0); 1 year, -9.3 (-10.9 to -7.7); 2 years, -4.8 (-6.3 to -3.2); 5 years, -6.1 (-8.8 to -3.4); and 10 years, -10.9 (-16.3 to -5.2). Additionally, a smaller proportion of the crossover cohort achieved a PASS on KOOS subscales at baseline and through the 1-, 2-, 5-, and 10-year follow-ups as compared with the early ACL reconstruction cohort. No differences were observed between crossover and nonreconstruction cases on either the KOOS4 or the PASS at any follow-up. Conclusion: A greater proportion of patients treated with early ACL reconstruction reported acceptable knee function and superior overall knee function as compared with patients who decided to cross over from nonreconstructive treatment to ACL reconstruction.
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| 8. |
- Berggren Kleja, Dan, et al.
(författare)
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Bismuth(III) Forms Exceptionally Strong Complexes with Natural Organic Matter
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56, s. 3076-3084
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Tidskriftsartikel (refereegranskat)abstract
- The use of bismuth in the society has steadily increased during the last decades, both as a substitute for lead in hunting ammunition and various metallurgical applications, as well as in a range of consumer products. At the same time, the environmental behavior of bismuth is largely unknown. Here, the binding of bismuth(III) to organic soil material was investigated using extended X-ray absorption spectroscopy (EXAFS) and batch experiments. Moreover, the capacity of suwannee river fulvic acid (SRFA) to enhance the solubility of metallic bismuth was studied in a long-term (2 years) equilibration experiment. Bismuth(III) formed exceptionally strong complexes with the organic soil material, where >99% of the added bismuth(III) was bound by the solid phase, even at pH 1.2. EXAFS data suggest that bismuth(III) was bound to soil organic matter as a dimeric Bi3+ complex where one carboxylate bridges two Bi3+ ions, resulting in a unique structural stability. The strong binding to natural organic matter was verified for SRFA, dissolving 16.5 mmol Bi per gram carbon, which largely exceeds the carboxylic acid group density of this compound. Our study shows that bismuth(III) will most likely be associated with natural organic matter in soils, sediments, and waters.
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| 9. |
- Berggren Kleja, Dan, et al.
(författare)
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Characterization of iron in floating surface films of some natural waters using EXAFS
- 2012
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Ingår i: Chemical Geology. - : Elsevier. - 0009-2541 .- 1872-6836. ; 326, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- Floating, iron bearing films have been observed in a wide range of environments, including wetlands, seep waters in ground water discharge areas, small rivers and lakes. To date, knowledge about their formation and composition is scarce. We have investigated the form of iron in floating iron-rich films of different origin, including a pond and a brook, as well as seep water pools of a groundwater discharge area. Sampling sites were located in southern (pond, brook) and central (seep pools) Sweden. Synchrotron-based X-ray absorption spectroscopy (EXAFS and XANES) allowed identification of the iron precipitates present in the films, without any pretreatment. The EXAFS data showed that the iron containing phase formed in the floating films varied in composition between the sites investigated. In the films from two ground water discharge areas, characterized by out-flowing iron(II) rich ground water being high in pH and low in DOC, the iron phase was completely dominated by ferrihydrite. In contrast, surface films sampled from the brook and the pond, the iron speciation showed a mixture of iron(III)-organic complexes and iron (hydr)oxide (most likely ferrihydrite). These waters were oxic and contained higher concentration of DOC than the seep water pools in the ground water discharge areas. The position of the pre-edge peak, which is sensitive to the oxidation state of iron, did not indicate occurrence of iron (II) in any of the films. Elemental composition of one film (seep water), suggested that films contained about one third of organic matter. Ferrihydrite is probably present as small particles with humic material sorbed onto surfaces or included in the particles, making the particles sufficiently hydrophobic to not settle without physical disturbance. The films are fragile and break easily down and become suspended upon disturbance. More studies are warranted in order to understand the mechanism of the formation of these fascinating films and their biogeochemical role.
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| 10. |
- Berggren Kleja, Dan, et al.
(författare)
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Silver(I) Binding Properties of Organic Soil Materials Are Different from Those of Isolated Humic Substances
- 2016
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 50:14, s. 7453-7460
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Tidskriftsartikel (refereegranskat)abstract
- The solubility of silver(I) in many soils is controlled by complexation reactions with organic matter. In this work we have compared the ability of isolated humic and fulvic acids to bind silver(I) with that of mor and peat materials. One new data set for Suwannee River Fulvic Acid was produced, which was consistent with published data sets for isolated fulvic and humic acids. The ability of soil materials to bind silver(I) was studied as a function of pH in the range 2.5-5.0, at a wide range of silver(I)-to-soil ratios (10(-4.2) - 10(-1.9) mol kg(-1)). By calibrating the Stockholm Humic Model on the humic and fulvic acids data sets, we showed that binding of silver(I) to both types of soil materials was much stronger (up to 2 orders of magnitude) than predicted from the silver(I) binding properties of the isolated humic materials. Thus, the approach taken for many other metals, that is, to model solubility in soils by using metal and proton binding parameters derived from isolated humic and fulvic acids, cannot be used for silver(I). One possible explanation for the discrepancy could be that silver(I) predominately interacted with various biomolecules in the soil samples, instead of humic- and fulvic-acid type materials.
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