| 1. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 2. |
- Björnsson, Bergthor, et al.
(författare)
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Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion
- 2014
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Co. Limited. - 1007-9327 .- 2219-2840. ; 20:28, s. 9506-9512
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the effects of preconditioning on inducible nitric oxide synthase (iNOS) and interleukin 1 (IL-1) receptor transcription in rat liver ischemia/reperfusion injury (IRI). METHODS: Seventy-two male rats were randomized into 3 groups: the one-hour segmental ischemia (IRI, n = 24) group, the ischemic preconditioning (IPC, n = 24) group or the remote ischemic preconditioning (R-IPC, n = 24) group. The IPC and R-IPC were performed as 10 min of ischemia and 10 min of reperfusion. The iNOS and the IL-1 receptor mRNA in the liver tissue was analyzed with real time PCR. The total Nitrite and Nitrate (NOx) in continuously sampled microdialysate (MD) from the liver was analyzed. In addition, the NOx levels in the serum were analyzed. RESULTS: After 4 h of reperfusion, the iNOS mRNA was significantly higher in the R-IPC (Delta Ct: 3.44 +/- 0.57) group than in the IPC (Delta Ct: 5.86 +/- 0.82) group (P = 0.025). The IL-1 receptor transcription activity was reduced in the IPC group (Delta Ct: 1.88 +/- 0.53 to 4.81 +/- 0.21), but not in the R-IPC group, during reperfusion (P = 0.027). In the MD, a significant drop in the NOx levels was noted in the R-IPC group (12.3 +/- 2.2 to 4.7 +/- 1.2 mu mol/L) at the end of ischemia compared with the levels in early ischemia (P = 0.008). A similar trend was observed in the IPC group (11.8 +/- 2.1 to 6.4 +/- 1.5 mu mol/L), although this difference was not statistically significant. The levels of NOx rose quickly during reperfusion in both groups. CONCLUSION: IPC, but not R-IPC, reduces iNOS and IL-1 receptor transcription during early reperfusion, indicating a lower inflammatory reaction. NOx is consumed in the ischemic liver lobe.
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| 3. |
- Björnsson, Bergthor, et al.
(författare)
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Remote or Conventional Ischemic Preconditioning -Local Liver Metabolism in Rats Studied with Microdialysis
- 2012
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Ingår i: Journal of Surgical Research. - : Elsevier. - 0022-4804 .- 1095-8673. ; 176:1, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- Background. Ischemic preconditioning (IPC) of the liver decreases liver injury secondary to ischemia and reperfusion. An attractive alternative to IPC is remote ischemic preconditioning (R-IPC), but these two methods have not previously been compared. Material and Methods. Eighty-seven rats were randomized into four groups: sham operated (n = 15), 1 h segmental ischemia (IRI, n = 24), preceeded by IPC (n = 24), or R-IPC (n = 24) (to the left hindleg). IPC and R-IPC were performed with 10 min ischemia and 10 min of reperfusion. Analyses of liver microdialysate (MD), serum transaminase levels, and liver histology were made. Results. Rats treated with IPC and R-IPC had significantly lower AST, 71.5 (19.6) IU/L respective 96.6 (12.4) at 4 h reperfusion than those subjected to IRI alone, 155 (20.9), P = 0.0004 and P = 0.04 respectively. IPC also had lower ALT levels, 41.6 (11.3) IU/L than had IRI 107.4 (15.5), P = 0.003. The MD glycerol was significantly higher during ischemia in the R-IPC = 759 (84) mu M] and the IRI = 732 (67)] groups than in the IPC 514 (70) group, P = 0.022 and P = 0.046 respectively. The MD glucose after ischemia was lower in the IPC group 7.1 (1.2) than in the IRI group 12.7 (1.6), P = 0.005. Preconditioning to the liver caused an direct increase in lactate, glucose and glycerol in the ischemic segment compared with the control segment an effect not seen in the R-IPC and IRI groups. Conclusions. IPC affects glucose metabolism in the rat liver, observed with MD. IPC reduces liver cell injury during ischemic and reperfusion in rats. R-IPC performed over the same length of time as IPC does not have the same effect as the latter on ALT levels and MD glycerol; this may suggest that R-IPC does not offer the same protection as IPC in this setting of rat liver IRI.
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| 4. |
- Gaines, Hans, et al.
(författare)
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Six-week follow-up after HIV-1 exposure: a position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
- 2016
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 48:2, s. 93-98
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Forskningsöversikt (refereegranskat)abstract
- In 2014 the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy (RAV) conducted a review and analysis of the state of knowledge on the duration of follow-up after exposure to human immunodeficiency virus (HIV). Up until then a follow-up of 12 weeks after exposure had been recommended, but improved tests and new information on early diagnosis motivated a re-evaluation of the national recommendations by experts representing infectious diseases and microbiology, county medical officers, the RAV, the Public Health Agency, and other national authorities. Based on the current state of knowledge the Public Health Agency of Sweden and the RAV recommend, starting in April 2015, a follow-up period of 6 weeks after possible HIV-1 exposure, if HIV testing is performed using laboratory-based combination tests detecting both HIV antibody and antigen. If point-of-care rapid HIV tests are used, a follow-up period of 8 weeks is recommended, because currently available rapid tests have insufficient sensitivity for detection of HIV-1 antigen. A follow-up period of 12 weeks is recommended after a possible exposure for HIV-2, since presently used assays do not include HIV-2 antigens and only limited information is available on the development of HIV antibodies during early HIV-2 infection. If pre- or post-exposure prophylaxis is administered, the follow-up period is recommended to begin after completion of prophylaxis. Even if infection cannot be reliably excluded before the end of the recommended follow-up period, HIV testing should be performed at first contact for persons who seek such testing.
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| 5. |
- Hasselgren, Kristina, 1976-
(författare)
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Colorectal Liver Metastases – Different Aspects on Treatment with Associated Liver Partition and Portal Vein Ligation for Staged Hepatectomy and on Portal Vein Occlusion
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: For patients with colorectal liver metastases (CRLM), the only treatment with a possibility for long-term survival and cure is radical resection. The majority of patients are at the time of diagnosis not assessed as resectable because they have advanced disease in the liver or unresectable extrahepatic disease or are too frail to withstand liver surgery. Patients who at the time of diagnosis are not assessed as resectable may be treated with conversion chemotherapy to downsize the tumor burden and render the patient eligible for resection. One concern with chemotherapy administered preoperatively has been the potential negative effect on the future liver remnant (FLR), especially for patients with a low volume of the FLR who are undergoing techniques to increase the volume. Established techniques to increase the volume are portal vein occlusion (PVO) and two-staged hepatectomy (TSH). A more recent method is Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS). Due to the relative novelty of ALPPS, the long-term oncological results are not known. For patients with CRLM, resection of liver metastases is more favorable from a health economic perspective than palliative treatment and results in a higher quality of life than palliative chemotherapy. For patients undergoing ALPPS as well as TSH, the data are scarce. Aim: The aim of the first study was to determine whether preoperative chemotherapy has a negative impact on the volume increase for patients undergoing ALPPS. The aim of the second study was to analyze the temporal course of the volume increase in the FLR for patients undergoing PVO. The aim of the third study was to study the long-term outcome for patients randomized to ALPPS or TSH. The aim of the fourth study was to perform a health economic analysis of patients randomized to ALPPS or TSH. Methods: The first study was based on data from the ALPPS registry, which is an international registry initiated 2012. All patients included in the registry between 2012 and 2016 were included. The patients were divided into the following four groups: no preoperative chemotherapy, 1 regimen of neoadjuvant chemotherapy, more than 1 regimen, and more than 1 regimen with the addition of monoclonal antibodies. The volume increase between interventions 1 and 2 was analyzed. In the second study, a retrospective analysis was performed of patients randomized to TSH. Forty-eight patients were included. The volume increase of the FLR was analyzed as the kinetic growth rate (KGR). The KGR was calculated from PVO until radical hepatectomy or exclusion, as well as between the first and second radiological evaluations. In the third and fourth studies, patients randomized to ALPPS and TSH were included. In the third study, survival, as well as factors affecting the outcome, were analyzed. In the fourth study, a calculation of resource use was performed, as was an analysis of health-related quality of life (HRQoL) for the groups. Results: In the first study, it was found that chemotherapy had no negative impact on the volume increase for patients undergoing ALPPS. In the second study, it was found that the volume increase of the FLR was largest the first week after ALPPS. In the third study, it was found that patients randomized to ALPPS had a longer survival than those randomized to TSH. Of the factors affecting the outcome, resection of liver metastases had a significant impact. In the fourth study, no significant difference could be found in resource use or HRQoL for patients randomized to ALPPS over TSH. Conclusion: Patients with advanced CRLM undergoing ALPPS should receive preoperative chemotherapy, if indicated. For those undergoing PVO, early evaluation is crucial to evaluate the volume increase, and for those with insufficient increase, additional techniques to increase the volume should be considered. Resection of liver metastases is an important factor to improve the outcome. Further studies are warranted to conclude whether ALPPS or TSH is most effective from a health economic perspective.
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| 6. |
- Persson, Per-Axel, et al.
(författare)
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Enhanced thermal dissociation of optically excited C60 chains.
- 2000
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Ingår i: Europhysics letters. - : EDP Sciences. - 0295-5075 .- 1286-4854. ; 49:5, s. 631-636
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Tidskriftsartikel (refereegranskat)abstract
- The thermal dissociation of C60 polymers has been studied using Raman scattering. The measured dissociation rate depends on the intensity of the 1064 nm NIR excitation, showing that i) the band gap is smaller than 1.17 eV and ii) a radiation-enhanced thermal breakdown path exists in addition to the "normal'' thermal breakdown mechanism. Quantum chemical calculations show that the energy barrier Ea for thermal breakdown is about 40% lower in the first (optically) excited state than in the ground state. This agrees well with the ratio between our radiation-enhanced value $E_{a} = (1.1 \pm 0.02)\,eV$ and values near 1.9 eV measured by purely thermal methods.
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| 7. |
- Persson, Per-Axel, et al.
(författare)
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High-pressure polymerized C60
- 1996
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Ingår i: Extended Abstracts of Carbon´96, European Carbon Conference, Newcastle-upon-Tyne 1996, volume 2. - : The British Carbon Group. ; , s. 746-747, s. 746-747
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Persson, Per-Axel, et al.
(författare)
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NMR and Raman characterization of pressure polymerized C-60
- 1996
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Ingår i: Chemical Physics Letters. - : Elsevier BV. - 0009-2614 .- 1873-4448. ; 258:5-6, s. 540-546
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Tidskriftsartikel (refereegranskat)abstract
- Bulk C60 has been treated at 1.1 GPa and 550–585 K, producing a dense insoluble material which on heating to above 600 K reverts to normal C60. Raman and IR studies on modified material show a large number of new lines, and the Raman pentagon pinch mode shifts from 1469 to 1458 cm−1 as on photopolymerization. MAS NMR shows one broadened line at the original C60 shift 144 ppm and a small peak at about 77 ppm due to the bridging carbons. None of the new resonances observed for C60 polymerized by other methods were observed. The results verify previously suggested polymeric structures where the fullerence cages are connected by four-membered rings.
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| 9. |
- Persson, Per-Axel, et al.
(författare)
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Physical properties of pressure polymerized C60
- 1996
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Ingår i: High Pressure Science and Technology. - Singapore : World Scientific. - 9810225474 ; , s. 716-718
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Konferensbidrag (refereegranskat)abstract
- The properties of C60 have been studied after treatment at high temperature and high pressure (1.1 GPa and 565 K for 2 h). The treated material is insoluble in organic solvents. We present results obtained in NMR and Raman studies and measured data for the specific heat and the thermal expansion. Our results show clearly that there are no covalent bonds and no molecular rotation, but suggest that the molecules are slightly deformed and held together by weak pi-type bonds.
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| 10. |
- Persson, Per-Axel, et al.
(författare)
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The physical properties of high-pressure polymerized C60
- 1997
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Ingår i: Journal of Physics and Chemistry of Solids, volume 58, issue 11. - : Elsevier B.V.. ; 58:11, s. 1881-1885
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Konferensbidrag (refereegranskat)abstract
- We have studied the structural, thermophysical, and spectroscopic properties of polymeric C60 obtained by high pressure treatment at pressures and temperatures near 1 GPa and 600 K. We present here a brief overview of our results for the structural and thermophysical properties and a more detailed report on recent results obtained by Raman spectroscopy on both thin films, polycrystalline, and single crystal material. The results presented include a comparison between Raman results for photopolymerized and pressure polymerized thin films and a preliminary estimate of the binding energy of polymeric C60.
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