| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 3. |
- Bost, Jeremy P., et al.
(författare)
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Novel endosomolytic compounds enable highly potent delivery of antisense oligonucleotides
- 2022
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The therapeutic and research potentials of oligonucleotides (ONs) have been hampered in part by their inability to effectively escape endosomal compartments to reach their cytosolic and nuclear targets. Splice-switching ONs (SSOs) can be used with endosomolytic small molecule compounds to increase functional delivery. So far, development of these compounds has been hindered by a lack of high-resolution methods that can correlate SSO trafficking with SSO activity. Here we present in-depth characterization of two novel endosomolytic compounds by using a combination of microscopic and functional assays with high spatiotemporal resolution. This system allows the visualization of SSO trafficking, evaluation of endosomal membrane rupture, and quantitates SSO functional activity on a protein level in the presence of endosomolytic compounds. We confirm that the leakage of SSO into the cytosol occurs in parallel with the physical engorgement of LAMP1-positive late endosomes and lysosomes. We conclude that the new compounds interfere with SSO trafficking to the LAMP1-positive endosomal compartments while inducing endosomal membrane rupture and concurrent ON escape into the cytosol. The efficacy of these compounds advocates their use as novel, potent, and quick-acting transfection reagents for antisense ONs.
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| 4. |
- Evans Axelsson, Susan, et al.
(författare)
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Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.
- 2014
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Ingår i: American journal of nuclear medicine and molecular imaging. - 2160-8407. ; 4:4, s. 311-323
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer.
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| 5. |
- Evans Axelsson, Susan, et al.
(författare)
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Radioimmunotherapy for Prostate Cancer-Current Status and Future Possibilities.
- 2016
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Ingår i: Seminars in Nuclear Medicine. - : Elsevier BV. - 0001-2998. ; 46:2, s. 165-179
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Forskningsöversikt (refereegranskat)abstract
- Prostate cancer (PCa) is one of the most common cancers in men and is the second leading cause of cancer-related deaths in the USA. In the United States, it is the second most frequently diagnosed cancer after skin cancer, and in Europe it is number one. According to the American Cancer Society, approximately 221,000 men in the United States would be diagnosed with PCa during 2015, and approximately 28,000 would die of the disease. According to the International Agency for Research on Cancer, approximately 345,000 men were diagnosed with PCa in Europe during 2012, and despite more emphasis placed on early detection through routine screening, 72,000 men died of the disease. Hence, the need for improved therapy modalities is of utmost importance. And targeted therapies based on radiolabeled specific antibodies or peptides are a very interesting and promising alternative to increase the therapeutic efficacy and overall chance of survival of these patients. There are currently several preclinical and some clinical studies that have been conducted, or are ongoing, to investigate the therapeutic efficacy and toxicity of radioimmunotherapy (RIT) against PCa. One thing that is lacking in a lot of these published studies is the dosimetry data, which are needed to compare results between the studies and the study locations. Given the complicated tumor microenvironment and overall complexity of RIT to PCa, old and new targets and targeting strategies like combination RIT and pretargeting RIT are being improved and assessed along with various therapeutic radionuclides candidates. Given alone or in combination with other therapies, these new and improved strategies and RIT tools further enhance the clinical response to RIT drugs in PCa, making RIT for PCa an increasingly practical clinical tool.
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| 6. |
- Hilling, Axel, et al.
(författare)
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Equal taxation as a basis for classifying financial instruments as debt or equity - a Swedish case study
- 2015
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Ingår i: eJournal of Tax Research. - 1448-2398. ; 13:3, s. 677-715
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Tidskriftsartikel (refereegranskat)abstract
- This article examines the way in which classification of financial instruments as debt or equity has developed in the Swedish income taxation system over the past 25 years. Although the structure of the tax system is based on the assumption that debt instruments are financial instruments with low risk, legal developments have not shared that assumption, resulting in several types of high-risk derivative instruments being covered by the definition of legal debt. This article illustrates how those developments, which can be recognized in most income-tax systems within OECD countries, seriously threatens the fundament of the tax system: equal taxation for capital income and income from labor. The article concludes by illustrating how the standard solution to the problem of classifying financial instruments as debt and equity – by treating them alike – does not fulfill the challenged principle of equal taxation, but actually intensifies the development towards unequal taxation.
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| 7. |
- Hilling, Axel, et al.
(författare)
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Lagen är lika för alla, men är alla verkligen lika inför lagen? : En studie av Skatteverkets processföring i PwC-målet
- 2018
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Ingår i: Förvaltningsrättslig tidskrift. - 0015-8585. ; :2, s. 269-286
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Tidskriftsartikel (refereegranskat)abstract
- För korrekt beskattning i komplicerade mål är det viktigt att Skatteverket kan utvärdera och presentera sakomständigheter på ett kvalificerat sätt. Skattebetalare med hög kompetens har annars större möjligheter att hävda sin rätt jämfört med skattebetalare som saknar sådan kompetens, vilket står i konflikt med likabehandlingsprincipen. I artikeln illustreras vikten av en kvalificerad förvaltningsmyndighet för att rättssäkerhet ska säkerställas. Det sker genom en studie av det s.k. PwC-målet, där sakfrågan rör marknadsvärdering av finansiella instrument. Artikeln visar att sakfrågan i målet inte kom att prövas av domstol som följd av att Skatteverket inte presenterade sakomständigheterna på ett övertygande och prövningsbart sätt. En motpart med stora ekonomiska resurser hade möjlighet att visa på bristerna i Skatteverkets argumentation, något som inte nödvändigtvis en motpart med mindre resurser hade kunnat göra. Lagen är då förvisso lika för alla, men alla är inte lika inför lagen.
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| 8. |
- Hulthén, Erik, 1980, et al.
(författare)
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Implementing Real-time Optimization on a secondary Cone Crusher for Iron Ore Production, part 1
- 2013
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Ingår i: Preprints Conference in Minerals Engineering, Luleå, 5-6 February 2013. ; , s. 71-80
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Cone crushers are often used as an intermediate comminution step in the mining industry. Real-time feedback data on the product streams can be obtained by applying mass-flow sensors to the process. Systems used for controlling the Closed Side Setting (CSS) on cone crushers are widely used to compensate for wear of the manganese crushing liners and to protect the machines from overloads. With a frequency converter also the eccentric speed in a cone crusher can be adjusted in real-time in addition to the CSS. The eccentric speed affects the dynamic interaction between the rock material and the crusher liners. The adjustment of these two online parameters in real time can result in an increased potential for production yield; however, a nontrivial optimization problem with a large solution space also arises. As the feed material also varies, and the wear is highly evident, the optimal setting for the parameters varies in time. In this paper we report on the preparation of a secondary cone crusher for real-time optimization. The cone crusher, a Sandvik CH680, has got a frequency converter installed and the temperature in the crusher is measured in order to ensure that the crusher as a mechanical machine is working under good operating conditions. The conveyor belts around the crusher have all been equipped with mass-flow meters. Thus the different product yields from the crushing plant can be monitored continuously. The results of the electrical and instrumental installations are that both the CSS and now also the eccentric speed can be operated and monitored in real time without interrupting the process at one of LKAB Malmbergets secondary cone crushers. The first guiding tests indicate a more beneficial operating point, where a higher power consumption can be achieved in the crusher without increasing the pressure as much. The results of the capacities, both the crusher and the crushing stage, indicate the same direction. There are operating points which are more beneficial than others, and it is not the nominal one that is the best. The range of the change in capacity of the circuit is -6.1% to +2.3% from the nominal point.
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| 9. |
- Kristiansson, Amanda, et al.
(författare)
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177Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α1-Microglobulin (A1M), Including Kidney Damage Assessment Using 99mTc-MAG3 Imaging
- 2021
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:2
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Tidskriftsartikel (refereegranskat)abstract
- Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α1-microglobulin (A1M) together with 177-Lutetium (177Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity. Nude mice with subcutaneous LNCaP xenografts were injected with 50 or 100 MBq of [177Lu]Lu-PSMA-617, with or without injections of recombinant A1M (rA1M) (at T = 0 and T = 24 h). Kidney absorbed dose was calculated to 7.36 Gy at 4 days post a 100 MBq injection. Activity distribution was imaged with Single-Photon Emission Computed Tomography (SPECT) at 24 h. Tumor volumes were measured continuously, and kidneys and blood were collected at termination (3-4 days and 3-4 weeks after injections). In a parallel set of experiments, mice were given [177Lu]Lu-PSMA-617 and rA1M as above and dynamic technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3) SPECT imaging was performed prior to injection, and 3- and 6-months post injection. Blood and urine were continuously sampled. At termination (6 months) the kidneys were resected. Biomarkers of kidney function, expression of stress genes and kidney histopathology were analyzed. [177Lu]Lu-PSMA-617 uptake, in tumors and kidneys, as well as treatment efficacy did not differ between rA1M and vehicle groups. In mice given rA1M, [99mTc]Tc-MAG3 imaging revealed a significantly higher slope of initial uptake at three months compared to mice co-injected with [177Lu]Lu-PSMA-617 and vehicle. Little or no change compared to control was seen in urine albumin, serum/plasma urea levels, RT-qPCR analysis of stress response genes and in the kidney histopathological evaluation. In conclusion, [99mTc]Tc-MAG3 imaging presented itself as a sensitive tool to detect changes in kidney function revealing that administration of rA1M has a potentially positive effect on kidney perfusion and tubular function when combined with [177Lu]Lu-PSMA-617 therapy. Furthermore, we could show that rA1M did not affect anti-PSMA radioligand therapy efficacy.
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| 10. |
- Kristiansson, Amanda, et al.
(författare)
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Hematological and renal toxicity in mice after three cycles of high activity [177Lu]Lu-PSMA-617 with or without human α1-microglobulin
- 2024
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Ingår i: Scientific Reports. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a human antioxidant previously shown to have radioprotective effects. In both groups, three cycles resulted in increased albuminuria for each cycle, with large individual variation. Another marker of kidney injury, serum blood urea nitrogen (BUN), was only significantly increased compared to control animals after the third cycle. The number of white and red blood cells decreased significantly and did not reach the levels of control animals during the experiment. rA1M did reduce absorbed dose to kidney but did not show significant protection here, but future studies are warranted due to the recent clinical studies showing a significant renoprotective effect in patients.
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| 11. |
- Kristiansson, Amanda, et al.
(författare)
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Hematological Toxicity in Mice after High Activity Injections of 177Lu-PSMA-617
- 2022
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PC) is one of the most common malignancies affecting men, with poor prognosis after progression to metastatic castration-resistant prostate cancer (mCRPC). Radioligand therapy (RLT) targeting the overexpressed PSMA on PC cells, with, e.g., 177Lu-PSMA-617, has been effective in reducing tumor burden and prolonging survival in mCRPC. However, it is not a curative method with kidney and bone marrow toxicity limiting the activity given to patients. Previous preclinical models have reported transient hematotoxicity for up to 120 MBq. This activity may still be too low to investigate the effect on renal function since it corresponds to an absorbed dose below 10 Gy, whereas the kidneys in a clinical setting usually receive an absorbed dose more than double. Here we investigated the hematotoxicity and recovery after administered activities of 120, 160, and 200 MBq in a 177Lu-PSMA-617 BALB/cAnNRj mouse model. The animals had an initial drop in white blood cells (WBC) starting 4 days post injection, which recovered after 21 days. The effect on red blood cells (RBC) and platelets was detected later; 17 days post-injection levels decreased compared to the control group. The reduction was restored again 32 days post injection. No correlation between injected activity and hematotoxicity was found. Our results suggest that activities up to 200 MBq of 177Lu-PSMA-617 give transient hematotoxicity from which animals recover within a month and no radiation-related deaths. Injecting these high activities could allow animal studies with increased clinical relevance when studying renal toxicity in animal models.
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| 12. |
- Kristiansson, Amanda, et al.
(författare)
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Kidney protection with the radical scavenger α1-microglobulin (A1m) during peptide receptor radionuclide and radioligand therapy
- 2021
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Ingår i: Antioxidants. - : MDPI AG. - 2076-3921. ; 10:8, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- α1-microglobulin (A1M) is an antioxidant found in all vertebrates, including humans. It has enzymatic reductase activity and can scavenge radicals and bind free heme groups. Infused recombinant A1M accumulates in the kidneys and has therefore been successful in protecting kidney injuries in different animal models. In this review, we focus on A1M as a radioprotector of the kidneys during peptide receptor radionuclide/radioligand therapy (PRRT/RLT). Patients with, e.g., neuroendocrine tumors or castration resistant prostate cancer can be treated by administration of radiolabeled small molecules which target and therefore enable the irradiation and killing of cancer cells through specific receptor interaction. The treatment is not curative, and kidney toxicity has been reported as a side effect since the small, radiolabeled substances are retained and excreted through the kidneys. In recent studies, A1M was shown to have radioprotective effects on cell cultures as well as having a similar biodistribution as the somatostatin analogue peptide177Lu-DOTA-TATE after intravenous infusion in mice. Therefore, several animal studies were conducted to investigate the in vivo radioprotective potential of A1M towards kidneys. The results of these studies demonstrated that A1M co-infusion yielded protection against kidney toxicity and improved overall survival in mouse models. Moreover, two different mouse studies reported that A1M did not interfere with tumor treatment itself. Here, we give an overview of radionuclide therapy, the A1M physiology and the results from the radioprotector studies of the protein.
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| 13. |
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| 14. |
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| 15. |
- Nossman, Marcus, et al.
(författare)
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Nonparametric forward-looking value-at-risk
- 2014
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Ingår i: Journal of Risk. - 1465-1211. ; 16:4, s. 103-123
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Tidskriftsartikel (refereegranskat)abstract
- This paper proposes a new model for computing value-at-risk forecasts. The model is fully nonparametric and easy to implement. Further, it incorporates information about the market's perceived uncertainty about the future. The forward-looking information is obtained from the option market via the Chicago Board Options Exchange's implied volatility index (VIX). Using S&P 500 data from 1990 to 2010 we find that the use of option implied volatility compares favorably with generalized autoregressive conditional heteroscedasticity (GARCH)-type models in terms of forecast performance. By comparing the model primarily used in the banking sector to our new model, we find that a financial institution using our model has on average a lower market induced capital requirement (MCR). However, during the time period leading up to the financial crisis our model gives a 40% higher MCR.
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| 16. |
- Timmermand, Oskar Vilhelmsson, et al.
(författare)
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Preclinical efficacy of hK2 targeted [177Lu]hu11B6 for prostate cancer theranostics
- 2019
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Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 9:8, s. 2129-2142
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Tidskriftsartikel (refereegranskat)abstract
- Androgen ablating drugs increase life expectancy in men with metastatic prostate cancer, but resistance inevitably develops. In a majority of these recurrent tumors, the androgen axis is reactivated in the form of increased androgen receptor (AR) expression. Targeting proteins that are expressed as a down-stream effect of AR activity is a promising rationale for management of this disease. The humanized IgG1 antibody hu11B6 internalizes into prostate and prostate cancer (PCa) cells by binding to the catalytic cleft of human kallikrein 2 (hK2), a prostate specific enzyme governed by the AR-pathway. In a previous study, hu11B6 conjugated with Actinium-225 (225Ac), a high linear energy transfer (LET) radionuclide, was shown to generate an AR-upregulation driven feed-forward mechanism that is believed to enhance therapeutic efficacy. We assessed the efficacy of hu11B6 labeled with a low LET beta-emitter, Lutetium-177 (177Lu) and investigated whether similar tumor killing and AR-enhancement is produced. Moreover, single-photon emission computed tomography (SPECT) imaging of 177Lu is quantitatively accurate and can be used to perform treatment planning. [177Lu]hu11B6 therefore has significant potential as a theranostic agent. Materials and Methods: Subcutaneous PCa xenografts (LNCaP s.c.) were grown in male mice. Biokinetics at 4-336 h post injection and uptake as a function of the amount of hu11B6 injected at 72 h were studied. Over a 30 to 120-day treatment period the therapeutic efficacy of different activities of [177Lu]hu11B6 were assessed by volumetric tumor measurements, blood cell counts, molecular analysis of the tumor as well as SPECT/CT imaging. Organ specific mean absorbed doses were calculated, using a MIRD-scheme, based on biokinetic data and rodent specific S-factors from a modified MOBY phantom. Tumor tissues of treated xenografts were immunohistochemically (IHC) stained for Ki-67 (proliferation) and AR, SA-β-gal activity (senescence) and analyzed by digital autoradiography (DAR). Results: Organ-to-blood and tumor-to-blood ratios were independent of hu11B6 specific activity except for the highest amount of antibody (150 µg). Tumor accumulation of [177Lu]hu11B6 peaked at 168 h with a specific uptake of 29 ± 9.1 percent injected activity per gram (%IA/g) and low accumulation in normal organs except in the submandibular gland (15 ± 4.5 %IA/g), attributed to a cross-reaction with mice kallikreins in this organ, was seen. However, SPECT imaging with therapeutic amounts of [177Lu]hu11B6 revealed no peak in tumor accumulation at 7 d, probably due to cellular retention of 177Lu and decreasing tumor volumes. For [177Lu]hu11B6 treated mice, tumor decrements of up to 4/5 of the initial tumor volume and reversible myelotoxicity with a nadir at 12 d were observed after a single injection. Tumor volume reduction correlated with injected activity and the absorbed dose. IHC revealed retained expression of AR throughout treatment and that Ki-67 staining reached a nadir at 9-14 d which coincided with high SA- β-gal activity (14 d). Quantification of nuclei staining showed that Ki-67 expression correlated negatively with activity uptake. AR expression levels in cells surviving therapy compared to previous timepoints and to controls at 30 d were significantly increased (p = 0.017). Conclusions: This study shows that hu11B6 labeled with the low LET beta-emitting radionuclide 177Lu can deliver therapeutic absorbed doses to prostate cancer xenografts with transient hematological side-effects. The tumor response correlated with the absorbed dose both on a macro and a small scale dosimetric level. Analysis of AR staining showed that AR protein levels increased late in the study suggesting a therapeutic mechanism, a feed forward mechanism coupled to AR driven response to DNA damage or clonal lineage selection, similar to that reported in high LET alpha-particle therapy using 225Ac labeled hu11B6, however emerging at a later timepoint.
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| 17. |
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| 18. |
- Vilhelmsson, Anders
(författare)
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Density Forecasting with Time Varying Higher Moments – A Model Confidence Set Approach
- 2013
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Ingår i: Journal of Forecasting. - : Wiley. - 1099-131X .- 0277-6693. ; 32:1, s. 19-31
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Tidskriftsartikel (refereegranskat)abstract
- Density forecasts contain a complete description of the uncertainty associated with a point forecast and are therefore important measures of financial risk. This paper aims to examine if the new more complicated models for financial returns that allow for time variation in higher moments lead to better out-of-sample density forecasts. Using two decades of daily Standard and Poor's 500 index returns I find that a model with time varying conditional variance, skewness and kurtosis produces significantly better density forecasts than the competing models.
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| 19. |
- Vilhelmsson, Andreas, et al.
(författare)
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Experiences from consumer reports on psychiatric adverse drug reactions with antidepressant medication : a qualitative study of reports to a consumer association
- 2012
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Ingår i: BMC Pharmacology. - : BioMed Central. - 1471-2210. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe new European pharmacovigilance legislation has been suggested as marking the beginning of a new chapter in drug safety, making patients an important part of pharmacovigilance. In Sweden since 2008 it has been possible for consumers to report adverse drug reactions (ADRs) to the Medical Products Agency (MPA), and these reports are now understood as an increasingly valuable contribution in the monitoring of safety aspects in medicines. Already in 2002 it was possible to report experiences with medicines to the non-profit and independent organization Consumer Association for Medicines and Health (KILEN) through a web-based report form with an opportunity to describe ADR experiences in free text comments. The aim of this study was to qualitatively analyze the free text comments appended to consumer reports on antidepressant medication.MethodsAll reports of suspected adverse reactions regarding antidepressant medications submitted from January 2002 to April 2009 to KILEN’s Internet-based reporting system in Sweden were analyzed according to reported narrative experience(s). Content analysis was used to interpret the content of 181 reports with free text comments.ResultsThree main categories emerged from the analyzed data material: (1) Experiences of drug treatment with subcategories (a) Severe psychiatric adverse reactions, and (b) Discontinuation symptoms; (2) Lack of communication and (3) Trust and distrust. A majority of the reports to KILEN were from patients experiencing symptoms of mental disturbances (sometimes severe) affecting them in many different ways, especially during discontinuation. Several report included narratives of patients not receiving information of potential ADRs from their doctor, but also that there were no follow-ups of the treatment. Trust was highlighted as especially important and some patients reported losing confidence in their doctor when they were not believed about the suspected ADRs they experienced, making them attempt to discontinue their antidepressant treatment on their own.ConclusionsThe present study indicates that free text comments as often contained in case reports directly submitted by patients can be of value in pharmacovigilance and provide important information on how a drug may affect the person using it and influence his or her personal life.
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| 20. |
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| 21. |
- Vilhelmsson, Andreas, et al.
(författare)
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Global folkhälsa : om livsvillkor, sjukdomar och social rättvisa
- 2016
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Aldrig i mänsklighetens historia har jordens befolkning haft det så bra som de har det nu. Världens rikedomar är större än de någonsin tidigare varit och i takt med det ökade välståndet blir världens invånare överlag allt friskare och allt äldre. Samtidigt har de generella välfärds- och hälsoökningarna inte kommit alla till del. En person som idag föds i USA förväntas tjäna 100 gånger mer under sin livstid än en samtida person i Zambia, samtidigt som en genomsnittlig japan förväntas leva 38 år längre än en sierra leonian. Ett stort problem är således att den globala hälsoförbättringen de senaste decennierna har varit djupt ojämlik. Syftet med denna bok är att redogöra för de globala folkhälsoproblem som idag utgör den största bördan för mänskligheten, liksom för de övergripande globala faktorer som har en påverkan på olika befolkningars hälsa. Boken syftar även till att presentera en begreppslig ram för folkhälsoområdet, och den diskuterar ett antal etiska aspekter rörande den globala hälsosituationen och dess olika orsaker. Den argumenterar slutligen för att det globala samfundet bör ta ett större ansvar för att åtgärda nuvarande problem och skapa en hållbar förändring.
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| 22. |
- Vilhelmsson, Anders, et al.
(författare)
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Is the VIX futures market able to predict the VIX index? A test of the expectation hypothesis
- 2009
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Ingår i: The Journal of Alternative Investments. - 1520-3255. ; 12:2, s. 54-67
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Tidskriftsartikel (refereegranskat)abstract
- This paper tests the expectation hypothesis by using the volatility index VIX and the futures written on that index. Because the VIX index is negatively correlated with the S&P 500 index returns the VIX futures price should contain a negative risk premium, which we do confirm in this study. When the futures price is not adjusted with the risk premium, the expectation hypothesis is rejected at the 5 percent significance level for 20 of 21 forecast horizons. However when we adjust the futures price with the risk premium, obtained from a stochastic volatility model, the expectation hypothesis cannot be rejected. Further, we find that the risk premium adjusted futures price forecasts the direction of the VIX index well. The one day ahead forecast predicts the direction correctly 73 percent of the time.
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| 23. |
- Vilhelmsson, Anders, et al.
(författare)
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Measuring Event Risk
- 2009
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Ingår i: Journal of Financial Econometrics. - : Oxford University Press (OUP). - 1479-8409 .- 1479-8417. ; 7:3, s. 265-287
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Tidskriftsartikel (refereegranskat)abstract
- This paper decomposes the popular risk measure Value-at-Risk (VaR) into one jump- and one continuous component. The continuous component corresponds to general market risk and the jump component is proportional to the event risk as defined in the Basel II accord. We find that event risk, which is currently not incorporated into most banks’ VaR models, comprises a substantial part of total VaR. It constitutes 30% of the risk for a portfolio of small cap stocks but less than 1% for a portfolio of large cap stocks. The national supervising agency in each membership country is advised by the Basel rules to add an additional capital charge to a bank whose models do not capture event risk. The large variation in event risk, also found across 10 individual stocks, suggests that an approach that varies the capital surcharge, based on the type of asset, should be used by the supervisors.
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| 24. |
- Vilhelmsson, Anders, et al.
(författare)
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Risk Premia: Exact Solutions vs. Log-Linear Approximations
- 2013
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Ingår i: Journal of Banking & Finance. - : Elsevier BV. - 1872-6372 .- 0378-4266. ; 37:11, s. 4256-4264
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Tidskriftsartikel (refereegranskat)abstract
- We derive exact expressions for the risk premia for general distributions in a Lucas economy and show that the errors when using log-linear approximations can be economically significant when the shocks are nonnormal. Assuming growth rates are Normal Inverse Gaussian (NIG) and fitting the distribution to the data used in Mehra and Prescott (1985), the coefficient of relative risk aversion required to match the equity premium is more than halved compared to the finding in their article. We also consider a standard long-run risk model and, by comparing our exact solutions to the log-linear approximations, we show that the approximation errors are substantial, especially for high levels of risk aversion.
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| 25. |
- Vilhelmsson, Anders, et al.
(författare)
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The Pernicious Effects of Contaminated Data in Risk Management
- 2011
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Ingår i: Journal of Banking & Finance. - : Elsevier BV. - 1872-6372 .- 0378-4266. ; 35:10, s. 2569-2583
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Tidskriftsartikel (refereegranskat)abstract
- Banks hold capital to guard against unexpected surges in losses and long freezes in financial markets. The minimum level of capital is set by banking regulators as a function of the banks’ own estimates of their risk exposures. As a result, a great challenge for both banks and regulators is to validate internal risk models. We show that a large fraction of US and international banks uses contaminated data when testing their models. In particular, most banks validate their market risk model using profit-and-loss (P/L) data that include fees and commissions and intraday trading revenues. This practice is inconsistent with the definition of the employed market risk measure. Using both bank data and simulations, we find that data contamination has dramatic implications for model validation and can lead to the acceptance of misspecified risk models. Moreover, our estimates suggest that the use of contaminated data can significantly reduce (market-risk induced) regulatory capital.
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| 26. |
- Vilhelmsson, Anders
(författare)
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Value at Risk with time varying variance, skewness and kurtosis-the NIG-ACD model
- 2009
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Ingår i: Econometrics Journal. - 1368-423X. ; 12:1, s. 82-104
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Tidskriftsartikel (refereegranskat)abstract
- A new model for financial returns with time varying variance, skewness and kurtosis based on the Normal Inverse Gaussian (NIG) distribution is proposed. The new model and two previously suggested NIG models are evaluated by their Value at Risk (VaR) forecasts on a long series of daily Standard and Poor's 500 returns. All three models perform very well compared with extant models and clearly outperform a Gaussian GARCH model. Moreover, the results show that only the new model cannot be rejected as providing correct conditional VaR forecasts.
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| 27. |
- Vilhelmsson, Anders, et al.
(författare)
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Volatility Risk Premium, Risk Aversion and the Cross-Section of Stock Returns
- 2010
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Ingår i: Financial Review. - 0732-8516. ; , s. 1079-1100
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Tidskriftsartikel (refereegranskat)abstract
- We test if innovations in investor risk aversion are a priced factor in the stock market. Time series tests show that the new factor partly explains the strong momentum effect in stock returns. Furthermore, using 25 portfolios sorted on book-to-market and size as test assets, our new factor together with the market factor explains 64% of the variation in average returns compared to 60% for the Fama-French model. The new factor is generally significant with an estimated risk premium close to its time series mean also when industry portfolios and portfolios sorted on previous returns are augmented to the test assets.
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| 28. |
- Vilhelmsson, Andreas, et al.
(författare)
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What can we learn from consumer reports on psychiatric adverse drug reactions with antidepressant medication? : Experiences from reports to a consumer association
- 2011
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Ingår i: BMC Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1472-6904. ; 11:16, s. 16-16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: According to the World Health Organization (WHO) the cost of adverse drug reactions (ADRs) in the general population is high and under-reporting by health professionals is a well-recognized problem. Another way to increase ADR reporting is to let the consumers themselves report directly to the authorities. In Sweden it is mandatory for prescribers to report serious ADRs to the Medical Products Agency (MPA), but there are no such regulations for consumers. The non-profit and independent organization Consumer Association for Medicines and Health, KILEN has launched the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. This study aimed to analyze these consumer reports.METHODS: All reports submitted from January 2002 to April 2009 to an open web site in Sweden where anyone could report their experience with the use of pharmaceuticals were analyzed with focus on common psychiatric side effects related to antidepressant usage. More than one ADR for a specific drug could be reported.RESULTS: In total 665 reports were made during the period. 442 reports concerned antidepressant medications and the individual antidepressant reports represented 2392 ADRs and 878 (37%) of these were psychiatric ADRs. 75% of the individual reports concerned serotonin-reuptake inhibitor (SSRI) and the rest serotonin-norepinephrine reuptake inhibitor (SNRI). Women reported more antidepressant psychiatric ADRs (71%) compared to men (24%). More potentially serious psychiatric ADRs were frequently reported to KILEN and withdrawal symptoms during discontinuation were also reported as a common issue.CONCLUSIONS: The present study indicates that consumer reports may contribute with important information regarding more serious psychiatric ADRs following antidepressant treatment. Consumer reporting may be considered a complement to traditional ADR reporting.
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| 29. |
- Vilhelmsson Timmermand, Oskar, et al.
(författare)
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A conjugation strategy to modulate antigen binding and FcRn interaction leads to improved tumor targeting and radioimmunotherapy efficacy with an antibody targeting prostate-specific antigen
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:14
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Tidskriftsartikel (refereegranskat)abstract
- Background: The humanized monoclonal antibody (mAb) hu5A10 specifically targets and internalizes prostate cancer cells by binding to prostate specific antigen (PSA). Preclinical evaluations have shown that hu5A10 is an excellent vehicle for prostate cancer (PCa) radiotheranostics. We studied the impact of different chelates and conjugation ratios on hu5A10′ s target affinity, neonatal fc-receptor interaction on in vivo targeting efficacy, and possible enhanced therapeutic efficacy. Methods: In our experiment, humanized 5A10 (hu5A10) was conjugated with DOTA or DTPA at a molar ratio of 3:1, 6:1, and 12:1. Surface plasmon resonance (SPR) was used to study antigen and FcRn binding to the antibody conjugates. [111 In]hu5A10 radio-immunoconjugates were administered intravenously into BALB/c mice carrying subcutaneous LNCaP xenografts. Serial Single-photon emission computed tomography (SPECT) images were obtained during the first week. Tumors were harvested and radionuclide distribution was analyzed by autoradiography along with microanatomy and immunohistochemistry. Results: As seen by SPR, the binding to PSA was clearly affected by the chelate-to-antibody ratio. Similarly, FcRn (neonatal fc-receptor) interacted less with antibodies conjugated at high ratios of chelator, which was more pronounced for DOTA conjugates. The autoradiography data indicated a higher distribution of radioactivity to the rim of the tumor for lower ratios and a more homogenous distribution at higher ratios. Mice injected with ratio 3:1111 In-DOTA-hu5A10 showed no significant difference in tumor volume when compared to mice given vehicle over a time period of 3 weeks. Mice given a similar injection of ratio 6:1111 In-DOTA-hu5A10 or 6:1111 In-DTPA-hu5A10 or 12:1111 In-DTPA-hu5A10 showed significant tumor growth retardation. Conclusions: The present study demonstrated that the radiolabeling strategy could positively modify the hu5A10′ s capacity to bind PSA and complex with the FcRn-receptor, which resulted in more homogenous activity distribution in tumors and enhanced therapy efficacy.
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| 30. |
- Vilhelmsson Timmermand, Oskar, et al.
(författare)
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Preclinical imaging of kallikrein-related peptidase 2 (hK2) in prostate cancer with a In-111-radiolabelled monoclonal antibody, 11B6
- 2014
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer is a leading cause of death in the male population of the western world. Human kallikrein-related peptidase 2 (hK2) is abundantly expressed in malignant prostatic tissue, and its gene, KLK2, is regulated by the androgen receptor. 11B6 is a murine IgG(1) monoclonal antibody directed against free human hK2. In this study, we performed a preclinical evaluation of In-111-labelled 11B6 in mouse xenografts to investigate its potential in the clinical staging and assessment of metastatic prostate cancer. Methods: 11B6 was radiolabelled with In-111 through CHX-A"-DTPA chelation. In vivo biodistribution and uptake of In-111-DTPA-11B6 were measured until 168 h post-injection in NMRI nude mice bearing subcutaneous LNCaP xenografts. The binding specificity to hK2 was evaluated by both in vivo competitive binding assays with excess non-labelled 11B6 and hK2-negative DU145 xenografts. SPECT/CT imaging of subcutaneous and intra-tibial LNCaP xenografts was used to visualize the tumours. Results: Tumour uptake of In-111-DTPA-11B6 in LNCaP xenografts was 19% +/- 0.78% IA/g at 48 h, giving a tumour-to-blood ratio of 1.6, which increases to 2.4 at 1 week post-injection. Accumulation was low in other organs except for the salivary glands, which is probably the result of cross-reactivity with mouse kallikreins. Significantly lower tumour accumulation was observed in competitive assays and DU145 xenografts. SPECT/CT imaging could clearly visualize the subcutaneous and intra-tibial LNCaP xenografts. Conclusions: Our study demonstrates the potential of In-111-DTPA-11B6 for the detection of metastatic prostate cancer and monitoring anti-androgen therapy, as it exhibits an increased uptake and accumulation in viable tumour when compared to normal tissue. A humanised version of the 11B6 monoclonal antibody is currently under evaluation.
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| 31. |
- Vilhelmsson Timmermand, Oskar, et al.
(författare)
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Radiolabeled antibodies in prostate cancer: A case study showing the effect of host immunity on antibody bio-distribution.
- 2015
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 1872-9614 .- 0969-8051. ; 42:4, s. 375-380
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Tidskriftsartikel (refereegranskat)abstract
- Human tumors xenografted in immunodeficient mice are crucial models in nuclear medicine to evaluate the effectiveness of candidate diagnostic and therapeutic compounds. However, little attention has been focused on the biological profile of the host model and its potential effects on the bio-distribution and tumor targeting of the tracer compound under study. We specifically investigated the dissimilarity in bio-distribution of (111)In-DTPA-5A10, which targets free prostate specific antigen (fPSA), in two animal models.
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