| 1. |
- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions.
- 2014
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 5:20, s. 9609-18
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Tidskriftsartikel (refereegranskat)abstract
- The development of novel therapies against melanoma would benefit from individualized tumor models to ensure the rapid and accurate identification of biomarkers of therapy response. Previous studies have suggested that patient-derived xenografts (PDXes) could be useful. However, the utility of PDXes in guiding real-time treatment decisions has only been reported in anecdotal forms. Here tumor biopsies from patients with stage III and IV metastatic malignant melanoma were transplanted into immunocompromised mice to generate PDXes. 23/26 melanoma biopsies generated serially transplantable PDX models, and their histology, mutation status and expression profile resembled their corresponding patient biopsy. The potential treatment for one patient was revealed by an in vitro drug screen and treating PDXes with the MEK inhibitor trametinib. In another patient, the BRAF mutation predicted the response of both the patient and its corresponding PDXes to MAPK-targeted therapy. Importantly, in this unselected group of patients, the time from biopsy for generation of PDXes until death was significantly longer than the time required to reach the treatment phase of the PDXes. Thus, it could be clinically meaningful to use this type of platform for melanoma patients as a pre-selection tool in clinical trials.
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| 2. |
- Forsberg, Elin, et al.
(författare)
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HER2 CAR-T Cells Eradicate Uveal Melanoma and T-cell Therapy-Resistant Human Melanoma in IL2 Transgenic NOD/SCID IL2 Receptor Knockout Mice
- 2019
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Ingår i: Cancer Research. - 0008-5472. ; 79:5, s. 899-904
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Tidskriftsartikel (refereegranskat)abstract
- Chimeric antigen receptors (CAR) can transmit signals akin to those from activated T-cell receptors when bound to a cell surface target. CAR-expressing T cells against CD19 can cause curative effects in leukemia and lymphoma and is approved for clinical use. However, no CAR-T therapy is currently approved for use in solid tumors. We hypothesize that the resistance of solid tumors to CAR-T can be overcome by similar means as those used to reactivate tumor-infiltrating T lymphocytes (TIL), for example, by cytokines or immune checkpoint blockade. Here we demonstrate that CAR-T cells directed against HER2 can kill uveal and cutaneous melanoma cells in vitro and in vivo. Curative effects in vivo were only observed in xenografts grown in a NOD/SCID IL2 receptor gamma (NOG) knockout mouse strain transgenic for human IL2. The effect was target-specific, as CRISPR/Cas9-mediated disruption of HER2 in the melanoma cells abrogated the killing effect of the CAR-T cells. The CAR-T cells were also able to kill melanoma cells from patients resistant to adoptive T-cell transfer (ACT) of autologous TILs. Thus, CAR-T therapy represents an option for patients that do not respond to immunotherapy with ACT of TIL or immune checkpoint blockade. In addition, our data highlight the use of IL2 transgenic NOG mice as models to prove efficacy of CAR-T-cell products, possibly even in a personalized manner. Significance: These findings demonstrate that a novel humanized mouse model can help clinical translation of CAR-T cells against uveal and cutaneous melanoma that do not respond to TIL therapy or immune checkpoint blockade.
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| 3. |
- Melke, Jonas, 1971, et al.
(författare)
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A polymorphism in the serotonin receptor 3A (HTR3A) gene and its association with harm avoidance in women.
- 2003
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Ingår i: Archives of general psychiatry. - : American Medical Association (AMA). - 0003-990X. ; 60:10, s. 1017-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance. OBJECTIVE: To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women. DESIGN: Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated. RESULTS: A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P =.04); this finding was subsequently replicated in sample 2 (P =.004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P =.001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P =.008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P =.002), including the subscales of social desirability (P<.001), indirect aggression (P =.002), verbal aggression (P =.05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity. CONCLUSION: The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.
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| 4. |
- Annerbrink, Kristina, 1974, et al.
(författare)
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Associations between the angiotensin-converting enzyme insertion/deletion polymorphism and monoamine metabolite concentrations in cerebrospinal fluid
- 2010
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Ingår i: Psychiatry Research. - : Elsevier BV. - 1872-7123 .- 0165-1781. ; 179:2, s. 231-234
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II has been suggested to influence central dopamine and serotonin turnover. Since the angiotensin-converting enzyme (ACE) plays a key role in angiotensin regulation by converting inactive angiotensin 1 to active angiotensin II, we hypothesised that the functional insertion/deletion (I/D) polymorphism in the ACE gene, which has previously been suggested to be associated with, depression and panic disorder, may influence monoamine activity. A well-established technique for assessing brain monoamine turnover in humans is to measure concentrations of monoamine metabolites in the cerebrospinal fluid (CSF). We thus investigated possible associations between the ACE I/D polymorphism and CSF monoamine metabolite concentrations in a population of healthy male subjects. After having found such an association between the ACE I/D polymorphism and CSF levels of the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindoleacetic acid in this sample, I carriers displaying lower levels, we tried to replicate this observation in a population of violent male offenders from which also both CSF and DNA were available. Also in this sample, the same associations were found. Our results suggest that the ACE I/D polymorphism may play a role in the modulation of serotonergic and dopaminergic turnover in men. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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| 5. |
- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
- 2018
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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| 6. |
- Forsberg, Elin, et al.
(författare)
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Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary CAR-T cells are immune cells equipped with a claw that enable them to bind cancer cells. Usually, CAR-T cells are made using immune cells from blood. Here, we tested the hypothesis that also immune cells that reside in the tumor, so called tumor-infiltrating lymphocytes, can also be modified to carry the claw. This may mean that these cells, called CAR-TILs, will be able to attack cancer cells in two ways, using the claw or binding using its normal protein on the cell surface, the so-called T cell receptor. We show that CAR-TILs can be generated, and that they can kill melanoma cells in cell culture and in mice. Finally, to prepare for clinical trials, we also assess if CAR-TILs can be safe in a human cancer patient-like model, a companion dog suffering from cancer. Our data suggest that CAR-TILs may be a way to treat patients with melanoma but human clinical trials are needed. Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma.
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| 7. |
- Jespersen, Henrik, et al.
(författare)
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Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model.
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 -a melanoma PDX model where tumor cells and tumor-infiltrating T cells from the same patient are transplanted sequentially in non-obese diabetic/severe combined immune-deficient/common gamma chain (NOG/NSG) knockout mouse. Key to T-cell survival/effect in this model is the continuous presence of interleukin-2 (IL-2). Tumors that grow in PDXv2.0 are eradicated if the autologous tumor cells and T cells come from a patient that exhibited an objective response to ACT in the clinic. However, T cells from patients that are non-responders to ACT cannot kill tumor cells in PDXv2.0. Taken together, PDXv2.0 provides the potential framework to further model genetically diverse human cancers for assessing the efficacy of immunotherapies as well as combination therapies.Combining different types of immune therapies might benefit certain patients. Here, the authors develop an autologous immune-humanized melanoma mouse model that allows the preclinical assessment of cancer cell-T cell interactions from each individual patient and the benefits of immunotherapies combinations.
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| 8. |
- Jespersen, Henrik, et al.
(författare)
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Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study.
- 2019
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- While recent years have seen a revolution in the treatment of metastatic cutaneous melanoma, no treatment has yet been able to demonstrate any prolonged survival in metastatic uveal melanoma. Thus, metastatic uveal melanoma remains a disease with an urgent unmet medical need. Reports of treatment with immune checkpoint inhibitors have thus far been disappointing. Based on animal experiments, it is reasonable to hypothesize that the effect of immunotherapy may be augmented by epigenetic therapy. Proposed mechanisms include enhanced expression of HLA class I and cancer antigens on cancer cells, as well as suppression of myeloid suppressor cells.The PEMDAC study is a multicenter, open label phase II study assessing the efficacy of concomitant use of the PD1 inhibitor pembrolizumab and the class I HDAC inhibitor entinostat in adult patients with metastatic uveal melanoma. Primary endpoint is objective response rate. Eligible patients have histologically confirmed metastatic uveal melanoma, ECOG performance status 0-1, measurable disease as per RECIST 1.1 and may have received any number of prior therapies, with the exception of anticancer immunotherapy. Twenty nine patients will be enrolled. Patients receive pembrolizumab 200mg intravenously every third week in combination with entinostat 5mg orally once weekly. Treatment will continue until progression of disease or intolerable toxicity or for a maximum of 24months.The PEMDAC study is the first trial to assess whether the addition of an HDAC inhibitor to anti-PD1 therapy can yield objective anti-tumoral responses in metastatic UM.ClinicalTrials.gov registration number: NCT02697630 . (Registered 3 March 2016). EudraCT registration number: 2016-002114-50.
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| 9. |
- Karlsson, Joakim, et al.
(författare)
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Molecular profiling of driver events in metastatic uveal melanoma
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has ahigh mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genesassociated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease. © 2020, The Author(s).
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| 10. |
- Nilsson, Maria E., et al.
(författare)
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Measurement of a comprehensive sex steroid profile in rodent serum by high-sensitive gas chromatography-tandem mass spectrometry.
- 2015
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 156:7, s. 2492-502
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Tidskriftsartikel (refereegranskat)abstract
- Accurate measurement of sex steroid concentrations in rodent serum is essential to evaluate mouse and rat models for sex steroid-related disorders. The aim of the present study was to develop a sensitive and specific gas chromatography-tandem mass spectrometry (GC-MS/MS) method to assess a comprehensive sex steroid profile in rodent serum. A major effort was invested in reaching an exceptionally high sensitivity for measuring serum estradiol concentrations. We established a GC-MS/MS assay with a lower limit of detection for estradiol, estrone, testosterone, dihydrotestosterone, progesterone, androstenedione and dehydroepiandrosterone of 0.3, 0.5, 4, 1.6, 8, 4 and 50 pg/ml, respectively, while the corresponding values for the lower limit of quantification were 0.5, 0.5, 8, 2.5, 74, 12 and 400 pg/ml, respectively. Calibration curves were linear, intra- and inter-assay CVs were low and accuracy was excellent for all analytes. The established assay was used to accurately measure a comprehensive sex steroid profile in female rats and mice according to estrus cycle phase. In addition, we characterized the impact of age, sex, gonadectomy, and estradiol treatment on serum concentrations of these sex hormones in mice. In conclusion, we have established a highly sensitive and specific GC-MS/MS method to assess a comprehensive sex steroid profile in rodent serum in a single run. This GC-MS/MS assay has, to the best of our knowledge, the best detectability reported for estradiol. Our method therefore represents an ideal tool to characterize sex steroid metabolism in a variety of sex steroid-related rodent models and in human samples with low estradiol levels.
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| 11. |
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| 12. |
- Ny, Lars, 1967, et al.
(författare)
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Supporting clinical decision making in advanced melanoma by preclinical testing in personalized immune-humanized xenograft mouse models
- 2020
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 31:2, s. 266-273
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Tidskriftsartikel (refereegranskat)abstract
- Background: The mouse strains usually used to generate patient-derived xenografts (PDXs) are immunocompromised, rendering them unsuitable for immunotherapy studies. Here we assessed the value of immune-PDX mouse models for predicting responses to anti-PD-1 checkpoint inhibitor therapy in patients. Patients and methods: Melanoma biopsies contained in a retrospective biobank were transplanted into NOG mice or NOG mice expressing interleukin 2 (hIL2-NOG mice). Tumor growth was monitored, and comparisons were made with clinical data, sequencing data, and current in silico predictive tools. Results: Biopsies grew readily in NOG mice but growth was heterogeneous in hIL2-NOG mice. IL2 appears to activate T-cell immunity in the biopsies to block tumor growth. Biopsy growth in hIL2-NOG mice was negatively associated with survival in patients previously treated with PD-1 checkpoint blockade. In two cases, the prospective clinical decisions of anti-PD-1 therapy or targeted BRAF/MEK inhibitors were supported by the observed responses in mice. Conclusions: Immune-PDX models represent a promising addition to future biomarker discovery studies and for clinical decision making in patients receiving immunotherapy.
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| 13. |
- Ny, Lars, 1967, et al.
(författare)
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The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- The authors report the results of the phase II PEMDAC clinical study testing the combination of the HDAC inhibitor entinostat with the anti- PD-1 antibody pembrolizumab in uveal melanoma. Low tumor burden, a wildtype BAP1 gene in the tumor or iris melanoma correlates with response and longer survival. Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results of the PEMDAC phase 2 clinical trial (n = 29; NCT02697630) where the HDAC inhibitor entinostat was combined with the PD-1 inhibitor pembrolizumab in patients with metastatic uveal melanoma (UM). The primary endpoint was objective response rate (ORR), and was met with an ORR of 14%. The clinical benefit rate at 18 weeks was 28%, median progression free survival was 2.1 months and the median overall survival was 13.4 months. Toxicities were manageable, and there were no treatment-related deaths. Objective responses and/or prolonged survival were seen in patients with BAP1 wildtype tumors, and in one patient with an iris melanoma that exhibited a UV signature. Longer survival also correlated with low baseline ctDNA levels or LDH. In conclusion, HDAC inhibition and anti-PD1 immunotherapy results in durable responses in a subset of patients with metastatic UM.
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| 14. |
- Sah, Vasu R., et al.
(författare)
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Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy
- 2023
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Ingår i: Cancer Research Communications. ; 3:5, s. 884-895
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Patients with metastatic uveal melanoma have limited therapeutic options and high mortality rate so new treatment options are needed.Patients and Methods: We previously reported that patients treated with the PD-1 inhibitor pembrolizumab and the histone deacetylase inhibitor entinostat in the PEMDAC trial, experienced clinical benefits if their tu-mor originated from iris or was wildtype for BAP1 tumor suppressor gene. Here we present the 2-year follow-up of the patients in the PEMDAC trial and identify additional factors that correlate with response or survival.Results: Durable responses were observed in 4 patients, with additional 8 patients exhibiting a stable disease. The median overall survival was 13.7 months. Grade 3 adverse events were reported in 62% of the patients, but they were all manageable. No fatal toxicity was observed. Activity of thymidine kinase 1 in plasma was higher in patients with stable disease or who progressed on treatment, compared with those with partial response. Chemokines and cytokines were analyzed in plasma. Three chemokines were significantly different when comparing patients with and without response. One of the factors, CCL21, was higher in the plasma of respond-ing patients before treatment initiation but decreased in the same patients upon treatment. In tumors, CCL21 was expressed in areas resembling ter -tiar y lymphoid structures (TLS). High plasma levels of CCL21 and presence of TLS-like regions in the tumor correlated with longer survival.Conclusions: This study provides insight into durable responses in the PEMDAC trial, and describes dynamic changes of chemokines and cytokines in the blood of these patients.Significance: The most significant finding from the 2-year follow-up study of the PEMDAC trial was that high CCL21 levels in blood was associated with response and survival. CCL21 was also expressed in TLS-like regions and presence of these regions was associated with longer survival. These analyses of soluble and tumor markers can inform on predictive biomark-ers needing validation and become hypothesis generating for experimental research.
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| 15. |
- Sah, Vasu R., et al.
(författare)
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Epigenetic therapy to enhance therapeutic effects of PD-1 inhibition in therapy-resistant melanoma
- 2022
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Ingår i: Melanoma Research. - : Ovid Technologies (Wolters Kluwer Health). - 0960-8931. ; 32:4, s. 241-248
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Tidskriftsartikel (refereegranskat)abstract
- Targeted therapy and immunotherapy have revolutionized the treatment of metastatic skin melanoma but around half of all patients develop resistance early or late during treatment. The situation is even worse for patients with metastatic uveal melanoma (UM). Here we hypothesized that the immunotherapy of therapy-resistant skin melanoma or UM can be enhanced by epigenetic inhibitors. Cultured B16F10 cells and human UM cells were treated with the histone deacetylase inhibitor (HDACi) entinostat or BETi JQ1. Entinostat-induced HLA expression and PD-L1, but JQ1 did not. A syngeneic mouse model carrying B16-F10 melanoma cells was treated with PD-1 and CTLA4 inhibitors, which was curative. Co-treatment with the bioavailable BETi iBET726 impaired the immunotherapy effect. Monotherapy of a B16-F10 mouse model with anti-PD-1 resulted in a moderate therapeutic effect that could be enhanced by entinostat. Mice carrying PD-L1 knockout B16-F10 cells were also sensitive to entinostat. This suggests HDAC inhibition and immunotherapy could work in concert. Indeed, co-cultures of UM with HLA-matched melanoma-specific tumor-infiltrating lymphocytes (TILs) resulted in higher TIL-mediated melanoma killing when entinostat was added. Further exploration of combined immunotherapy and epigenetic therapy in metastatic melanoma resistant to PD-1 inhibition is warranted.
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| 16. |
- Westberg, Lars, 1973, et al.
(författare)
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Influence of androgen receptor repeat polymorphisms on personality traits in men
- 2009
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Ingår i: Journal of Psychiatry and Neuroscience. - 1488-2434 .- 1180-4882. ; 34:3, s. 205-213
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Tidskriftsartikel (refereegranskat)abstract
- Background Testosterone has been attributed importance for various aspects of behaviour. The aim of our study was to investigate the potential influence of 2 functional polymorphisms in the amino terminal of the androgen receptor on personality traits in men. Methods We assessed and genotyped 141 men born in 1944 recruited from the general population. We used 2 different instruments: the Karolinska Scales of Personality and the Temperament and Character Inventory. For replication, we similarly assessed 63 men recruited from a forensic psychiatry study group. Results In the population-recruited sample, the lengths of the androgen receptor repeats were associated with neuroticism, extraversion and self-transcendence. The association with extraversion was replicated in the independent sample. Limitations Our 2 samples differed in size; sample 1 was of moderate size and sample 2 was small. In addition, the homogeneity of sample 1 probably enhanced our ability to detect significant associations between genotype and phenotype. Conclusion Our results suggest that the repeat polymorphisms in the androgen receptor gene may influence personality traits in men.
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| 17. |
- Abarenkov, Kessy, et al.
(författare)
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Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
- 2016
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Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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| 18. |
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| 19. |
- Andersson, Anna, et al.
(författare)
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Waterworks-specific composition of drinking water disinfection by-products
- 2019
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Ingår i: Environmental Science. - Cambridge : Royal Society of Chemistry. - 2053-1400 .- 2053-1419. ; :5, s. 861-872
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Tidskriftsartikel (refereegranskat)abstract
- Reactions between chemical disinfectants and natural organic matter (NOM) upon drinking water treatment result in formation of potentially harmful disinfection by-products (DBPs). The diversity of DBPs formed is high and a large portion remains unknown. Previous studies have shown that non-volatile DBPs are important, as much of the total toxicity from DBPs has been related to this fraction. To further understand the composition and variation of DBPs associated with this fraction, non-target analysis with ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was employed to detect DBPs at four Swedish waterworks using different types of raw water and treatments. Samples were collected five times covering a full year. A common group of DBPs formed at all four waterworks was detected, suggesting a similar pool of DBP precursors in all raw waters that might be related to phenolic moieties. However, the largest proportion (64–92%) of the assigned chlorinated and brominated molecular formulae were unique, i.e. were solely found in one of the four waterworks. In contrast, the compositional variations of NOM in the raw waters and samples collected prior to chemical disinfection were rather limited.This indicated that waterworks-specific DBPs presumably originated from matrix effects at the point of disinfection, primarily explained by differences in bromide levels, disinfectants (chlorine versus chloramine) and different relative abundances of isomers among the NOM compositions studied. The large variation of observed DBPs in the toxicologically relevant non-volatile fraction indicates that non-targeted monitoring strategies might be valuable to ensure relevant DBP monitoring in the future.
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| 20. |
- Andersson, Mats X., 1977, et al.
(författare)
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Involvement of the Electrophilic Isothiocyanate Sulforaphane in Arabidopsis Local Defense Responses
- 2015
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Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 167:1
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Tidskriftsartikel (refereegranskat)abstract
- Plants defend themselves against microbial pathogens through a range of highly sophisticated and integrated molecular systems. Recognition of pathogen-secreted effector proteins often triggers the hypersensitive response (HR), a complex multicellular defense reaction where programmed cell death of cells surrounding the primary site of infection is a prominent feature. Even though the HR was described almost a century ago, cell-to-cell factors acting at the local level generating the full defense reaction have remained obscure. In this study, we sought to identify diffusible molecules produced during the HR that could induce cell death in naive tissue. We found that 4-methylsulfinylbutyl isothiocyanate (sulforaphane) is released by Arabidopsis (Arabidopsis thaliana) leaf tissue undergoing the HR and that this compound induces cell death as well as primes defense in naive tissue. Two different mutants impaired in the pathogen-induced accumulation of sulforaphane displayed attenuated programmed cell death upon bacterial and oomycete effector recognition as well as decreased resistance to several isolates of the plant pathogen Hyaloperonospora arabidopsidis. Treatment with sulforaphane provided protection against a virulent H. arabidopsidis isolate. Glucosinolate breakdown products are recognized as antifeeding compounds toward insects and recently also as intracellular signaling and bacteriostatic molecules in Arabidopsis. The data presented here indicate that these compounds also trigger local defense responses in Arabidopsis tissue.
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| 21. |
- Berggren, Peter, 1971-, et al.
(författare)
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The importance of using the designated duty officers when assessing the medical response organization
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundAn important aspect of disaster medicine is to be proactive and respond quickly when disaster strikes. In Sweden, the role responsible for swift medical response on the regional level is the designated duty officer.MethodsA large exercise to assess national medical response ability was conducted. Seven medical regional staffs (a total of 93 individuals participated as tested participants) were involved in handling a large train accident scenario. The exercise was run for 5 hours, where the different regional staffs were located at their regular command posts. The exercise was organized using Emergo Train Systems.ResultsSeveral capabilities were identified during the exercise as important for the organization to maintain the ability to handle a similar event: documentation and operational picture, communication and terminology, command of resources, strategy for distribution of resources, national co-ordination, and exercise development.The designated duty officers were central to the exercise in several aspects: 1) in developing and verifying a realistic scenario and preparing background information, 2) as participants in the exercise, 3) assessors of the staffs’ behaviors, and 4) as domain experts when interpreting the exercise outcome.ConclusionsUsing subject matter experts is central to many research domains. However, the more complex a situation is the larger the demand of expertise is. The technical platform allows for coordinating complex exercises, whereas the subject matter expert in terms of the designated duty officer is required to guarantee validity and reliability in these large-scale exercises.Key messages:Running complex scenarios to train and test abilities requires subject matter experts in both planning, preparation, implementation, and assessment.Sophisticated simulator and training platforms, such as Emergo Train Systems, facilitates while the designated duty officers are necessary to guarantee validity and reliability in the exercise.
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| 22. |
- Colldén, Hannah, et al.
(författare)
-
The gut microbiota is a major regulator of androgen metabolism in intestinal contents.
- 2019
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - 1522-1555. ; 317:6
-
Tidskriftsartikel (refereegranskat)abstract
- Androgens exert important effects both in androgen-responsive tissues and in the intestinal tract. To determine the impact of the gut microbiota (GM) on intestinal androgen metabolism, we measured unconjugated (free) and glucuronidated androgen levels in intestinal contents from the small intestine, with a low bacterial density, and from cecum and colon, with a high bacterial density. Using a specific, sensitive gas chromatography-tandem mass spectrometry method, we detected high levels of glucuronidated testosterone (T) and dihydrotestosterone (DHT) in small intestinal content of mice of both sexes, whereas in the distal intestine we observed remarkably high levels of free DHT, exceeding serum levels by >20-fold. Similarly, in young adult men high levels of unconjugated DHT, >70-fold higher than in serum, were detected in feces. In contrast to mice with a normal GM composition, germ-free mice had high levels of glucuronidated T and DHT, but very low free DHT levels, in the distal intestine. These findings demonstrate that the GM is involved in intestinal metabolism and deglucuronidation of DHT and T, resulting in extremely high free levels of the most potent androgen, DHT, in the colonic content of young and healthy mice and men.
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| 23. |
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| 24. |
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| 25. |
- Gracias, J., et al.
(författare)
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Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia
- 2022
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia risk has been associated with the complement component 4 (C4) genes. Here the authors show that C4A is elevated in individuals with schizophrenia. Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.
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| 26. |
- Gustafsson, Jenny K, 1981, et al.
(författare)
-
Bicarbonate and functional CFTR channel are required for proper mucin secretion and link cystic fibrosis with its mucus phenotype.
- 2012
-
Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 209:7, s. 1263-72
-
Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis (CF) is caused by a nonfunctional chloride and bicarbonate ion channel (CF transmembrane regulator [CFTR]), but the link to the phenomenon of stagnant mucus is not well understood. Mice lacking functional CFTR (CftrΔ508) have no lung phenotype but show similar ileal problems to humans. We show that the ileal mucosa in CF have a mucus that adhered to the epithelium, was denser, and was less penetrable than that of wild-type mice. The properties of the ileal mucus of CF mice were normalized by secretion into a high concentration sodium bicarbonate buffer (~100 mM). In addition, bicarbonate added to already formed CF mucus almost completely restored the mucus properties. This knowledge may provide novel therapeutic options for CF.
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| 27. |
- Hansson, Mattias, et al.
(författare)
-
Artifactual insulin release from differentiated embryonic stem cells.
- 2004
-
Ingår i: Diabetes. - 0012-1797. ; 53:10, s. 2603-9
-
Tidskriftsartikel (refereegranskat)abstract
- Several recent reports claim the generation of insulin-producing cells from embryonic stem cells via the differentiation of progenitors that express nestin. Here, we investigate further the properties of these insulin-containing cells. We find that although differentiated cells contain immunoreactive insulin, they do not contain proinsulin-derived C-peptide. Furthermore, we find variable insulin release from these cells upon glucose addition, but C-peptide release is never detected. In addition, many of the insulin-immunoreactive cells are undergoing apoptosis or necrosis. We further show that cells cultured in the presence of a phosphoinositide 3-kinase inhibitor, which previously was reported to facilitate the differentiation of insulin(+) cells, are not C-peptide immunoreactive but take up fluorescein isothiocyanate-labeled insulin from the culture medium. Together, these data suggest that nestin(+) progenitor cells give rise to a population of cells that contain insulin, not as a result of biosynthesis but from the uptake of exogenous insulin. We conclude that C-peptide biosynthesis and secretion should be demonstrated to claim insulin production from embryonic stem cell progeny.
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| 28. |
-
Hälso- och sjukvårdens förmåga att hantera en allvarlig händelse med många skadade : erfarenheter och lärdomar av Övning TYKO
- 2016
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den 3 mars 2016 fick Socialstyrelsen i uppdrag av regeringen att öva hälsooch sjukvårdens förmåga att hantera en allvarlig händelse med många skadade. Myndigheten beslutade att genomföra övningen som en funktionell simuleringsövning med motspel. De övade utvärderades med hjälp av mätbara kvalitetsindikatorer som tidigare identifierats inom ramen för Socialstyrelsens arbete med att ta fram en gemensam modell för särskild sjukvårdsledning vid allvarlig händelse. Inför övningen skapades ett scenario som var utmanande för hälso- och sjukvården men, för att möjliggöra genomförandet inte innefattade alla potentiella komplexa faktorer. En kritisk observation är att analysen utifrån en övning bör vara restriktiv med slutsatser ifall dessa inte samtidigt kan styrkas utifrån tidigare övningar eller verkliga händelser. Övningens scenario samt patienternas skadepanorama och utfall visualiserades med hjälp av simuleringsverktyget Emergo Train System® och dess instruktörer vid Katastrofmedicinskt Centrum i Linköping. Ett väsentligt mål med övningen var att den ska utgöra ett underlag för att stärka förmågan inom hälso- och sjukvården genom att identifiera utvecklingsområden. I rapporten redovisas under övningen identifierade förmågor och utvecklingsområden som myndigheten bedömer som viktiga för att upprätthålla, säkra och förbättra förmågan att hantera allvarliga händelser: • Dokumentation och lägesbild • Kommunikation och terminologi • Mobilisering och dirigering av resurser • Fördelningsstrategi och gränssättande kapacitet • Nationell samordning • Övningsteknisk utveckling En gemensam lägesbild är viktig efter som det stödjer de involverade aktörerna i arbetet med att värdera behovet av stöd under pågående händelse. Därför var en viktig del i övningens utvärdering huruvida påverkade landsting hade förmågan att snabbt skapa sig en uppfattning om aktuellt behov, tillgängliga resurser och hur ytterligare pre- hospitala samt hospitala resurser skulle kunna mobiliseras. Dessa kritiska faktorer skapar förutsättningar för att korrekta fördelningsstrategier för de skadande patienterna ska kunna utarbetas. Övning Tyko visade att staber med hög upplevd arbetsbelastning och låg upplevd situationsmedvetenhet hade svårt att värdera sitt eget behov av stöd från andra aktörer. Att i förväg ha kännedom om vilken typ av stöd man behöver och kan förvänta sig i olika situationer kräver ett arbete för att identifiera detta redan i före-perspektivet. Det går inte att utesluta att en annan överblick av tillgängliga resurser och en annan förutsägbarhet i vad som kan förväntas av andra hade föranlett en annan fördelningsstrategi som hade förbättrat patientfallet i övningen. För att avgöra effektiviteten av fattade beslut i enlighet med framtagna strategier behövs även en förmåga till 8 HÄLSO- OCH SJUKVÅRDENS FÖRMÅGA ATT HANTERA EN ALLVARLIG HÄNDELSE MED MÅNGA SKADADE SOCIALSTYRELSEN uppföljning huruvida tagna beslut får förväntad effekt inom rimlig tid, under övningen observerades kommunikationsproblem gällande kvittens, förfrågan och bekräftelse. En viktig sammanfattande slutsats som Socialstyrelsen drar inför fortsatt arbete är att myndigheten ska verka för att etablera en funktion för nationell samordning med syfte att ge förutsättningar till en bättre behovs- och resursmatchning vid stora skadeutfall. Inom ramen för en sådan samordning bör gemensamma triage och larmkriterier, medicinska bedömningskriterier och skadeklassificeringar, gemensamma rapportmallar och system för distribution av diagnostiskt material samt gemensam terminologi m.m. inkluderas. Metoder och teknik för framtagandet och kommunikationen av fördelningsnycklar och aktuella kapacitetsbedömningar över tid behöver tas fram för att skapa förutsättningar för en aktuell bild av resurstillgången. Socialstyrelsen vill skapa förutsättningar för ett nationellt kompetenscentrum med inriktning på ökad förmåga och samordning i hela traumavårskedjan. I detta arbete kan även arbetet med Socialstyrelsens förmåga till nationell samordning under pågående händelse utarbetas, definieras och implementeras. Myndigheten vill slutligen lyfta fram att en samlad nationell plan för både trauma- och katastrofmedicinsk utbildning och övning ger ytterligare förutsättningar att upprätthålla och öka förmågan att hantera allvarliga händelser. Dessa viktiga slutsatser avser myndigheten ta med sig in i sitt fortsatta arbete med att stärka hälso-och sjukvårdens förmåga vid allvarlig händelse.
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| 29. |
- Kallunki, Juha-Pecka, et al.
(författare)
-
Why do insiders trade? : Evidence based on unique data on Swedish insiders
- 2009
-
Ingår i: Journal of Accounting & Economics. - : Elsevier. - 0165-4101 .- 1879-1980. ; 48:1, s. 37-53
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we examine if corporate insiders have other motives for trading besides exploitation of private information. Our results show that insiders’ portfolio re- balancing objectives, tax considerations and behavioral biases play the most important role in their trading decisions. We also find that insiders who have allocated a great (small) proportion of their wealth to insider stock sell more (less) before bad news earnings disclosures. Finally, insider selling is informative for future returns among those insiders who have the greatest proportion of wealth allocated to insider stocks.
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| 30. |
- Nilsson, Anders K., 1982, et al.
(författare)
-
Preterm infant circulating sex steroid levels are not altered by transfusion with adult male plasma: a retrospective multicentre cohort study
- 2022
-
Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ. - 1359-2998 .- 1468-2052. ; 107:6, s. 577-582
-
Tidskriftsartikel (refereegranskat)abstract
- Sex hormones delivered via plasma transfusions from adult male donors to very preterm infants do not alter the circulating plasma concentrations in the infant, irrespective of gender. Objective To determine if plasma transfusions with male donor plasma to very preterm infants affect circulatory levels of sex steroids. Design and patients Retrospective multicentre cohort study in 19 infants born at gestational age Setting Three neonatal intensive care units in Sweden. Main outcome measures Concentrations of sex steroids and sex hormone-binding globulin (SHBG) in donor plasma and infant plasma measured before and after a plasma transfusion and at 6, 12, 24 and 72 hours. Results The concentrations of progesterone, dehydroepiandrosterone and androstenedione were significantly lower in donor plasma than in infant plasma before the transfusion (median (Q1-Q3) 37.0 (37.0-37.0), 1918 (1325-2408) and 424 (303-534) vs 901 (599-1774), 4119 (2801-14 645) and 842 (443-1684) pg/mL), while oestrone and oestradiol were higher in donor plasma (17.4 (10.4-20.1) and 16.0 (11.7-17.2) vs 3.1 (1.1-10.2) and 0.25 (0.25-0.25) pg/mL). Median testosterone and dihydrotestosterone (DHT) levels were 116-fold and 21-fold higher in donor plasma than pre-transfusion levels in female infants, whereas the corresponding difference was not present in male infants. Plasma sex steroid levels were unchanged after completed transfusion compared with pre-transfusion levels, irrespective of the gender of the receiving infant. The SHBG concentration was significantly higher in donor than in recipient plasma (22.8 (17.1-33.5) vs 10.2 (9.1-12.3) nmol/L) before transfusion but did not change in the infants after the transfusion. Conclusions A single transfusion of adult male plasma to preterm infants had no impact on circulating sex steroid levels.
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| 31. |
- Nilsson, Henrik, 1971-
(författare)
-
Essays on the value relevance of financial statment information
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis consists of an introductory chapter and four self-contained essays on the value relevance of financial statement information.Essay 1: The purpose of this essay is to examine relevance of environmental information from an investor’s perspective. The study proposes that the market value of companies will reflect both financial and environmental performance. The theoretical foundation of the study is the accounting based valuation theory outlined by Ohlson (1995). This study provides new insights into how environmental performance is reflected in the market value of Swedish companies listed on the Swedish Stock market.Essay 2: In financial accounting research, much effort has been devoted to study the relation between accounting earnings and stock prices. The primary purpose of the second essay is to investigate the effect of alternative return-earnings model specifications to the estimated returns-earnings relation, that is, the earnings response coefficients. The returns-earnings models investigated include the traditional earnings levels and changes, and models including analysts’ earnings forecasts based on Ohlson’s (1995) extended residual income model.Essay 3: Fundamental analysis research that focuses on the use of accounting information to estimate equity value, has surfaced as a central theme in market based accounting research of the 1990s (Lee, 1999). The purpose of third essay is to compare two different approaches to valuation based on the theory presented in Ohlson (1995) in terms of explanatory and predictive power of the value estimates. Both approaches are implemented with and without the use of analysts forecasts.Essay 4: In this essay data from the Swedish stock market is used to investigate the profitability of two different types of investment strategies based on fundamental-to-value ratios and past insider trading activity. The purpose of the research is to explore four related research questions: (i) Do accounting based trading strategies generate abnormal returns on the Swedish stock market?; (ii) Do trading strategies based on insider trading behaviour generate abnormal returns on the Swedish stock market?; (iii) Do insiders who buy stocks tend to favour value stocks and do insiders who sell stocks tend to dispose growth stocks?; and (iv) Are insiders able to discriminate between temporary high/low fundamentals and temporary low/high prices when buying/selling value stocks and growth stocks?
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| 32. |
- Nilsson, Henrik, 1971-
(författare)
-
Exploring environmental information in sell-side analysts' research reports
- 2008
-
Ingår i: Progress in Industrial Ecology, An International Journal. - : InderScience Publishers. - 1476-8917 .- 1478-8764. ; 5:2, s. 213-235
-
Tidskriftsartikel (refereegranskat)abstract
- This study shows how environmental information is used by financial analysts when valuing companies. Unlike the previous studies on analysts' perceptions, we use content analysis to examine the actual use of environmental information in valuations. Research reports from large investment banks in the USA and Europe are collected. The sample consists of reports from two industries, oil and chemicals, where the operations have a considerable impact on the environment. The results show that analysts do use environmental information in 35% of the valuations. Most of the information utilised is for environmental expenditures and risk assessment. For instance, the information about environmental provisions and emissions is of relative importance. We also find that analysts use environmental information not only for the evaluations of risk, but also for the assessment of the future upside potential when valuing chemical companies. They make use of this information to motivate the relative valuations.
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| 33. |
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| 34. |
- Nilsson, Henrik, 1971-
(författare)
-
Hållbar ägarstyrning
- 2011. - 1
-
Ingår i: Hållbar utveckling. - Lund : Studentlitteratur AB. - 9144075324 - 9789144075327 ; , s. 21-30
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 35. |
- Ohlsson, Claes, 1965, et al.
(författare)
-
Comparisons of Immunoassay and Mass Spectrometry Measurements of Serum Estradiol Levels and Their Influence on Clinical Association Studies in Men
- 2013
-
Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:6
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Immunoassay-based techniques, routinely used to measure serum estradiol (E2), are known Objective: Our objective was to compare immunoassay and MS measurements of E2 levels in men and Design and Setting: Middle-aged and older male subjects participating in the population-based Main Outcome Measures: Immunoassay and MS measurements of serum E2 were compared and Results: Within each cohort, serum E2 levels obtained by immunoassay and MS correlated moderately Conclusions: Our findings suggest interference in the immunoassay E2 analyses, possibly by CRP or a
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| 36. |
- Rydberg Sterner, Therese, et al.
(författare)
-
The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population.
- 2019
-
Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209
-
Tidskriftsartikel (refereegranskat)abstract
- To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
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| 37. |
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| 38. |
- Undeman, Emma, 1981-, et al.
(författare)
-
The potential of the EU Water Framework Directive for reducing emissions of pollutants is limited : a case study on river basin specific pollutants in Swedish environmental permitting processes
- 2022
-
Ingår i: Environmental Sciences Europe. - : Springer Nature. - 2190-4707 .- 2190-4715. ; 34:1
-
Tidskriftsartikel (refereegranskat)abstract
- River basin specific pollutants (RBSPs) are supposedly a key tool to fulfil the EU’s Water Framework Directive (WFD) goal of good ecological status in all European waterbodies. The RBSPs provide a tool to manage chemical pollution identified as a national priority. An important question is if the costly management related to RBSPs leads to reduced emissions, an issue we investigated here using Sweden as a case. Swedish measures implemented under the WFD mainly rely on environmental permitting and supervision. We, therefore, specifically assessed how RBSPs have influenced permit proceedings in the Land and Environment Court of Appeal, where precedents for judgements in lower courts and authorities is established, during the 2010s. Despite permit-review being an important measure highlighted in the WFD and in Swedish programs of measures, all cases appealed to higher court were initiated by the operators/permit holders. The permissibility of environmentally hazardous activities was not impacted by RBSPs in any instance. Permit conditions addressing RBSPs were discussed in ⁓1% of all environmental cases, mainly resulting in conditions demanding further inquiries regarding emissions and concentrations of a limited number of RBSPs (i.e., metals and nitrogen in the forms of nitrate and ammonia). Open-ended conditions and delegation allowing for updating permit conditions if additional RBSPs are identified were suggested but rejected by court as these conflict with fundamental principles of precision and predictability of permit conditions stated in Swedish and European law. We conclude that RBSPs as management tool has little impact on emissions from activities requiring environmental permits and thereby water quality.
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| 39. |
- Vedantha Krishna, Amogh, 1990-, et al.
(författare)
-
Influence of different post-processing methods on surface topography of fused deposition modelling samples
- 2020
-
Ingår i: Surface Topography: Metrology and Properties. - Bristol : Institute of Physics Publishing (IOPP). - 2051-672X. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Additive Manufacturing (AM) is gaining prominence due to its massive advantage in fabricating components without any geometrical limitations. The most widely used AM technique is Fused Deposition Modelling (FDM). FDM is an extrusion-based AM mostly focused on producing functional prototypes and in some cases as an end-product. One of the most common challenges associated with FDM is its reduced dimensional accuracy and surface quality. A fair amount of research has been carried out to identify the factors affecting print quality and measures to reduce surface roughness. On a few occasions, it is still necessary to achieve higher precision and quality to meet the standards set by conventional manufacturing. Hence, post-processing is employed as an additional step to reach the finish required. This paper focuses on enhancing the surface quality of FDM parts by subjecting it to Acetone vapour smoothening, Shot-blasting and Laser-assisted finishing post-processing methods. A comparative study is presented in this paper, where surface produced by different post-processing methods were compared to the reference injection moulding components. The results suggest that the acetone-based process has the best surface finish compared to the other two means; however, it leaves a very glossy appearance to the part. Shot blasting is very aggressive, and blasting time has a strong influence on the part quality. Laser-assisted finishing slightly ignites the top layer during melting leading to discolouration of the part. The optimum solution was found to be combining the post-processes, which not only reduced the roughness but also enhanced the aesthetic properties of the product. © 2020 IOP Publishing Ltd.
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| 40. |
- Wikström, Sofia A., et al.
(författare)
-
Ekosystemansatsen – praktiska erfarenheter från svensk havs- och vattenförvaltning
- 2020
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten sammanfattar resultaten från forskningsprojektet ”Ekosystemansatsen – praktiska erfarenheter och nästa steg”. Projektet har undersökt erfarenheter av det praktiska införandet av ekosystembaserad havs-, vattenoch fiskförvaltning i Sverige, utifrån publicerad litteratur och intervjuer med nyckelpersoner i Sverige, Tyskland, Norge och USA. Sammanställningen visar att Sverige tagit flera steg mot en mer ekosystembaserad förvaltning, men pekar också på svårigheter. En viktig erfarenhet är att ekosystembaserad förvaltning ställer höga krav på samverkan och kommunikation mellan aktörer och att en stabil och tillräcklig finansiering är en viktig förutsättning. Det finns behov av en tydligare styrning och uppföljning från centrala myndigheter, en mer långsiktig finansiering och tydligare processer för kunskapsutbyte mellan olika aktörer. Det finns även ett behov av att kartlägga bristande överensstämmelse mellan olika sektorslagstiftningar och olika samhällsmål och att diskutera målkonflikter på nationell nivå. Implementeringen av åtgärdsprogram och planer behöver stärkas genom att berörda aktörer ges ett tydligt ansvar för att förvaltningsmål uppfylls och för en ambitiös uppföljning av framsteg mot målen. Det vore också önskvärt att vidareutveckla indikatorer för ekosystembaserad förvaltning som kvantitativt mäter framstegen mot dess principer.
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| 41. |
- Zhang, Renyun, et al.
(författare)
-
Soap-film coating : High-speed deposition of multilayer nanofilms
- 2013
-
Ingår i: Scientific Reports. - Nature Publishing Group : Springer Science and Business Media LLC. - 2045-2322. ; 3, s. Art. no. 1477-
-
Tidskriftsartikel (refereegranskat)abstract
- The coating of thin films is applied in numerous fields and many methods are employed for the deposition of these films. Some coating techniques may deposit films at high speed; for example, ordinary printing paper is coated with micrometre-thick layers of clay at a speed of tens of meters per second. However, to coat nanometre thin films at high speed, vacuum techniques are typically required, which increases the complexity of the process. Here, we report a simple wet chemical method for the high-speed coating of films with thicknesses at the nanometre level. This soap-film coating technique is based on forcing a substrate through a soap film that contains nanomaterials. Molecules and nanomaterials can be deposited at a thickness ranging from less than a monolayer to several layers at speeds up to meters per second. We believe that the soap-film coating method is potentially important for industrial-scale nanotechnology.
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