| 1. |
- Rajwa, Pawel, et al.
(författare)
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Research protocol for an observational health data analysis on the adverse events of systemic treatment in patients with metastatic hormone-sensitive prostate cancer : big data analytics using the PIONEER platform
- 2024
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 63, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in “real-life” patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.
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| 2. |
- Sparrman, Anna, 1965-, et al.
(författare)
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Child Studies Multiple : Collaborative play for thinking through theories and methods
- 2023
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Ingår i: Culture Unbound. - : Linköping University Electronic Press. - 2000-1525. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- This text is an exploration of collaborative thinking and writing through theories, methods, and experiences on the topic of the child, children, and childhood. It is a collaborative written text (with 32 authors) that sprang out of the experimental workshop Child Studies Multiple. The workshop and this text are about daring to stay with mess, “un-closure” , and uncertainty in order to investigate the (e)motions and complexities of being either a child or a researcher. The theoretical and methodological processes presented here offer an opportunity to shake the ground on which individual researchers stand by raising questions about scientific inspiration, theoretical and methodological productivity, and thinking through focusing on process, play, and collaboration. The effect of this is a questioning of the singular academic ‘I’ by exploring and showing what a plural ‘I’ can look like. It is about what the multiplicity of voice can offer research in a highly individualistic time. The article allows the reader to follow and watch the unconventional trial-and-error path of the ongoing-ness of exploring theories and methods together as a research community via methods of drama, palimpsest, and fictionary.
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| 3. |
- Anand, Aseem, et al.
(författare)
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Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide
- 2016
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Ingår i: EJNMMI Research. - : Springer. - 2191-219X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide.METHODS: Retrospectively, we included patients who received enzalutamide as a clinically approved therapy for mCRPC and had undergone bone scan prior to starting therapy. Automated BSI, prostate-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI Bone(BSI) version 2. Kendall's tau (τ) was used to assess the correlation of BSI with other blood-based biomarkers. Concordance index (C-index) was used to evaluate the discriminating strength of automated BSI in predicting OS.RESULTS: Eighty mCRPC patients with baseline bone scans were included in the study. There was a weak correlation of automated BSI with PSA (τ = 0.30), with HgB (τ = -0.17), and with ALP (τ = 0.56). At baseline, the automated BSI was observed to be predictive of OS (C-index 0.72, standard error (SE) 0.03). Adding automated BSI to the blood-based model significantly improved the C-index from 0.67 to 0.72, p = 0.017. Treatment follow-up bone scans were available from 62 patients. Both change in BSI and percent change in PSA were predictive of OS. However, the combined predictive model of percent PSA change and change in automated BSI (C-index 0.77) was significantly higher than that of percent PSA change alone (C-index 0.73), p = 0.041.CONCLUSIONS: The upgraded and analytically validated automated BSI was found to be a strong predictor of OS in mCRPC patients. Additionally, the change in automated BSI demonstrated an additive clinical value to the change in PSA in mCRPC patients being treated with enzalutamide.
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| 4. |
- Arp, Hans Peter H., et al.
(författare)
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Native Oxy-PAHs, N-PACs, and PAHs in historically contaminated soils from Sweden, Belgium, and France : their soil-porewater partitioning behavior, bioaccumulation in Enchytraeus crypticus, and bioavailability
- 2014
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 48:19, s. 11187-11195
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Tidskriftsartikel (refereegranskat)abstract
- Soil quality standards are based on partitioning and toxicity data for laboratory-spiked reference soils, instead of real world, historically contaminated soils, which would be more representative. Here 21 diverse historically contaminated soils from Sweden, Belgium, and France were obtained, and the soil-porewater partitioning along with the bioaccumulation in exposed worms (Enchytraeus crypticus) of native polycyclic aromatic compounds (PACs) were quantified. The native PACs investigated were polycyclic aromatic hydrocarbons (PAHs) and, for the first time to be included in such a study, oxygenated-PAHs (oxy-PAHs) and nitrogen containing heterocyclic PACs (N-PACs). The passive sampler polyoxymethylene (POM) was used to measure the equilibrium freely dissolved porewater concentration, C-pw, of all PACs. The obtained organic carbon normalized partitioning coefficients, K-TOC, show that sorption of these native PACs is much stronger than observed in laboratory-spiked soils (typically by factors 10 to 100), which has been reported previously for PAHs but here for the first time for oxy-PAHs and N-PACs. A recently developed K-TOC model for historically contaminated sediments predicted the 597 unique, native K-TOC values in this study within a factor 30 for 100% of the data and a factor 3 for 58% of the data, without calibration. This model assumes that TOC in pyrogenic-impacted areas sorbs similarly to coal tar, rather than octanol as typically assumed. Black carbon (BC) inclusive partitioning models exhibited substantially poorer performance. Regarding bioaccumulation, C-pw combined with liposome-water partition coefficients corresponded better with measured worm lipid concentrations, C-lipid (within a factor 10 for 85% of all PACs and soils), than C-pw combined with octanol-water partition coefficients (within a factor 10 for 76% of all PACs and soils). E. crypticus mortality and reproducibility were also quantified. No enhanced mortality was observed in the 21 historically contaminated soils despite expectations from PAH spiked reference soils. Worm reproducibility weakly correlated to C-lipid of PACs, though the contributing influence of metal concentrations and soil texture could not be taken into account. The good agreement of POM-derived C-pw with independent soil and lipid partitioning models further supports that soil risk assessments would improve by accounting for bioavailability. Strategies for including bioavailability in soil risk assessment are presented.
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| 5. |
- Aulin, Christian, et al.
(författare)
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Nanoscale Cellulose Films with Different Crystallinities and Mesostructures : Their Surface Properties and Interaction with Water
- 2009
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 25:13, s. 7675-7685
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Tidskriftsartikel (refereegranskat)abstract
- A systematic study of the degree of molecular ordering and swelling of different nanocellulose model films has been conducted. Crystalline cellulose II surfaces were prepared by spin-coating of the precursor cellulose solutions onto oxidized silicon wafers before regeneration in water or by using the Langmuir-Schaefer (LS) technique. Amorphous cellulose films were also prepared by spin-coating of a precursor cellulose solution onto oxidized silicon wafers. Crystalline cellulose I surfaces were prepared by spin-coating wafers with aqueous suspensions of sulfate-stabilized cellulose nanocrystals and low-charged microfibrillated cellulose (LC-MFC). In addition, a dispersion of high-charged MFC was used for the buildup of polyelectrolyte multilayers with polyetheyleneimine on silica with the aid of the layer-by-layer (LbL) technique. These preparation methods produced smooth thin films on the nanometer scale Suitable for X-ray diffraction and swelling measurements. The surface morphology and thickness of the cellulose films were characterized in detail by atomic force microscopy (AFM) and ellipsometry measurements, respectively. To determine the surface energy of the cellulose surfaces, that Is, their ability to engage in different interactions with different materials, they were characterized through contact angle measurements against water, glycerol, and methylene iodide. Small incidence angle X-ray diffraction revealed that the nanocrystal and MFC films exhibited a cellulose I crystal structure and that the films prepared from N-methylmorpholine-N-oxide (NMMO), LiCl/DMAc solutions, using the LS technique, possessed a cellulose II structure. The degree of crystalline ordering was highest in the nanocrystal films (similar to 87%), whereas the MFC, NMMO, and LS films exhibited a degree of crystallinity of about 60%. The N,N-dimethylacetamide(DMAc)/LiCl film possessed very low crystalline ordering (<15%). It was also established that the films ha different mesostructures, that is, structures around 10 nm, depending on the preparation conditions. The LS and LiCl/DMAc films are smooth without any clear mesostructure, whereas the other films have a clear mesostructure in which the dimensions are dependent oil the size of the nanocrystals, fibrillar cellulose, and electrostatic charge of the MFC. The swelling of the films was studied using a quartz crystal microbalance with dissipation. To understand the swelling properties of the films, it was necessary to consider both the difference in crystalline ordering and the difference in mesostructure of the films.
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| 6. |
- Brechensbauer Brandin, Madeleine, et al.
(författare)
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Centralen : Studier i området kring Stockholms Centralstation
- 1989
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Rapport (populärvet., debatt m.m.)abstract
- Denna skrift handlar om Centralen i Stockholm och dess närmaste omgivningar, Centralplan, T-centralen, Vasagatan och Klarabergsgatan. Den är resultatet av Arkitekturskolans arbete läsåret 1983- 84 och innehåller förutom en rad projekt också historiska utblickar och samtidskritiska resonemang. En stor del av innehållet redovisades redan våren 1984 - det skedde genom en utställning på Arkitekturmuseet och en preliminär publikation. Materialet har sedan svällt ut med innehållsrika uppsatser om Centralen, om äldre och nyare insatser för att förena konst och arkitektur och om den föga kända, ännu obebyggda Blekholmen.
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| 7. |
- Carlsson, Andreas, et al.
(författare)
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Prediction of designer drugs: Synthesis and spectroscopic analysis of synthetic cathinone analogs that may appear on the Swedish drug market
- 2018
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Ingår i: Drug Testing and Analysis. - : WILEY. - 1942-7603 .- 1942-7611. ; 10:7, s. 1076-1098
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Tidskriftsartikel (refereegranskat)abstract
- The use of hyphenated analytical techniques in forensic drug screening enables simultaneous identification of a wide range of different compounds. However, the appearance of drug seizures containing new substances, mainly new psychoactive substances (NPS), is steadily increasing. These new and other already known substances often possess structural similarities and consequently they exhibit spectral data with slight differences. This situation has made the criteria that ensure indubitable identification of compounds increasingly important. In this work, 6 new synthetic cathinones that have not yet appeared in any Swedish drug seizures were synthesized. Their chemical structures were similar to those of already known cathinone analogs of which 42 were also included in the study. Hence, a total of 48 synthetic cathinones making up sets of homologous and regioisomeric compounds were used to challenge the capabilities of various analytical techniques commonly applied in forensic drug screening, ie, gas chromatography-mass spectrometry (GC-MS), gas chromatography-Fourier transform infrared spectroscopy (GC-FTIR), nuclear magnetic resonance (NMR), and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Special attention was paid to the capabilities of GC-MS and GC-FTIR to distinguish between the synthetic cathinones and the results showed that neither GC-MS nor GC-FTIR alone can successfully differentiate between all synthetic cathinones. However, the 2 techniques proved to be complementary and their combined use is therefore beneficial. For example, the structural homologs were better differentiated by GC-MS, while GC-FTIR performed better for the regioisomers. Further, new spectroscopic data of the synthesized cathinone analogs is hereby presented for the forensic community. The synthetic work also showed that cathinone reference compounds can be produced in few reaction steps.
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| 8. |
- Carlsson, Andreas
(författare)
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Synthesis and spectroscopic characterization of emerging synthetic cannabinoids and cathinones
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The application of different analytical techniques is fundamental in forensic drug analysis. In the wake of the occurrence of large numbers of new psychoactive substances possessing similar chemical structures as already known ones, focus has been placed on applied criteria for their univocal identification. These criteria vary, obviously, depending on the applied technique and analytical approach. However, when two or more substances are proven to have similar analytical properties, these criteria no longer apply, which imply that complementary techniques have to be used in their differentiation.This work describes the synthesis of some structural analogues to synthetic cannabinoids and cathinones based on the evolving patterns in the illicit drug market. Six synthetic cannabinoids and six synthetic cathinones were synthesized, that, at the time for this study, were not as yet found in drug seizures. Further, a selection of their spectroscopic data is compared to those of already existing analogues; mainly isomers and homologues. The applied techniques were mass spectrometry (MS), Fourier transformed infrared (FTIR, gas phase) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. In total, 59 different compounds were analyzed with the selected techniques.The results from comparison of spectroscopic data showed that isomeric substances may in some cases be difficult to unambiguously identify based only on their GC-MS EI spectra. On the other hand, GC-FTIR demonstrated more distinguishable spectra. The spectra for the homologous compounds showed however, that the GC-FTIR technique was less successful compared to GC-MS. Also a pronounced fragmentation pattern for some of the cathinones was found.In conclusion, this thesis highlights the importance of using complementary techniques for the univocal identification of synthetic cannabinoids and cathinones. By increasing the number of analogues investigated, the more may be learnt about the capabilities of different techniques for structural differentiations, and thereby providing important identification criteria leading to trustworthy forensic evidence.
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| 9. |
- Chalachanová, Anna, et al.
(författare)
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Critical exploration of researchers’ experiences within the field of participatory research
- 2022
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Ingår i: International Conference on Work Integrated Learning. - Trollhättan : University West. - 9789189325302 ; , s. 50-51
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Research question: Autoethnographic critical scrutiny as a step towards more inclusive research practices in participatory research?In this presentation we would like to discuss a paper draft. The paper examines the autoethnographic accounts of four researchers to highlight and critically explore our experiences within the participatory action research (PAR) (Schubotz, 2020). PAR is based on the principles of close co-operation between researchers and participants with experience-based knowledge, in this case people with disabilities. Hancock et al. (2012) define three justifications for the participation of people with experience-based competence in research: the ethical, the qualitative and the "therapeutic". The recipients of health and welfare services should have a voice in research in areas that will have a direct impact on their life situation. The qualitative aspect concerns that people with experience -based knowledge can strengthen the quality of the research with new approaches by asking relevant questions or by recruiting participants. This can strengthen the research's relevance, validity and focus on the development of knowledge relevant to those concerned. The third rationale is the therapeutic or empowerment rationale, i.e., that the research can have a positive impact on people who receive services and who are involved in the research (Askheim et al., 2019; Hancock et al., 2012). PAR is connected to democratic values, co-creation of knowledge and the believe that this form of co-operation can influence practice. Participatory action research creates space to develop new research communities where the researcher and the researcher's agenda are pushed aside to create space for the research community that develops as a result of interaction between researchers and participants with different backgrounds (experiences) (Nind, 2014 a; Northway, 2010). PAR is a context-bound research that is most often based on dialogue-based collaboration, and which aims to develop new knowledge or insight that can primarily be recognized in the context in which it takes place (Levin, 2017). It should also be based on local challenges that participants in the research encounter in their everyday lives (Lawson et al., 2015). Collaboration with people with experience-based knowledge in research can be the key to creating opportunities to co -create an inclusive democratic society. All the authors have been doing PAR in different research projects. In various academic meetings, we often discussed methodological approaches, our research role, things not working as expected, or when we felt unsure of whether or what we were doing was right or wrong. This paper will try to bring to light and exemplify some of the tensions and challenges we have met in our research practice with PAR. Based on four autoethnographic accounts and theory on autoethnography as a background, the article will reflect upon, critically analyze, and discuss researchers' roles, power, and epistemic privileges in PAR. The autoethnographic approach is based on the researcher's reflections and critical examination of their identities, roles, power, or penalties within one or several cultural contexts (Hughes & Pennington, 2016). It is a critical reflexive action research in which the researcher takes an active, scientific, and systematic view of personal experience concerning cultural groups identified by the researcher as similar to the self (i.e., us) or as others who differ from the self (i.e., them) (Hughes & Pennington, 2016, s.8).51Establishing data:Four of us wrote two reflections each containing autoethnographic thoughts that reflected tensions in our research practice, for example challenging privileged academic discourses or traditional researcher roles. The logs had roughly the following structure: describe the setting (where, when, why) and your reflections/tensions. Then we read all the logs and wrote down our reactions, keywords, and reflections based on our own research experience. We wrote whether the examples sounded familiar or whether they were unfamiliar or differed from our experiences. All researchers presented the reflections they had written based on the logs, and we summarized central themes based on all the logs.By reading the other authors reflections and at the same time reflecting on their texts using our own experience and taking notes, writing keywords to their texts, started the analysis process in familiarizing with the data (Braun & Clarke, 2014). The analysis was conducted by summarizing the material through the active process of identifying similar themes in the texts, using all the keywords and reflections (Braun & Clarke, 2014). The main themes identified so far were power and power (in)balance, researcher’s role, and epistemic privileges in PAR. Next, we discussed these themes, scrutinizing structures and processes that can influence the research or unconscious processes and power relations tipping the research in one particular direction (Alvesson & Sköldberg, 1994, 2017). Reflections so far The autoethnographic texts touch upon power and power balance in relationships between researchers and participants with experience-based knowledge. The power connects to decision-making for example who is making decisions, what kind of cooperation and co-production of knowledge is happening, and how deadlines sets premises for collaboration. The topic of power may be described on a micro level, what the researchers intend to do in the meetings but may also be connected to the framework of the research projects such as projects goals and progression within the project. Projects depend on a certain pace and effectiveness to fulfil the goals. This has to do with financing and funds that can run out. This effectiveness might be challenging when we do research with people with experience-based knowledge, especially if there is a gap between researchers' starting position, theoretical background and expectations, and co-researchers' needs, interests, or expectations. Although researchers are aware of their power and try to adapt the process so that co-researchers can experience a real contribution, it might seem that the researchers have the final word in the end, and we should discuss whether and how we should address that. Co-researchers must usually adjust to the academic world rather than vice versa.
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| 10. |
- Chung, Sui Chu, et al.
(författare)
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A high cannabinoid CB(1) receptor immunoreactivity is associated with disease severity and outcome in prostate cancer
- 2009
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 45:1, s. 174-182
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Tidskriftsartikel (refereegranskat)abstract
- In the light of findings indicating that cannabinoids can affect the proliferation of a number of cancer cell types and that cannabinoid receptor expression is higher in prostate cancer cell lines than in non-malignant cells, we investigated whether the level of cannabinoid 1 receptor immunoreactivity (CB(1)IR) in prostate cancer tissues is associated with disease severity and outcome. Formalin-fixed paraffin-embedded non-malignant and tumour tissue samples from patients who were diagnosed with prostate cancer at a transurethral resection for voiding problems were used. CB(1)IR, which was scored in a total of 399 cases, was associated with the epithelial cell membranes, with little staining in the stroma. Patients with a tumour CB(1)IR score greater or equal to the median (2) had a significantly higher proportion of Gleason scores 8-10, metastases at diagnosis, tumour size and rate of cell proliferation at diagnosis than patients with a score<2. For 269 cases, tumour CB(1)IR was measured for patients who only received palliative therapy at the end stages of the disease, allowing the influence of CB(1)IR upon the disease outcome to be determined. Receiver operating characteristic (ROC) curves showed an area under the curve of 0.67 (95% confidence limits 0.59-0.74) for CB(1)IR in the tumour. CB(1)IR in non-malignant tissue was not associated with disease outcome. A tumour CB(1)IR score >or=2 was associated with a significantly lower disease specific survival. A Cox proportional hazards regression indicated that the tumour CB(1)IR score and the Gleason score were independent prognostic variables. It is concluded that a high tumour CB(1)IR score is associated with prostate cancer severity and outcome.
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| 11. |
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| 12. |
- Enell, Anja, et al.
(författare)
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Combining Leaching and Passive Sampling To Measure the Mobility and Distribution between Porewater, DOC, and Colloids of Native Oxy-PAHs, N-PACs, and PAHs in Historically Contaminated Soil
- 2016
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 50:21, s. 11797-11805
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Tidskriftsartikel (refereegranskat)abstract
- Different methods to quantify soil porewater concentrations of contaminants will provide different types of information. Passive sampling measurements give freely dissolved porewater concentrations (C-pw,C-free), while leaching tests provide information on the mobile concentration (C-pw,C-leach), including contaminants associated with dissolved organic carbon (DOC) and particles/colloids in the porewater. This study presents a novel combination of these two measurements, to study the sorption and mobility of polycyclic aromatic compounds (PACs) to DOC and particulate organic carbon (POC) in 10 historically contaminated soils. The PACs investigated were polycyclic aromatic hydrocarbons (PAHs), oxygenated-PAHs, and nitrogen containing heterocyclic PACs. Observed C-pw,C-leach was up to 5 orders of magnitude higher than C-pw,C-free; implying large biases when C-pw,C-leach is used to assess bioavailability or soil partitioning. Sorption of PACs to DOC and POC was important for the mobility of compounds with log K-OW > 4. Average DOC/water-partitioning coefficients (K-DOC) correlated well with KOW (log K-DOC = 0.89 x log K-OW +1.03 (r(2) = 0.89)). This relationship is likely more accurate for historically contaminated soils than previously published data, which suffer from artifacts caused by problems in measuring C-pw,C-free correctly or not using historically contaminated soils. POC/water-partitioning coefficients (K-POC) were orders of magnitude larger than corresponding K-DOC, suggesting sorption to mobile particles/colloids is the dominant mechanism for PAC mobility.
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| 13. |
- Englund, Daniel, et al.
(författare)
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Metod- och kvalitetsbeskrivning för geografiskt fördelade emissioner till luft (submission 2023)
- 2023
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sverige rapporterar årligen nationella utsläpp till luft till UNFCCC (FN:s klimatkonvention) och CLRTAP (UNECE:s konvention om gränsöverskridande luftföroreningar), så kallade submissioner. SMED har sedan rapporteringsåret 2001 ansvaret att på uppdrag av Naturvårdsverket ta fram allt dataunderlag och det mesta av tillhörande dokumentation för dessa rapporteringar. Förutom emissioner på nationell nivå finns även behov av data med högre geografisk upplösning. För regional uppföljning av miljömålen behövs emissioner på kommun- och länsnivå. Detta dokument utgör en metod- och kvalitetsbeskrivning av geografiskt fördelade emissioner för åren 1990, 2000, 2005, 2010 samt 2015-2021, rapporterade i submission 2023. Emissionerna presenteras i 54 olika sektorer uppdelade på nio huvudsektorer.Den geografiska fördelningen utförs huvudsakligen enligt konceptet ”top-down”. Detta innebär att emissioner bryts ner från en nationell totalemission för att uppnå en högre rumslig upplösning på lokal nivå. Nedbrytningen till högre rumslig upplösning kräver en geografisk begränsning av emissionerna och statistik på regional nivå.Metoden för geografisk fördelning tillåter för vissa utsläppskällor en hög rumslig upplösning (t.ex. för vägtrafik och industriprocesser). För flera sektorer är emellertid resultaten otillförlitliga om de ska studeras med högre upplösning än kommunnivå (i vissa fall även länsnivå). Resultaten från den geografiska fördelningen lagras i årsvisa emissionsdatabaser i SMHI:s tekniska system för luftvårdsarbete; Clair. Ur Clair exporteras emissionerna till Excel-tabeller på läns- och kommunnivå.Rapporten beskriver större förändringar som har skett i nationella totalemissioner samt större förändringar i fördelningsmetodik jämfört med föregående år.
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| 14. |
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| 15. |
- Fowler, Christopher J., et al.
(författare)
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Tumour epithelial expression levels of endocannabinoid markers modulate the value of endoglin-positive vascular density as a prognostic marker in prostate cancer
- 2013
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981 .- 1879-2618. ; 1831:10, s. 1579-1587
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of the endogenous cannabinoid (CB) receptor ligand anandamide. Here we have investigated whether the expression levels of FAAH and CB1 receptors influence the prognostic value of markers of angiogenesis in prostate cancer. Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for lower urinary tract symptoms, of whom approximately 2/3 had been followed by expectancy, were used. Scores for the angiogenesis markers endoglin and von Willebrand factor (vWf), the endocannabinoid markers fatty acid amide hydrolase (FAAH) and cannabinoid CB1 receptors and the cell proliferation marker Ki-67 were available in the database. For the cases followed by expectancy, the prognostic value of endoglin was dependent upon the tumour epithelial FAAH immunoreactivity (FAAH-IR) and CB1IR scores, and the non-malignant epithelial FAAH-IR scores, but not the non-malignant CB1IR scores or the tumour blood vessel FAAH-IR scores. This dependency upon the tumour epithelial FAAH-IR or CB1IR scores was less apparent for vWf, and was not seen for Ki-67. Using an endoglin cut-off value of 10 positively stained vessels per core and a median split of tumour FAAH-IR, four groups could be generated, with 15 year of disease-specific survival (%) of 68 +/- 7 (low endoglin, low FAAH), 45 +/- 11 (high endoglin, low FAAH), 77 +/- 6 (low endoglin, high FAAH) and 21 +/- 10 (high endoglin, high FAAH). Thus, the cases with high endoglin and high FAAH scores have the poorest rate of disease-specific survival. At diagnosis, the number of cases with tumour stages 1a-1b relative to stages 2-4 was sensitive to the endoglin score in a manner dependent upon the tumour FAAH-IR. It is concluded that the prognostic value of endoglin as a marker of neovascularisation in prostate cancer can be influenced by the expression level of markers of the endocannabinoid system. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.
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| 16. |
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| 17. |
- Hammarsten, Peter, et al.
(författare)
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Immunoreactivity for prostate specific antigen and Ki67 differentiates subgroups of prostate cancer related to outcome
- 2019
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 32, s. 1310-1319
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Tidskriftsartikel (refereegranskat)abstract
- Based on gene-expression profiles, prostate tumors can be subdivided into subtypes with different aggressiveness and response to treatment. We investigated if similar clinically relevant subgroups can be identified simply by the combination of two immunohistochemistry markers: one for tumor cell differentiation (prostate specific antigen, PSA) and one for proliferation (Ki67). This was analyzed in men with prostate cancer diagnosed at transurethral resection of the prostate 1975–1991 (n = 331) where the majority was managed by watchful waiting. Ki67 and PSA immunoreactivity was related to outcome and to tumor characteristics previously associated with prognosis. Increased Ki67 and decreased PSA were associated with poor outcome, and they provided independent prognostic information from Gleason score. A combinatory score for PSA and Ki67 immunoreactivity was produced using the median PSA and Ki67 levels as cut-off (for Ki67 the upper quartile was also evaluated) for differentiation into subgroups. Patients with PSA low/Ki67 high tumors showed higher Gleason score, more advanced tumor stage, and higher risk of prostate cancer death compared to other patients. Their tumor epithelial cells were often ERG positive and expressed higher levels of ErbB2, phosphorylated epidermal growth factor receptor (pEGF-R) and protein kinase B (pAkt), and their tumor stroma showed a reactive response with type 2 macrophage infiltration, high density of blood vessels and hyaluronic acid, and with reduced levels of caveolin-1, androgen receptors, and mast cells. In contrast, men with PSA high/Ki67 low tumors were characterized by low Gleason score, and the most favorable outcome amongst PSA/Ki67-defined subgroups. Men with PSA low/Ki67 low tumors showed clinical and tumor characteristics intermediate of the two groups above. A combinatory PSA/Ki67 immunoreactivity score identifies subgroups of prostate cancers with different epithelial and stroma phenotypes and highly different outcome but the clinical usefulness of this approach needs to be validated in other cohorts. © 2019, The Author(s).
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| 18. |
- Hammarsten, Peter, et al.
(författare)
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Low levels of phosphorylated epidermal growth factor receptor in nonmalignant and malignant prostate tissue predict favorable outcome in prostate cancer patients.
- 2010
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 16:4, s. 1245-1255
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To explore if the expression of phosphorylated epidermal growth factor receptor (pEGFR) in nonmalignant and malignant prostate tissue is a potential prognostic marker for outcome in prostate cancer patients. EXPERIMENTAL DESIGN: We used formalin-fixed tissues obtained through the transurethral resection of the prostate from 259 patients diagnosed with prostate cancer after the transurethral resection of the prostate, and patients were then followed with watchful waiting. Tissue microarrays of nonmalignant and malignant prostate tissue were stained with an antibody against pEGFR. The staining pattern was scored and related to clinicopathologic parameters and to outcome. RESULTS: Low phosphorylation of EGFR in prostate epithelial cells, both in the tumor and surprisingly also in the surrounding nonmalignant tissue, was associated with significantly longer cancer-specific survival in prostate cancer patients. This association remained significant when Gleason score and local tumor stage were added together with pEGFR to a Cox regression model. Tumor epithelial pEGFR immunoreactivity was significantly correlated to tumor cell proliferation, tumor vascular density, and nonmalignant epithelial pEGFR immunoreactivity. Patients with metastases had significantly higher immunoreactivity for tumor and nonmalignant epithelial pEGFR compared with patients without metastases. CONCLUSIONS: Low pEGFR immunoreactivity is associated with the favorable prognosis in prostate cancer patients and may provide information about which patients with Gleason score 6 and 7 tumors that will survive their disease even without treatment. Changes in the nonmalignant tissue adjacent to prostate tumors give prognostic information.
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| 19. |
- Hammarsten, Peter, et al.
(författare)
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Phospho-Akt Immunoreactivity in Prostate Cancer : Relationship to Disease Severity and Outcome, Ki67 and Phosphorylated EGFR Expression
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10, s. e47994-
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the present study, we have investigated the prognostic usefulness of phosphorylated Akt immunoreactivity (pAkt-IR) in prostate cancer using a well-characterised tissue microarray from men who had undergone transurethral resection due to lower urinary tract symptoms. Methodology/Principal Findings: pAkt-IR in prostate epithelial and tumour cells was assessed using a monoclonal anti-pAkt (Ser(473)) antibody. Immunoreactive intensity was determined for 282 (tumour) and 240 (non-mlignant tissue) cases. Tumour pAkt-IR scores correlated with Gleason score, tumour Ki67-IR (a marker of cell proliferation) and tumour phosphorylated epidermal growth factor receptor (pEGFR)-IR. For cases followed with expectancy, a high tumour pAkt-IR was associated with a poor disease-specific survival, and the prognostic information provided by this biomarker was additive to that provided by either (but not both) tumour pEFGR-IR or Ki67-IR. Upon division of the cases with respect to their Gleason scores, the prognostic value of pAkt-IR was seen for patients with Gleason score 8-10, but not for patients with Gleason score 6-7. Conclusions/Significance: Tumour pAkt-IR is associated with both disease severity and disease-specific survival. However, its clinical use as a biomarker is limited, since it does not provide prognostic information in patients with Gleason scores 6-7.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Hägglöf, Christina, et al.
(författare)
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TMPRSS2-ERG Expression Predicts Prostate Cancer Survival and Associates with Stromal Biomarkers
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFR beta and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.
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| 24. |
- Josefsson, Andreas, 1979-, et al.
(författare)
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Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)
- 2023
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:4, s. 372-380
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Tidskriftsartikel (refereegranskat)abstract
- Background: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).Materials and Methods: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8–10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.Results: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0–5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50–0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49–0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.Conclusion: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.
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| 25. |
- Josefsson, Andreas, et al.
(författare)
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Prostate cancer increases hyaluronan in surrounding nonmalignant stroma, and this response is associated with tumor growth and an unfavorable outcome
- 2011
-
Ingår i: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 179:4, s. 1961-1968
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to investigate whether the presence of a tumor increases hyaluronan (HA) levels in surrounding prostate tissues and whether this extratumoral HA influences tumor growth and outcome. From a series of 287 men diagnosed with prostate cancer at transurethral resection and followed up with watchful waiting, tissue microarrays were constructed, stained, and scored for HA. A high HA staining score in the tumor stroma or in nonmalignant prostate tissue stroma were both associated positively with higher Gleason score and larger tumor volume, and was associated with a poor outcome. HA staining score was not an independent marker for outcome (multivariate Cox, with Gleason score, tumor volume, stage, and HA variables). In an orthotopic rat prostate cancer model, hyaluronic acid synthase-1 mRNA levels and HA staining were increased in normal prostate tissue surrounding prostate cancer. Orthotopic prostate cancer growth was increased by intraprostatic injection of HA. In conclusion, cancer in the prostate apparently stimulates HA synthesis both in tumor stroma and in the surrounding normal tissue. This promoted tumor growth and was associated with an unfavorable outcome.
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| 26. |
- Josefsson, Peter
(författare)
-
Biochemical modification of wood components
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The degradation of cellulose found in wood is one of the most important degradation processes for the carbon flux on earth. The degradation is performed by microorganisms that typically use enzymes. Since the cellulose in wood is crystalline and embedded in other polymers, making it inaccessible and durable, the enzymatic methods of cellulose degradation is also complex. In this thesis, the action of some of these enzymes, called cellulases, have been studied both fundamentally and for industrial purposes. By using model cellulose films and a quartz crystal microbalance it was found that endoglucanases not only depolymerize but also swell model cellulose films. Most probably, this contributes to the synergy seen between endoglucanases and exoglucanases. When an pulp fibers were pre--treated with endoglucanases and beaten subsequently, the fibers became more swollen than reference fibers. The effects of beating enzyme pre--treated fibers were investigated, indicating that endoglucanases improves the fiber/fiber interaction but also alters the behavior of the fibers in the beating process to become more susceptible to the beating. The second part of the thesis has been focused on the use of an albino fungi in order to decrease the amount of wood extractives in wood chips prior to thermo mechanical pulp production. The fungus decreased the most troublesome component, the triglycerides, by more than 90 percent in two weeks without any detrimental effects on pulp properties. On the contrary, pulp strength and optical properties were improved.
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| 27. |
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| 28. |
- Josefsson, Peter, et al.
(författare)
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Controlled seasoning of scots pine chips using an albino strain of ophiostoma
- 2006
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Ingår i: Journal of Industrial and Engineering Chemistry. - : American Chemical Society (ACS). - 1226-086X .- 1876-794X .- 0888-5885 .- 1520-5045. ; 45:7, s. 2374-2380
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Tidskriftsartikel (refereegranskat)abstract
- Traditional seasoning of wood chips normally results in significant yield losses and brightness reduction due to the uncontrolled action of microorganisms. Techniques for reduction of the amount of wood extractives with minimal yield and brightness loss are therefore of interest for the pulp and paper industry. To study a biotechnological approach for reduction of wood extractives, wood chips from sapwood of Scots pine (Pinus sylvestris) and Norway spruce (Picea abies) were treated with a commercial albino strain of the sap stain fungus Ophiostoma piliferum. During 2 weeks of controlled seasoning, the content of wood extractives decreased by approximately 40% for Scots pine and 25% for Norway spruce, where the triglyceride contents were degraded to a greater degree. Thermomechanical pulps were produced from untreated and pretreated pine chips. The properties of these pulps and corresponding laboratory sheets were investigated. The pretreated pulps showed less shortened fibers, lower amounts of triglycerides, and enhanced strength properties. The mechanisms behind these effects are discussed. Furthermore, the ability of the albino Ophiostoma piliferum to displace mould growth from wood chips was investigated in a series of experiments. It was concluded that the fungus should preferably be inoculated on fresh chips in order to repress mould growth.
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| 29. |
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| 30. |
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| 31. |
- Josefsson, Peter, et al.
(författare)
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The physical action of cellulases revealed by a quartz crystal microbalance study using ultrathin cellulose films and pure
- 2008
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Ingår i: Biomacromolecules. - : American Chemical Society (ACS). - 1525-7797 .- 1526-4602. ; 9:1, s. 249-254
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Tidskriftsartikel (refereegranskat)abstract
- The effects of fungal cellulases on model cellulose films were studied using a high-resolution quartz crystal microbalance (QCM) sensitive to minute changes of the nanometer thick model cellulose films. It was found that endoglucanases not only produce new end groups but also cause a swelling of the cellulose film. The cellobiohydrolases degraded the films quickly, which was detected as a rapid decrease in the remaining amount of cellulose on the QCM crystal. However, changing viscoelastic properties of the films also indicated a softening of the film during the degradation. A defined mixture of selected cellulases caused a significantly higher rate of degradation than only cellobiohydrolases. Cellulase synergism is discussed with the endoglucanase swelling effects and film softening added.
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| 32. |
- Josefsson, Sarah, et al.
(författare)
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Determination of polyoxymethylene (POM) - water partition coefficients for oxy-PAHs and PAHs
- 2015
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 119, s. 1268-1274
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Tidskriftsartikel (refereegranskat)abstract
- Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are a class of ubiquitously occurring pollutants of which little is known. They can be co-emitted with PAHs or formed from PAHs in the environment. The environmental fate and risk of oxy-PAHs are difficult to assess due to a lack of methods to quantify their pore water concentrations. One sampler that can be used to determine freely dissolved concentrations of organic contaminants is polyoxymethylene (POM). In this study, POM - water partition coefficients (K-POM) were determined for 11 oxy-PAHs. K-POM values of 8 PAHs with similar hydrophobicities as the oxy-PAHs were determined for comparison. Results showed that log K-POM values ranged from 2.64 to 4.82 for the PAHs (2-4 rings), similar to previously determined values. LogK(pom) values for investigated oxy-PAHs ranged from 0.96 to 5.36. The addition of carbonylic oxygen on a parent PAH generally lowered K-POM by 0.5 to 1.0 log units, which is attributable to the presence of carbonylic oxygens increasing water solubility. The K-POM values presented here will facilitate simultaneous assessments of freely dissolved water concentrations of oxy-PAHs and PAHs in environmental media.
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| 33. |
- Karlsson, Peter, 1970-, et al.
(författare)
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Training high school students in resisting disinformation and conspiracy theories – Preliminary findings and experiences from an ongoing research project
- 2023
-
Ingår i: 2023: Book of abstracts.
-
Konferensbidrag (refereegranskat)abstract
- This paper draws on findings from an ongoing research project called ”Effects of a multi-module intervention designed to increase critical thinking and the ability to identify misinformation, disinformation, and conspiracy theories in high school students”. The aim of this project is to empirically evaluate an educational intervention consisting of six one-hour sessions. The sessions include traditional lectures regarding critical thinking, misinformation, disinformation, and conspiracy theories but also includes a game (Bad news), and group discussions, all designed to train high school students in critical thinking as well as the capacity to identify disinformation and conspiracy theories. The project combines competences from media and communication studies, psychology, political science, and data communication, and the intervention has so far been implemented in three Swedish high schools. In the paper we discuss preliminary findings and experiences drawn from the first phase of the project. We will also discuss the applicability of the intervention, and challenges that we have identified. © Author/s
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| 34. |
- Kwiecinski, Jakub, 1985, et al.
(författare)
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Staphylokinase controls Staphylococcus aureus biofilm formation and detachment through host plasminogen activation.
- 2016
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 213:1, s. 139-148
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus biofilms, a leading cause of persistent infections, are highly resistant to immune defenses and antimicrobial therapies. In this study, we investigated the contribution of fibrin and staphylokinase to biofilm formation. Both in clinical S. aureus isolates and in laboratory strains, high staphylokinase-producing strains formed less biofilm than strains that lacked staphylokinase, suggesting that staphylokinase prevents biofilm formation. Additionally, staphylokinase induced detachment of mature biofilms. This effect depended on plasminogen activation by staphylokinase. Host-derived fibrin, the main substrate cleaved by staphylokinase-activated plasminogen, was a major component of biofilm matrix and dissolution of this fibrin scaffold greatly increased susceptibility of biofilms to antibiotics and neutrophil phagocytosis. Staphylokinase also attenuated biofilm-associated catheter infections in mouse models. In conclusion, our results reveal a novel role for staphylokinase-induced plasminogen activation that prevents S. aureus biofilm formation and induces detachment of existing biofilms through proteolytic cleavage of biofilm matrix components.
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| 35. |
- Lopatko Lindman, Karin, et al.
(författare)
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Herpesvirus infections, antiviral treatment, and the risk ofdementia : a registry-based cohort study in Sweden
- 2021
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Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Herpesviruses, including Herpes simplex virus type 1 (HSV1) and varicella zoster‐virus (VZV), have been implicated in Alzheimer's disease (AD) development. Likewise, antiviral treatment has been suggested to protect against dementia development in herpes‐infected individuals.Methods: The study enrolled 265,172 subjects aged ≥ 50 years, with diagnoses of VZV or HSV, or prescribed antiviral drugs between 31 December 2005 and 31 December 2017. Controls were matched in a 1:1 ratio by sex and birth year.Results: Antiviral treatment was associated with decreased risk of dementia (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.86 to 0.92), while herpes infection without antiviral drugs increased the risk of dementia (adjusted HR 1.50, 95% CI 1.29 to 1.74).Discussion: Antiviral treatment was associated with a reduced long‐term risk of dementia among individuals with overt signs of herpes infection. This is consistent with earlier findings indicating that herpesviruses are involved in the pathogenesis of AD.
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| 36. |
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| 37. |
- Stenvinkel, Peter, et al.
(författare)
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Metabolic Changes in Summer Active and Anuric Hibernating Free-Ranging Brown Bears (Ursus arctos)
- 2013
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e72934-
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Tidskriftsartikel (refereegranskat)abstract
- The brown bear (Ursus arctos) hibernates for 5 to 6 months each winter and during this time ingests no food or water and remains anuric and inactive. Despite these extreme conditions, bears do not develop azotemia and preserve their muscle and bone strength. To date most renal studies have been limited to small numbers of bears, often in captive environments. Sixteen free-ranging bears were darted and had blood drawn both during hibernation in winter and summer. Samples were collected for measurement of creatinine and urea, markers of inflammation, the calcium-phosphate axis, and nutritional parameters including amino acids. In winter the bear serum creatinine increased 2.5 fold despite a 2-fold decrease in urea, indicating a remarkable ability to recycle urea nitrogen during hibernation. During hibernation serum calcium remained constant despite a decrease in serum phosphate and a rise in FGF23 levels. Despite prolonged inactivity and reduced renal function, inflammation does not ensue and bears seem to have enhanced antioxidant defense mechanisms during hibernation. Nutrition parameters showed high fat stores, preserved amino acids and mild hyperglycemia during hibernation. While total, essential, non-essential and branched chain amino acids concentrations do not change during hibernation anorexia, changes in individual amino acids ornithine, citrulline and arginine indicate an active, although reduced urea cycle and nitrogen recycling to proteins. Serum uric acid and serum fructose levels were elevated in summer and changes between seasons were positively correlated. Further studies to understand how bears can prevent the development of uremia despite minimal renal function during hibernation could provide new therapeutic avenues for the treatment of human kidney disease.
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| 38. |
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| 39. |
- Thomasson, Marcus, et al.
(författare)
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LRIG1 and the liar paradox in prostate cancer: a study of the expression and clinical significance of LRIG1 in prostate cancer
- 2011
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 128:12, s. 2843-2852
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Tidskriftsartikel (refereegranskat)abstract
- The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In our study, the expression of LRIG1 protein in prostate cancer was evaluated for the first time. Immunohistochemistry was performed on tissue microarrays from two different patient series: 355 Swedish patients diagnosed by transurethral resection and 293 American patients who underwent radical prostatectomy. In the Swedish series, high expression of LRIG1 correlated with Gleason score, T-stage, tumor cell proliferation, vascular density and epidermal growth factor receptor (EGFR) phosphorylation. Among the 256 Swedish patients, followed by watchful waiting, high LRIG1 expression was significantly associated with short overall and prostate cancer-specific survival. In contrast, in the US series, high LRIG1 expression was significantly associated with long overall survival. In vitro cell experiments showed that LRIG1 was induced by androgen stimulation, and its expression inhibited prostate cancer cell proliferation. Thus, LRIG1 expression was an independent marker for poor survival in the untreated patient series, perhaps as a secondary marker of androgen receptor and/or EGFR activation. On the contrary, LRIG1 was a marker for good prognosis after prostatectomy, which might be due to its growth inhibiting properties. We propose that LRIG1 is an important determinant of prostate cancer growth, and the implications of its expression on patient outcome depend on the clinical and biological circumstances.
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| 40. |
- Tidehag, Viktor, et al.
(författare)
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High density of S100A9 positive inflammatory cells in prostate cancer stroma is associated with poor outcome
- 2014
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 50:10, s. 1829-1835
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To elucidate if the density of inflammatory cells expressing S100A9 in malignant and surrounding non-malignant prostate tissues is a prognostic marker for outcome in prostate cancer patients. Experimental design: Tissue was obtained from 358 men diagnosed with prostate cancer at transurethral resection of the prostate due to obstructive voiding problems, of which 260 were then followed with watchful waiting. Tissue microarrays of both malignant and non-malignant tissues were stained with an antibody against S100A9. The number of stained inflammatory cells was scored and related to clinical outcome and histopathological parameters of known prognostic value. Results: A high number of inflammatory cells expressing S100A9 in both malignant and surrounding non-malignant tissues were associated with significantly shorter cancer-specific survival. This association remained significant when Gleason score and local tumour stage were analysed together with S100A9 in a Cox regression model. Low number of S100A9 positive cells in non-malignant stroma was correlated to significantly longer cancer-specific survival also in patients with Gleason score 8-10 tumours. S100A9 positive cells in tumour stroma were correlated with Gleason score, hyaluronan, platelet-derived growth factor receptor beta (PDGFR-beta), and androgen receptor (inverse correlation) in tumour stroma. S100A9 positive cells in non-malignant stroma correlated with androgen receptor in this tissue compartment (inverse correlation). Conclusions: A high number of S100A9 positive inflammatory cells in tumour stroma and in non-malignant stroma were associated with shorter cancer-specific survival in prostate cancer patients.
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| 41. |
- Wallgren, Jakob, et al.
(författare)
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Synthesis and identification of an important metabolite of AKB-48 with a secondary hydroxyl group on the adamantyl ring
- 2017
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Ingår i: Tetrahedron Letters. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0040-4039 .- 1359-8562. ; 58:15, s. 1456-1458
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Tidskriftsartikel (refereegranskat)abstract
- Studies on the metabolism of bioactive substances containing the adamantyl moiety have shown that hydroxylation is likely to occur at a tertiary carbon of adamantane. Herein, we report the synthesis and identification of one major metabolite of AKB-48, a new illicit psychoactive substance with a hydroxyl group at a secondary carbon of the adamantyl ring. (C) 2017 Elsevier Ltd. All rights reserved.
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| 42. |
- Wallgren, Jakob, et al.
(författare)
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Synthesis and identifications of potential metabolites as biomarkers of the synthetic cannabinoid AKB-48
- 2018
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Ingår i: Tetrahedron. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0040-4020 .- 1464-5416. ; 74:24, s. 2905-2913
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Tidskriftsartikel (refereegranskat)abstract
- AKB-48 belongs to the family of synthetic cannabinoids. It has strong binding affinity to CBI receptor and is psychoactive. It is banned in many countries including USA, Japan, Germany, New Zealand, Singapore and China etc. But the difficulty in detecting the parent compound in urine samples highlights the importance of studies of its metabolites. Here we report the synthesis of 19 potential metabolites of AKB-48, among which, compounds 2, 9, 10, 30 and 31, together with the commercially available substance 5 were identified as metabolites of AKB-48 by comparison with one authentic human urine sample and human liver microsomal data. Compounds 10 and 30 could be of use as biomarkers in detecting AKB-48 in human urine samples. (C) 2018 Elsevier Ltd. All rights reserved.
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| 43. |
- Weidung, Bodil, et al.
(författare)
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Longitudinal Effects of Herpesviruses on Multiple Cognitive Outcomes in Healthy Elderly Adults
- 2023
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 94:2, s. 751-762
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Tidskriftsartikel (refereegranskat)abstract
- Background: Herpesviruses have been proposed to be involved in Alzheimer's disease development as potentially modifiable pathology triggers. Objective: To investigate associations of serum antibodies for herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) and anti-herpesvirus treatment with cognitive outcomes in relation to interactions with APOE epsilon 4.Methods: The study included 849 participants in the population-based Prospective Investigation of the Vasculature in Uppsala Seniors study. Cognitive performance at the ages of 75 and 80 years was assessed using the Mini-Mental State Examination (MMSE), trail-making test (TMT) A and B, and 7-minute screening test (7MS).Results: Anti-HSV-1 IgG positivity was associated cross-sectionally with worse performance on the MMSE, TMT-A, TMT-B, 7MS, enhanced free recall, and verbal fluency tests (p = 0.016, p = 0.016, p < 0.001, p = 0.001, p = 0.033, and p < 0.001, respectively), but not orientation or clock drawing. Cognitive scores did not decline over time and longitudinal changes did not differ according to HSV-1 positivity. Anti-CMV IgG positivity was not associated cross-sectionally with cognition, but TMT-B scores declined more in anti-CMV IgG carriers. Anti-HSV-1 IgG interacted with APOE epsilon 4 in association with worse TMT-A and better enhanced cued recall. Anti-HSV IgM interacted with APOE epsilon 4 and anti-herpesvirus treatment in association with worse TMT-A and clock drawing, respectively.Conclusion: These findings indicate that HSV-1 is linked to poorer cognition in cognitively healthy elderly adults, including impairments in executive function, memory, and expressive language. Cognitive performance did not decline over time, nor was longitudinal decline associated with HSV-1.
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| 44. |
- Wennerberg, Ann, 1955, et al.
(författare)
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Nanoporous TiO(3) Thin Film on Titanium Oral Implants for Enhanced Human Soft Tissue Adhesion: A Light and Electron Microscopy Study.
- 2011
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Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899.
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Background: Previous experimental studies have demonstrated direct soft tissue attachment for nanoporous titanium dioxide (TiO(2)) thin film on implants, while implants without TiO(2) thin film have not shown this capability. Purpose: The aims were to evaluate and compare TiO(2) surface-modified experimental microimplants with unmodified microimplants with respect to tissue interaction of the human oral mucosa evaluated by light microscopy on ground sections and semithin sections and transmission electron microscopy on ultrathin sections, and to characterize the inflammatory response and the level of the marginal bone resorption. Materials and Methods: The study was a single-center, randomized, comparative, clinical investigation with intrasubject comparison of implants with and without TiO(2) thin film in 15 patients. Results: Two comparator microimplants showed mild erythema and expulsion of fluids. The surrounding tissues around all test implants were clinically healthy. The oral mucosa in contact with the abutment part of the microimplant was 72% for the test implants and 48% for the comparator implants, a statistically significant difference (p = .0268). No statistically significant difference was found in other histological variables. The marginal bone loss in 14 weeks was 0.5 mm for the stable test (n = 11) and 1.7 mm for the stable comparator implants (n = 9; p = .0248). Conclusions: The nanoporous TiO(2) surface modification has potential clinical benefits because of increased adherence of soft tissue and possible reduced bone resorption.
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| 45. |
- Wiesner, Rebecca, et al.
(författare)
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An interlaboratory capillary zone electrophoresis-UV study of various monoclonal antibodies, instruments, and ε-aminocaproic acid lots
- 2023
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 44:15-16, s. 1247-1257
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Tidskriftsartikel (refereegranskat)abstract
- Capillary zone electrophoresis ultraviolet (CZE-UV) has become increasingly popular for the charge heterogeneity determination of mAbs and vaccines. The ε-aminocaproic acid (eACA) CZE-UV method has been used as a rapid platform method. However, in the last years, several issues have been observed, for example, loss in electrophoretic resolution or baseline drifts. Evaluating the role of eACA on the reported issues, various laboratories were requested to provide their routinely used eACA CZE-UV methods, and background electrolyte compositions. Although every laboratory claimed to use the He et al. eACA CZE-UV method, most methods actually deviate from He's. Subsequently, a detailed interlaboratory study was designed wherein two commercially available mAbs (Waters’ Mass Check Standard mAb [pI 7] and NISTmAb [pI 9]) were provided to each laboratory, along with two detailed eACA CZE-UV protocols for a short-end, high-speed, and a long-end, high-resolution method. Ten laboratories participated each using their own instruments, and commodities, showing excellence method performance (relative standard deviations [RSDs] of percent time-corrected main peak areas from 0.2% to 1.9%, and RSDs of migration times from 0.7% to 1.8% [n = 50 per laboratory], analysis times in some cases as short as 2.5 min). This study clarified that eACA is not the main reason for the abovementioned variations.
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| 46. |
- Wohlfarth, Ariane, et al.
(författare)
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25C-NBOMe and 25I-NBOMe metabolite studies in human hepatocytes, in vivo mouse and human urine with high-resolution mass spectrometry.
- 2017
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Ingår i: Drug Testing and Analysis. - : John Wiley & Sons. - 1942-7603 .- 1942-7611. ; 9:5, s. 680-698
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Tidskriftsartikel (refereegranskat)abstract
- 25C-NBOMe and 25I-NBOMe are potent hallucinogenic drugs that recently emerged as new psychoactive substances. To date, a few metabolism studies were conducted for 25I-NBOMe, whereas 25C-NBOMe metabolism data are scarce. Therefore, we investigated the metabolic profile of these compounds in human hepatocytes, an in vivo mouse model and authentic human urine samples from forensic cases. Cryopreserved human hepatocytes were incubated for 3 h with 10 μM 25C-NBOMe and 25I-NBOMe; samples were analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) on an Accucore C18 column with a Thermo QExactive; data analysis was performed with Compound Discoverer software (Thermo Scientific). Mice were administered 1.0 mg drug/kg body weight intraperitoneally, urine was collected for 24 h and analyzed (with or without hydrolysis) by LC-HRMS on an Acquity HSS T3 column with an Agilent 6550 QTOF; data were analyzed manually and with WebMetabase software (Molecular Discovery). Human urine samples were analyzed similarly. In vitro and in vivo results matched well. 25C-NBOMe and 25I-NBOMe were predominantly metabolized by O-demethylation, followed by O-di-demethylation and hydroxylation. All methoxy groups could be demethylated; hydroxylation preferably occurred at the NBOMe ring. Phase I metabolites were extensively conjugated in human urine with glucuronic acid and sulfate. Based on these data and a comparison with synthesized reference standards for potential metabolites, specific and abundant 25C-NBOMe urine targets are 5'-desmethyl 25C-NBOMe, 25C-NBOMe and 5-hydroxy 25C-NBOMe, and for 25I-NBOMe 2' and 5'-desmethyl 25I-NBOMe and hydroxy 25I-NBOMe. These data will help clinical and forensic laboratories to develop analytical methods and to interpret results. Copyright © 2016 John Wiley & Sons, Ltd.
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| 47. |
- Wu, Xiongyu, et al.
(författare)
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Synthesis and identification of metabolite biomarkers of 25C-NBOMe and 25I-NBOMe
- 2017
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Ingår i: Tetrahedron. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0040-4020 .- 1464-5416. ; 73:45, s. 6393-6400
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Tidskriftsartikel (refereegranskat)abstract
- Synthetic routes have been developed for synthesis of potential metabolites of 25C-NBOMe and 25I-NBOMe. Nine potential metabolites have been synthesized, among which compounds 8 and 20a could be used as metabolite biomarkers of 25C-NBOMe and 20b of 25I-NBOMe in urinary detection at forensic laboratories to prove intake. (C) 2017 Elsevier Ltd. All rights reserved.
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