| 1. |
- Blomstrand, Peter, et al.
(författare)
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Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain
- 2018
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Ingår i: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- AimsObesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons.MethodsWe prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight < 25 kg/m2, overweight 25–29 kg/m2, and obesity ≥ 30 kg/m2). Echocardiography was performed at the beginning of the study and after 4-years in the patient group.ResultsUnivariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/é (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. − 18.6% (2.3%) for normal weight patients, 53% (8%) vs. − 17.5% (2.3%) for overweight, and 49% (9%) vs. − 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05). Corresponding results in the control group were 58% (6%) vs. − 22.3% (3.0%), 55% (7%) vs. − 20.8% (3.1%) and 54% (8%) − 19.6% (4.0%) (p < 0.05 vs. p < 0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by − 1.0 (9.0) % (n = 187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n = 179) (p < 0.05).ConclusionOverweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.
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| 2. |
- Glimelius, Bengt, et al.
(författare)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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| 3. |
- Bengtsson, Mattias, et al.
(författare)
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‘Well, it’s up to me now’ – young care leavers’ strategies for handling adversities when leaving out-of-home care in Sweden
- 2018
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Ingår i: Nordic Social Work Research. - : Routledge. - 2156-857X .- 2156-8588. ; 8:sup 1
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Tidskriftsartikel (refereegranskat)abstract
- AbstractThis qualitative longitudinal study of 20 young Swedish care leavers investigates their subjective experience of and strategies for handling adversities when being in the process of leaving out-of-home care. The empirical data is based on two sets of interviews, the first conducted at time 1 (T1) when they were still in care but the moving out process had begun, the second (T2) 6-10 months later when the vast majority had left care. The thematic analysis based on resilience theory showed that the majority of the informants over time developed process-oriented strategies, which in our categorization emanated either from the inner world of the informants (e.g. through re-framing of experiences and an emerging self-reliance) or from their outer contextual world (e.g. through a restructuring of the social network). The results are discussed from a resilience theoretical perspective in which the informants' strategies are illustrated by the conceptual pair of 'navigation' and 'negotiation', used to make sense of their inner and outer world-oriented strategies.
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| 4. |
- Bengtsson, Mattias, et al.
(författare)
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Young care leavers’ expectations of their future : A question of time horizon
- 2018
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Ingår i: Child & Family Social Work. - : Wiley. - 1356-7500 .- 1365-2206. ; 23:2, s. 188-195
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates young care leavers’ expectations of their future after discharge from care. The results are based on qualitative longitudinal data where 16- to 21-year-old care leavers (n = 15) were interviewed twice, first when still in care but planning for their discharge (T1) and the second time 6–9 months later (T2). The analysis using a general inductive approach showed that their expectations were dependent on the time horizon and that there was an obvious difference between the young informants’ short- and long-term expectations. Their short-term expectations consisted of worries connected to their approaching discharge (at T1) and how to cope with challenges of everyday life after discharge from care (at T2). These results seem to echo negative outcomes shown in previous quantitative research. However, the informants’ long-term expectations provide a different picture, being mainly positive in both interviews (T1 and T2). The results are discussed from a life course perspective, where the informants’ visions of their future are framed and understood in terms of the different stages of their transition process.
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| 5. |
- Convey, Peter, et al.
(författare)
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The importance of understanding annual and shorter term temperature patterns and variation in the surface levels of polar soils for terrestrial biota
- 2018
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Ingår i: Polar Biology. - : Springer Publishing Company. - 0722-4060 .- 1432-2056. ; 41:8, s. 1587-1605
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Tidskriftsartikel (refereegranskat)abstract
- Ground temperatures in the top few centimetres of the soil profile are key in many biological processes yet remain very poorly documented, especially in the polar regions or over longer timescales. They can vary greatly seasonally and at various spatial scales across the often highly complex and heterogeneous polar landscapes. It is challenging and often impossible to extrapolate soil profile temperatures from meteorological air temperature records. Furthermore, despite the justifiably considerable profile given to contemporary large-scale climate change trends, with the exception of some sites on Greenland, few biological microclimate datasets exist that are of sufficient duration to allow robust linkage and comparison with these large-scale trends. However, it is also clear that the responses of the soil-associated biota of the polar regions to projected climate change cannot be adequately understood without improved knowledge of how landscape heterogeneity affects ground and sub-surface biological microclimates, and of descriptions of these microclimates and their patterns and trends at biologically relevant physical and temporal scales. To stimulate research and discussion in this field, we provide an overview of multi-annual temperature records from 20 High Arctic (Svalbard) and maritime Antarctic (Antarctic Peninsula and Scotia Arc) sites. We highlight important features in the datasets that are likely to have influence on biology in polar terrestrial ecosystems, including (a) summer ground and sub-surface temperatures vary much more than air temperatures; (b) winter ground temperatures are generally uncoupled from air temperatures; (c) the ground thawing period may be considerably shorter than that of positive air temperatures; (d) ground and air freeze–thaw patterns differ seasonally between Arctic and Antarctic; (e) rates of ground temperature change are generally low; (f) accumulated thermal sum in the ground usually greatly exceeds air cumulative degree days. The primary purpose of this article is to highlight the utility and biological relevance of such data, and to this end the full datasets are provided here to enable further analyses by the research community, and incorporation in future wider comparative studies.
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| 6. |
- Dahlgren, David, et al.
(författare)
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Preclinical Effect of Absorption Modifying Excipients on Rat Intestinal Transport of Model Compounds and the Mucosal Barrier Marker 51Cr-EDTA
- 2017
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 14:12, s. 4243-4251
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Tidskriftsartikel (refereegranskat)abstract
- There is a renewed interest from the pharmaceutical field to develop oral formulations of compounds, such as peptides, oligonucleotides, and polar drugs. However, these often suffer from insufficient absorption across the intestinal mucosal barrier. One approach to circumvent this problem is the use of absorption modifying excipient(s) (AME). This study determined the absorption enhancing effect of four AMEs (sodium dodecyl sulfate, caprate, chitosan, N-acetylcysteine) on five model compounds in a rat jejunal perfusion model. The aim was to correlate the model compound absorption to the blood-to-lumen clearance of the mucosal marker for barrier integrity, 51Cr-EDTA. Sodium dodecyl sulfate and chitosan increased the absorption of the low permeation compounds but had no effect on the high permeation compound, ketoprofen. Caprate and N-acetylcysteine did not affect the absorption of any of the model compounds. The increase in absorption of the model compounds was highly correlated to an increased blood-to-lumen clearance of 51Cr-EDTA, independent of the AME. Thus, 51Cr-EDTA could be used as a general, sensitive, and validated marker molecule for absorption enhancement when developing novel formulations.
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| 7. |
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| 8. |
- Karlsson, Henning, et al.
(författare)
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Mechanistic characterization of a copper containing thiosemicarbazone with potent antitumor activity
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:18, s. 30217-30234
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Tidskriftsartikel (refereegranskat)abstract
- Background: The thiosemicarbazone CD 02750 (VLX50) was recently reported as a hit compound in a phenotype-based drug screen in primary cultures of patient tumor cells. We synthesized a copper complex of VLX50, denoted VLX60, and characterized its antitumor and mechanistic properties. Materials and Methods: The cytotoxic effects and mechanistic properties of VLX60 were investigated in monolayer cultures of multiple human cell lines, in tumor cells from patients, in a 3-D spheroid cell culture system and in vivo and were compared with those of VLX50. Results: VLX60 showed ?3-fold higher cytotoxic activity than VLX50 in 2-D cultures and, in contrast to VLX50, retained its activity in the presence of additional iron. VLX60 was effective against non-proliferative spheroids and against tumor xenografts in vivo in a murine model. In contrast to VLX50, gene expression analysis demonstrated that genes associated with oxidative stress were considerably enriched in cells exposed to VLX60 as was induction of reactive oxygen. VLX60 compromised the ubiquitin-proteasome system and was more active in BRAF mutated versus BRAF wild-type colon cancer cells. Conclusions: The cytotoxic effects of the copper thiosemicarbazone VLX60 differ from those of VLX50 and shows interesting features as a potential antitumor drug, notably against BRAF mutated colorectal cancer.
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| 9. |
- Mezheyeuski, Artur, et al.
(författare)
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Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II/III colon cancer
- 2019
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Ingår i: British Journal of Cancer. - : NATURE PUBLISHING GROUP. - 0007-0920 .- 1532-1827. ; 121:4, s. 303-311
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task. METHODS: Vessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area. RESULTS: High stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. Stroma-normalised VD in the invasive margin and treatment effect were significantly associated according to a formal interaction test (p = 0.009). Similarly, in the validation cohort, high stroma-normalised VD was associated with OS in adjuvant-treated patients, although statistical significance was not reached (p = 0.051). CONCLUSION: Through the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stroma-normalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. The findings, indicating particular importance of vessels in the invasive margin, also suggest biological mechanisms for further exploration.
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| 10. |
- Sandell, Niklas, et al.
(författare)
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Berättelserna i "VD har ordet" - i dialog med omvärlden
- 2018
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Ingår i: Balans Fördjupning. ; :1, s. 14-17
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- ”Vd har ordet” är det avsnitt i årsredovisningen som många anser vara allra viktigast och mest läst. Men vilken berättelse, eller snarare vilka berättelser, om företaget är det som lämnas under rubriken ”Vd har ordet”? I en studie av 30 årsredovisningar har olika berättelser identifierats, såsom exempelvis den kamerala berättelsen och den strategiska berättelsen. I denna artikel beskrivs och utvecklas dessa berättelser utifrån dess förankring i samtiden och i kulturellt förankrade idealbilder av företaget.
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| 11. |
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| 12. |
- Sjöblom, Peter, et al.
(författare)
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Motion control system of MAX IV Laboratory soft x-ray beamlines
- 2016
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Ingår i: Proceedings of the 12th International Conference on Synchrotron Radiation Instrumentation, SRI 2015. - : Author(s). - 9780735413986 ; 1741
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Konferensbidrag (refereegranskat)abstract
- At the MAX IV Laboratory, five new soft x-ray beamlines are under development. The first is Species and it will be used to develop and set the standard of the control system, which will be common across the facility. All motion axes at MAX IV will be motorized using stepper motors steered by the IcePAP motion controller and a mixture of absolute and incremental encoders following a predefined coordinate system. The control system software is built in Tango and uses the Python-based Sardana framework. The user controls the entire beamline through a synoptic overview and Sardana is used to run the scans.
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| 13. |
- Uhlén, Mathias, et al.
(författare)
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A pathology atlas of the human cancer transcriptome
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 357:6352, s. 660-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.
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| 14. |
- Urpelainen, Samuli, et al.
(författare)
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The SPECIES beamline at the MAX IV Laboratory : A facility for soft X-ray RIXS and APXPS
- 2017
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Ingår i: Journal of Synchrotron Radiation. - 1600-5775 .- 0909-0495. ; 24:1, s. 344-353
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Tidskriftsartikel (refereegranskat)abstract
- SPECIES is an undulator-based soft X-ray beamline that replaced the old I511 beamline at the MAX II storage ring. SPECIES is aimed at high-resolution ambient-pressure X-ray photoelectron spectroscopy (APXPS), near-edge X-ray absorption fine-structure (NEXAFS), X-ray emission spectroscopy (XES) and resonant inelastic X-ray scattering (RIXS) experiments. The beamline has two branches that use a common elliptically polarizing undulator and monochromator. The beam is switched between the two branches by changing the focusing optics after the monochromator. Both branches have separate exit slits, refocusing optics and dedicated permanent endstations. This allows very fast switching between two types of experiments and offers a unique combination of the surface-sensitive XPS and bulk-sensitive RIXS techniques both in UHV and at elevated ambient-pressure conditions on a single beamline. Another unique property of the beamline is that it reaches energies down to approximately 27 eV, which is not obtainable on other current APXPS beamlines. This allows, for instance, valence band studies under ambient-pressure conditions. In this article the main properties and performance of the beamline are presented, together with selected showcase experiments performed on the new setup.
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