| 41. |
- Fenhammar, Johan, et al.
(author)
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Renal effects of treatment with a TLR4-inhibitor in conscious septic sheep
- 2014
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In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 18:5, s. 488-
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Journal article (peer-reviewed)abstract
- Introduction: Acute kidney injury (AKI) is a common and feared complication of sepsis. The pathogenesis of sepsis-induced AKI is largely unknown, and therapeutic interventions are mainly supportive. In the present study, we tested the hypothesis that pharmacological inhibition of Toll-like receptor 4 (TLR4) would improve renal function and reduce renal damage in experimental sepsis, even after AKI had already developed. Methods: Sheep were surgically instrumented and subjected to a 36-hour intravenous infusion of live Escherichia coli. After 12 hours, they were randomized to treatment with a selective TLR4 inhibitor (TAK-242) or vehicle. Results: The E. coli caused normotensive sepsis characterized by fever, increased cardiac index, hyperlactemia, oliguria, and decreased creatinine clearance. TAK-242 significantly improved creatinine clearance and urine output. The increase in N-acetyl-beta-D-glucosaminidas, a marker of tubular damage, was attenuated. Furthermore, TAK-242 reduced the renal neutrophil accumulation and glomerular endothelial swelling caused by sepsis. These effects were independent of changes in renal artery blood flow and renal microvascular perfusion in both cortex and medulla. TAK-242 had no effect per se on the measured parameters. Conclusions: These results show that treatment with a TLR4 inhibitor is able to reverse a manifest impairment in renal function caused by sepsis. In addition, the results provide evidence that the mechanism underlying the effect of TAK-242 on renal function does not involve improved macro-circulation or micro-circulation, enhanced renal oxygen delivery, or attenuation of tubular necrosis. TLR4-mediated inflammation resulting in glomerular endothelial swelling may be an important part of the pathogenesis underlying Gram-negative septic acute kidney injury.
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| 42. |
- Galbany, Lluis, et al.
(author)
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TYPE Ia SUPERNOVA PROPERTIES AS A FUNCTION OF THE DISTANCE TO THE HOST GALAXY IN THE SDSS-II SN SURVEY
- 2012
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 755:2, s. 125-
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Journal article (peer-reviewed)abstract
- We use Type Ia supernovae (SNe Ia) discovered by the Sloan Digital Sky Survey-II SN Survey to search for dependencies between SN Ia properties and the projected distance to the host-galaxy center, using the distance as a proxy for local galaxy properties (local star formation rate, local metallicity, etc.). The sample consists of almost 200 spectroscopically or photometrically confirmed SNe Ia at redshifts below 0.25. The sample is split into two groups depending on the morphology of the host galaxy. We fit light curves using both MLCS2k2 and SALT2, and determine color (A(V), c) and light-curve shape (Delta, x(1)) parameters for each SN Ia, as well as its residual in the Hubble diagram. We then correlate these parameters with both the physical and the normalized distances to the center of the host galaxy and look for trends in the mean values and scatters of these parameters with increasing distance. The most significant (at the 4 sigma level) finding is that the average fitted A(V) from MLCS2k2 and c from SALT2 decrease with the projected distance for SNe Ia in spiral galaxies. We also find indications that supernovae (SNe) in elliptical galaxies tend to have narrower light curves if they explode at larger distances, although this may be due to selection effects in our sample. We do not find strong correlations between the residuals of the distance moduli with respect to the Hubble flow and the galactocentric distances, which indicates a limited correlation between SN magnitudes after standardization and local host metallicity.
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| 43. |
- Ghaneh, Paula, et al.
(author)
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The Impact of Positive Resection Margins on Survival and Recurrence Following Resection and Adjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma
- 2019
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In: Annals of Surgery. - 0003-4932 .- 1528-1140. ; 269:3, s. 520-529
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Journal article (peer-reviewed)abstract
- Objective and Background: Local and distant disease recurrence are frequently observed following pancreatic cancer resection, but an improved understanding of resection margin assessment is required to aid tailored therapiesMethods: Analyses were carried out to assess the association between clinical characteristics and margin involvement as well as the effects of individual margin involvement on site of recurrence and overall and recurrence-free survival using individual patient data from the European Study Group for Pancreatic Cancer (ESPAC)-3 randomized controlled trial.Results: There were 1151 patients, of whom 505 (43.9%) had an RI resection. The median and 95% confidence interval (CI) overall survival was 24.9 (22.9-27.2) months for 646 (56.1%) patients with resection margin negative R0 >1 mm) tumors, 25.4 (21.6 30.4) months for 146 (12.7%) patients with RI <1 mm positive resection margins, and 18.7 (17.2-21.1) months for 359 (31.2%) patients with R1-direct positive margins (P < 0.001). In multivariable analysis, overall R 1-direct tumor margins, poor tumor differentiation, positive lymph node status, WHO performance status ≥ 1, maximum tumor size, and RI-direct posterior resection margin were all independently significantly associated with reduced overall and recurrence-free survival. Competing risks analysis showed that overall R1-direct positive resection margin status, positive lymph node status. WHO performance status 1, and R1-direct positive superior mesenteric/medial margin resection status were all significantly associated with local recurrence.Conclusions: RI-direct resections were associated with significantly reduced overall and recurrence-free survival following pancreatic cancer resection. Resection margin involvement was also associated with an increased risk for local recurrence.
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| 44. |
- Grübler, Arnulf, et al.
(author)
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Policies for the Energy Technology Innovation System (ETIS)
- 2012
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In: Global Energy Assessment: Toward a Sustainable Future. - 9780521182935 ; , s. 1665-1744
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Book chapter (peer-reviewed)abstract
- The development and introduction of heat pumps provides an interesting illustration of policy influence and effectiveness in relation to energy technology innovation. Heat pumps have been supported by several countries since the 1970s as a strategy to improve energy efficiency, support energy security, reduce environmental degradation, and combat climate change. Sweden and Switzerland have been essential to the development and commercialization of heat pumps in Europe. In both countries, numerous policy incentives have lined the path of technology and market development. Early policy initiatives were poorly coordinated but supported technology development, entrepreneurial experimentation, knowledge development, and the involvement of important actors in networks and organisations. The market collapse in the mid 1980s could have resulted in a total failure ‐ but did not. The research programmes continued in the 1980s, and a new set of stakeholders formed ‐ both publicly and privately funded researchers, authorities, and institutions ‐ and provided an important platform for further development. In the 1990s and 2000s, Sweden and Switzerland introduced more coordinated and strategic policy incentives for the development of heat pumps. The approaches were flexible and adjusted over time. The policy interventions in both countries supported learning, successful development and diffusion processes, and cost reductions. This assessment of innovation and diffusion policies for heat pump systems can be used to generalise some insights for energy technology innovation policy.
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| 45. |
- Hantke, Max F., et al.
(author)
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A data set from flash X-ray imaging of carboxysomes
- 2016
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In: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 3
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Journal article (peer-reviewed)abstract
- Ultra-intense femtosecond X-ray pulses from X-ray lasers permit structural studies on single particles and biomolecules without crystals. We present a large data set on inherently heterogeneous, polyhedral carboxysome particles. Carboxysomes are cell organelles that vary in size and facilitate up to 40% of Earth’s carbon fixation by cyanobacteria and certain proteobacteria. Variation in size hinders crystallization. Carboxysomes appear icosahedral in the electron microscope. A protein shell encapsulates a large number of Rubisco molecules in paracrystalline arrays inside the organelle. We used carboxysomes with a mean diameter of 115±26 nm from Halothiobacillus neapolitanus. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min. Every diffraction pattern is a unique structure measurement and high-throughput imaging allows sampling the space of structural variability. The different structures can be separated and phased directly from the diffraction data and open a way for accurate, high-throughput studies on structures and structural heterogeneity in biology and elsewhere.
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| 46. |
- Hantke, Max F., et al.
(author)
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High-throughput imaging of heterogeneous cell organelles with an X-ray laser
- 2014
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In: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 8:12, s. 943-949
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Journal article (peer-reviewed)abstract
- We overcome two of the most daunting challenges in single-particle diffractive imaging: collecting many high-quality diffraction patterns on a small amount of sample and separating components from mixed samples. We demonstrate this on carboxysomes, which are polyhedral cell organelles that vary in size and facilitate up to 40% of Earth's carbon fixation. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min with the Linac Coherent Light Source running at 120 Hz. We separate different structures directly from the diffraction data and show that the size distribution is preserved during sample delivery. We automate phase retrieval and avoid reconstruction artefacts caused by missing modes. We attain the highest-resolution reconstructions on the smallest single biological objects imaged with an X-ray laser to date. These advances lay the foundations for accurate, high-throughput structure determination by flash-diffractive imaging and offer a means to study structure and structural heterogeneity in biology and elsewhere.
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| 47. |
- Harris, Michael, et al.
(author)
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How European primary care practitioners think the timeliness of cancer diagnosis can be improved : a thematic analysis
- 2019
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:9, s. 1-10
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Journal article (peer-reviewed)abstract
- Background National European cancer survival rates vary widely. Prolonged diagnostic intervals are thought to be a key factor in explaining these variations. Primary care practitioners (PCPs) frequently play a crucial role during initial cancer diagnosis; their knowledge could be used to improve the planning of more effective approaches to earlier cancer diagnosis. Objectives This study sought the views of PCPs from across Europe on how they thought the timeliness of cancer diagnosis could be improved. Design In an online survey, a final open-ended question asked PCPs how they thought the speed of diagnosis of cancer in primary care could be improved. Thematic analysis was used to analyse the data. Setting A primary care study, with participating centres in 20 European countries. Participants A total of 1352 PCPs answered the final survey question, with a median of 48 per country. Results The main themes identified were: patient-related factors, including health education; care provider-related factors, including continuing medical education; improving communication and interprofessional partnership, particularly between primary and secondary care; factors relating to health system organisation and policies, including improving access to healthcare; easier primary care access to diagnostic tests; and use of information technology. Re-allocation of funding to support timely diagnosis was seen as an issue affecting all of these. Conclusions To achieve more timely cancer diagnosis, health systems need to facilitate earlier patient presentation through education and better access to care, have well-educated clinicians with good access to investigations and better information technology, and adequate primary care cancer diagnostic pathway funding.
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| 48. |
- Harris, Michael, et al.
(author)
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Identifying important health system factors that influence primary care practitioners' referrals for cancer suspicion : a European cross-sectional survey.
- 2018
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 8:9, s. 1-13
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: Cancer survival and stage of disease at diagnosis and treatment vary widely across Europe. These differences may be partly due to variations in access to investigations and specialists. However, evidence to explain how different national health systems influence primary care practitioners' (PCPs') referral decisions is lacking.This study analyses health system factors potentially influencing PCPs' referral decision-making when consulting with patients who may have cancer, and how these vary between European countries.DESIGN: Based on a content-validity consensus, a list of 45 items relating to a PCP's decisions to refer patients with potential cancer symptoms for further investigation was reduced to 20 items. An online questionnaire with the 20 items was answered by PCPs on a five-point Likert scale, indicating how much each item affected their own decision-making in patients that could have cancer. An exploratory factor analysis identified the factors underlying PCPs' referral decision-making.SETTING: A primary care study; 25 participating centres in 20 European countries.PARTICIPANTS: 1830 PCPs completed the survey. The median response rate for participating centres was 20.7%.OUTCOME MEASURES: The factors derived from items related to PCPs' referral decision-making. Mean factor scores were produced for each country, allowing comparisons.RESULTS: Factor analysis identified five underlying factors: PCPs' ability to refer; degree of direct patient access to secondary care; PCPs' perceptions of being under pressure; expectations of PCPs' role; and extent to which PCPs believe that quality comes before cost in their health systems. These accounted for 47.4% of the observed variance between individual responses.CONCLUSIONS: Five healthcare system factors influencing PCPs' referral decision-making in 20 European countries were identified. The factors varied considerably between European countries. Knowledge of these factors could assist development of health service policies to produce better cancer outcomes, and inform future research to compare national cancer diagnostic pathways and outcomes.
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| 49. |
- Hart, Andrew R, et al.
(author)
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Diet in the aetiology of ulcerative colitis: A European prospective cohort study
- 2008
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In: Digestion. - : S. Karger AG. - 1421-9867 .- 0012-2823. ; 77:1, s. 57-64
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Journal article (peer-reviewed)abstract
- Background/Aims: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake of nutrients and the development of ulcerative colitis in a cohort study. Methods: The study population was 260,686 men and women aged 20-80 years, participating in a large European prospective cohort study (EPIC). Participants were residents in the UK, Sweden, Denmark, Germany or Italy. Information on diet was supplied and the subjects were followed up for the development of ulcerative colitis. Each incident case was matched with four controls and dietary variables were divided into quartiles. Results: A total of 139 subjects with incident ulcerative colitis were identified. No dietary associations were detected, apart from a marginally significant positive association with an increasing percentage intake of energy from total polyunsaturated fatty acids (trend across quartiles OR = 1.19 (95% CI = 0.99-1.43) p = 0.07). Conclusions: No associations between ulcerative colitis and diet were detected, apart from a possible increased risk with a higher total polyunsaturated fatty acid intake. A biological mechanism exists in that polyunsaturated fatty acids are metabolised to pro-inflammatory mediators.
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| 50. |
- Holmberg, Johan, et al.
(author)
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Catalytic and structural effects of W-substitution in M2 Mo-V-Te-oxide for propene ammoxidation
- 2007
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In: Catalysis Today. - : Elsevier BV. - 0920-5861. ; 128:3-4, s. 153-160
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Journal article (peer-reviewed)abstract
- Substitution of W for the Mo in M2-type Mo-V-Te-oxide was investigated. XRD, FTIR, XANES, and HRTEM verified that the substitution is possible in the whole range up to complete replacement of Mo by W. Catalytic measurements for propene ammoxidation show that both the specific activity and the selectivity to acrylonitrile pass through a maximum with increase of the W-content of the catalyst. XRD analysis indicates that the catalytic results, in part, can be explained by a disordered distribution of Mo, W, and V among the octahedral sites in M2 giving better catalytic performance than a more ordered arrangement does. Moreover, SEM and HRTEM imaging show that with increasing W-content, the M2 crystals change from μm-sized elongated crystals to spherical crystals of nm-size, influencing the type of surfaces being exposed and consequently the catalytic properties. Among the catalysts investigated, a catalyst with the composition (Mo0.3W0.7)1.9V1.0Te1.1O10 is the most active and selective one, giving 80% selectivity to acrylonitrile.
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