| 1. |
- Andersson, Bodil, et al.
(författare)
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Gastrointestinal complications after cardiac surgery - improved risk stratification using a new scoring model.
- 2010
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 10:3, s. 366-370
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal (GI) complications are serious consequences of cardiac surgery. The aim of this study was to develop, evaluate and validate a new risk score model for GI complications after cardiac surgery. The risk score model, named gastrointestinal complication score (GICS), was developed using prospectively collected data from 5593 patients who underwent 5636 cardiac surgical procedures between 1996 and 2001. The model was validated on 1031 cardiac surgery patients between 2005 and 2006. The scoring system's ability to predict GI complications was estimated by receiver operating characteristic (ROC)-curves and Hosmer-Lemeshow test. Fifty GI complications were identified in 47 patients (0.8%) in the developmental data set and eight (0.8%) in the validation data set. The ROC area in the developmental data set was 0.81 with a good calibration estimated by Hosmer-Lemeshow test (p=0.89). In the validation data set, the area under the curve was 0.83. The estimated probability for the patient to develop a GI complication after cardiac surgery at a GICS >/=15 is >20% and at a GICS
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| 2. |
- Bakkman, Linda, et al.
(författare)
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Reduced respiratory capacity in muscle mitochondria of obese subjects.
- 2010
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Ingår i: Obesity Facts. - : S. Karger AG. - 1662-4025 .- 1662-4033. ; 3:6, s. 371-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: The extent of weight gain varies among individuals despite equal calorie overconsumption. Furthermore, weight gain is often less than expected from energy excess. This suggests differences in metabolic efficiency and basal metabolism. Since mitochondrial uncoupling accounts for a substantial portion of the basal metabolic rate, we compared skeletal muscle mitochondrial respiration in obese subjects to normal-weight reference groups with various degrees of physical activity.METHODS: Muscle biopsies were taken from the vastus lateralis muscle of 9 healthy obese subjects (BMI 40 ± 3). Mitochondria were isolated and analyzed for coupled (state 3) and uncoupled (state 4) respirations as well as mitochondrial efficiency (P/O ratio) using pyruvate as a substrate. Respiratory data were compared to reference groups A, normal-weight untrained (BMI 24 ± 0.7), and B, normal-weight trained (BMI 24 ± 0.6).RESULTS: Obese subjects had a decreased respiratory capacity per mitochondrial volume compared to the reference groups: this was evident in state 4 (65% and 35% of reference group A and B, respectively) and state 3 (53% and 29% of A and B, respectively) (p < 0.05).CONCLUSION: Obese subjects had a low capacity for fuel oxidation, which may play a role in the predisposition of obesity. However, whether lower mitochondrial capacity is a cause or a consequence of obesity requires further research.
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| 3. |
- Benning, Pierre, et al.
(författare)
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Collaboration processes A State of the Art
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The key objective of InPro is to define and support a new way of working with integrateddesign from a life cycle perspective, capturing client requirements and collaboration betweenstakeholders during the early design phase of a construction project. This phasestarts with the first client contact and ends with the delivery of a design proposal, withrecognisable functions, visualised for easy understanding and with a cost calculation tosupport the clients' go/no-go decision.The aim of Work Package 2 is to develop model-based and knowledge-based workingmethods for the Early Design phase. This will result in a systematic integration of lifecycledesign processes in new construction or renovation of buildings, taking into accountthe added values for society/citizens, clients/users, and the construction sector. ThisWork Package will also propose a framework for the collaboration process between involvedparties.The aim of Task 2.2 "Collaboration Processes" is to develop this framework for collaborationin the Early Design process, where all partners share information in a common OpenInformation Environment delivered by WP5 and add knowledge to the project. Thisframework of collaboration is a concept related to the needs of shared guidelines in orderto work efficiently together, generally defined in a contract. This framework will answerto the main question:How to create concurrent and iterative working processes with clear decisionmilestones?and includes other key questions:How to create functional working groups that represent different competenciesor backgrounds, including conflict resolution conceptsHow to to establish trustHow to balance between formal and informal communication channelsHow to communicate design changes in a virtual building model between concurrentlyworking design teams, e.g. by managing, categorising and highlightingdesign changesHow to reuse knowledgeIt also includes project and contractual issues management, progress monitoring, strategiesfor delegation of responsibility, methods for risk assessment and strategies for continuousimprovements based on measured Key Performance Indicators developed in Task1.3.
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| 4. |
- Bergman, Åke, et al.
(författare)
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Science and policy on endocrine disrupters must not be mixed : a reply to a "common sense" intervention by toxicology journal editors
- 2013
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
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| 5. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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| 7. |
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| 8. |
- Brandt, Peter, et al.
(författare)
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Deconstruction of Non-Nucleoside Reverse Transcriptase Inhibitors of Human Immunodeficiency Virus Type 1 for Exploration of the Optimization Landscape of Fragments
- 2011
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804.
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Tidskriftsartikel (refereegranskat)abstract
- This study has taken a closer look at the theoretical basis for protein-fragment interactions. The approach involved the deconstruction of 3 non-nucleoside inhibitors of HIV-1 reverse transcriptase and investigation of the interaction between 21 substructures and the enzyme. It focused on the concept of ligand efficiency and showed that ligand independent free energy fees (ΔG(ind)) are crucial for the understanding of the binding affinities of fragments. A value of 7.0 kcal mol(-1) for the ΔG(ind) term is shown to be a lower limit for the NNRTI binding pocket of HIV-1 RT. The addition of the ΔG(ind) term to the dissociation free energy in the calculation of a corrected ligand efficiency, in combination with the lack of an efficient ligand binding hot spot in the NNIBP, fully explains the existence of nonbinding NNRTI substructures. By applying the concept to a larger set of ligands, we could define a binding site profile that indicates the absence of an efficient fragment binding hot spot but an efficient binding of full-sized NNRTIs. The analysis explains some of the challenges in identifying fragments against flexible targets involving conformational changes and how fragments may be prioritized.
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| 9. |
- Geitmann, Matthis, et al.
(författare)
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Identification of a Novel Scaffold for Allosteric Inhibition of Wild Type and Drug Resistant HIV-1 Reverse Transcriptase by Fragment Library Screening
- 2011
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54:3, s. 699-708
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Tidskriftsartikel (refereegranskat)abstract
- A novel scaffold inhibiting wild type and drug resistant variants of human immunodeficiency virus type 1 reverse transcriptase (HIV-1RT) has been identified in a library consisting of 1040 fragments. The fragments were significantly different from already known non-nucleoside reverse transcriptase inhibitors (NNRTIs), as indicated by a Tversky similarity analysis. A screening strategy involving SPR biosensor-based interaction analysis and enzyme inhibition was used. Primary biosensor-based screening, using short concentration series, was followed by analysis of nevirapine competition and enzyme inhibition, thus identifying inhibitory fragments binding to the non-nucleoside reverse transcriptase inhibitor (NNRTI) binding site. Ten hits were discovered, and their affinities and resistance profiles were evaluated with wild type and three drug resistant enzyme variants (K103N, Y181C, and L100I). One fragment exhibited submillimolar K(D) and IC(50) values against all four tested enzyme variants. A substructure comparison between the fragment and 826 structurally diverse published NNRTIs confirmed that the scaffold was novel. The fragment is a bromoindanone with a ligand efficiency of 0.42 kcal/mol(-1).
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| 10. |
- Hansen, A. M. K., et al.
(författare)
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Organosulfates and organic acids in Arctic aerosols : speciation, annual variation and concentration levels
- 2014
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:15, s. 7807-7823
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Tidskriftsartikel (refereegranskat)abstract
- Sources, composition and occurrence of secondary organic aerosols in the Arctic were investigated at Zeppelin Mountain, Svalbard, and Station Nord, northeastern Greenland, during the full annual cycle of 2008 and 2010, respectively. Speciation of organic acids, organosulfates and nitrooxy organosulfates - from both anthropogenic and biogenic precursors were in focus. A total of 11 organic acids (terpenylic acid, benzoic acid, phthalic acid, pinic acid, suberic acid, azelaic acid, adipic acid, pimelic acid, pinonic acid, diaterpenylic acid acetate and 3-methyl-1,2,3-butanetricarboxylic acid), 12 organosulfates and 1 nitrooxy organosulfate were identified in aerosol samples from the two sites using a high-performance liquid chromatograph (HPLC) coupled to a quadrupole Time-of-Flight mass spectrometer. At Station Nord, compound concentrations followed a distinct annual pattern, where high mean concentrations of organosulfates (47 +/- 14 ng m(-3)) and organic acids (11.5 +/- 4 ng m(-3)) were observed in January, February and March, contrary to considerably lower mean concentrations of organosulfates (2 +/- 3 ng m(3-)) and organic acids (2.2 +/- 1 ng m(-3)) observed during the rest of the year. At Zeppelin Mountain, organosulfate and organic acid concentrations remained relatively constant during most of the year at a mean concentration of 15 +/- 4 ng m(-3) and 3.9 +/- 1 ng m(-3), respectively. However during four weeks of spring, remarkably higher concentrations of total organosulfates (23-36 ng m(-3)) and total organic acids (7-10 ngm(-3)) were observed. Elevated organosulfate and organic acid concentrations coincided with the Arctic haze period at both stations, where northern Eurasia was identified as the main source region. Air mass transport from northern Eurasia to Zeppelin Mountain was associated with a 100% increase in the number of detected organosulfate species compared with periods of air mass transport from the Arctic Ocean, Scandinavia and Greenland. The results from this study suggested that the presence of organic acids and organosulfates at Station Nord was mainly due to long-range transport, whereas indications of local sources were found for some compounds at Zeppelin Mountain. Furthermore, organosulfates contributed significantly to organic matter throughout the year at Zeppelin Mountain (annual mean of 13 +/- 8 %) and during Arctic haze at Station Nord (7 +/- 2 %), suggesting organosulfates to be important compounds in Arctic aerosols.
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