| 1. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368 .- 1550-7998. ; 91:5
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Aad, G., et al.
(författare)
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- 2014
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :6
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Aad, G., et al.
(författare)
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- 2014
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Tidskriftsartikel (refereegranskat)
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| 4. |
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| 5. |
- Ahmad, Tariq, et al.
(författare)
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Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients
- 2018
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Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Background-Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials. We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response. Methods and Results-The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information. We applied random forest modeling to identify predictors of 1-year survival. Cluster analysis was performed and validated using serial bootstrapping. Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity-matched clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012. Random forest modeling demonstrated excellent calibration and discrimination for survival (C-statistic=0.83) whereas left ventricular ejection fraction did not (C-statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1-year survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1-year survival. There were significant interactions between propensity-matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin-converting enzyme inhibitors, )i-blockers, and nitrates, Pamp;lt;0.001, all). Conclusions-Machine learning algorithms accurately predicted outcomes in a large data set of HF patients. Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in response to therapeutics. Use of these novel analytic approaches has the potential to enhance effectiveness of current therapies and transform future HF clinical trials.
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| 6. |
- Ahmad Tajudin, Asilah
(författare)
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Biomarker detection via lab-on-a-chip integrated immunoaffinity approach for fluorescence and mass spectrometry readout
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The blood/plasma protein biomarker profile represents the pathological and physiological changes relating to human diseases. However, the plasma proteome reflects a high degree of complexity that results in a challenge for most analytical methods in clinical diagnostics. The focus in this thesis is the development and application of several integrated platforms to detect already established protein/peptide biomarkers from blood and plasma (Prostate Specific Antigen, PSA and Angiotensin I, Ang I). The integrated platforms that are described in the papers included in this thesis utilize protein/peptide immunoaffinity-capturing since it offers insights into dealing with the challenges of the plasma proteome analysis by reducing complexity and enriching the proteins/peptides of interest. Several integrated platforms were developed with the overall main aim of detecting biomarkers from complex biological samples: • porous silicon antibody microarray with signal amplification step (Paper I) • microfluidic whole blood immunoassay (Paper II and III) • integrated protein immunoaffinity capturing with microfabricated proteomic sample processing platform (ISET) enabling a direct interface to MALDI MS/MS analysis (Paper IV) • integrated peptide immunoaffinity capturing via porous silicon array-based immuno-MALDI (Paper V) enabling a direct interface to MALDI MS/MS analysis Ultimately, these platforms target future use in point-of-care settings (Paper I-III) and immuno-MALDI mass spectrometry immunoassays for identification and quantitative measurements of biomarkers using isotope labelled standards (Paper V) as well as outlook for use in the development of SRM/MRM assays (Paper IV).
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| 7. |
- Fenhammar, Johan
(författare)
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Renal failure in experimental sepsis : role of endothelin and the toll-like receptor 4
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sepsis is the leading cause of renal failure in critically ill patients, but the pathogenesis of septic kidney dysfunction is poorly defined. The current paradigm states that hypoperfusion and excessive renal vasoconstriction results in renal ischemia. However, experimental data also exist indicating a direct immune-mediated basis of septic renal impairment. This thesis aimed to investigate the contribution of both a potent vasoconstrictor peptide, endothelin-1 (ET-1), and a receptor that activates the immune system in response to a bacterial infection, the Toll-like receptor 4 (TLR4), to the renal failure caused by sepsis. The first part of this thesis investigated the role of the endothelin system in renal microcirculatory and functional impairment caused by experimental septic renal failure, by studying the effects of dual endothelin type A and B (ETA/ETB) antagonism and selective ETA-antagonism during porcine endotoxemia. ET-1 is a vasoconstrictor peptide that is a potent modulator of microcirculatory blood flow. It is released in high amounts during sepsis and experimental data have shown that ET-1 reduces renal blood flow. In paper I and II pigs were subjected to lipopolysaccharide (LPS) infusion and the renal microcirculatory effects of dual ETA/ETB or selective ETA antagonism were investigated. The main findings were that dual ETA/ETB blockade attenuated the endotoxemia induced reduction in renal cortical microcirculation, as well as the increase in plasma creatinine levels (paper I). In addition, selective ETA antagonism reduced the decline in renal medullary microcirculation, but had no significant effect on diuresis or creatinine clearance (paper II). The second part of this thesis investigated the role of TLR4 activation in renal failure caused by hyperdynamic endotoxemia or sepsis. Conscious surgically prepared sheep were subjected to LPS or live Escherichia coli infusion and observed for 24-36 hours. A main finding was that pretreatment with a TLR4-inhibitor attenuated renal failure and hypotension caused by endotoxemia in sheep. This effect was greater compared to norepinephrine treatment, in a dose that prevented hypotension (paper III). Moreover, it was observed that septic renal failure developed without renal hypoperfusion and that treatment with a TLR4-inhibitor reversed renal failure when administered 12 hours into sepsis (paper IV). This effect was independent of changes in systemic or renal hemodynamics but was associated with a reduced renal neutrophil accumulation. In conclusion, despite no reduction in renal perfusion or arterial blood pressure, septic renal failure may still develop. During hyperdynamic sepsis, stimulation of the innate immune system, via TLR4 activation, may contribute to the development of renal failure. In addition, TLR4-inhibition is an effective treatment to improve renal function in ovine sepsis induced by E.coli. In hypodynamic endotoxemia, ET-1 contributes to renal vasoconstriction. By acting on ETA, ET-1 reduces renal medullary blood flow causing ischemia but has no short-term effect on renal function.
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| 8. |
- Klintman, Mikael, et al.
(författare)
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Toy Consumption as Political : Challenges for Making Dreams Come True
- 2018
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Ingår i: The Oxford Handbook of Political Consumerism. - 9780190629038
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Bokkapitel (refereegranskat)abstract
- This chapter looks at political consumerism in the toy sector, offering a brief history of consumer concerns and distinguishing among four strands of political consumerist research in this sector. A primary factor facilitating political consumerism of toys is that toy companies are extremely concerned about their reputation. Manufacturers cannot assume that parents and other carers do their usual risk-benefit analysis with the same level of risk acceptance concerning toys. Factors constraining political consumerism in this sector include long product chains and difficulties in discovering unethical practices and dangerous substances. Actors involved in the political consumerism of toys come from all societal spheres, including retailers. Regulators take action when risks have been discovered by civil society actors or scientists, but international divergence in regulation constitutes an obstacle to concerted action. Future research needs to examine synergies and trade-offs among various risks in toy products.
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| 9. |
- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 10. |
- Klintman, Mikael, et al.
(författare)
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The role of epistemic signalling in transdisciplinary knowledge production : Examples from the field of sustainable water management
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The number of arrangements where academia collaborates with governmental andnongovernmental organisations, as well as industries, have increased over the last decades.While research has focused on whether knowledge produced in such collaborations is genuinelyinfluenced by others than the ‘experts’, or those with the highest status and power, this reportexplores the influence of framings and re-framings of what the participants and society shouldperceive as the nature of knowledge: epistemology. We analyse the framings of epistemologythrough the concept ‘epistemic signalling’. Epistemic signalling refers to communication orrule-making that indicates what type(s) of knowledge is considered relevant, valuable or usefulin knowledge collaboration. Empirically we draw on two examples of transdisciplinarycollaborations in the field of water management (one from the UK and one from the US). Indepthinterviews were combined with document analysis.We have analysed three themes of epistemic signalling that we suggest influence knowledgecollaborations. The first one concerns how the form and theme of the collaboration weredecided upon and is based on Arnstein’s (1969) ladder of participation. The second refers towhat type(s) of participants were considered suitable – as for example experts or lay people.Here we use the framework of aggregate (bargaining-oriented) versus integrative (deliberative)processes of knowledge collaboration in our analysis. The third and last theme concerns whatis perceived as valuable and successful in the collaborations, something that we discuss in termsof procedural and epistemic virtues of knowledge collaborations.The epistemology of organisations and participants in knowledge collaborations ought to be adistinct subject of open discussions from the earliest planning stage and onwards. It is easy toassume that epistemic signalling would be esoteric parts of practical, collaborative knowledgeproduction. To the contrary, open epistemological reflections may help highlight situationswhere hierarchies turn out to be remains of routines inconsistent with new goals of moreprofound exchange of practical and scientific knowledge. In such cases, the epistemologiesneed to be revised to better fit the new goals.
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