Biomarkers of extracellular matrix metabolism (MMP-9 and TIMP-1) and risk of stroke, myocardial infarction and cause-specific mortality : cohort study

Objective: Turnover of the extracellular matrix in all solid organs is governed mainly by a balance between the degrading matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). An altered extracellular matrix metabolism has been implicated in a variety of diseases. We investigated relations of serum levels of MMP-9 and TIMP-1 to mortality risk from an etiological perspective. Design: The prospective Uppsala Longitudinal Study of Adult Men (ULSAM) cohort, followed from 1991–1995 for up to 18.1 years. A random population-based sample of 1,082 71-year-old men, no loss to follow-up. Endpoints were all-cause (n = 628), cardiovascular (n = 230), non-cardiovascular (n = 398) and cancer mortality (n = 178), and fatal or non-fatal myocardial infarction (n = 138) or stroke (n = 163). Results: Serum MMP-9 and TIMP-1 levels were associated with risk of all-cause mortality (Cox proportional hazard ratio [HR] per standard deviation 1.10, 95% confidence interval [CI] 1.03–1.19; and 1.11, 1.02–1.20; respectively). TIMP-1 levels were mainly related to risks of cardiovascular mortality and stroke (HR per standard deviation 1.22, 95% CI 1.09–1.37; and 1.18, 1.04–1.35; respectively). All relations except those of TIMP-1 to stroke risk were attenuated by adjustment for cardiovascular disease risk factors. Relations in a subsample without cardiovascular disease or cancer were similar to those in the total sample. Conclusion: In this community-based cohort of elderly men, serum MMP-9 and TIMP-1 levels were related to mortality risk. An altered extracellular matrix metabolism may be involved in several detrimental pathways, and circulating MMP-9 or TIMP-1 levels may be relevant markers thereof.

Estimation of Parameters in Random Effect Models with Incidence Matrix Uncertainty

Random effect models have been widely applied in many fields of research. However, models with uncertain design matrices for random effects have been little investigated before. In some applications with such problems, an expectation method has been used for simplicity. This method does not include the extra information of uncertainty in the design matrix is not included. The closed solution for this problem is generally difficult to attain. We therefore propose an two-step algorithm for estimating the parameters, especially the variance components in the model. The implementation is based on Monte Carlo approximation and a Newton-Raphson-based EM algorithm. As an example, a simulated genetics dataset was analyzed. The results showed that the proportion of the total variance explained by the random effects was accurately estimated, which was highly underestimated by the expectation method. By introducing heuristic search and optimization methods, the algorithm can possibly be developed to infer the 'model-based' best design matrix and the corresponding best estimates.

Utmaningen från andra berättelser : En studie om moraliskt omdöme, utvidgat tänkande och kritiskt reflekterande berättelser i dialogbaserad feministisk etik

The present study has a threefold aim: First, the theoretical aim is to give a contribution to refinement of the theory of dialogue based feminist ethics, concerning the understanding of judgment and narration within such an ethics.  The study also has an empirical aim, defined as to clarify what kind of knowledge, relevant to the moral judgment of an engaged outsider actor, can be received from dialogical interpretation and analysis of a limited selection of critically reflecting life stories. Third, a methodological aim is defined as to develop an approach to interpretation and analysis of reflecting life stories, which renders the storyteller visible as a reflecting moral subject, and makes the story accessible as a source of knowledge for the moral judgment of an engaged outsider actor. The thesis combines philosophical reflection and argumentation, with a narrative-hermeneutic method for interpretation of life stories, relating the two to each other in a hermeneutic process.  The theoretical reflection draws on Seyla Benhabibs theory of communicative ethics. A dialogue based model for moral justification and a likewise dialogue based model for political legitimacy are at the heart of this universalistic theory, although in combination with a conception of a narratively and hermeneutically constituted context sensitive moral judgment, based on Hannah Arendt’s concept “enlarged thought”. In the reflection, this model is related to other feminist theorizing within the tradition of dialogue based feminist ethics, as found in the works of Iris M. Young, Georgia Warnke and Shari Stone-Mediatore. The empirical study draws on three critically reflecting life stories from Israeli-Palestinian women activists for a just peace. The methodology for interpretation and analysis that is worked out combines dialogical interpretation as presented in Arthur W. Frank’s socio-narratology with a method for structural analysis derived from Shari Stone-Mediatores theory of storytelling as an expression of political resistance struggle. The results show that some stories drawing on marginalized experiences have a potential­ to stimulate further public debate through their capacity to enable a stereoscopic seeing, elucidating a tension between ideologically structured discourse and non-linguistic experience; implying that narrative-hermeneutic competence should be considered crucial for public debate.