Impact of CKD Progression on Cardiovascular Disease Risk in a Contemporary UK Cohort of Individuals With Diabetes

Introduction: It remains unclear whether an increased progression rate of chronic kidney disease (CKD) adds predictive information regarding cardiovascular disease (CVD) risk. The aim of this study was to evaluate the association between CKD progression, based on estimated glomerular filtration rate (eGFR) slope estimates and the risk for CVD. Methods: We compared the updated eGFR slope calculated over multiple overlapping 2-year periods and the updated mean eGFR. Incident CKD subjects were selected from a prevalent population with diabetes (T2DM). Subjects from the UK Clinical Practice Research Data Link GOLD (CPRD) were followed from CKD diagnosis (n = 30,222) until heart failure (HF), myocardial infarction (MI), ischemic stroke (IS), or a composite end point including all 3 event types (MACE plus), mortality, database dropout, or end of study follow-up. Results: Both the updated eGFR slope and updated mean eGFR were associated with MACE plus and HF. Updated eGFR slope decline of > –3 ml/min/1.73 m2 increased the risk for MACE plus (adjusted hazard ratio [HR] = 1.45; 95% confidence interval [CI], 1.26–1.67), HF (HR = 1.50; 95% CI, 1.27–1.76), and MI (HR = 1.39; 95% CI, 1.01–1.91). Conclusions: This study strongly supports current evidence that CKD is an independent risk factor for CVD. From a clinical perspective, both rate of progression and cumulative status of CKD describe distinct aspects of the cardiorenal risk among persons with diabetes. This evidence is essential to enable more timely and improved use of treatments in this population

Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis

The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 × 10−32 and P = 1.8 × 10−22 in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DRβ chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (Hepatology 2011;53:1967-1976

Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33 000 women from the general population

<p>Abstract</p> <p>Background</p> <p>Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women.</p> <p>Methods</p> <p>Dietary intake was estimated using a food frequency questionnaire among 33 623 women aged 30-49 years at enrolment (1991/92). Information on psychotic-like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic-like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression.</p> <p>Results</p> <p>18 411 women were classified as having a low level of psychotic-like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic-like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic-like symptoms.</p> <p>Conclusion</p> <p>Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic-like symptoms.</p

Formación profesional : revista europea

El resumen está tomado de la revistaRepetidamente se ha criticado a las escuelas por divorciarse de la realidad y no ser capaces de desarrollar los conocimientos y cualificaciones que la vida profesional exige. El objetivo de este estudio de caso consiste en examinar la forma en que algunas escuelas con programas de formación profesional han organizado su labor, por un lado a fin de impartir los conocimientos que la vida profesional moderna requiere y por otro, para dar a conocer a los jóvenes adolescentes la vida activa y los entornos profesionales.LU

EM Estimation in Phase Type Models

This thesis consists of four articles whose theme in common is the class of phase type distributions. In the first article an EM algorithm is presented to estimate the parameters of a phase type distribution of fixed order. Also, it is shown that the algorithm can be used to approximate other continuous distributions by phase type distributions. In article number two, the EM algorithm is adjusted to handle fitting of phase type distributions to samples containing right censored and/or interval censored observations. The third article deals with approximations of standard errors of identifiable functions (e.g. the distribution function at a fixed point) of a fitted phase type distribution. Standard error approximations are calculated both by using asymptotic theory and by using the jackknife technique. The two methods are compared and evaluated by simulations in several examples. The last article presents a parametric model for estimation of the relapse time of a disease in certain clinical trials. The model is a special phase type model where the state space of the underlying Markov process is split into two parts; the first set of states represents the patient still being healthy, a transition to a second set of states takes place when the patient get a relapse, and a transition to an absorbing state represents the patient getting symptoms of the disease

EM Estimation in Phase Type Models

This thesis consists of four articles whose theme in common is the class of phase type distributions. In the first article an EM algorithm is presented to estimate the parameters of a phase type distribution of fixed order. Also, it is shown that the algorithm can be used to approximate other continuous distributions by phase type distributions. In article number two, the EM algorithm is adjusted to handle fitting of phase type distributions to samples containing right censored and/or interval censored observations. The third article deals with approximations of standard errors of identifiable functions (e.g. the distribution function at a fixed point) of a fitted phase type distribution. Standard error approximations are calculated both by using asymptotic theory and by using the jackknife technique. The two methods are compared and evaluated by simulations in several examples. The last article presents a parametric model for estimation of the relapse time of a disease in certain clinical trials. The model is a special phase type model where the state space of the underlying Markov process is split into two parts; the first set of states represents the patient still being healthy, a transition to a second set of states takes place when the patient get a relapse, and a transition to an absorbing state represents the patient getting symptoms of the disease