Population-based prediction of atrial fibrillation

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and increases in prevalence. As AF confers increased risk of morbidity, stroke, dementia and mortality, a major objective of cardiovascular epidemiology today is the development of tools for prediction and prevention of AF and its consequences. Although AF has traditionally been considered a non-heritable disease, a familial component to AF has recently been established and genetic polymorphisms associated with AF risk. The aim of this thesis was therefore to evaluate the ability of genetic polymorphisms, conventional cardiovascular risk factors and blood biomarkers reflecting diverse pathophysiological pathways to predict onset of AF in the general population.Methods: Individuals with incident AF were identified from a large, population-based cohort study (Malmö Diet and Cancer, n=30 447) using national registers during up to 17.8 years follow-up. Genetic polymorphisms on chromosomes 4q25, 16q22 and in the KCNH2 gene reproducibly associated with AF were genotyped in the entire cohort. Six blood biomarkers (MR-proANP, MR-proADM, NT-proBNP, copeptin, CRP and cystatin c) were measured in a random subcohort (n=6104).Results: Case validity of AF diagnoses in national registers was estimated to be high, 95-97%. A substantial proportion of population risk was conferred by conventional risk factors (hypertension, 34-38%; obesity, 10-11%). Conventional risk factors predicted AF with reasonable accuracy (C-statistic 0.732), although age and sex considered alone were only modestly less accurate. Addition of blood MR-proANP and CRP improved predictive accuracy modestly (C-statistic 0.753). Polymorphisms on chromosomes 4q25 and 16q22 but not in KCNH2 were associated with AF independently of conventional risk factors, but did not significantly improve predictive accuracy. In a meta-analysis of published studies including up to 150 000 individuals, the association of polymorphisms with AF was robust across diverse study designs, but with widely varying risk estimates. Genetic polymorphisms but not conventional risk factors were associated with AF in heart failure (HF) patients. A SNP on chromosome 16q22 was more strongly associated with AF in this context (p for interaction = 7x10-4), suggestive of a pathophysiological interaction of the gene affected by this SNP and HF.Conclusion: The results of this thesis have implications for population-based prediction of AF and provides novel information on risk factors for AF in HF patients

Acute Stent Thrombosis Following Concomitant Balloon Aortic Valvuloplasty and Percutaneous Coronary Intervention

Balloon aortic valvuloplasty is often used as a palliative measure or as a bridge to transcatheter aortic valve replacement in the management of aortic stenosis in high risk or inoperable patients. Severe aortic stenosis coexisting with coronary artery disease is not uncommon. In these circumstances, adjuvant percutaneous coronary intervention may be warranted. The safety and efficacy of combined valve and coronary intervention strategies has been recently studied. An increased incidence of complications when both procedures are performed in the same setting may throw new challenges. We report a case of fatal acute stent thrombosis following balloon aortic valvuloplasty and percutaneous coronary intervention

Mechanical Thrombectomy in Post-Transplant Heart

Coronary allograft vasculopathy (CAV) is an accelerated form of coronary artery disease that is responsible for significant mortality after cardiac transplantation. We report a case of CAV with significant thrombus burden which was managed with mechanical thrombectomy. Both aspiration and mechanical thrombectomy can be safely done in cardiac transplant recipients and may be considered in order to minimize exposure to coronary artery bypass procedure. This is especially valuable in emergency circumstances

Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction.

Increased levels of cardio-enriched microRNAs (miRNAs) have been described in patients with myocardial infarction (MI). We wanted to evaluate the diagnostic and prognostic potential of cardio-enriched miRNAs in patients presenting with a suspected acute coronary syndrome (ACS)

Band dispersion in the deep 1s core level of graphene

Chemical bonding in molecules and solids arises from the overlap of valence electron wave functions, forming extended molecular orbitals and dispersing Bloch states, respectively. Core electrons with high binding energies, on the other hand, are localized to their respective atoms and their wave functions do not overlap significantly. Here we report the observation of band formation and considerable dispersion (up to 60 meV) in the $1s$ core level of the carbon atoms forming graphene, despite the high C $1s$ binding energy of $\approx$ 284 eV. Due to a Young's double slit-like interference effect, a situation arises in which only the bonding or only the anti-bonding states is observed for a given photoemission geometry.Comment: 12 pages, 3 figures, including supplementary materia

Predation effects on mean time to extinction under demographic stochasticity

Methods for predicting the probability and timing of a species' extinction are typically based on a combination of theoretical models and empirical data, and focus on single species population dynamics. Of course, species also interact with each other, forming more or less complex networks of interactions. Models to assess extinction risk often lack explicit incorporation of these interspecific interactions. We study a birth and death process in which the death rate includes an effect from predation. This predation rate is included via a general nonlinear expression for the functional response of predation to prey density. We investigate the effects of the foraging parameters (e.g. attack rate and handling time) on the mean time to extinction. Mean time to extinction varies by orders of magnitude when we alter the foraging parameters, even when we exclude the effects of these parameters on the equilibrium population size. In particular we observe an exponential dependence of the mean time to extinction on handling time. These findings clearly show that accounting for the nature of interspecific interactions is likely to be critically important when estimating extinction risk.Comment: 11 pages, 4 figures; Typos removed. For further discussion about the paper go to http://purl.org/net/extinctio

Sutherlandia frutescens: The meeting of science and traditional knowledge

Sutherlandia frutescens (L.) R.Br. (syn. Lessertia frutescens (L.) Goldblatt and J.C. Manning) is an indigenous medicinal plant extensively used in South Africa to treat a variety of health conditions. It is a fairly widespread, drought-resistant plant that grows in the Western, Eastern, and Northern Cape provinces and some areas of KwaZulu-Natal, varying in its chemical and genetic makeup across these geographic areas.1 Sutherlandia is widely used as a traditional medicine. Extensive scientific studies are being carried out on the safety, quality, and the efficacy of this medicinal plant to validate the traditional claims, elucidate the bioactive constituents, and conduct clinical trials. This has resulted in a unique situation in South Africa’s history, where traditional knowledge and science intersect to provide insight into this popular plant. This photoessay attempts to illustrate the interlinkage of science with the indigenous knowledge of traditional healers, the local knowledge of people who care for the sick, product development, and innovation agenda of the country as it relates to this plant.Web of Scienc

Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study

Objective: High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes. Methods and Results: Leukocyte count and its subtypes (neutrophils, lymphocytes and mixed cells) were analyzed in 26,667 men and women, 45–73 years old, from the population-based Malmö Diet and Cancer study. Information about the R262W polymorphism (rs3184504) in SH2B3 was genotyped in 24,489 subjects. Incidence of diabetes was studied during a mean follow-up of 14 years. Cox proportional hazards regression was used to examine incidence of diabetes by total and differential leukocyte counts. Mendelian randomization analysis using R262W as an instrumental variable was performed with two-stage least squares regression. A total of 2,946 subjects developed diabetes during the follow-up period. After taking several possible confounders into account, concentrations of total leukocyte count, neutrophils and lymphocytes were all significantly associated with incidence of diabetes. The adjusted hazard ratios (95% confidence interval; quartile 4 vs quartile 1) were 1.37 (1.22–1.53) for total leukocytes, 1.33 (1.19–1.49) for neutrophils and 1.29 (1.15–1.44) for lymphocytes. The R262W polymorphism was strongly associated with leukocytes (0.11x109 cells/l per T allele, p = 1.14 x10-12), lymphocytes (p = 4.3 x10-16), neutrophils (p = 8.0 x10-6) and mixed cells (p = 3.0 x10-6). However, there was no significant association between R262W and fasting glucose, HbA1c or incidence of diabetes. Conclusions: Concentrations of total leukocytes, neutrophils and lymphocytes are associated with incidence of diabetes. However, the lack of association with the R262W polymorphism suggests that the associations may not be causal, although limitations in statistical power and balancing pleiotropic effects cannot be excluded