Fast flowing populations are not well mixed

In evolutionary dynamics, well-mixed populations are almost always associated with all-to-all interactions; mathematical models are based on complete graphs. In most cases, these models do not predict fixation probabilities in groups of individuals mixed by flows. We propose an analytical description in the fast-flow limit. This approach is valid for processes with global and local selection, and accurately predicts the suppression of selection as competition becomes more local. It provides a modelling tool for biological or social systems with individuals in motion.Comment: 19 pages, 8 figure

The time is now: Achieving FH paediatric screening across Europe – The Prague Declaration

ReviewFamilial Hypercholesterolaemia (FH) is severely under-recognized, under-diagnosed and under-treated in Europe, leading to a significantly higher risk of premature cardiovascular diseases in those affected. FH stands for inherited, very high cholesterol and affects 1:300 individuals regardless of their age, race, sex, and lifestyle, making it the most common inherited metabolic disorder and a non-modifiable cardiovascular disease risk factor in the world..info:eu-repo/semantics/publishedVersio

Recommendations for the treatment of epilepsy in adult patients in general practice in Belgium: an update

In 2008, a group of Belgian epilepsy experts published recommendations for antiepileptic drug (AED) treatment of epilepsies in adults and children. Selection of compounds was based on the registration and reimbursement status in Belgium, the level of evidence for efficacy, common daily practice and the personal views and experiences of the authors. In November 2011 the validity of these recommendations was reviewed by the same group of Belgian epilepsy experts who contributed to the preparation of the original paper. The recommendations made in 2008 for initial monotherapy in paediatric patients were still considered to be valid, except for the first choice treatment for childhood absence epilepsy. This update therefore focuses on the treatment recommendations for initial monotherapy and add-on treatment in adult patients. Several other relevant aspects of treatment with AEDs are addressed, including considerations for optimal combination of AEDs (rational polytherapy), pharmacokinetic properties, pharmacodynamic and pharmacokinetic interaction profile, adverse effects, comorbidity, treatment of elderly patients, AED treatment during pregnancy, and generic substitution of AEDs

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia A Global Call to Action

Q1Q1Artículo completoE1-E13IMPORTANCE Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. OBSERVATIONS In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. CONCLUSIONS AND RELEVANCE By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well

Microphysics of relativistic collisionless electron-ion-positron shocks

We perform particle-in-cell simulations to elucidate the microphysics of relativistic weakly magnetized shocks loaded with electron-positron pairs. Various external magnetizations $\sigma\lesssim 10^{-4}$ and pair-loading factors $Z_\pm \lesssim 10$ are studied, where $Z_\pm$ is the number of loaded electrons and positrons per ion. We find the following. (1) The shock becomes mediated by the ion Larmor gyration in the mean field when $\sigma$ exceeds a critical value $\sigma_{\rm L}$ that decreases with $Z_\pm$. At $\sigma\lesssim\sigma_{\rm L}$ the shock is mediated by particle scattering in the self-generated microturbulent fields, the strength and scale of which decrease with $Z_\pm$, leading to lower $\sigma_{\rm L}$. (2) The energy fraction carried by the post-shock pairs is robustly in the range between 20% and 50% of the upstream ion energy. The mean energy per post-shock electron scales as $\overline{E}_{\rm e}\propto (Z_\pm+1)^{-1}$. (3) Pair loading suppresses nonthermal ion acceleration at magnetizations as low as $\sigma\approx 5\times 10^{-6}$. The ions then become essentially thermal with mean energy $\overline{E}_{\rm i}$, while electrons form a nonthermal tail, extending from $E\sim (Z_\pm + 1)^{-1}\overline{E}_{\rm i}$ to $\overline{E}_{\rm i}$. When $\sigma = 0$, particle acceleration is enhanced by the formation of intense magnetic cavities that populate the precursor during the late stages of shock evolution. Here, the maximum energy of the nonthermal ions and electrons keeps growing over the duration of the simulation. Alongside the simulations, we develop theoretical estimates consistent with the numerical results. Our findings have important implications for models of early gamma-ray burst afterglows.Comment: 20 pages, 16 figures, submitted to Ap