Trends in Secondary Prevention of Coronary Heart Disease in Tunisia: Prevention of Recurrences of MI and Stroke

ObjectivesThe survival benefits achieved by prescription of antiplatelet agents, B-adrenoreceptor antagonists (beta-blockers), angiotensin II receptor blockers (ARB), and lipid lowering agents in patients surviving the myocardial infarction (MI) have been well documented in large clinical trial. Despite well-established benefits, these pharmacological agents continue to be underutilized. The main objective of this study was to evaluate the progress of cardiovascular secondary prevention practices in Tunisia.MethodsThe PREMISE (Prevention of Recurrence of Myocardial Infarction and Stroke) is a descriptive, cross-sectional study conducted in Tunisia in two phases (2002 and 2009). Seven hundred eighty two patients were recruited. The recruitment criteria were: previous MI, stable angina, unstable angina, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA) or carotid endarterectomy. This analysis is limited to coronary heart disease (CHD) patients. Five hundred hospital patients were interviewed and their medical records were reviewed: 250 in 2002 and 250 in 2009. Patients were included if they had confirmed diagnosis of MI, angina, CABG or PTCA, and if their first cardiovascular event had occurred more than one month but not later than 3 years ago. We compared the total of both patient groups, using the prevalence of Cardio-Vascular Risk Factors (CVRF) and the treatment prescribed at hospital discharge.ResultsThe proportion of patients with reported hypertension, diabetes, hypercholesterolemia and current smoker patients had decreased. Concerning pharmacological prescriptions, a significant increase was observed in prescribing statins (38.9% vs. 70.3%) and ACE inhibitors (49.3% vs. 69.9%), non pharmacological prescriptions as healthy diet or tobacco cessation had opposite trends. Adherence to treatment did not change substantially.ConclusionAlthough the use of cardioprotective drugs had increased in CHD patients, there are still gaps in secondary prevention in Tunisia. The recommended strategies of secondary prevention need to be applied more intensively in clinical practice

Ginzburg-Landau model with small pinning domains

We consider a Ginzburg-Landau type energy with a piecewise constant pinning term $a$ in the potential $(a^2 - |u|^2)^2$. The function $a$ is different from 1 only on finitely many disjoint domains, called the {\it pinning domains}. These pinning domains model small impurities in a homogeneous superconductor and shrink to single points in the limit $\v\to0$; here, \v is the inverse of the Ginzburg-Landau parameter. We study the energy minimization in a smooth simply connected domain $\Omega \subset \mathbb{C}$ with Dirichlet boundary condition $g$ on \d \O, with topological degree {\rm deg}_{\d \O} (g) = d >0. Our main result is that, for small \v, minimizers have $d$ distinct zeros (vortices) which are inside the pinning domains and they have a degree equal to 1. The question of finding the locations of the pinning domains with vortices is reduced to a discrete minimization problem for a finite-dimensional functional of renormalized energy. We also find the position of the vortices inside the pinning domains and show that, asymptotically, this position is determined by {\it local renormalized energy} which does not depend on the external boundary conditions.Comment: 39 page

The Transition to a Giant Vortex Phase in a Fast Rotating Bose-Einstein Condensate

We study the Gross-Pitaevskii (GP) energy functional for a fast rotating Bose-Einstein condensate on the unit disc in two dimensions. Writing the coupling parameter as 1 / \eps^2 we consider the asymptotic regime \eps \to 0 with the angular velocity $\Omega$ proportional to (\eps^2|\log\eps|)^{-1} . We prove that if \Omega = \Omega_0 (\eps^2|\log\eps|)^{-1} and $\Omega_0 > 2(3\pi)^{-1}$ then a minimizer of the GP energy functional has no zeros in an annulus at the boundary of the disc that contains the bulk of the mass. The vorticity resides in a complementary `hole' around the center where the density is vanishingly small. Moreover, we prove a lower bound to the ground state energy that matches, up to small errors, the upper bound obtained from an optimal giant vortex trial function, and also that the winding number of a GP minimizer around the disc is in accord with the phase of this trial function.Comment: 52 pages, PDFLaTex. Minor corrections, sign convention modified. To be published in Commun. Math. Phy

A cost effectiveness analysis of salt reduction policies to reduce coronary heart disease in four Eastern Mediterranean countries.

BACKGROUND: Coronary Heart Disease (CHD) is rising in middle income countries. Population based strategies to reduce specific CHD risk factors have an important role to play in reducing overall CHD mortality. Reducing dietary salt consumption is a potentially cost-effective way to reduce CHD events. This paper presents an economic evaluation of population based salt reduction policies in Tunisia, Syria, Palestine and Turkey. METHODS AND FINDINGS: Three policies to reduce dietary salt intake were evaluated: a health promotion campaign, labelling of food packaging and mandatory reformulation of salt content in processed food. These were evaluated separately and in combination. Estimates of the effectiveness of salt reduction on blood pressure were based on a literature review. The reduction in mortality was estimated using the IMPACT CHD model specific to that country. Cumulative population health effects were quantified as life years gained (LYG) over a 10 year time frame. The costs of each policy were estimated using evidence from comparable policies and expert opinion including public sector costs and costs to the food industry. Health care costs associated with CHDs were estimated using standardized unit costs. The total cost of implementing each policy was compared against the current baseline (no policy). All costs were calculated using 2010 PPP exchange rates. In all four countries most policies were cost saving compared with the baseline. The combination of all three policies (reducing salt consumption by 30%) resulted in estimated cost savings of $235,000,000 and 6455 LYG in Tunisia;$39,000,000 and 31674 LYG in Syria; $6,000,000 and 2682 LYG in Palestine and$1,3000,000,000 and 378439 LYG in Turkey. CONCLUSION: Decreasing dietary salt intake will reduce coronary heart disease deaths in the four countries. A comprehensive strategy of health education and food industry actions to label and reduce salt content would save both money and lives

Vortex Rings in Fast Rotating Bose-Einstein Condensates

When Bose-Eintein condensates are rotated sufficiently fast, a giant vortex phase appears, that is the condensate becomes annular with no vortices in the bulk but a macroscopic phase circulation around the central hole. In a former paper [M. Correggi, N. Rougerie, J. Yngvason, {\it arXiv:1005.0686}] we have studied this phenomenon by minimizing the two dimensional Gross-Pitaevskii energy on the unit disc. In particular we computed an upper bound to the critical speed for the transition to the giant vortex phase. In this paper we confirm that this upper bound is optimal by proving that if the rotation speed is taken slightly below the threshold there are vortices in the condensate. We prove that they gather along a particular circle on which they are evenly distributed. This is done by providing new upper and lower bounds to the GP energy.Comment: to appear in Archive of Rational Mechanics and Analysi

Vortex density models for superconductivity and superfluidity

We study some functionals that describe the density of vortex lines in superconductors subject to an applied magnetic field, and in Bose-Einstein condensates subject to rotational forcing, in quite general domains in 3 dimensions. These functionals are derived from more basic models via Gamma-convergence, here and in a companion paper. In our main results, we use these functionals to obtain descriptions of the critical applied magnetic field (for superconductors) and forcing (for Bose-Einstein), above which ground states exhibit nontrivial vorticity, as well as a characterization of the vortex density in terms of a non local vector-valued generalization of the classical obstacle problem.Comment: 34 page

Heterozygote Advantage for Fecundity

Heterozygote advantage, or overdominance, remains a popular and persuasive explanation for the maintenance of genetic variation in natural populations in the face of selection. However, despite being first proposed more than 80 years ago, there remain few examples that fit the criteria for heterozygote advantage, all of which are associated with disease resistance and are maintained only in the presence of disease or other gene-by-environment interaction. Here we report five new examples of heterozygote advantage, based around polymorphisms in the BMP15 and GDF9 genes that affect female fecundity in domesticated sheep and are not reliant on disease for their maintenance. Five separate mutations in these members of the transforming growth factor β (TGFβ) superfamily give phenotypes with fitness differentials characteristic of heterozygous advantage. In each case, one copy of the mutant allele increases ovulation rate, and ultimately litter size per ewe lambing, relative to the wildtype. However, homozygous ewes inheriting mutant alleles from both parents have impaired oocyte development and maturation, which results in small undeveloped ovaries and infertility. Using data collected over many years on ovulation rates, litter size, and lambing rates, we have calculated the equilibrium solution for each of these polymorphisms using standard population genetic theory. The predicted equilibrium frequencies obtained for these mutant alleles range from 0.11 to 0.23, which are amongst the highest yet reported for a polymorphism maintained by heterozygote advantage. These are amongst the most frequent and compelling examples of heterozygote advantage yet described and the first documented examples of heterozygote advantage that are not reliant on a disease interaction for their maintenance

Structure and Functional Analysis of the RNA- and Viral Phosphoprotein-Binding Domain of Respiratory Syncytial Virus M2-1 Protein

Respiratory syncytial virus (RSV) protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp) complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties are related to the core region of M2-1 encompassing residues S58 to K177. Here we report the NMR structure of the RSV M2-158–177 core domain, which is structurally homologous to the C-terminal domain of Ebola virus VP30, a transcription co-factor sharing functional similarity with M2-1. The partial overlap of RNA and P interaction surfaces on M2-158–177, as determined by NMR, rationalizes the previously observed competitive behavior of RNA versus P. Using site-directed mutagenesis, we identified eight residues located on these surfaces that are critical for an efficient transcription activity of the RdRp complex. Single mutations of these residues disrupted specifically either P or RNA binding to M2-1 in vitro. M2-1 recruitment to cytoplasmic inclusion bodies, which are regarded as sites of viral RNA synthesis, was impaired by mutations affecting only binding to P, but not to RNA, suggesting that M2-1 is associated to the holonucleocapsid by interacting with P. These results reveal that RNA and P binding to M2-1 can be uncoupled and that both are critical for the transcriptional antitermination function of M2-1

Genome-wide scans identify known and novel regions associated with prolificacy and reproduction traits in a sub-Saharan African indigenous sheep (Ovis aries)

Maximizing the number of offspring born per female is a key functionality trait in commercial- and/or subsistence-oriented livestock enterprises. Although the number of offspring born is closely associated with female fertility and reproductive success, the genetic control of these traits remains poorly understood in sub-Saharan Africa livestock. Using selection signature analysis performed on Ovine HD BeadChip data from the prolific Bonga sheep in Ethiopia, 41 candidate regions under selection were identified. The analysis revealed one strong selection signature on a candidate region on chromosome X spanning BMP15, suggesting this to be the primary candidate prolificacy gene in the breed. The analysis also identified several candidate regions spanning genes not reported before in prolific sheep but underlying fertility and reproduction in other species. The genes associated with female reproduction traits included SPOCK1 (age at first oestrus), GPR173 (mediator of ovarian cyclicity), HB-EGF (signalling early pregnancy success) and SMARCAL1 and HMGN3a (regulate gene expression during embryogenesis). The genes involved in male reproduction were FOXJ1 (sperm function and successful fertilization) and NME5 (spermatogenesis). We also observed genes such as PKD2L2, MAGED1 and KDM3B, which have been associated with diverse fertility traits in both sexes of other species. The results confirm the complexity of the genetic mechanisms underlying reproduction while suggesting that prolificacy in the Bonga sheep, and possibly African indigenous sheep is partly under the control of BMP15 while other genes that enhance male and female fertility are essential for reproductive fitness