Analyzing Recent Coronary Heart Disease Mortality Trends in Tunisia between 1997 and 2009.

BACKGROUND: In Tunisia, Cardiovascular Diseases are the leading causes of death (30%), 70% of those are coronary heart disease (CHD) deaths and population studies have demonstrated that major risk factor levels are increasing. OBJECTIVE: To explain recent CHD trends in Tunisia between 1997 and 2009. METHODS: DATA SOURCES: Published and unpublished data were identified by extensive searches, complemented with specifically designed surveys. ANALYSIS: Data were integrated and analyzed using the previously validated IMPACT CHD policy model. Data items included: (i)number of CHD patients in specific groups (including acute coronary syndromes, congestive heart failure and chronic angina)(ii) uptake of specific medical and surgical treatments, and(iii) population trends in major cardiovascular risk factors (smoking, total cholesterol, systolic blood pressure (SBP), body mass index (BMI), diabetes and physical inactivity). RESULTS: CHD mortality rates increased by 11.8% for men and 23.8% for women, resulting in 680 additional CHD deaths in 2009 compared with the 1997 baseline, after adjusting for population change. Almost all (98%) of this rise was explained by risk factor increases, though men and women differed. A large rise in total cholesterol level in men (0.73 mmol/L) generated 440 additional deaths. In women, a fall (-0.43 mmol/L), apparently avoided about 95 deaths. For SBP a rise in men (4 mmHg) generated 270 additional deaths. In women, a 2 mmHg fall avoided 65 deaths. BMI and diabetes increased substantially resulting respectively in 105 and 75 additional deaths. Increased treatment uptake prevented about 450 deaths in 2009. The most important contributions came from secondary prevention following Acute Myocardial Infarction (AMI) (95 fewer deaths), initial AMI treatments (90), antihypertensive medications (80) and unstable angina (75). CONCLUSIONS: Recent trends in CHD mortality mainly reflected increases in major modifiable risk factors, notably SBP and cholesterol, BMI and diabetes. Current prevention strategies are mainly focused on treatments but should become more comprehensive

Postprocessing for quantum random number generators: entropy evaluation and randomness extraction

Quantum random-number generators (QRNGs) can offer a means to generate information-theoretically provable random numbers, in principle. In practice, unfortunately, the quantum randomness is inevitably mixed with classical randomness due to classical noises. To distill this quantum randomness, one needs to quantify the randomness of the source and apply a randomness extractor. Here, we propose a generic framework for evaluating quantum randomness of real-life QRNGs by min-entropy, and apply it to two different existing quantum random-number systems in the literature. Moreover, we provide a guideline of QRNG data postprocessing for which we implement two information-theoretically provable randomness extractors: Toeplitz-hashing extractor and Trevisan's extractor.Comment: 13 pages, 2 figure

Robustness and Generalization

We derive generalization bounds for learning algorithms based on their robustness: the property that if a testing sample is "similar" to a training sample, then the testing error is close to the training error. This provides a novel approach, different from the complexity or stability arguments, to study generalization of learning algorithms. We further show that a weak notion of robustness is both sufficient and necessary for generalizability, which implies that robustness is a fundamental property for learning algorithms to work

Forecasting Tunisian type 2 diabetes prevalence to 2027: validation of a simple model.

BACKGROUND: Most projections of type 2 diabetes (T2D) prevalence are simply based on demographic change (i.e. ageing). We developed a model to predict future trends in T2D prevalence in Tunisia, explicitly taking into account trends in major risk factors (obesity and smoking). This could improve assessment of policy options for prevention and health service planning. METHODS: The IMPACT T2D model uses a Markov approach to integrate population, obesity and smoking trends to estimate future T2D prevalence. We developed a model for the Tunisian population from 1997 to 2027, and validated the model outputs by comparing with a subsequent T2D prevalence survey conducted in 2005. RESULTS: The model estimated that the prevalence of T2D among Tunisians aged over 25 years was 12.0% in 1997 (95% confidence intervals 9.6%-14.4%), increasing to 15.1% (12.5%-17.4%) in 2005. Between 1997 and 2005, observed prevalence in men increased from 13.5% to 16.1% and in women from 12.9% to 14.1%. The model forecast for a dramatic rise in prevalence by 2027 (26.6% overall, 28.6% in men and 24.7% in women). However, if obesity prevalence declined by 20% in the 10 years from 2013, and if smoking decreased by 20% over 10 years from 2009, a 3.3% reduction in T2D prevalence could be achieved in 2027 (2.5% in men and 4.1% in women). CONCLUSIONS: This innovative model provides a reasonably close estimate of T2D prevalence for Tunisia over the 1997-2027 period. Diabetes burden is now a significant public health challenge. Our model predicts that this burden will increase significantly in the next two decades. Tackling obesity, smoking and other T2D risk factors thus needs urgent action. Tunisian decision makers have therefore defined two strategies: obesity reduction and tobacco control. Responses will be evaluated in future population surveys

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

Ancient DNA derived from alkenone-biosynthesizing haptophytes and other algae in Holocene sediments from the Black Sea

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 21 (2006): PA1005, doi:10.1029/2005PA001188.Holocene sea surface temperatures (SST) of the Black Sea have been reconstructed using sedimentary C37 unsaturated alkenones assumed to be derived from the coccolithophorid haptophyte Emiliania huxleyi, whose fossil coccoliths are an important constituent of the unit I sediments. However, alkenones can also be biosynthesized by haptophyte species that do not produce microscopic recognizable coccoliths. A species-specific identification of haptophytes is important in such U 37 K′-based past SST reconstructions since different species have different alkenone-SST calibrations. We showed that 18S rDNA of E. huxleyi made up only a very small percentage (less than 0.8%) of the total eukaryotic 18S rDNA within the up to 3600-year-old fossil record obtained from the depocenter (>2000 m) of the Black Sea. The predominant fossil 18S rDNA was derived from dinoflagellates (Gymnodinium spp.), which are predominant members of the summer phytoplankton bloom in the modern Black Sea. Using a polymerase chain reaction/denaturing gradient gel electrophoresis method selective for haptophytes, we recovered substantial numbers of a preserved 458-base-pair (bp)-long 18S rDNA fragment of E. huxleyi from the Holocene Black Sea sediments. Additional fossil haptophyte sequences were not detected, indicating that the E. huxleyi alkenone-SST calibration can be applied for at least the last ∼3600 years. The ancient E. huxleyi DNA was well protected against degradation since the DNA/alkenone ratio did not significantly decrease throughout the whole sediment core and 20% of ∼2700-year-old fossil E. huxleyi DNA was still up to 23,000 base pairs long. We showed that fossil DNA offers great potential to study the Holocene paleoecology and paleoenvironment of anoxic deep-sea settings in unprecedented detail.This work was supported by a grant from the Netherlands Organization for Scientific Research (NWO) (Open Competition Program 813.13.001 to M.J.L.C.) and NSF grant OCE0117824 to S.G.W., which we greatly appreciate

Modern venomics – Current insights, novel methods and future perspectives in biological and applied animal venom research

Venoms have evolved >100 times in all major animal groups, and their components, known as toxins, have been fine-tuned over millions of years into highly effective biochemical weapons. There are many outstanding questions on the evolution of toxin arsenals, such as how venom genes originate, how venom contributes to the fitness of venomous species, and which modifications at the genomic, transcriptomic, and protein level drive their evolution. These questions have received particularly little attention outside of snakes, cone snails, spiders, and scorpions. Venom compounds have further become a source of inspiration for translational research using their diverse bioactivities for various applications. We highlight here recent advances and new strategies in modern venomics and discuss how recent technological innovations and multi-omic methods dramatically improve research on venomous animals. The study of genomes and their modifications through CRISPR and knockdown technologies will increase our understanding of how toxins evolve and which functions they have in the different ontogenetic stages during the development of venomous animals. Mass spectrometry imaging combined with spatial transcriptomics, in situ hybridization techniques, and modern computer tomography gives us further insights into the spatial distribution of toxins in the venom system and the function of the venom apparatus. All these evolutionary and biological insights contribute to more efficiently identify venom compounds, which can then be synthesized or produced in adapted expression systems to test their bioactivity. Finally, we critically discuss recent agrochemical, pharmaceutical, therapeutic, and diagnostic (so-called translational) aspects of venoms from which humans benefit

A mutated dph3 gene causes sensitivity of Schizosaccharomyces pombe cells to cytotoxic agents

Dph3 is involved in diphthamide modification of the eukaryotic translation elongation factor eEF2 and in Elongator-mediated modifications of tRNAs, where a 5-methoxycarbonyl-methyl moiety is added to wobble uridines. Lack of such modifications affects protein synthesis due to inaccurate translation of mRNAs at ribosomes. We have discovered that integration of markers at the msh3 locus of Schizosaccharomyces pombe impaired the function of the nearby located dph3 gene. Such integrations rendered cells sensitive to the cytotoxic drugs hydroxyurea and methyl methanesulfonate. We constructed dph3 and msh3 strains with mutated ATG start codons (ATGmut), which allowed investigating drug sensitivity without potential interference by marker insertions. The dph3- ATGmut and a dph3::loxP-ura4-loxM gene disruption strain, but not msh3-ATGmut, turned out to be sensitive to hydroxyurea and methyl methanesulfonate, likewise the strains with cassettes integrated at the msh3 locus. The fungicide sordarin, which inhibits diphthamide modified eEF2 of Saccharomyces cerevisiae, barely affected survival of wild type and msh3Δ S. pombe cells, while the dph3Δ mutant was sensitive. The msh3-ATG mutation, but not dph3Δ or the dph3-ATG mutation caused a defect in mating-type switching, indicating that the ura4 marker at the dph3 locus did not interfere with Msh3 function. We conclude that Dph3 is required for cellular resistance to the fungicide sordarin and to the cytotoxic drugs hydroxyurea and methyl methanesulfonate. This is likely mediated by efficient translation of proteins in response to DNA damage and replication stress

Interaction of Rio1 Kinase with Toyocamycin Reveals a Conformational Switch That Controls Oligomeric State and Catalytic Activity

Rio1 kinase is an essential ribosome-processing factor required for proper maturation of 40 S ribosomal subunit. Although its structure is known, several questions regarding its functional remain to be addressed. We report that both Archaeoglobus fulgidus and human Rio1 bind more tightly to an adenosine analog, toyocamycin, than to ATP. Toyocamycin has antibiotic, antiviral and cytotoxic properties, and is known to inhibit ribosome biogenesis, specifically the maturation of 40 S. We determined the X-ray crystal structure of toyocamycin bound to Rio1 at 2.0 Å and demonstrated that toyocamycin binds in the ATP binding pocket of the protein. Despite this, measured steady state kinetics were inconsistent with strict competitive inhibition by toyocamycin. In analyzing this interaction, we discovered that Rio1 is capable of accessing multiple distinct oligomeric states and that toyocamycin may inhibit Rio1 by stabilizing a less catalytically active oligomer. We also present evidence of substrate inhibition by high concentrations of ATP for both archaeal and human Rio1. Oligomeric state studies show both proteins access a higher order oligomeric state in the presence of ATP. The study revealed that autophosphorylation by Rio1 reduces oligomer formation and promotes monomerization, resulting in the most active species. Taken together, these results suggest the activity of Rio1 may be modulated by regulating its oligomerization properties in a conserved mechanism, identifies the first ribosome processing target of toyocamycin and presents the first small molecule inhibitor of Rio1 kinase activity