Evidence of suppression of onchocerciasis transmission in the Venezuelan Amazonian focus.

BACKGROUND: The World Health Organization (WHO) has set goals for onchocerciasis elimination in Latin America by 2015. Most of the six previously endemic countries are attaining this goal by implementing twice a year (and in some foci, quarterly) mass ivermectin (Mectizan®) distribution. Elimination of transmission has been verified in Colombia, Ecuador and Mexico. Challenges remain in the Amazonian focus straddling Venezuela and Brazil, where the disease affects the hard-to-reach Yanomami indigenous population. We provide evidence of suppression of Onchocerca volvulus transmission by Simulium guianense s.l. in 16 previously hyperendemic Yanomami communities in southern Venezuela after 15 years of 6-monthly and 5 years of 3-monthly mass ivermectin treatment. METHODS: Baseline and monitoring and evaluation parasitological, ophthalmological, entomological and serological surveys were conducted in selected sentinel and extra-sentinel communities of the focus throughout the implementation of the programme. RESULTS: From 2010 to 2012–2015, clinico-parasitological surveys indicate a substantial decrease in skin microfilarial prevalence and intensity of infection; accompanied by no evidence (or very low prevalence and intensity) of ocular microfilariae in the examined population. Of a total of 51,341 S. guianense flies tested by PCR none had L3 infection (heads only). Prevalence of infective flies and seasonal transmission potentials in 2012–2013 were, respectively, under 1 % and 20 L3/person/transmission season. Serology in children aged 1–10 years demonstrated that although 26 out of 396 (7 %) individuals still had Ov-16 antibodies, only 4/218 (2 %) seropositives were aged 1–5 years. CONCLUSIONS: We report evidence of recent transmission and morbidity suppression in some communities of the focus representing 75 % of the Yanomami population and 70 % of all known communities. We conclude that onchocerciasis transmission could be feasibly interrupted in the Venezuelan Amazonian focus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1313-z) contains supplementary material, which is available to authorized users

AC-KBO Revisited

Equational theories that contain axioms expressing associativity and commutativity (AC) of certain operators are ubiquitous. Theorem proving methods in such theories rely on well-founded orders that are compatible with the AC axioms. In this paper we consider various definitions of AC-compatible Knuth-Bendix orders. The orders of Steinbach and of Korovin and Voronkov are revisited. The former is enhanced to a more powerful version, and we modify the latter to amend its lack of monotonicity on non-ground terms. We further present new complexity results. An extension reflecting the recent proposal of subterm coefficients in standard Knuth-Bendix orders is also given. The various orders are compared on problems in termination and completion.Comment: 31 pages, To appear in Theory and Practice of Logic Programming (TPLP) special issue for the 12th International Symposium on Functional and Logic Programming (FLOPS 2014

Using Representation Theorems for Proving Polynomials Non-negative

Proving polynomials non-negative when variables range on a subset of numbers (e.g., [0, +∞)) is often required in many applications (e.g., in the analysis of program termination). Several representations for univariate polynomials P that are non-negative on [0, +∞) have been investigated. They can often be used to characterize the property, thus providing a method for checking it by trying a match of P against the representation. We introduce a new characterization based on viewing polynomials P as vectors, and find the appropriate polynomial basis B in which the non-negativeness of the coordinates [P]B representing P in B witnesses that P is non-negative on [0, +∞). Matching a polynomial against a representation provides a way to transform universal sentences ∀x ∈ [0, +∞) P(x) ≥ 0 into a constraint solving problem which can be solved by using efficient methods. We consider different approaches to solve both kind of problems and provide a quantitative evaluation of performance that points to an early result by P´olya and Szeg¨o’s as an appropriate basis for implementations in most cases.Lucas Alba, S. (2014). Using Representation Theorems for Proving Polynomials Non-negative. En Artificial Intelligence and Symbolic Computation: 12th International Conference, AISC 2014, Seville, Spain, December 11-13, 2014. Proceedings. Springer Verlag (Germany). 21-33. doi:10.1007/978-3-319-13770-4_4S2133Alarcón, B., Gutiérrez, R., Lucas, S., Navarro-Marset, R.: Proving Termination Properties with mu-term. In: Johnson, M., Pavlovic, D. (eds.) AMAST 2010. LNCS, vol. 6486, pp. 201–208. Springer, Heidelberg (2011)Basu, S., Pollack, R., Roy, M.-F.: Algorithms in Real Algebraic Geometry. Springer, Berlin (2006)Bernstein, S.: Démonstration du théorème de Weierstrass fondée sur le calcul des probabilités. Communic. Soc. Math. de Kharkow 13(2), 1–2 (1912)Bernstein, S.: Sur la répresentation des polynômes positifs. Communic. Soc. Math. de Kharkow 14(2), 227–228 (1915)Borralleras, C., Lucas, S., Oliveras, A., Rodríguez, E., Rubio, A.: SAT Modulo Linear Arithmetic for Solving Polynomial Constraints. Journal of Automated Reasoning 48, 107–131 (2012)Boudaoud, F., Caruso, F., Roy, M.-F.: Certificates of Positivity in the Bernstein Basis. Discrete Computational Geometry 39, 639–655 (2008)Choi, M.D., Lam, T.Y., Reznick, B.: Sums of squares of real polynomials. In: Proc. of the Symposium on Pure Mathematics, vol. 4, pp. 103–126. American Mathematical Society (1995)Contejean, E., Marché, C., Tomás, A.-P., Urbain, X.: Mechanically proving termination using polynomial interpretations. Journal of Automated Reasoning 32(4), 315–355 (2006)Hilbert, D.: Über die Darstellung definiter Formen als Summe von Formenquadraten. Mathematische Annalen 32, 342–350 (1888)Hong, H., Jakuš, D.: Testing Positiveness of Polynomials. Journal of Automated Reasoning 21, 23–38 (1998)Karlin, S., Studden, W.J.: Tchebycheff systems: with applications in analysis and statistics. Interscience, New York (1966)Lucas, S.: Polynomials over the reals in proofs of termination: from theory to practice. RAIRO Theoretical Informatics and Applications 39(3), 547–586 (2005)Polya, G., Szegö, G.: Problems and Theorems in Analysis II. Springer (1976)Powers, V., Reznick, B.: Polynomials that are positive on an interval. Transactions of the AMS 352(10), 4677–4692 (2000)Powers, V., Wörmann, T.: An algorithm for sums of squares of real polynomials. Journal of Pure and Applied Algebra 127, 99–104 (1998

Physical limits of flight performance in the heaviest soaring bird

Flight costs are predicted to vary with environmental conditions, and this should ultimately determine the movement capacity and distributions of large soaring birds. Despite this, little is known about how flight effort varies with environmental parameters. We deployed bio-logging devices on the world’s heaviest soaring bird, the Andean condor (Vultur gryphus), to assess the extent to which these birds can operate without resorting to powered flight. Our records of individual wingbeats in >216 hours of flight show that condors can sustain soaring across a wide range of wind and thermal conditions, only flapping for 1 % of their flight time. This is amongst the very lowest estimated movement costs in vertebrates. One bird even flew for > 5 hours without flapping, covering ~ 172 km. Overall, > 70 % of flapping flight was associated with take-offs. Movement between weak thermal updrafts at the start of the day also imposed a metabolic cost, with birds flapping towards the end of glides to reach ephemeral thermal updrafts. Nonetheless, the investment required was still remarkably low, and even in winter conditions with weak thermals, condors are only predicted to flap for ~ 2 s per km. The overall flight effort in the largest soaring birds therefore appears to be constrained by the requirements for take-off

Genetic noise control via protein oligomerization

Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamic role of protein-protein interactions. Here we have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch), integrating quantitative results from previous in vivo and in vitro studies. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its random switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced) state from randomly being induced (uninduced). The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise

The effects of thymoquinone on pancreatic cancer: Evidence from preclinical studies

Thymoquinone (TQ) is a secondary metabolite found in abundance in very few plant species including Nigella sativa L., Monarda fistulosa L., Thymus vulgaris L. and Satureja montana L. Preclinical pharmacological studies have shown that TQ has many biological activities, such as anti-inflammatory, antioxidant and anticancer. Both in vivo and in vitro experiments have shown that TQ acts as an antitumor agent by altering cell cycle progression, inhibiting cell proliferation, stimulating apoptosis, inhibiting angiogenesis, reducing metastasis and affecting autophagy. In this comprehensive study, the evidence on the pharmacological potential of TQ on pancreatic cancer is reviewed. The positive results of preclinical studies support the view that TQ can be considered as an additional therapeutic agent against pancreatic cancer. The possibilities of success for this compound in human medicine should be further explored through clinical trials. © 2022 The Author

Acceptance towards COVID-19 vaccination in Latin America and the Caribbean: A systematic review and meta-analysis

Introduction: Vaccination represents an important strategy to mitigate COVID-19 related morbidity and mortality by protecting against severe forms of the disease and reducing hospitalization and death rates. In this sense, the objective of this study is to estimate the prevalence of Vaccination Intention (VI) against COVID-19 in Latin America and Caribbean (LAC). Methods: We conducted a systematic review with a comprehensive search strategy for the following databases: PubMed, Scopus and Web of Science. A random-effect model meta-analysis was carried out using observational studies assessing the intention to vaccines against COVID-19 in LAC countries. The Clopper-Pearson method was used to estimate 95% Confidence Intervals. The quality assessment was developed using the Newcastle-Ottawa Scale adapted for cross-sectional studies. A subgroup analysis by study location and a sensitivity analysis were developed. Results: Nineteen cross-sectional studies were included. Five meta-analyzes were performed according to the target population of the included studies. The VI in the general population of LAC was 78.0% (95%CI: 74.0%–82.0%). The VI for non-pregnant women was 78.0% (95%CI: 58.0%–99.0%), for elderly population was 63.0% (95%CI: 59.0%–69.0%), for pregnant women was 69.0% (95%CI: 61.0%–76.0%) and for health-personnel was 83.0% (95% CI: 71.0%–96.0%). The sensitivity analysis for general population meta-analysis that included only low risk of bias studies showed a 77.0% VI (95%CI: 73.0%–82.0%) and for non-pregnant women, 85.0% VI (95%CI: 79.0%–90.0%). Conclusion: Despite the high prevalence of VI in general population found in our study, VI prevalence from elderly people and pregnant women are lower than other population groups and overall population.Revisión por pare

Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.National Institutes of Health grants: (UL1RR025741, K24AR002138, P602AR30692, P01AR49084, UL1TR000165, P01AI083194, RO1AR43814, P60AR053308, UL1TR000004, AR43727, R21AI070304, RO1AR057172, UL1RR025014, R01AR051545-03, UL1RR029882, P60AR062755, P30AR53483, U19AI082714, P30GM103510, U01AI101934, AI063274, AR056360, AI083194, R37AI024717, P01083194, P01AR049084, PR094002); Northwestern University Feinberg School of Medicine; University of Alabama Birmingham; National Institute of Arthritis and Musculoskeletal and Skin Diseases; University of California Los Angeles; University of California San Francisco; Hopkins University; University of Colorado School of Medicine; University of Southern California; Seattle Children's Research Institute Arthritis Foundation; Medical University of South Carolina; Oklahoma Medical Research Foundation; Cincinnati Children's Hospital Medical Center; US Departments of Defense grant: (PR094002); Veterans Affairs; Alliance for Lupus Research; Kirkland Scholar Award; Korea Healthcare technology R & D project: (A121983); Ministry for Health and Welfare; Republic of Korea; Swedish Research Council; Instituto de Salud Carlos III grant: (PS09/00129); European Union FEDER funds; Fundação para a Ciência e Tecnologia fellowships: (SFRH/BPD/29354/2006, SFRH/BPD/34648/2007)

Organising multi-dimensional biological image information: The BioImage Database

Nowadays it is possible to unravel complex information at all levels of cellular organization by obtaining multi-dimensional image information. at the macromolecular level, three-dimensional (3D) electron microscopy, together with other techniques, is able to reach resolutions at the nanometer or subnanometer level. The information is delivered in the form of 3D volumes containing samples of a given function, for example, the electron density distribution within a given macromolecule. The same situation happens at the cellular level with the new forms of light microscopy, particularly confocal microscopy, all of which produce biological 3D volume information. Furthermore, it is possible to record sequences of images over time (videos), as well as sequences of volumes, bringing key information on the dynamics of living biological systems. It is in this context that work on bioimage started two years ago, and that its first version is now presented here. In essence, Bioimage is a database specifically designed to contain multi-dimensional images, perform queries and interactively work with the resulting multi-dimensional information on the World Wide Web, as well as accomplish the required cross-database links. Two sister home pages of bioimage can be accessed at http://www.bioimage.org and http://www-embl.bioimage.or