Large deviations for non-uniformly expanding maps

We obtain large deviation results for non-uniformly expanding maps with non-flat singularities or criticalities and for partially hyperbolic non-uniformly expanding attracting sets. That is, given a continuous function we consider its space average with respect to a physical measure and compare this with the time averages along orbits of the map, showing that the Lebesgue measure of the set of points whose time averages stay away from the space average decays to zero exponentially fast with the number of iterates involved. As easy by-products we deduce escape rates from subsets of the basins of physical measures for these types of maps. The rates of decay are naturally related to the metric entropy and pressure function of the system with respect to a family of equilibrium states. The corrections added to the published version of this text appear in bold; see last section for a list of changesComment: 36 pages, 1 figure. After many PhD students and colleagues having pointed several errors in the statements and proofs, this is a correction to published article answering those comments. List of main changes in a new last sectio

Robust exponential decay of correlations for singular-flows

We construct open sets of Ck (k bigger or equal to 2) vector fields with singularities that have robust exponential decay of correlations with respect to the unique physical measure. In particular we prove that the geometric Lorenz attractor has exponential decay of correlations with respect to the unique physical measure.Comment: Final version accepted for publication with added corrections (not in official published version) after O. Butterley pointed out to the authors that the last estimate in the argument in Subsection 4.2.3 of the previous version is not enough to guarantee the uniform non-integrability condition claimed. We have modified the argument and present it here in the same Subsection. 3 figures, 34 page

Testing macroecological hypotheses in sandy beach populations: the wedge clam Donax hanleyanus in South America

Large-scale spatial and temporal variability in environmental conditions may result in differences in life-history traits, population demography, and abundance of sandy-beach species. We analyzed the effects of salinity, chlorophyll a (chl a), and sea surface temperature (SST) on population parameters of the wedge clam Donax hanleyanus from 75 South American sandy beaches covering a 15° latitudinal range. Generalized modeling results showed that betweenbeach differences in abundance, population structure, growth performance, productivity, mortality, and individual shell mass were mainly explained by salinity fluctuations, with chl a and SST as secondary contributors, overriding, in most cases, local habitat features (Dean’s parameter, grain size, slope). Our results provide valuable insights into macroscale ecological processes, setting a basis to delineate conservation guidelines at large spatial scales that respond to the potential effects of climate variability and change on sandy beach populations

The European Cancer Patient’s Bill of Rights, update and implementation 2016

In this implementation phase of the European Cancer Patient’s Bill of Rights (BoR), we confirm the following three patient-centred principles that underpin this initiative: 1: The right of every European citizen to receive the most accurate information and to be proactively involved in his/her care. 2: The right of every European citizen to optimal and timely access to a diagnosis and to appropriate specialised care, underpinned by research and innovation. 3: The right of every European citizen to receive care in health systems that ensure the best possible cancer prevention, the earliest possible diagnosis of their cancer, improved outcomes, patient rehabilitation, best quality of life and affordable health care. The key aspects of working towards implementing the BoR are: - Agree our high-level goal. The vision of 70% long-term survival for patients with cancer in 2035, promoting cancer prevention and cancer control and the associated progress in ensuring good patient experience and quality of life. - Establish the major mechanisms to underpin its delivery. (1) The systematic and rigorous sharing of best practice between and across European cancer healthcare systems and (2) the active promotion of Research and Innovation focused on improving outcomes; (3) Improving access to new and established cancer care by sharing best practice in the development, approval, procurement and reimbursement of cancer diagnostic tests and treatments. - Work with other organisations to bring into being a Europe based centre that will (1) systematically identify, evaluate and validate and disseminate best practice in cancer management for the different countries and regions and (2) promote Research and Innovation and its translation to maximise its impact to improve outcomes

Primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms

BACKGROUND: Primaquine is an anti-malarial used to prevent Plasmodium vivax relapses and malaria transmission. However, PQ metabolites cause haemolysis in patients deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Fifteen PQ-thiazolidinone derivatives, synthesized through one-post reactions from primaquine, arenealdehydes and mercaptoacetic acid, were evaluated in parallel in several biological assays, including ability to block malaria transmission to mosquitoes. RESULTS: All primaquine derivatives (PQ-TZs) exhibited lower cell toxicity than primaquine; none caused haemolysis to normal or G6PD-deficient human erythrocytes in vitro. Sera from mice pretreated with the test compounds thus assumed to have drug metabolites, caused no in vitro haemolysis of human erythrocytes, whereas sera from mice pretreated with primaquine did cause haemolysis. The ability of the PQ-TZs to block malaria transmission was evaluated based on the oocyst production and percentage of mosquitoes infected after a blood meal in drug pre-treated animals with experimental malaria caused by either Plasmodium gallinaceum or Plasmodium berghei; four and five PQ-TZs significantly inhibited sporogony in avian and in rodent malaria, respectively. Selected PQ-TZs were tested for their inhibitory activity on P. berghei liver stage development, in mice and in vitro, one compound (4m) caused a 3-day delay in the malaria pre-patent period. CONCLUSIONS: The compound 4m was the most promising, blocking malaria transmissions and reducing the number of exoerythrocytic forms of P. berghei (EEFs) in hepatoma cells in vitro and in mice in vivo. The same compound also caused a 3-day delay in the malaria pre-patent period. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12936-017-1755-6) contains supplementary material, which is available to authorized users

Fitness Trade-Offs in the Evolution of Dihydrofolate Reductase and Drug Resistance in Plasmodium falciparum

Background: Patterns of emerging drug resistance reflect the underlying adaptive landscapes for specific drugs. In Plasmodium falciparum, the parasite that causes the most serious form of malaria, antifolate drugs inhibit the function of essential enzymes in the folate pathway. However, a handful of mutations in the gene coding for one such enzyme, dihydrofolate reductase, confer drug resistance. Understanding how evolution proceeds from drug susceptibility to drug resistance is critical if new antifolate treatments are to have sustained usefulness. Methodology/Principal Findings: We use a transgenic yeast expression system to build on previous studies that described the adaptive landscape for the antifolate drug pyrimethamine, and we describe the most likely evolutionary trajectories for the evolution of drug resistance to the antifolate chlorcycloguanil. We find that the adaptive landscape for chlorcycloguanil is multi-peaked, not all highly resistant alleles are equally accessible by evolution, and there are both commonalities and differences in adaptive landscapes for chlorcycloguanil and pyrimethamine. Conclusions/Significance: Our findings suggest that cross-resistance between drugs targeting the same enzyme reflect the fitness landscapes associated with each particular drug and the position of the genotype on both landscapes. The possibl