Assessing Euro-Med Trade Preferences: The Case of Entry Price Reduction

The EU protects some of its fruits and vegetables through the entry price system. This system consists on a two-tiered tariff, with high-priced exports paying an ad valorem tariff, whereas low-priced exports pay also a supplementary specific tariff. The breaking point between high and low export prices is the entry price level decided by the EU, generally the same level for all third countries. In a few cases, some Southern Mediterranean partners of the EU have agreed a reduced entry price for their exports, together with the more common ad valorem tariff reduction. Among the indicators used for gauge the value of preferences, there is no one devoted to this case of reduced entry price, hence we develop a new indicator that allows to split which part of the preferential gains corresponds to the entry price reduction and which part corresponds to the "usual" ad valorem tariff reduction. We apply this methodology to Moroccan clementines trade flows, with two main findings: 1) The entry price reduction ranges up to 39% of the economic value of preferences in some months; 2) Morocco is not maximizing the gains due to this reduction, and could take some trade and policy lessons, mainly trying to better fit to the concession or, if impossible, use it as negotiating capital in future reviews of the agreement.International Relations/Trade,

Arsenic Exposure and the Induction of Human Cancers

Arsenic is a metalloid, that is, considered to be a human carcinogen. Millions of individuals worldwide are chronically exposed through drinking water, with consequences ranging from acute toxicities to development of malignancies, such as skin and lung cancer. Despite well-known arsenic-related health effects, the molecular mechanisms involved are not fully understood; however, the arsenic biotransformation process, which includes methylation changes, is thought to play a key role. This paper explores the relationship of arsenic exposure with cancer development and summarizes current knowledge of the potential mechanisms that may contribute to the neoplastic processes observed in arsenic exposed human populations

Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here

Should we use closed or open infusion containers for prevention of bloodstream infections?

<p>Abstract</p> <p>Background</p> <p>Hospitalized patients in critical care settings are at risk for bloodstream infections (BSI). Most BSIs originate from a central line (CL), and they increase length of stay, cost, and mortality. Open infusion containers may increase the risk of contamination and administration-related (CLAB) because they allow the entry of air into the system, thereby also providing an opportunity for microbial entry. Closed infusion containers were designed to overcome this flaw. However, open infusion containers are still widely used throughout the world.</p> <p>The objective of the study was to determine the effect of switching from open (glass, burettes, and semi-rigid) infusion containers to closed, fully collapsible, plastic infusion containers (Viaflex^®) on the rate and time to onset of central line-associated bloodstream infections CLABs.</p> <p>Methods</p> <p>An open label, prospective cohort, active healthcare-associated infection surveillance, sequential study was conducted in four ICUs in Mexico. Centers for Disease Control National Nosocomial Infections Surveillance Systems definitions were used to define device-associated infections.</p> <p>Results</p> <p>A total of 1,096 adult patients who had a central line in place for >24 hours were enrolled. The CLAB rate was significantly higher during the open versus the closed container period (16.1 versus 3.2 CLAB/1000 central line days; RR = 0.20, 95% CI = 0.11-0.36, P < 0.0001). The probability of developing CLAB remained relatively constant in the closed container period (1.4% Days 2-4 to 0.5% Days 8-10), but increased in the open container period (4.9% Days 2-4 to 5.4% Days 8-10). The chance of acquiring a CLAB was significantly decreased (81%) in the closed container period (Cox proportional hazard ratio 0.19, P < 0.0001). Mortality was statistically significantly lower during the closed versus the open container period (23.4% versus 16.1%; RR = 0.69, 95% CI = 0.54-0.88, P < 0.01).</p> <p>Conclusions</p> <p>Closed infusion containers significantly reduced CLAB rate, the probability of acquiring CLAB, and mortality.</p

Oncogenetics of Lung Cancer Induced by Environmental Carcinogens

The molecular landscape of non-tobacco-induced primary lung tumors displays specific oncogenetic features. The etiology of these tumors has been largely associated with exposure to well-established environmental lung carcinogens such as radon, arsenic, and asbestos. Environmental carcinogens can induce specific genetic and epigenetic alterations in lung tissue, leading to aberrant function of lung cancer oncogenes and tumor suppressor genes. These molecular events result in the disruption of key cellular mechanisms, such as protection against oxidative stress and DNA damage-repair, which promotes tumor development and progression. This chapter provides a comprehensive discussion of the specific carcinogenic mechanisms associated with exposure to radon, arsenic, and asbestos. It also summarizes the main protein-coding and non-coding genes affected by exposure to these environmental agents, and the underlying molecular mechanisms promoting their deregulation in lung cancer. Finally, the chapter examines the anticipated challenges in personalized intervention strategies in non-tobacco-induced lung cancer

Design of the Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) AIR Study.

IntroductionPopulation-based epidemiological evidence suggests that exposure to ambient air pollutants increases hospitalisations and mortality from chronic obstructive pulmonary disease (COPD), but less is known about the impact of exposure to air pollutants on patient-reported outcomes, morbidity and progression of COPD.Methods and analysisThe Subpopulations and Intermediate Outcome Measures in COPD (SPIROMICS) Air Pollution Study (SPIROMICS AIR) was initiated in 2013 to investigate the relation between individual-level estimates of short-term and long-term air pollution exposures, day-to-day symptom variability and disease progression in individuals with COPD. SPIROMICS AIR builds on a multicentre study of smokers with COPD, supplementing it with state-of-the-art air pollution exposure assessments of fine particulate matter, oxides of nitrogen, ozone, sulfur dioxide and black carbon. In the parent study, approximately 3000 smokers with and without airflow obstruction are being followed for up to 3 years for the identification of intermediate biomarkers which predict disease progression. Subcohorts undergo daily symptom monitoring using comprehensive daily diaries. The air monitoring and modelling methods employed in SPIROMICS AIR will provide estimates of individual exposure that incorporate residence-specific infiltration characteristics and participant-specific time-activity patterns. The overarching study aim is to understand the health effects of short-term and long-term exposures to air pollution on COPD morbidity, including exacerbation risk, patient-reported outcomes and disease progression.Ethics and disseminationThe institutional review boards of all the participating institutions approved the study protocols. The results of the trial will be presented at national and international meetings and published in peer-reviewed journals

Quantisation without Gauge Fixing: Avoiding Gribov Ambiguities through the Physical Projector

The quantisation of gauge invariant systems usually proceeds through some gauge fixing procedure of one type or another. Typically for most cases, such gauge fixings are plagued by Gribov ambiguities, while it is only for an admissible gauge fixing that the correct dynamical description of the system is represented, especially with regards to non perturbative phenomena. However, any gauge fixing procedure whatsoever may be avoided altogether, by using rather a recently proposed new approach based on the projection operator onto physical gauge invariant states only, which is necessarily free on any such issues. These different aspects of gauge invariant systems are explicitely analysed within a solvable U(1) gauge invariant quantum mechanical model related to the dimensional reduction of Yang-Mills theory.Comment: 22 pages, no figures, plain LaTeX fil

Risk related to pre–diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial

Background—The prevalence of pre–diabetes mellitus and its consequences in patients with heart failure and reduced ejection fraction are not known. We investigated these in the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. Methods and Results—We examined clinical outcomes in 8399 patients with heart failure and reduced ejection fraction according to history of diabetes mellitus and glycemic status (baseline hemoglobin A1c [HbA1c]: &lt;6.0% [&lt;42 mmol/mol], 6.0%–6.4% [42–47 mmol/mol; pre–diabetes mellitus], and ≥6.5% [≥48 mmol/mol; diabetes mellitus]), in Cox regression models adjusted for known predictors of poor outcome. Patients with a history of diabetes mellitus (n=2907 [35%]) had a higher risk of the primary composite outcome of heart failure hospitalization or cardiovascular mortality compared with those without a history of diabetes mellitus: adjusted hazard ratio, 1.38; 95% confidence interval, 1.25 to 1.52;P&lt;0.001. HbA1c measurement showed that an additional 1106 (13% of total) patients had undiagnosed diabetes mellitus and 2103 (25%) had pre–diabetes mellitus. The hazard ratio for patients with undiagnosed diabetes mellitus (HbA1c, &gt;6.5%) and known diabetes mellitus compared with those with HbA1c&lt;6.0% was 1.39 (1.17–1.64); P&lt;0.001 and 1.64 (1.43–1.87); P&lt;0.001, respectively. Patients with pre–diabetes mellitus were also at higher risk (hazard ratio, 1.27 [1.10–1.47];P&lt;0.001) compared with those with HbA1c&lt;6.0%. The benefit of LCZ696 (sacubitril/valsartan) compared with enalapril was consistent across the range of HbA1c in the trial. Conclusions—In patients with heart failure and reduced ejection fraction, dysglycemia is common and pre–diabetes mellitus is associated with a higher risk of adverse cardiovascular outcomes (compared with patients with no diabetes mellitus and HbA1c &lt;6.0%). LCZ696 was beneficial compared with enalapril, irrespective of glycemic status

Small Noncoding RNA Expression in Cancer

Despite an inability to encode proteins, small noncoding RNAs (sncRNAs) have critical functions in the regulation of gene expression. They have demonstrated roles in cancer development and progression and are frequently dysregulated. Here we review the biogenesis and mechanism of action, expression patterns, and detection methods of two types of sncRNAs frequently described in cancer: miRNAs and piRNAs. Both miRNAs and piRNAs have been observed to play both oncogenic and tumor-suppressive roles, with miRNAs acting to directly regulate the mRNA of key cancer-associated genes, while piRNAs play crucial roles in maintaining the integrity of the epigenetic landscape. Elucidating these important functions of sncRNAs in normal and cancer biology relies on numerous in silico workflows and tools to profile sncRNA expression. Thus, we also discuss the key detection methods for cancer-relevant sncRNAs, including the discovery of genes that have yet to be described

Structure-Guided Directed Evolution of Highly Selective P450-Based Magnetic Resonance Imaging Sensors for Dopamine and Serotonin

New tools that allow dynamic visualization of molecular neural events are important for studying the basis of brain activity and disease. Sensors that permit ligand-sensitive magnetic resonance imaging (MRI) are useful reagents due to the noninvasive nature and good temporal and spatial resolution of MR methods. Paramagnetic metalloproteins can be effective MRI sensors due to the selectivity imparted by the protein active site and the ability to tune protein properties using techniques such as directed evolution. Here, we show that structure-guided directed evolution of the active site of the cytochrome P450‐BM3 heme domain produces highly selective MRI probes with submicromolar affinities for small molecules. We report a new, high‐affinity dopamine sensor as well as the first MRI reporter for serotonin, with which we demonstrate quantification of neurotransmitter release in vitro. We also present a detailed structural analysis of evolved cytochrome P450‐BM3 heme domain lineages to systematically dissect the molecular basis of neurotransmitter binding affinity, selectivity, and enhanced MRI contrast activity in these engineered proteins