Architectural mismatch tolerance

The integrity of complex software systems built from existing components is becoming more dependent on the integrity of the mechanisms used to interconnect these components and, in particular, on the ability of these mechanisms to cope with architectural mismatches that might exist between components. There is a need to detect and handle (i.e. to tolerate) architectural mismatches during runtime because in the majority of practical situations it is impossible to localize and correct all such mismatches during development time. When developing complex software systems, the problem is not only to identify the appropriate components, but also to make sure that these components are interconnected in a way that allows mismatches to be tolerated. The resulting architectural solution should be a system based on the existing components, which are independent in their nature, but are able to interact in well-understood ways. To find such a solution we apply general principles of fault tolerance to dealing with arch itectural mismatche

Cognition-Enhancing Drugs: Can We Say No?

Normative analysis of cognition-enhancing drugs frequently weighs the liberty interests of drug users against egalitarian commitments to a level playing field. Yet those who would refuse to engage in neuroenhancement may well find their liberty to do so limited in a society where such drugs are widespread. To the extent that unvarnished emotional responses are world-disclosive, neurocosmetic practices also threaten to provide a form of faulty data to their users. This essay examines underappreciated liberty-based and epistemic rationales for regulating cognition-enhancing drugs

Prevalencia de esofagitis eosinofílica: estudio multicéntrico en población pediátrica evaluada en 36 centros de gastroenterología de América Latina

Introducción y objetivo: La esofagitis eosinofílica es una enfermedad crónica, mediada inmunológicamente, descrita en series y publicaciones alrededor del mundo. En los últimos 20 años diversos estudios han intentado evaluar la incidencia y prevalencia de la enfermedad. El objetivo del presente trabajo es estimar la prevalencia de esofagitis eosinofílica en un grupo de niños atendidos en 36 centros de gastroenterología pediátrica de 10 países latinoamericanos. Materiales y métodos: A través de un protocolo multicéntrico, observacional y transversal se estimó la prevalencia de período de esofagitis eosinofílica entre los niños atendidos en consulta externa y sometidos a endoscopia superior diagnóstica por cualquier motivo en 36 centros de 10 países latinoamericanos durante un período de 3 meses. Resultados: Entre abril y junio de 2016 108 casos de esofagitis eosinofílica fueron evaluados. Asimismo, un promedio de 29,253 consultas ambulatorias y 4,152 endoscopias superiores de carácter diagnóstico fueron realizadas en los 36 centros participantes. La tasa de prevalencia de esofagitis eosinofílica en la población estudiada (n = 29,253) fue de 3,69 casos × 1,000 (IC 95%: 3.04 a 4.44) y entre los niños sometidos a endoscopia superior de rutina (n = 4,152) fue de 26 x 1,000 (IC 95%: 22.6 a 29.4). Conclusión: La tasa general de prevalencia de período de esofagitis eosinofílica en un grupo de niños evaluados en 36 centros latinoamericanos de gastroenterología pediátrica resultó de 3,69 × 1,000, y entre aquellos sometidos a endoscopia fue de 26 × 1,000. La prevalencia mostró una importante variabilidad entre los países y centros participantes. Este es el primer estudio de prevalencia de esofagitis eosinofílica pediátrica en Latinoamérica. Abstract: Introduction and objective: Eosinophilic esophagitis is a chronic, immune-mediated disease described in case series and publications worldwide. Over the past twenty years, the authors of different studies have attempted to evaluate its incidence and prevalence. The objetive of the present study was to estimate the prevalence of eosinophilic esophagitis in a group of children seen at 36 pediatric gastroenterology centers in ten Latin American countries. Materials and methods: A multicenter, observational, and cross-sectional study was conducted that estimated the period prevalence of eosinophilic esophagitis in children seen at outpatient consultation and that underwent diagnostic upper gastrointestinal endoscopy for any indication at 36 centers in 10 Latin American countries, within a 3-month time frame. Results: Between April and June 2016, 108 cases of eosinophilic esophagitis were evaluated. Likewise, an average of 29,253 outpatient consultations and 4,152 diagnostic upper gastrointestinal endoscopies were carried out at the 36 participating centers. The period prevalence of eosinophilic esophagitis in the population studied (n = 29,253) was 3.69 cases × 1,000 (95% CI: 3.04 to 4.44), and among the children that underwent routine upper gastrointestinal endoscopy (n = 4,152), it was 26 x 1,000 (95% CI: 22.6 to 29.4). Conclusions: The general period prevalence of eosinophilic esophagitis in a group of children evaluated at 36 Latin American pediatric gastroenterology centers was 3.69 × 1,000, and in the children that underwent endoscopy, it was 26 × 1,000. There was important prevalence variability between the participating countries and centers. The present analysis is the first study conducted on the prevalence of pediatric eosinophilic esophagitis in Latin America. Palabras clave: Esofagitis, Eosinofílica, Niños, Prevalencia, Latinoamérica, Keywords: Esophagitis, Eosinophilic, Children, Prevalence, Latin Americ

A Functional NQO1 609C>T Polymorphism and Risk of Gastrointestinal Cancers: A Meta-Analysis

Background: The functional polymorphism (rs1800566) in the NQO1 gene, a 609C.T substitution, leading to proline-toserine amino-acid and enzyme activity changes, has been implicated in cancer risk, but individually published studies showed inconclusive results. Methodology/Principal Findings: We performed a meta-analysis of 20 publications with a total of 5,491 cases and 5,917 controls, mainly on gastrointestinal (GI) cancers. We summarized the data on the association between the NQO1 609C.T polymorphism and risk of GI cancers and performed subgroup analyses by ethnicity, cancer site, and study quality. We found that the variant CT heterozygous and CT/TT genotypes of the NQO1 609 C.T polymorphism were associated with a modestly increased risk of GI cancers (CT vs. CC: OR = 1.10, 95 % CI = 1.01 – 1.19, P heterogeneity = 0.27, I 2 = 0.15; CT/TT vs. CC: OR = 1.11, 95%CI = 1.02 – 1.20, Pheterogeneity = 0.14; I 2 = 0.27). Following further stratified analyses, the increased risk was only observed in subgroups of Caucasians, colorectal cancer in Caucasians, and high quality studies. Conclusions: This meta-analysis suggests that the NQO1 609T allele is a low-penetrance risk factor for GI cancers. Although the effect on GI cancers may be modified by ethnicity and cancer sites, small sample seizes of the subgroup analyse

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

Variations in Helicobacter pylori Cytotoxin-Associated Genes and Their Influence in Progression to Gastric Cancer: Implications for Prevention

Helicobacter pylori (HP) is a bacterium that colonizes the human stomach and can establish a long-term infection of the gastric mucosa. Persistent Hp infection often induces gastritis and is associated with the development of peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. Virulent HP isolates harbor the cag (cytotoxin-associated genes) pathogenicity island (cagPAI), a 40 kb stretch of DNA that encodes components of a type IV secretion system (T4SS). This T4SS forms a pilus for the injection of virulence factors into host target cells, such as the CagA oncoprotein. We analyzed the genetic variability in cagA and other selected genes of the HP cagPAI (cagC, cagE, cagL, cagT, cagV and cag Gamma) using DNA extracted from frozen gastric biopsies or from clinical isolates. Study subjects were 95 cagA+ patients that were histologically diagnosed with chronic gastritis or gastric cancer in Venezuela and Mexico, areas with high prevalence of Hp infection. Sequencing reactions were carried out by both Sanger and next-generation pyrosequencing (454 Roche) methods. We found a total of 381 variants with unambiguous calls observed in at least 10% of the originally tested samples and reference strains. We compared the frequencies of these genetic variants between gastric cancer and chronic gastritis cases. Twenty-six SNPs (11 non-synonymous and 14 synonymous) showed statistically significant differences (P<0.05), and two SNPs, in position 1039 and 1041 of cagE, showed a highly significant association with cancer (p-value = 2.07×10−6), and the variant codon was located in the VirB3 homology domain of Agrobacterium. The results of this study may provide preliminary information to target antibiotic treatment to high-risk individuals, if effects of these variants are confirmed in further investigations

Vagueness in Geography

Some have argued that the vagueness exhibited by geographic names and descriptions such as ''Albuquerque,'' ''the Outback,'' or ''Mount Everest'' is ultimately ontological: these terms are vague because they refer to vague objects , objects with fuzzy boundaries. I take the opposite stand and hold the view that geographic vagueness is exclusively semantic, or conceptual at large. There is no such thing as a vague mountain. Rather, there are many things where we conceive a mountain to be, each with its precise boundary, and when we say ''Everest'' we are just being vague as to which thing we are referring to. This paper defends this view against some plausible objections

Gut-central nervous system axis is a target for nutritional therapies

Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies