A Generalization of Linear Multistep Methods

A generalization of the methods that are currently available to solve systems of ordinary differential equations is made. This generalization is made by constructing linear multistep methods from an arbitrary set of monotone interpolating and approximating functions. Local truncation error estimates as well as stability analysis is given. Specifically, the class of linear multistep methods of the Adams and BDF type are discussed

La aplicación del principio precautorio y su influencia en la legislación ambiental peruana, entre los años 2015-2021

En el presente trabajo de investigación, se realizó un análisis de la normativa ambiental peruana y su eficacia respecto a hechos que generan un menoscabo al medio ambiente, ello con el fin de comprender el contexto en el cual nos encontramos donde los problemas o daños ambientales son constantes, asimismo, se analizó la aplicación del principio precautorio en resoluciones administrativas ambientales y sentencias del Tribunal Constitucional sobre perjuicio al medio ambiente y la salud. El principio precautorio se considera un principio relevante para prevenir los daños ambientales, porque su aplicación se presenta antes de que se produzcan hechos que involucren acciones directas al ambiente por realización de otra actividad económica, inclusive se aplicaría antes que el principio de prevención. Sin embargo, por diversos motivos, los daños igualmente pueden ser ocasionados, y es cuando el organismo público encargado de la fiscalización ambiental interviene. En ese sentido, la finalidad del presente trabajo es determinar como el principio precautorio de la legislación ambiental peruana y su aplicación en resoluciones administrativas dentro del período 2015 al 2020. Para el presente trabajo, se delimitó como población a la normativa ambiental, jurisprudencias y doctrinas nacionales, que contribuyan al sustento del impacto de la aplicación del principio precautorio, de igual manera, se analizó la doctrina comparada ambiental de Argentina, Costa Rica, México y Colombia, con la finalidad de evidenciar la realidad ambiental y la interacción con este principio. La presente tesis tiene un enfoque cualitativo – descriptivo, debido que, para el análisis se procedió a la recolección de información de diversas publicaciones de relevancia para el tema, resoluciones administrativas con referencia a regulaciones del contexto peruano y se buscó realizar una comprensión de los cuerpos normativos internacionales que tienen como objeto la protección del medio ambiente, a través de la aplicación del principio precautorio. La conclusión obtenida del presente trabajo de investigación versa en el déficit de la relación de la legislación ambiental peruana sobre la aplicación del principio precautorio en la realidad ambiental peruana, y cómo a pesar de contar con una normativa, su ambigüedad no permite que se establezcan medidas asertivas para prevenir daños lesivos que se generen en detrimento o menoscabo del medio ambiente y la población peruana.In this research work, an analysis was made of Peruvian environmental regulations and their effectiveness with respect to facts that generate environmental damage, in order to understand the context in which we find ourselves where environmental problems or damages are constant, also, the application of the precautionary principle was analyzed in environmental administrative resolutions and sentences of the Constitutional Court on damage to the environment and health. The precautionary principle is considered a relevant principle to prevent environmental damages, because its application occurs before the occurrence of facts that involve direct actions to the environment by other economic activity, and it would even be applied before the prevention principle. However, for various reasons, damage can also be caused, and that is when the public agency in charge of environmental control intervenes. In this sense, the purpose of this paper is to determine the precautionary principle of Peruvian environmental legislation and its application in administrative resolutions within the period 2015 to 2020. For the present work, the environmental regulations, jurisprudences and national doctrines that contribute to the support of the impact of the application of the precautionary principle were delimited as population, likewise, the comparative environmental doctrine of Argentina, Costa Rica, Mexico and Colombia was analyzed, with the purpose of evidencing the environmental reality and the interaction with this principle. The present thesis has a qualitative-descriptive approach, due to the fact that, for the analysis, we proceeded to the collection of information from various publications of relevance to the subject, administrative resolutions with reference to regulations of the Peruvian context and we sought to make an understanding of the international normative bodies that have as an object the protection of the environment, through the application of the precautionary principle. The conclusion obtained from this research work deals with the deficit of the relationship of the Peruvian environmental legislation on the application of the precautionary principle in the Peruvian reality, and how in spite of having a regulation, its ambiguity does not allow the establishment of assertive measures to prevent harmful damages that are generated to the detriment of the environment and the Peruvian population

Model Parameters and Outbreak Control for SARS

Control of the 2002–2003 severe acute respiratory syndrome (SARS) outbreak was based on rapid diagnosis coupled with effective patient isolation. We used uncertainty and sensitivity analysis of the basic reproductive number R0 to assess the role that model parameters play in outbreak control. The transmission rate and isolation effectiveness have the largest fractional effect on R0. We estimated the distribution of the reproductive number R0 under perfect isolation conditions. The distribution lies in the interquartile range 0.19–1.08, with a median of 0.49. Even though the median of R0 is \u3c1, we found that 25% of our R0 distribution lies at R0 \u3e 1, even with perfect isolation. This implies the need to simultaneously apply more than one method of control

Three-dimensional cardiac fibre disorganization as a novel parameter for ventricular arrhythmia stratification after myocardial infarction

Aims: Myocardial infarction (MI) alters cardiac fibre organization with unknown consequences on ventricular arrhythmia. We used diffusion tensor imaging (DTI) of three-dimensional (3D) cardiac fibres and scar reconstructions to identify the main parameters associated with ventricular arrhythmia inducibility and ventricular tachycardia (VT) features after MI. Methods and results: Twelve pigs with established MI and three controls underwent invasive electrophysiological characterization of ventricular arrhythmia inducibility and VT features. Animal-specific 3D scar and myocardial fibre distribution were obtained from ex vivo high-resolution contrast-enhanced T1 mapping and DTI sequences. Diffusion tensor imaging-derived parameters significantly different between healthy and scarring myocardium, scar volumes, and left ventricular ejection fraction (LVEF) were included for arrhythmia risk stratification and correlation analyses with VT features. Ventricular fibrillation (VF) was the only inducible arrhythmia in 4 out of 12 infarcted pigs and all controls. Ventricular tachycardia was also inducible in the remaining eight pigs during programmed ventricular stimulation. A DTI-based 3D fibre disorganization index (FDI) showed higher disorganization within dense scar regions of VF-only inducible pigs compared with VT inducible animals (FDI: 0.36; 0.36-0.37 vs. 0.32; 0.26-0.33, respectively, P = 0.0485). Ventricular fibrillation induction required lower programmed stimulation aggressiveness in VF-only inducible pigs than VT inducible and control animals. Neither LVEF nor scar volumes differentiated between VF and VT inducible animals. Re-entrant VT circuits were localized within areas of highly disorganized fibres. Moreover, the FDI within heterogeneous scar regions was associated with the median VT cycle length per animal (R2 = 0.5320). Conclusion: The amount of scar-related cardiac fibre disorganization in DTI sequences is a promising approach for ventricular arrhythmia stratification after MI.The CNIC (Madrid, Spain) is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation. The CNIC and the BSC (Barcelona, Spain) are Severo Ochoa Centers of Excellence (SEV-2015-0505 and SEV-2011-0067, respectively). This study was supported by grants from Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (RD12/0042/0036, CB16/11/00458), Spanish Ministry of Science, Innovation and Universities (SAF2016-80324-R, PI16/02110, and DTS17/00136), and by the European Commission [ERA-CVD Joint Call (JTC2016/APCIN-ISCIII-2016), grant#AC16/00021]. The study was also partially supported by the Fundacion Interhospitalaria para la Investigacion Cardiovascular (FIC, Madrid, Spain), the Spanish Society of Cardiology (Dr. Pedro Zarco award) and the Heart Rhythm section of the Spanish Society of Cardiology (DFR). J.J. is supported by R01 Grant HL122352 from the National Heart Lung and Blood Institute, USA National Institutes of Health. J.A.S. is funded by the CompBioMed project, H2020-EU.1.4.1.3 European Union's Horizon 2020 research and innovation programme, grant#675451. D.G.L. has received financial support through the 'la Caixa' Fellowship Grant for Doctoral Studies, 'la Caixa' Banking Foundation, Barcelona, Spain.S

Risk thresholds for alcohol consumption : combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies

Background Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease. Methods We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12.5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5.6 years [5th-95th percentile 1.04-13.5]) from 71 011 participants from 37 studies. Findings In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5.4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1.14, 95% CI, 1.10-1.17), coronary disease excluding myocardial infarction (1.06, 1.00-1.11), heart failure (1.09, 1.03-1.15), fatal hypertensive disease (1.24, 1.15-1.33); and fatal aortic aneurysm (1.15, 1.03-1.28). By contrast, increased alcohol consumption was loglinearly associated with a lower risk of myocardial infarction (HR 0.94, 0.91-0.97). In comparison to those who reported drinking >0-100-200-350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively. Interpretation In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

BACKGROUND Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia (N = 11,095), using a single image analysis protocol. METHODS We included T1-weighted data from 46 datasets (5,080 affected individuals and 6,015 controls) from the ENIGMA Consortium. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Analyses were also performed with respect to the use of antipsychotic medication and other clinical variables, as well as age and sex. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029). RESULTS Small average differences between cases and controls were observed for asymmetries in cortical thickness, specifically of the rostral anterior cingulate (d = −0.08, pFDR = 0.047) and the middle temporal gyrus (d = −0.07, pFDR = 0.048), both driven primarily by thinner cortices in the left hemisphere in schizophrenia. These asymmetries were not significantly associated with the use of antipsychotic medication or other clinical variables. Older individuals with schizophrenia showed a stronger average leftward asymmetry of pallidum volume than older controls (d = 0.08, pFDR = 9.0 × 10−3). The multivariate analysis revealed that 7% of the variance across all structural asymmetries was explained by case-control status (F = 1.87, p = 1.25 × 10−5). CONCLUSIONS Altered trajectories of asymmetrical brain development and/or lifespan asymmetry may contribute to schizophrenia pathophysiology. Small case-control differences of brain macro-structural asymmetry may manifest due to more substantial differences at the molecular, cytoarchitectonic or circuit levels, with functional relevance for lateralized cognitive processes

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder