News from compositions, the R package

The R-package “compositions”is a tool for advanced compositional analysis. Its basic functionality has seen some conceptual improvement, containing now some facilities to work with and represent ilr bases built from balances, and an elaborated subsys- tem for dealing with several kinds of irregular data: (rounded or structural) zeroes, incomplete observations and outliers. The general approach to these irregularities is based on subcompositions: for an irregular datum, one can distinguish a “regular” sub- composition (where all parts are actually observed and the datum behaves typically) and a “problematic” subcomposition (with those unobserved, zero or rounded parts, or else where the datum shows an erratic or atypical behaviour). Systematic classification schemes are proposed for both outliers and missing values (including zeros) focusing on the nature of irregularities in the datum subcomposition(s). To compute statistics with values missing at random and structural zeros, a projection approach is implemented: a given datum contributes to the estimation of the desired parameters only on the subcompositon where it was observed. For data sets with values below the detection limit, two different approaches are provided: the well-known imputation technique, and also the projection approach. To compute statistics in the presence of outliers, robust statistics are adapted to the characteristics of compositional data, based on the minimum covariance determinant approach. The outlier classification is based on four different models of outlier occur- rence and Monte-Carlo-based tests for their characterization. Furthermore the package provides special plots helping to understand the nature of outliers in the dataset. Keywords: coda-dendrogram, lost values, MAR, missing data, MCD estimator, robustness, rounded zeros

La inmunidad de jurisdiccion como fuente de responsabilidad patrimonial del estado en Colombia

El acuerdo militar entre Colombia y los Estados Unidos, la Ley 418 de 1997, la ley 975 de 2005, y la amnistia e indulto como casos de inmunidad de jurisdicción para establecer los títulos de imputación que pueden configurar una responsabilidad del estado patrimonial en Colombia.

Responsabilidad penal médica, imputación objetiva y atención médico asistencial a personas pertenecientes a grupos armados al margen de la ley

En una reciente decisión, la Corte Suprema de Justicia Colombiana condenó a un médico por haber prestado sus servicios profesionales a personas pertenecientes a un grupo armado al margen de la Ley. En el presente escrito revisamos ese fallo a la luz de la teoría de la imputación objetiva para diferir de la opinión del Alto Tribunal, por cuanto entendemos que el ejercicio de la medicina jamás constituirá un riesgo desaprobado y éste es un elemento necesario para que pueda hablarse de un delito.

Apuntes sobre el delito de falsedad ideológica. A propósito del fallo del 16 de marzo de 2011 emanado de la Corte Suprema de Justicia, Sala de Casación Penal

El pasado 16 de marzo de 2011, la Corte Suprema de Justicia se ocupó de un caso donde se califica a un Juez con el delito de falsedad ideológica en documento público. En este fallo se trazaron los lineamientos fundamentales de este delito, mismos que son analizados en el presente escrito para concluir que si bien el resultado del proceso en la Corte −la condena del procesado− es correcto, es necesario superar el entendimiento causal de este delito para interpretarlo de acuerdo con la moderna teoría de la imputación objetiva.

La responsabilidad patrimonial del Estado por la falla en la prestación del servicio médico asistencial. Acto médico defectuoso en las entidades de salud del Estado. -Una visión desde la doctrina y desarrollo jurisprudencial del Consejo de Estado-.

La complejidad que supone abarcar el estudio de la responsabilidad patrimonial del Estado en el ámbito médico sanitario, hace preciso prestar atención a ciertos temas que resultan especialmente relevantes y que han sido decantados jurisprudencialmente por el Honorable Consejo de Estado. De esta manera el presente trabajo desarrolla temas descollantes y novedosos en materia de imputabilidad como viene a ser la prueba de la falla médica mediante la teoría "res ipsa loquitur"; la prueba del nexo causal a través de la prueba indiciaria y la teoría de la probabilidad preponderante. Así mismo se estudian los diversos tipos de daños antijurídicos que pueden darse dentro de la prestación médica a cargo del Estado, destacando especialmente la lesión al derecho a recibir una atención oportuna y eficaz, la pérdida de una oportunidad debida a la no obtención del consentimiento informado del paciente, lo que supone, a su vez, el cercenamiento del derecho de este a elegir someterse o no a determinado tratamiento, previo valoración de pros y contras de la terapia sugerida por el galeno (principio de no agravación). Así mismo se analizanlas hipótesis de daños antijurídicos derivados del error en el diagnóstico, la falla por la omisión de las entidades de control y vigilancia, falla en gineco-obstetricia, así como las hipótesis de responsabilidad objetiva del Estado por óblito quirúrgico, para finalmente tratar el tema novedoso del alea terapéutica con sus particulares características y eventual aplicabilidad en el sistema jurídico colombiano.

PTPN22 Association in Systemic Lupus Erythematosus (SLE) with Respect to Individual Ancestry and Clinical Sub-Phenotypes

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with European ancestry. Since the rs2476601 risk allele frequency differs dramatically across ethnicities, we assessed robustness of PTPN22 association with SLE and its clinical subphenotypes across four ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and 7369 controls from in European-Americans (EA), African-Americans (AA), Asians (AS), and Hispanics (HS). We performed imputation-based association followed by conditional analysis to identify independent associations. Significantly associated SNPs were tested for association with SLE clinical sub-phenotypes, including autoantibody profiles. Multiple testing was accounted for by using false discovery rate. We successfully imputed and tested allelic association for 107 SNPs within the PTPN22 region and detected evidence of ethnic-specific associations from EA and HS. In EA, the strongest association was at rs2476601 (P = 4.761029, OR = 1.40 (95% CI = 1.25–1.56)). Independent association with rs1217414 was also observed in EA, and both SNPs are correlated with increased European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis-eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67–0.94). No significant associations were observed in AA or AS. Case-only analysis using lupus-related clinical criteria revealed differences between EA SLE patients positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG .20) versus negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced when these cases were compared to controls (P = 2.761025, OR = 2.11). Our results validate that rs2476601 is the most significantly associated SNP in individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be associated with SLE. Further studies are required to confirm the involvement of rs2476601 with aCL IgG.

Preferential binding to elk-1 by sle-associated il10 risk allele upregulates il10 expression

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans.

Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4

We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P = 1.71×10-34, OR = 1.43[1.26-1.60]) and rs1234317-T (P = 1.16×10-28, OR = 1.38[1.24-1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5′ region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5′ risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait. © 2013 Manku et al.

La responsabilidad del Estado por el hecho del legislador

Analizar el fenómeno de la responsabilidad del Estado causada por los hechos del legislador ha sido un trabajo desarrollado tanto por la doctrina como por la jurisprudencia internacional a mediados del siglo xx. En Francia, por ejemplo, se presentó el primer antecedente jurisprudencial en el año de 1934. En España, su estudio empezó a gestionarse con la promulgación de la Constitución de 1978, dándose el primer fallo judicial en elaño de 1993. Para el caso colombiano, la Constitución de 1991 introdujo en su artículo 90 el fundamento constitucional de la responsabilidad patrimonial del Estado, sin que esto significase que la jurisprudencia del Consejo de Estado encontrase las bases de esta responsabilidad en diferentes disposiciones de la Constitución de 1886, tales como los artículos 2º, 16 y 30, que consagró el principio de legalidad del Estado para proteger la vida, honra y bienes de los ciudadanos, y garantizar la propiedad privada y los demás derechos adquiridos con el título de derecho. Sin embargo, los primeros fallos relacionados con este título de imputación en Colombia fueron emitidos por el máximo Tribunal de lo Contencioso Administrativo colombiano en el año de 1998 y por la Corte Constitucional a través de la Sentencia C-038 de 2006, providencia judicial que estableció algunas de las características que posee esta figura jurídica.

Aplicación en Colombia de la responsabilidad internacional agravada del Estado por violaciones graves a Derechos Humanos

Al igual que ocurre en los regímenes de responsabilidad Estatal internacional y Regional -SIDH-, donde se hace una distinción entre los hechos ilícitos internacionales y las violaciones a normas Ius cogens, se plantea la posibilidad de aplicar en el régimen interno de responsabilidad estatal la denominada “responsabilidad internacional agravada”, en aquellos casos específicos de violaciones graves a derechos humanos, dada la necesidad de establecer la aludida distinción frente a la imputación del daño al Estado en ese tipo de casos.

El levantamiento del velo en la doctrina y la jurisprudencia ecuatoriana

La persona jurídica es un centro de imputación diferenciado, en el cual se limita la responsabilidad patrimonial de quienes se asocian. sin embargo, a veces esta figura puede ser mal utilizada para alcanzar metas prohibidas por la ley o para perjudicar a terceros. La legislación ha previsto mecanismos para evitar esta utilización indebida de la persona jurídica, pero, excepcionalmente, se dan casos en que la solución legislativa no es suficiente, por lo que, partiendo de los principios generales del derecho de la buena fe, la lealtad y la equidad, la jurisprudencia ha desestimado la personalidad jurídica y ha llegado hasta quienes, amparándose en la figura societaria, han pretendido burlar la ley o abusar del derecho. Se ha desarrollado la teoría del regard of legal entity, que recibe muchos nombres en español (se ha preferido el de levantamiento del velo) que permite al juez, excepcionalmente, levantar el velo que separa al espectador de la realidad, a fin de imponer a los responsables del fraude o el abuso, la responsabilidad que les corresponda. en primer lugar se hace una breve exposición de la teoría, reseñando lo que han dicho los autores, para continuar examinando la situación ecuatoriana, las disposiciones legales aplicables y las sentencias en las cuales los jueces se han referido a esta teoría, y concluir señalando la naturaleza procesal de la figura, la inconveniencia de dictar una ley que la incorpore al ordenamiento jurídico y el riesgo de una utilización masiva e indiscriminada.

La responsabilidad estatal en la Constitución del Ecuador de 2008 (Tema Central)

La Constitución ecuatoriana promulgada el 20 de octubre de 2008 prescribe en el art. 11.9 que la responsabilidad estatal consiste en la reparación de las violaciones a los derechos por la falta o deficiente prestación de servicios públicos o por acciones u omisiones en el ejercicio de potestades públicas, reparación que es integral conforme el principio garantista de protección los derechos previsto en el art. 86.3. El presente estudio aborda aspectos generales de la naturaleza jurídica de la responsabilidad estatal –de la irresponsabilidad a la responsabilidad estatal–, su evolución –de la concepción civil indemnizatoria a la concepción reparadora integral–, y los denominados títulos jurídicos de imputación objetiva –falla del servicio, desequilibrio de las cargas públicas–, que serán de trascendental importancia para la comprensión de nuevo régimen, y cuyos aspectos específicos ameritarían un examen más amplio.

Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk)

Background: Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. Objective: To investigate associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk). Design: Data was available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Results: Median intake of total flavan-3-ols was 1034 mg/d (range: 0 – 8531 mg/d) for men and 970 mg/d (0 – 6695 mg/d) for women, median intake of flavan-3-ol monomers was 233 mg/d (0 – 3248 mg/d) for men and 217 (0 – 2712 mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow up, there were 8463 cardio-vascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI:0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Conclusions: Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk.

Crimes financeiros e política criminal : estudo de acórdãos do TRF da 3ª Região sobre os crimes de gestão fraudulenta e gestão temerária no período de 2001 a 2010

Este trabalho visa produzir conhecimento sobre como o Tribunal Regional Federal da 3ª Região tem decidido sobre dois dos principais crimes afetos à administração das instituições financeiras: gestão fraudulenta e gestão temerária. Trata-se de delitos criticados pela doutrina em razão das falhas de definição dos tipos, desde a edição da Lei 7.492, em 1986. Além disso, a sua previsão legislativa possui características que os aproximam do paradigma do direito penal do risco, ou seja: são crimes de perigo abstrato, que tutelam bem jurídico supra-individual, praticados por administradores detentores do dever de probidade na condução das instituições frente aos riscos inerentes à dinâmica do sistema financeiro. A adoção desse paradigma é controversa na doutrina penal por implicar a flexibilização de garantias do Estado Democrático de Direito sob a perspectiva do paradigma do direito penal tradicional. Diante disso, adota-se a metodologia de análise de conteúdo de decisões para se responder a dois problemas de pesquisa: (1) Quais os critérios adotados pelo Tribunal para a configuração dos crimes? (2) As decisões aproximam-se de algum paradigma de direito penal? As hipóteses objeto de teste são: (1) que o Tribunal considera principalmente a prática da conduta sem analisar a sua potencialidade lesiva sob uma perspectiva ex ante; e, (2) que esse discurso de imputação de responsabilidade aproxima as decisões do paradigma do direito penal do risco, considerados, em contexto, outros elementos presentes nas decisões. Na primeira parte, é feita uma introdução metodológica; na segunda, estabelece-se o referencial teórico; na terceira e na quarta, realizam-se as análises dos resultados quantitativos e qualitativos obtidos com a sua discussão; por fim, procede-se à conclusão, levantando-se novo problema a ser investigado.

Modelagem estocástica do índice de radiação ultravioleta na costa leste do nordeste do Brasil

The increase in ultraviolet radiation (UV) at surface, the high incidence of non-melanoma skin cancer (NMSC) in coast of Northeast of Brazil (NEB) and reduction of total ozone were the motivation for the present study. The overall objective was to identify and understand the variability of UV or Index Ultraviolet Radiation (UV Index) in the capitals of the east coast of the NEB and adjust stochastic models to time series of UV index aiming make predictions (interpolations) and forecasts / projections (extrapolations) followed by trend analysis. The methodology consisted of applying multivariate analysis (principal component analysis and cluster analysis), Predictive Mean Matching method for filling gaps in the data, autoregressive distributed lag (ADL) and Mann-Kendal. The modeling via the ADL consisted of parameter estimation, diagnostics, residuals analysis and evaluation of the quality of the predictions and forecasts via mean squared error and Pearson correlation coefficient. The research results indicated that the annual variability of UV in the capital of Rio Grande do Norte (Natal) has a feature in the months of September and October that consisting of a stabilization / reduction of UV index because of the greater annual concentration total ozone. The increased amount of aerosol during this period contributes in lesser intensity for this event. The increased amount of aerosol during this period contributes in lesser intensity for this event. The application of cluster analysis on the east coast of the NEB showed that this event also occurs in the capitals of Paraiba (João Pessoa) and Pernambuco (Recife). Extreme events of UV in NEB were analyzed from the city of Natal and were associated with absence of cloud cover and levels below the annual average of total ozone and did not occurring in the entire region because of the uneven spatial distribution of these variables. The ADL (4, 1) model, adjusted with data of the UV index and total ozone to period 2001-2012 made a the projection / extrapolation for the next 30 years (2013-2043) indicating in end of that period an increase to the UV index of one unit (approximately), case total ozone maintain the downward trend observed in study period