Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.

Age in antiretroviral therapy programmes in South Africa: a retrospective, multicentre, observational cohort study.

BACKGROUND As access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the effect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the effect of age on mortality of patients on ART in South Africa and whether this effect is mediated by baseline immunological status. METHODS In this retrospective cohort analysis, we studied HIV-positive patients aged 16-80 years who started ART for the first time in six large South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, in KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three hospitals, and a large rural cohort). The primary outcome was mortality. We ascertained patients' vital status through linkage to the National Population Register. We used inverse probability weighting to correct mortality for loss to follow-up. We estimated mortality using Cox's proportional hazards and competing risks regression. We tested the interaction between baseline CD4 cell count and age. FINDINGS Between Jan 1, 2004, and Dec 31, 2013, 84,078 eligible adults started ART. Of these, we followed up 83,566 patients for 174,640 patient-years. 8% (1817 of 23,258) of patients aged 16-29 years died compared with 19% (93 of 492) of patients aged 65 years or older. The age adjusted mortality hazard ratio was 2·52 (95% CI 2·01-3·17) for people aged 65 years or older compared with those 16-29 years of age. In patients starting ART with a CD4 count of less than 50 cells per μL, the adjusted mortality hazard ratio was 2·52 (2·04-3·11) for people aged 50 years or older compared with those 16-39 years old. Mortality was highest in patients with CD4 counts of less than 50 cells per μL, and 15% (1103 of 7295) of all patients aged 50 years or older starting ART were in this group. The proportion of patients aged 50 years or older enrolling in ART increased with successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13, comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304 (14%) of 44,909 patients still alive and in care were aged 50 years or older. INTERPRETATION Health services need reorientation towards HIV diagnosis and starting of ART in older individuals. Policies are needed for long-term care of older people with HIV. FUNDING National Institutes of Health (National Institute of Allergy and Infectious Diseases), US Agency for International Development, and South African Centre for Epidemiological Modelling and Analysis.

Teaching art and history to photonics students

The case to be reported in this paper is the teaching of topics involving the relation among Photonics, its history, the international situation and the artistic movements in each period. These kind of new studies correspond to a new tendency in teaching interdisciplinary topics to students coming from different areas. Two main courses, one in History and other one in Art, will be taken as examples. Theses two courses have been taught for several years in Madrid, Spain, for Telecomm students and the results have been very satisfactory

La identificaciónde de los daños estructurales, herramienta de la nueva atribución de responsabilidades : análisis crítico de la transición del art. 1591 cc al art. 17 LOE

RESUMEN Su objetivo esencial: Regular el proceso de la edificación, está basado en 3 grandes pilares: 1.- Completar la configuración legal de los agentes que intervienen en el mismo, fijando sus obligaciones para así establecer las responsabilidades. 2.- Fomentar la calidad de los edificios. 3.- Fijar las garantías a los usuarios frente a los posibles daños. Estos tres fundamentos están intensamente relacionados, ya que, las obligaciones y responsabilidades de los agentes son la base de la constitución de las garantías a los usuarios, definidas mediante los requisitos básicos que deben satisfacer los edificios. Partiendo del análisis cualitativo y cuantitativo del grado de cumplimiento del objetivo de la nueva Ley, elaborado a través del estudio de sus tres pilares fundamentales, proponemos medidas tendentes a la plena entrada en vigor de la misma. Para ello se deberá desarrollar el Real Decreto previsto en la Disposición Adicional 2ª, una vez conseguido el grado de madurez de los sectores de la edificación y del seguro. En todo este proceso de estudio hemos podido apreciar que la objetiva identificación de los daños y en especial los que afectan la estabilidad del edificio, constituye una herramienta fundamental para la correcta atribución de responsabilidades a los agentes, basada en la aplicación de los tres grados de responsabilidad “ex lege” por daños materiales y sus plazos de prescripción surgidos del nuevo régimen impuesto por el art. 17 LOE Para avalar esta propuesta hemos analizado: 1.- El entorno económico, general y pormenorizado al sector de la edificación, en Europa y España durante el período comprendido entre los años 1990 y 2013, años previos y posteriores a la entrada en vigor de la Ley, dada la influencia de los ciclos de actividad producidos en la regulación del sector, las responsabilidades atribuidas a los agentes, el fomento de la calidad y las garantías ofrecidas a los adquirentes. 2.- Las diversas legislaciones sobre responsabilidades y garantías de los agentes de la edificación en los países de nuestro entorno económico. 3.- La gestación de la LOE, incidiendo en la evolución de los últimos borradores y su tramitación parlamentaria. 4.- El desarrollo doctrinal de la Transición desde el régimen de responsabilidades, fijado por el art. 1591 de Código Civil, y su Jurisprudencia, hacia el nuevo régimen de responsabilidades establecido por el art. 17 LOE. En esta tarea además de apreciar la asimilación, por parte de los Jueces y Magistrados, de los principios doctrinales de la LOE, hemos observado la labor de los peritos, de cuya experta identificación de las causas de los daños depende la justa y eficaz atribución de responsabilidades. 5 -. El grado de eficacia de la LOE a la vista de la estadística siniestral, de la que ya hay datos consolidados, tras la cancelación de casi 15.000 expedientes de reclamación a Arquitectos. 6 -. También hemos estudiado el grado de cumplimiento con el usuario y propietario de las garantías previstas en el art. 19 de la Ley y en la D.A. 1ª, los efectos reales alcanzados y las tareas pendientes por delante. Analizando la atribución de responsabilidades a los agentes de la edificación, dentro del primer pilar fundamental de la LOE, hemos estudiado las actuaciones de los peritos expertos y su incidencia en este objetivo, previa selección de casos de gran interés y dificultad. Fruto de ello se han formulado propuestas tendentes a la especialización de este colectivo, evitando conductas “irregulares” que tanto daño provocan a los agentes reclamados como a los propietarios afectados. Este daño es evidente pudiendo ocasionar condenas injustas, enriquecimientos ilícitos o bien falsas expectativas de satisfacción de daños mal dictaminados y costosas e ineficaces reparaciones. De cara a la consecución del pilar de la calidad de la edificación, mediante los requisitos básicos planteados por la LOE y desarrollados por el Código Técnico de la Edificación (Real Decreto 314/2006, de 17 de marzo), hemos procesado datos de expedientes de reclamaciones por daños que afectan a edificios ejecutados bajo el nuevo régimen LOE. Con esta base se han analizado las causas generadoras de las diversas lesiones y su frecuencia para que de este análisis puedan establecerse pautas de actuación para su prevención. Finalmente, tras demostrar que las garantías obligatorias impuestas por la LOE sólo abarcan un pequeño porcentaje de los posibles daños a la edificación, insistimos en la necesidad de la plena eficacia de la Ley mediante la aprobación de todas las garantías previstas y para todo tipo de edificaciones. En suma, se ha diseñado la tesis como una matriz abierta en la que podremos continuar incorporando datos de la evolución de la doctrina, la jurisprudencia y la estadística de los daños en la edificación. ABSTRACT The approval of Law 38/1999 on November 5, 1999, (Official Gazette BOE 266/1999 of 11.6.1999, p. 38925), was the culmination of a long period of over 20 years of gestation for which deep agreements were needed between all stakeholders affected. Although several parliamentary groups denounced its incomplete approval, regarding mandatory guarantees to the purchaser, its enactment caused general satisfaction among most of the the building agents. This assessment remains after fourteen years since its partial enactment. Its essential purpose, “to regulate the building process”, is based on 3 pillars: 1.- To complete the legal configuration of the agents involved in it, setting their obligations in order to establish their responsibilities. 2.- To promote the buildings quality. 3.- To specify users´guarantees against possible buildings damage. These three issues are strongly related, since the obligations and responsibilities of the actors are the basis of the users’guarantees constitution, defined by the basic performance required by buildings. Based on the qualitative and quantitative analysis of the fulfillment of the new law’s objectives, made by monitoring the three pillars, we propose measures to the full enactment of this Directive, by the development of the Royal Decree, provided in its Second Additional Provision, once maturity in the sectors of the building and insurance is achieved. Throughout this process of study we have seen that the skill identification of damage, particularly those affecting the stability of the building, is an essential tool for the proper allocation of responsibilities of the new regime installed by the art. 17 LOE, based on the application of the three degrees of responsibility "ex lege" for property damage and limitation periods. To support this proposal, we have analyzed: 1.- The evolution of the building sector in Europe and Spain during the years before and after the enactment of the Law, due to the influence of cycles of activity produced in industry regulation, the responsibilities attributed to agents, promotion of the quality and the assurances given to acquirers. 2.- The scope of various laws on liability and building agents warranties in the countries of our economic environment. 3.- The long period of LOE generation, focusing on the developments in recent drafts and parliamentary procedure. 4.- The doctrinal development in the Transition from the regime of responsibilities, set by art. 1591 of the Civil Code, and its Jurisprudence, to the new liability regime established by art. 17 LOE. In this task, while we have noted assimilation by the Judges and Magistrates of the doctrinal principles of the LOE, we have also analyzed the work of experts, whose skilled identification of the damage causes helps the fair and efficient allocation of responsibilities. 5 - The effectiveness of the LOE based on knowledge of the siniestral statistics, which are already consolidated data, after the cancellation of nearly 15,000 claims to Architects. 6.- We have also studied the degree of compliance with the user and owner guarantees, established in art. 19 and the D.A. 1th of the LOE, exposing the real effects achieved and the pending tasks ahead. Analyzing the allocation of the building agents´ responsibilities, within the first cornerstone of the LOE, we have studied the expert witnesses actions and their impact on this duty, selecting cases of great interest and difficulty in this aim. The result of this enterprise has been to propose the specialization of this group, avoiding "irregular" behaviors that create as much damage as the agents claimed to affected owners. This damage is evident and can cause wrong convictions, illicit enrichment, false expectations and inefficient and costly damage repairs. In order to achieve the pillar of building quality through the basic requirements set by the LOE and developed by the Technical Building Code (Royal Decree 314/ 2006 of 17 March), we have analyzed records of damage claims involving buildings executed under the new regime LOE. On this basis we have analyzed the root causes of various damages and their frequency, from these data it will be easy to propose lines of action for prevention. Finally, after demonstrating that mandatory warranties imposed by LOE cover only a small percentage of the potential building damage, we emphasize the need for the full effectiveness of the Law by the obligation all the guarantees provided in the art. 19 LOE, and for all types of buildings. In conclusion, this thesis is designed as an open matrix in which we will continue including data on the evolution of the doctrine, jurisprudence and the statistics of the damage to the building.

Rotten Symbol Mongering: Scapegoating in Post-9/11 American War Literature

A rhetorical approach to the fiction of war offers an appropriate vehicle by which one may encounter and interrogate such literature and the cultural metanarratives that exist therein. My project is a critical analysis—one that relies heavily upon Kenneth Burke’s dramatistic method and his concepts of scapegoating, the comic corrective, and hierarchical psychosis—of three war novels published in 2012 (The Yellow Birds by Kevin Powers, FOBBIT by David Abrams, and Billy Lynn’s Long Halftime Walk by Ben Fountain). This analysis assumes a rhetorical screen in order to subvert and redirect the grand narratives the United States perpetuates in art form whenever it goes to war. Kenneth Burke’s concept of ad bellum purificandum (the purification of war) sought to bridge the gap between war experience and the discourse that it creates in both art and criticism. My work extends that project. I examine the symbolic incongruity of convenient symbols that migrate from war to war (“Geronimo” was used as code for Osama bin Laden’s death during the S.E.A.L team raid; “Indian Country” stands for any dangerous land in Iraq; hajji is this generation’s epithet for the enemy other). Such an examination can weaken our cultural “symbol mongering,” to borrow a phrase from Walker Percy. These three books, examined according to Burke’s methodology, exhibit a wide range of approaches to the soldier’s tale. Notably, however, whether they refigure the grand narratives of modern culture or recast the common redemptive war narrative into more complex representations, this examination shows how one can grasp, contend, and transcend the metanarrative of the typical, redemptive war story.