Risk charts to guide targeted HIV-1 viral load monitoring of ART: development and validation in patients from resource-limited settings.

BACKGROUND HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20% or 40% of patients in seven cohorts of patients starting ART in South Africa, and plotted cut-offs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia and the Asia-Pacific. FINDINGS 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African, from 64% to 93% in the Zambian and from 73% to 96% in the Asia-Pacific cohorts. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia and from 37% to 71% in Asia-Pacific. The area under the receiver-operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia and from 0.77 to 0.92 in Asia Pacific. INTERPRETATION CD4-based risk charts with optimal cut-offs for targeted VL testing may be useful to monitor ART in settings where VL capacity is limited.

Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.

BACKGROUND HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific. RESULTS In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific. CONCLUSIONS CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.

Die Rechtsstellung der Reichspensionäre : (Artikel 33 (5), 3, 14, 19, 123 (1), 131, 134 Grundgesetz. § 77 des Gesetzes zu Art. 131 GG vom 11.5.51)

George Tzschirner

Na 1 Nachlass Max Horkheimer, 637 - "Art and Mass Culture" (p. IX 14.1-2)

"Art and Mass Culture" (GS 4, S. 419-438); 1. Aufsatz, veröffentlicht in: SPSS IX, 1941, S. 290-304; 2. Exzerpt aus: Mortimer Adler, "Art and Prudence", Part II und VI. Typoskript mit handschriftlichen Korrekturen. 18 Blatt;

Na 1 Nachlass Max Horkheimer, 686 - Rosenzweig-Test, "Art Project on Fascist Agitator" (p. IX 148.1-2 - IX 149.1-7)

Zum Rosenzweig-Test, 1945; Brown, J.F.: "Memorandum on the Modification of the Rosenzweig Picture Frustration Test". Typoskript, 3 Blatt; Rosenzweig, Saul. "The Picture-Association Method and Its Application in a Study of Reactions to Frustration.", Sonderdruck aus: Journal of Personality, September 1945, S. 3-23; Materialien zum "Art Project on Fascist Agitator" (1945):; 1. "What is a Fascist Agitator?", a) Typoskript, 1 Blatt, b) Typoskript mit handschriftlichen Korrekturen, 2 Blatt; 2. "Some Traits of the Fascist Agitator". Typoskript, 5 Blatt; 3. "Pamphlet", a) Typoskript, 1 Blatt, b) Typoskript, 1 Blatt, c) Typoskript mit dem Titel 'Devices of the Agitator', 1 Blatt; 4. Max Horkheimer: eigenhändige Notizen über den Agitator, 1 Blatt; 5. "Quotes from the Agitator (pages refer to Leo Löwenthals manuscript vol. III)". Typoskript, 7 Blatt; 6. Adressenlisten, 3 Blatt; 7. Materialien zum 'Agitator-Projekt': Photos, Reproduktionen von Zeichnungen und Zeitungsausschnitten;

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.