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Objective To evaluate the pharmacokinetics of tenofovir alafenamide (TAF) 10 mg with cobicistat and 25 mg without boosting in pregnant and postpartum women with HIV and to characterize TAF placental transfer and infant washout pharmacokinetics. Design Open-label, multicenter phase IV prospective study of TAF pharmacokinetics during pregnancy, postpartum, delivery, and infant washout. Methods Pregnant women receiving TAF 10 mg with cobicistat or TAF 25 mg without boosting as part of clinical care had intensive pharmacokinetic assessments performed during the second and third trimesters, and 6-12 weeks postpartum. Maternal and cord blood samples were collected at delivery, and washout pharmacokinetic samples were collected in infants. TAF concentrations were quantified using liquid chromatography/mass spectrometry. Comparisons between pregnancy and postpartum were made using geometric mean ratios (90% confidence intervals) and Wilcoxon signed-rank tests. Results Thirty-one pregnant women receiving TAF 10 mg with cobicistat-boosting and 27 women receiving TAF 25 mg without boosting were enrolled. TAF exposures did not significantly differ between pregnancy and postpartum when administered as 10 mg with cobicistat. Antepartum TAF exposures with the 25 mg dose were 33-43% lower in comparison with postpartum, but comparable with those measured in nonpregnant adults. TAF was below the lower limit of quantitation in 43 of 44 cord blood, 41 of 45 maternal blood at delivery, and all infant washout samples. Conclusion TAF exposures were comparable or higher than those measured in nonpregnant adults during pregnancy and postpartum. These findings provide reassurance on adequate TAF exposures during pregnancy, and support efforts to expand the use of TAF in pregnant women with HIV.

Background Globally, the number of infected women of childbearing age living with human immunodeficiency virus (HIV) and conceiving on antiretroviral therapy (ART) is increasing. Evidence of ART safety at conception and during pregnancy and adverse pregnancy outcomes remains conflicting. The Promoting Maternal and Infant Survival Everywhere (PROMISE) 1077 breastfeeding (BF) and formula feeding (FF) international multisite trials provide an opportunity to examine the impact of ART at conception on pregnancy outcomes with subsequent pregnancies. Methods The PROMISE 1077BF/1077FF trials were designed to address key questions in the management of HIV-infected women who did not meet clinical guidelines for ART treatment during the time of the trials. After the period of risk of mother-to-child transmission was over, women were randomized to either continue or discontinue ART. We compared subsequent pregnancy outcomes of nonbreastfeeding women randomized to continue ART following delivery, or breastfeeding women randomized to continue ART following breastfeeding cessation who conceived while on ART to women randomized to discontinue ART, who restarted ART after pregnancy was diagnosed. Results Pregnancy outcomes of 939 subsequent pregnancies of 826 mothers were recorded. The intention-to-treat analyses showed increased incidence of low birth weight (, Globally more women living with HIV conceive on antiretroviral therapy (ART). This study reports an increased risk of low birth weight, spontaneous abortion, stillbirth, and neonatal death for women conceiving on ART compared to those not on ART at conception.

BackgroundAntiretroviral therapy (ART) during pregnancy is important for both maternal health and prevention of perinatal HIV-1 transmission; however adequate data on the safety and efficacy of different ART regimens that are likely to be used by pregnant women are scarce. In this trial we compared the safety and efficacy of three antiretroviral regimens started in pregnancy: dolutegravir, emtricitabine, and tenofovir alafenamide fumarate; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; and efavirenz, emtricitabine, and tenofovir disoproxil fumarate.MethodsThis multicentre, open-label, randomised controlled, phase 3 trial was done at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Pregnant women (aged ≥18 years) with confirmed HIV-1 infection and at 14-28 weeks' gestation were eligible. Women who had previously taken antiretrovirals in the past were excluded (up to 14 days of ART during the current pregnancy was permitted), as were women known to be pregnant with multiple fetuses, or those with known fetal anomaly or a history of psychiatric illness. Participants were randomly assigned (1:1:1) using a central computerised randomisation system. Randomisation was done using permuted blocks (size six) stratified by gestational age (14-18, 19-23, and 24-28 weeks' gestation) and country. Participants were randomly assigned to receive either once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir alafenamide fumarate 25 mg; once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; or once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. The primary efficacy outcome was the proportion of participants with viral suppression, defined as an HIV-1 RNA concentration of less than 200 copies per mL, at or within 14 days of delivery, assessed in all participants with an HIV-1 RNA result available from the delivery visit, with a prespecified non-inferiority margin of -10% in the combined dolutegravir-containing groups versus the efavirenz-containing group (superiority was tested in a pre-planned secondary analysis). Primary safety outcomes, compared pairwise among treatment groups, were the occurrence of a composite adverse pregnancy outcome (ie, either preterm delivery, the infant being born small for gestational age, stillbirth, or spontaneous abortion) in all participants with a pregnancy outcome, and the occurrence of grade 3 or higher maternal and infant adverse events in all randomised participants. This trial was registered with ClinicalTrials.gov, NCT03048422.FindingsBetween Jan 19, 2018, and Feb 8, 2019, we enrolled and randomly assigned 643 pregnant women: 217 to the dolutegravir, emtricitabine, and tenofovir alafenamide fumarate group, 215 to the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group, and 211 to the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group. At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), the median HIV-1 RNA concentration among participants was 902·5 copies per mL (152·0-5182·5; 181 [28%] of 643 participants had HIV-1 RNA concentrations of

espanolEn la decada de 1950 aparece la imagen del joven rebelde en el cine estadounidense. Este estudio se propone aportar elementos para comprender las razones de su origen y ahondar en lo que puede transmitir de la sociedad estadounidense de aquellos anos. Bajo una metodologia cualitativa, fueron analizadas, por un lado, una seleccion de peliculas protagonizadas por jovenes rebeldes correspondientes a la decada de 1950 y, por otro lado, una serie de articulos sobre estas realizados por criticos de cine de la epoca en la revista Variety y en el periodico The New York Times. A partir de una revision historica enfocada en los valores arraigados en la estructura social de los Estados Unidos, se eligio como categorias de analisis el individualismo y, particularmente, el protestantismo, y con base en ellas se contrasto la informacion primaria para rastrear continuidades o discrepancias. Mientras que algunas investigaciones rescatan el sustrato contestatario de la representacion del joven rebelde en la pantalla, viendo en ellas una reivindicacion juvenil, los resultados del presente estudio senalan, en cambio, un mayor influjo de los adultos, quienes imprimieron en la imagen del joven rebelde sus preocupaciones e idealizaciones respecto a sus hijos y los jovenes en general, a la vez que la revistieron de valores tradicionales estadounidenses. El protagonismo que cobro la imagen del joven rebelde en aquella epoca parece responder a un contexto historico que promovio la angustia en los adultos de aquel entonces en torno a la familia y las nuevas generaciones EnglishIn the 1950s, the image of the young rebel appeared in American cinema. This study thus offers the elements to understand the reasons for its origin and delve into what it can convey about American society in the given period. By using a qualitative methodology, first, a selection of films starring young rebels from the 1950s and, second, a series of articles on these films by critics from that period in Variety magazine and The New York Times were analyzed. Employing a historical review focused on the values rooted in the social structure of the United States, individualism and, particularly, Protestantism were selected as analysis categories. Based on them, the primary information was contrasted to track continuities or discrepancies. While some research studies reclaim the contentious substratum of the representation of the young rebel in films, seeing in them a vindication of youth, the results of this study indicate a greater influx of adults instead who branded the image of the young rebel with their concerns and idealizations regarding their children and youth in general and clothed this image with traditional American values. The leading role that the image of the young rebel played at that time seems to respond to a historical context that promoted the anguish in adults during that period regarding American families and the new generations. portuguesNa decada de 1950 aparece a imagem do jovem rebelde no cinema estado-unidense. Este estudo propoe-se aportar elementos para compreender os motivos de sua origem e aprofundar no que pode transmitir da sociedade estado-unidense daqueles anos. Sob uma metodologia qualitativa, foram analisadas, por um lado, uma selecao de filmes protagonizadas por jovens rebeldes correspondentes a decada de 1950 e, por outro lado, uma serie de artigos sobre estas realizados por criticos de cinema da epoca na revista Variety e no jornal The New York Times. A partir de uma revisao historica enfocada nos valores arraigados na estrutura social dos Estados Unidos, se elege como categorias de analise o individualismo e, particularmente, o protestantismo, e com base nelas se contrastou a informacao primaria para rastrear continuidades ou discrepâncias. Enquanto algumas pesquisas resgatam o substrato contestatario da representacao do jovem rebelde no ecra, vendo nelas uma reivindicacao juvenil, os resultados do presente estudo assinalam, por outro lado, um maior influxo dos adultos, quem imprimiram na imagem do jovem rebelde suas preocupacoes e idealizacoes respeito aos seus filhos e aos jovens em geral, ao mesmo tempo que a revestiram de valores tradicionais estado-unidenses. O protagonismo que tomou a imagem do jovem rebelde naquela epoca parece responder a um contexto historico que promoveu a angustia nos adultos daquela epoca sobre a familia e as novas geracoes.

In the case of many Colombian cities, the foundational grid layout remained the organizing principle of the urban form until the 20th century. In the theoretical model of tower and slab it would be possible to recognize an agreement on the idea that the modern city could emerge as an extended metamorphosis of the traditional city and not against it. The circumstances in which the modern movement managed to settle in Colombia is the subject of the second article prepared especially for the magazine by a group of Colombian research architects led by professors Hugo Mondragón and Rodrigo Cortés. En el caso de muchas ciudades colombianas, el trazado fundacional se mantuvo como principio ordenador de la forma urbana hasta entrado el siglo XX. En el modelo teórico de placa y torre resultaría posible reconocer un acuerdo disciplinar en torno a la idea de que la ciudad moderna podría surgir como una metamorfosis proyectada de la ciudad tradicional y no en contra de ella. Las circunstancias en que la modernidad logró asentarse en Colombia es el tema del segundo artículo preparado especialmente para la revista por un grupo de arquitectos investigadores colombianos liderados por los académicos Hugo Mondragón y Rodrigo Cortés.

The impact of healthcare reform under the Affordable Care Act (ACA) on individuals living in cities has not yet been quantified by local Departments of Health. This makes it difficult for safety net sources of healthcare, such as free clinics, to plan for the future. Therefore, members of Clinica Esperanza/Hope Clinic conducted a survey in predominantly Latino communities of South and West Providence, RI, using a convenience sample method (N = 206). Survey results were compared to a prior survey conducted in the same communities prior to ACA implementation. Despite gains due to Obamacare, a much higher level of uninsurance was reported in this survey than has been reported statewide. In 2014, as compared to 2010, 48% vs. 95% of respondents reported being uninsured, and more held private (20% vs. 5%) or government-subsidized health insurance (32% vs. 1%). Undocumented immigration status and cost were the two most commonly reported reasons for remaining uninsured under the ACA. First-generation immigrants living in urban centers are still reporting significantly higher rates of uninsurance (48%) than the general population in RI (7.4%).

Este artículo describe los componentes básicos de la estructura ecológica de la Sabana de Bogotá y su relación con la latitud y las condiciones de topografía que generan el clima particular del lugar, exponiendo algunos aspectos relevantes de las relaciones tensas y contradictorias que con tales componentes han establecido el crecimiento urbano y el aumento de población, invitando a establecer un compromiso del ejercicio local de la arquitectura para asumir con respeto la estructura ecológica del territorio.AbstractThis article describes the main components of the ecological structure of the Bogotá Plateau related to the latitude and topographic conditions that create its specific climate. It introduces outstanding aspects of the tense and contradictory relationships built between urban growth, population increase and these components, calling for a commitment of respect of local architecture to the territory’s ecological structure.