Exploring the Equity Effects of VMT Mitigation Measures

In 2018, pursuant to Senate Bill (SB) 743 (2013), the Governor’s Office of Planning and Research (OPR) and the California Natural Resources Agency promulgated regulations and technical guidance that eliminated automobile level of service (LOS) as a transportation impact metric for land development projects under the California Environmental Quality Act (CEQA), and replaced it with Vehicle Miles Traveled (VMT). The authors investigated the equity effects of VMT mitigation measures and developed a framework for evaluating those effects at the project level. The authors then applied the framework to two highway expansion case studies in California. They found that most VMT mitigation would be implemented at least partially within the project impact areas, as well as some disadvantaged communities, but would generally benefit communities outside of the project area, too. Most of the proposed mitigation measures would not displace existing residences or businesses or pose a significant risk of gentrification. Many of the measures showed substantial potential to improve accessibility to jobs, though less potential to improve accessibility to grocery stores. Community engagement and empowerment was harder to gauge. Overall, the five-part framework can provide a first-cut assessment of the equity effects of VMT mitigation measures during the environmental review phase of VMT-generating projects, like roadway expansions.View the NCST Project Webpag

Prognostic accuracy of 70 individual frailty biomarkers in predicting mortality in the Canadian Longitudinal Study on Aging

The frailty index (FI) uses a deficit accumulation approach to derive a single, comprehensive, and replicable indicator of age-related health status. Yet, many researchers continue to seek a single "frailty biomarker" to facilitate clinical screening. We investigated the prognostic accuracy of 70 individual biomarkers in predicting mortality, comparing each with a composite FI. A total of 29,341 individuals from the comprehensive cohort of the Canadian Longitudinal Study on Aging were included (mean, 59.4 ± 9.9 years; 50.3% female). Twenty-three blood-based biomarkers and 47 test-based biomarkers (e.g., physical, cardiac, cardiology) were examined. Two composite FIs were derived: FI-Blood and FI-Examination. Mortality status was ascertained using provincial vital statistics linkages and contact with next of kin. Areas under the curve were calculated to compare prognostic accuracy across models (i.e., age, sex, biomarker, FI) in predicting mortality. Compared to an age-sex only model, the addition of individual biomarkers demonstrated improved model fit for 24/70 biomarkers (11 blood, 13 test-based). Inclusion of FI-Blood or FI-Examination improved mortality prediction when compared to any of the 70 biomarker-age-sex models. Individual addition of seven biomarkers (walking speed, chair rise, time up and go, pulse, red blood cell distribution width, C-reactive protein, white blood cells) demonstrated an improved fit when added to the age-sex-FI model. FI scores had better mortality risk prediction than any biomarker. Although seven biomarkers demonstrated improved prognostic accuracy when considered alongside an FI score, all biomarkers had worse prognostic accuracy on their own. Rather than a single biomarker test, implementation of routine FI assessment in clinical settings may provide a more accurate and reliable screening tool to identify those at increased risk of adverse outcomes

The Interplay Between Neoantigens and Immune Cells in Sarcomas Treated With Checkpoint Inhibition

INTRODUCTION: Sarcomas are comprised of diverse bone and connective tissue tumors with few effective therapeutic options for locally advanced unresectable and/or metastatic disease. Recent advances in immunotherapy, in particular immune checkpoint inhibition (ICI), have shown promising outcomes in several cancer indications. Unfortunately, ICI therapy has provided only modest clinical responses and seems moderately effective in a subset of the diverse subtypes. METHODS: To explore the immune parameters governing ICI therapy resistance or immune escape, we performed whole exome sequencing (WES) on tumors and their matched normal blood, in addition to RNA-seq from tumors of 31 sarcoma patients treated with pembrolizumab. We used advanced computational methods to investigate key immune properties, such as neoantigens and immune cell composition in the tumor microenvironment (TME). RESULTS: A multifactorial analysis suggested that expression of high quality neoantigens in the context of specific immune cells in the TME are key prognostic markers of progression-free survival (PFS). The presence of several types of immune cells, including T cells, B cells and macrophages, in the TME were associated with improved PFS. Importantly, we also found the presence of both CD8+ T cells and neoantigens together was associated with improved survival compared to the presence of CD8+ T cells or neoantigens alone. Interestingly, this trend was not identified with the combined presence of CD8+ T cells and TMB; suggesting that a combined CD8+ T cell and neoantigen effect on PFS was important. DISCUSSION: The outcome of this study may inform future trials that may lead to improved outcomes for sarcoma patients treated with ICI

Case Report: Characterization of known (c.607G>C) and novel (c.416C>G) ELANE mutations in two Mexican families with congenital neutropenia

The most common causes of congenital neutropenia are mutations in the ELANE (Elastase, Neutrophil Expressed) gene (19p13.3), mostly in exon 5 and the distal portion of exon 4, which result in different clinical phenotypes of neutropenia. Here, we report two pathogenic mutations in ELANE, namely, c.607G>C (p.Gly203Arg) and a novel variant c.416C>G (p.Pro139Arg), found in two Mexican families ascertained via patients with congenital neutropenia who responded positively to the granulocyte colony-stimulating factor (G-CSF) treatment. These findings highlight the usefulness of identifying variants in patients with inborn errors of immunity for early clinical management and the need to rule out mosaicism in noncarrier parents with more than one case in the family

The Social Vulnerability Index, Mortality and Disability in Mexican Middle-Aged and Older Adults

The social vulnerability index (SVI) independently predicts mortality and others adverse outcomes across different populations. There is no evidence that the SVI can predict adverse outcomes in individuals living in countries with high social vulnerability such as Latin America. The aim of this study was to analyze the association of the SVI with mortality and disability in Mexican middle-aged and older adults. This is a longitudinal study with a follow-up of 47 months, the Mexican Health and Aging Study, including people over the age of 40 years. A SVI was calculated using 42 items stratified in three categories low (0.47) vulnerability. We examined the association of SVI with three-year mortality and incident disability. Cox and logistic regression models were fitted to test these associations. We included 14,217 participants (58.4% women) with a mean age of 63.9 years (+/- SD 10.1). The mean SVI was of 0.42 (+/- SD 0.12). Mortality rate at three years was 6% (n = 809) and incident disability was 13.2% (n = 1367). SVI was independently associated with mortality, with a HR of 1.4 (95% CI 1.1-1.8, p < 0.001) for the highest category of the SVI compared to the lowest. Regarding disability, the OR was 1.3 (95% CI 1.1-1.5, p = 0.026) when comparing the highest and the lowest levels of the SVI. The SVI was independently associated with mortality and disability. Our findings support previous evidence on the SVI and builds on how this association persists even in those individuals with underlying contextual social vulnerability

Discovery of conformationally constrained ALK2 inhibitors

Despite decades of research on new diffuse intrinsic pontine glioma (DIPG) treatments, little or no progress has been made on improving patient outcomes. In this work, we explored novel scaffold modifications of M4K2009, a 3,5-diphenylpyridine ALK2 inhibitor previously reported by our group. Here we disclose the design, synthesis, and evaluation of a first-in-class set of 5- to 7-membered ether-linked and 7-membered amine-linked constrained inhibitors of ALK2. This rigidification strategy led us to the discovery of the ether-linked inhibitors M4K2308 and M4K2281 and the amine-linked inhibitors M4K2304 and M4K2306, each with superior potency against ALK2. Notably, M4K2304 and M4K2306 exhibit exceptional selectivity for ALK2 over ALK5, surpassing the reference compound. Preliminary studies on their in vivo pharmacokinetics, including blood-brain barrier penetration, revealed that these constrained scaffolds have favorable exposure and do open a novel chemical space for further optimization and future evaluation in orthotopic models of DIPG

The interplay between neoantigens and immune cells in sarcomas treated with checkpoint inhibition

IntroductionSarcomas are comprised of diverse bone and connective tissue tumors with few effective therapeutic options for locally advanced unresectable and/or metastatic disease. Recent advances in immunotherapy, in particular immune checkpoint inhibition (ICI), have shown promising outcomes in several cancer indications. Unfortunately, ICI therapy has provided only modest clinical responses and seems moderately effective in a subset of the diverse subtypes.MethodsTo explore the immune parameters governing ICI therapy resistance or immune escape, we performed whole exome sequencing (WES) on tumors and their matched normal blood, in addition to RNA-seq from tumors of 31 sarcoma patients treated with pembrolizumab. We used advanced computational methods to investigate key immune properties, such as neoantigens and immune cell composition in the tumor microenvironment (TME).ResultsA multifactorial analysis suggested that expression of high quality neoantigens in the context of specific immune cells in the TME are key prognostic markers of progression-free survival (PFS). The presence of several types of immune cells, including T cells, B cells and macrophages, in the TME were associated with improved PFS. Importantly, we also found the presence of both CD8+ T cells and neoantigens together was associated with improved survival compared to the presence of CD8+ T cells or neoantigens alone. Interestingly, this trend was not identified with the combined presence of CD8+ T cells and TMB; suggesting that a combined CD8+ T cell and neoantigen effect on PFS was important.DiscussionThe outcome of this study may inform future trials that may lead to improved outcomes for sarcoma patients treated with ICI

Evidencia empírica en el contexto del noviazgo, el acoso y la vida en pareja

Imagina por un momento que mañana tienes una cita que has esperado desde hace un tiempo. De alguna manera, pensabas que tal vez ya no sucedería. Tenía más de un mes que habías conocido a esa persona y habías dejado de pensar en la posibilidad de que la cita se diese. Sin embargo, y al lado de toda expectativa, recibiste la llamada. Te invitó a salir. Inmediatamente, llegan a ti ideas, pensamientos relacionados a la cita. ¿Qué ropa usarás?, ¿quizás sea mejor un pantalón formal?, algo que quizás sea bastante llamativo, pero no como para parecer demasiado, como algo prefabricado. Estas ideas asaltan a tu mente, y no sólo las relacionadas a cómo vestirte, sino también a cómo comportarte y como ensayar una linda sonrisa. En este momento, el lector -que ha imaginado esta interacción entre dos personas-, ha encontrado algo extraño. Quizás para una lectora sea mucho más fácil identificarse con la historia, pero, para un chico, quizás esto sea más difícil. Pensar en que ponerse durante la cita y esperar la llamada de alguien nos hace pensar en un rol asociado a las mujeres. Pero ¿por qué nos es más fácil pensar que son las chicas quienes esperan la llamada de los chicos y no viceversa? Incluso, cuando la persona se ha preguntado sobre qué vestir, ¿qué nos hace identificarnos más con una chica, que con un chico? De hecho, en ningún momento afirmamos que la persona que recibió la llamada fuera una chica y que, aquel que iniciaba la llamada para pedir una cita, fuese un chico

Consideraciónes geohidrológicas y legales en la gestión del agua subterránea del valle de Mexicali, Baja California, ante el revestimiento del canal Todo Americano

Maestría en Administración Integral del Ambient

Obesidad en niños y niñas de 6 a 11 años en El Salvador, México, Argentina y Perú, 2015 a 2020.

Esta investigación está basada en la Obesidad en niños de 6 a 11 años en nuestro país, El Salvador; así también en países como México, Argentina y Perú, destacándose el estudio principalmente entre los años 2015 a 2020. Objetivo: Analizar la Obesidad en niñez de 6 a 11 años en El Salvador, México, Argentina y Perú, en el período 2015 a 2020. Metodología: La metodología aplicada en este trabajo se fundamentó a través de la revisión bibliográfica, la información que se obtuvo fue con la finalidad de identificar y comparar estudios realizados sobre el tema. El método que se utilizó fue cualitativo con base a estadísticas de datos existentes en estudios de cada país, con los cuales valoramos la magnitud del problema de la Obesidad y su impacto en la sociedad infantil; así como, determinar las bases científicas que sustenten el fenómeno. Los datos se presentaron en forma narrativa mediante el análisis y síntesis respectivos a través de la lectura crítica de la información obtenida de documentos oficiales sobre la salud en El Salvador, México, Argentina y Perú. Resultados: Los resultados obtenidos demuestran que el consumo de grasas, azúcares, la frecuencia en los tiempos de comida, períodos para ver televisión, uso de otros aparatos tecnológicos, como computadoras, móviles y una importante disminución de la actividad física en la población, contribuyen a que la Obesidad infantil permanezca a lo largo de su vida, siendo parte del origen de muchas enfermedades a edades tempranas