The fecal resistome of dairy cattle is associated with diet during nursing.

Antimicrobial resistance is a global public health concern, and livestock play a significant role in selecting for resistance and maintaining such reservoirs. Here we study the succession of dairy cattle resistome during early life using metagenomic sequencing, as well as the relationship between resistome, gut microbiota, and diet. In our dataset, the gut of dairy calves serves as a reservoir of 329 antimicrobial resistance genes (ARGs) presumably conferring resistance to 17 classes of antibiotics, and the abundance of ARGs declines gradually during nursing. ARGs appear to co-occur with antibacterial biocide or metal resistance genes. Colostrum is a potential source of ARGs observed in calves at day 2. The dynamic changes in the resistome are likely a result of gut microbiota assembly, which is closely associated with diet transition in dairy calves. Modifications in the resistome may be possible via early-life dietary interventions to reduce overall antimicrobial resistance

The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro

Aims: Diet-derived short chain fatty acids (SCFAs) improve glucose homeostasis in vivo, but the role of individual SCFAs and their mechanisms of action have not been defined. This study evaluated the effects of increasing colonic delivery of the SCFA propionate on β-cell function in humans and the direct effects of propionate on isolated human islets in vitro. Materials and Methods: For 24 weeks human subjects ingested an inulin-propionate ester that delivers propionate to the colon. Acute insulin, GLP-1 and non-esterified fatty acid (NEFA) levels were quantified pre- and post-supplementation in response to a mixed meal test. Expression of the SCFA receptor FFAR2 in human islets was determined by western blotting and immunohistochemistry. Dynamic insulin secretion from perifused human islets was quantified by radioimmunoassay and islet apoptosis was determined by quantification of caspase 3/7 activities. Results: Colonic propionate delivery in vivo was associated with improved β-cell function with increased insulin secretion that was independent of changes in GLP-1 levels. Human islet β-cells expressed FFAR2 and propionate potentiated dynamic glucose-stimulated insulin secretion in vitro, an effect that was dependent on signalling via protein kinase C. Propionate also protected human islets from apoptosis induced by the NEFA sodium palmitate and inflammatory cytokines. Conclusions: Our results indicate that propionate has beneficial effects on β-cell function in vivo, and in vitro analyses demonstrated that it has direct effects to potentiate glucose-stimulated insulin release and maintain β-cell mass through inhibition of apoptosis. These observations support ingestion of propiogenic dietary fibres to maintain healthy glucose homeostasis

Proyecto condominio El Olivar – 2da y 3ra etapa

La presente tesis tiene como objetivo desarrollar un proyecto de vivienda social en el distrito de Carabayllo, que signifique un cambio al producto ofrecido en la 1era Etapa. La 1era etapa, consistió en 60 departamentos de 60.89 m2 y 26 casas de 111.86 m2, sala de usos múltiples, cancha de fulbito y juego para niños; sin embargo, la alta competencia que se desarrolló en el distrito durante la ejecución del proyecto 2014-2015, así como un producto que no se ajustó a las necesidades del público objetivo hicieron que las ventas no fueran las previstas, por lo que a la fecha aún se tienen disponibles 12 departamentos y 7 casas, siendo la 1era etapa inviable económicamente. De esa manera, surge el proyecto Condominio El Olivar 2da y 3ra Etapa renovado, en el que se decide cambiar el producto inicialmente ofrecido y dirigirlo hacia viviendas de interés social subvencionadas por el Estado, que consiste en un mix de viviendas del programa “Techo Propio” y el “Fondo Mivivienda”, considerando un igual porcentaje de viviendas por cada tipo, asegurando así un mayor velocidad de venta para el programa Mi Vivienda y una mayor rentabilidad con las viviendas del Fondo Mi Vivienda. Para lograr dicho objetivo, como primer punto de partida, se realizará el análisis de situación y su proyección temporal del macroentorno, analizando variables como situación de los mercados internacionales, el ciclo económico mundial y la situación política, económica, empresarial en el Perú. Asimismo, se analizará el microentorno donde se evalúa la investigación de mercado realizada, la influencia de las autoridades municipales en el proyecto, la competencia, los actores relevantes para la empresa y la situación actual del plan de marketing. También se definirán los objetivos del plan estratégico de marketing que están relacionados con el aumento de la velocidad de ventas y la rentabilidad del proyecto. En segundo lugar, se detallará el plan de marketing del proyecto y se definirá la segmentación y target del proyecto que comprende; familias jóvenes que vivan el Cono Norte, en una vivienda alquilada o familiar no propia, cuyos jefes de familia pueden ser profesionales o no profesionales en el rango de 25 a 40 años de edad, con uno o dos hijos pequeños, pertenecientes al nivel socioeconómico C y D, con ingresos familiares promedio de S/3,500.00 y que sean potencialmente elegibles por el sistema financiero para acceder a un crédito hipotecario. Además, Natturale Inmobiliaria, con este proyecto, se pretende posicionar en la mente del consumidor como una empresa socialmente responsable que brinde a sus clientes productos de buena calidad a precios accesibles, con una arquitectura moderna, distribución funcional y buenos acabados en la zona de Carabayllo, sacando provecho al potencial crecimiento de dicho distrito. También, se desarrollará el marketing mix del proyecto analizando las diferentes variables de producto, precio, plaza y promoción. Finalmente, la inversión total del proyecto será de S/. 29,311,486 que incluyen todos los gastos directos e indirectos hasta la finalización y comercialización de este. Este monto estará compuesto por aportes de capital de los accionistas de las preventas, así como de la línea de crédito proporcionada por el Banco BBVA, dentro del Convenio Marco, dado que es la entidad financiera que promueve el proyecto inmobiliario. El proyecto tendrá una duración de 46 meses desde la firma del contrato con las partes involucradas hasta la entrega de los departamentos. El proyecto tendrá una utilidad proyectada después de impuestos S/. 4,063,514. El margen neto sobre ventas sobre las ventas (ROS) será de 12.2% y un VAN de S/. 2,613,843.Tesi

Aplicación de gestión de inventarios para mejorar la productividad en los despachos en la empresa L&R Industrias S.A.C., Lima, 2021

La presente investigación titulada “Aplicación de gestión de inventarios para mejorar la productividad en los despachos en la empresa L&R Industrias S.A.C., Lima, 2021”. Tuvo como objetivo general: Establecer la forma en que la aplicación de gestión de inventarios mejora la productividad en los despachos en la empresa L&R Industrias S.A.C., Lima año 2021. Teniendo como población los despachos diarios y se registraron de forma mensual, así mismo se tiene como variables de investigación la gestión de inventarios y la productividad. La presente investigación posee un enfoque cuantitativo, tipo de investigación básica, con un diseño no experimental. A partir de la información obtenida se va a analizar la situación del nivel de servicio que tienen como dimensiones las entregas a tiempo y las entregas completas, en cuanto al nivel de investigación es propositivo, donde el instrumento utilizado para medir la variable productividad, fueron los registros de despachos diarios y las fórmulas matemáticas validadas mediante el criterio de juicio de expertos, en donde los resultados se presentan mediante tablas y gráficos. En conclusión, el estudio de la investigación nos brinda resultados que concluyen que mediante la aplicación de una adecuada gestión de inventarios se incrementó la productividad de despachos, lo cual se evidencia por un cambio en la eficiencia de 43% a 61% y en el incremento de la eficacia de 59% a 80%; todo ello trae como resultado la mejora de la productividad de 25% a 49%

Left subclavian artery coverage during thoracic endovascular aortic aneurysm repair does not mandate revascularization

ObjectiveThis study assessed the risk of left subclavian artery (LSA) coverage and the role of revascularization in a large population of patients undergoing thoracic endovascular aortic aneurysm repair.MethodsA retrospective multicenter review of 1189 patient records from 2000 to 2010 was performed. Major adverse events evaluated included cerebrovascular accident (CVA) and spinal cord ischemia (SCI). Subgroup analysis was performed for noncovered LSA (group A), covered LSA (group B), and covered/revascularized LSA (group C).ResultsOf 1189 patients, 394 had LSA coverage (33.1%), and 180 of these patients (46%) underwent LSA revascularization. In all patients, emergency operations (9.5% vs 4.3%; P = .001), renal failure (12.7% vs 5.3%; P = .001), hypertension (7% vs 2.3%; P = .01), and number of stents placed (1 = 3.7%, 2 = 7.4%, ≥3 = 10%; P = .005) were predictors of SCI. History of cerebrovascular disease (9.6% vs 3.5%; P = .002), chronic obstructive pulmonary disease (9.5% vs 5.4%; P = .01), coronary artery disease (8.5% vs 5.3%; P = .03), smoking (8.9% vs 4.2%) and female gender (5.3% men vs 8.2% women; P = .05) were predictors of CVA. Subgroup analysis showed no significant difference between groups B and C (SCI, 6.3% vs 6.1%; CVA, 6.7% vs 6.1%). LSA revascularization was not protective for SCI (7.5% vs 4.1%; P = .3) or CVA (6.1% vs 6.4%; P = .9). Women who underwent revascularization had an increased incidence of CVA event compared with all other subgroups (group A: 5.6% men, 8.4% women, P = .16; group B: 6.6% men, 5.3% women, P = .9; group C: 2.8% men, 11.9% women, P = .03).ConclusionsLSA coverage does not appear to result in an increased incidence of SCI or CVA event when a strategy of selective revascularization is adopted. Selective LSA revascularization results in similar outcomes among the three cohorts studied. Revascularization in women carries an increased risk of a CVA event and should be reserved for select cases

\u3ci\u3eIn Vivo\u3c/i\u3e Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

One strategy for enhancing the establishment of probiotic bacteria in the human intestinal tract is via the parallel administration of a prebiotic, which is referred to as a synbiotic. Here we present a novel method that allows a rational selection of putative probiotic strains to be used in synbiotic applications: in vivo selection (IVS). This method consists of isolating candidate probiotic strains from fecal samples following enrichment with the respective prebiotic. To test the potential of IVS, we isolated bifidobacteria from human subjects who consumed increasing doses of galactooligosaccharides (GOS) for 9 weeks. A retrospective analysis of the fecal microbiota of one subject revealed an 8-fold enrichment in Bifidobacterium adolescentis strain IVS-1 during GOS administration. The functionality of GOS to support the establishment of IVS-1 in the gastrointestinal tract was then evaluated in rats administered the bacterial strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific quantitative real-time PCR showed that the addition of GOS increased B. adolescentis IVS-1 abundance in the distal intestine by nearly 2 logs compared to rats receiving only the probiotic. Illumina 16S rRNA sequencing not only confirmed the increased establishment of IVS-1 in the intestine but also revealed that the strain was able to outcompete the resident Bifidobacterium population when provided with GOS. In conclusion, this study demonstrated that IVS can be used to successfully formulate a synergistic synbiotic that can substantially enhance the establishment and competitiveness of a putative probiotic strain in the gastrointestinal tract

\u3ci\u3eIn Vivo\u3c/i\u3e Selection To Identify Bacterial Strains with Enhanced Ecological Performance in Synbiotic Applications

One strategy for enhancing the establishment of probiotic bacteria in the human intestinal tract is via the parallel administration of a prebiotic, which is referred to as a synbiotic. Here we present a novel method that allows a rational selection of putative probiotic strains to be used in synbiotic applications: in vivo selection (IVS). This method consists of isolating candidate probiotic strains from fecal samples following enrichment with the respective prebiotic. To test the potential of IVS, we isolated bifidobacteria from human subjects who consumed increasing doses of galactooligosaccharides (GOS) for 9 weeks. A retrospective analysis of the fecal microbiota of one subject revealed an 8-fold enrichment in Bifidobacterium adolescentis strain IVS-1 during GOS administration. The functionality of GOS to support the establishment of IVS-1 in the gastrointestinal tract was then evaluated in rats administered the bacterial strain alone, the prebiotic alone, or the synbiotic combination. Strain-specific quantitative real-time PCR showed that the addition of GOS increased B. adolescentis IVS-1 abundance in the distal intestine by nearly 2 logs compared to rats receiving only the probiotic. Illumina 16S rRNA sequencing not only confirmed the increased establishment of IVS-1 in the intestine but also revealed that the strain was able to outcompete the resident Bifidobacterium population when provided with GOS. In conclusion, this study demonstrated that IVS can be used to successfully formulate a synergistic synbiotic that can substantially enhance the establishment and competitiveness of a putative probiotic strain in the gastrointestinal tract

Transition of Electric Mobility in Colombia: Technical and Economic Evaluation of Scenarios for the Integration of E-taxis in Bucaramanga

Globally, the transport sector has been directed towards electric mobility by policies, regulations, development strategies and economic incentives. The transport sector has an important strategic role in the economic development of a country, the sustainability of this sector has an impact on political and scientific discussions due to its environmental impact. In Colombia, the global targets for reducing polluting emissions begin to drive the renewal of the automotive park towards electric mobility, therefore, this research was carried out with the aim of carrying out a technical and economic analysis of scenarios for the e-taxis in Bucaramanga, the incentives applied in the two projects developed in the two most important cities of Colombia were taken as the basis to compare possible implementation scenarios in the short and medium term. Three technologies (gasoline, gas and electric) were evaluated that were tested using the TAC/km indicator, the financial viability was assessed based on two financial kindness criteria (NPV and IRR). The results obtained allow to conclude two strategies that make it possible to incorporate the e-taxis in Bucaramanga, 1) exemption from payment of taxi registration, in case of incorporation of a new vehicle; 2) economic incentive of more than 20% at the time of purchase of the EV, accompanied by a 25% increase in the cost of the minimum service fee, in the case of the replacement of a taxi.Keywords: electric taxi Colombia, e-taxi policies, electric mobility, electric vehicle, public transport sector.JEL Classifications: Q01, Q4, Q42DOI: https://doi.org/10.32479/ijeep.11084</p

A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2-Altered Advanced Solid Tumor Malignancies (NCI 10170).

UNLABELLED: We sought to evaluate the efficacy of WEE1 inhibitor adavosertib in patients with solid tumor malignancies (cohort A) and clear cell renal cell carcinoma (ccRCC; cohort B). NCT03284385 was a parallel cohort, Simon two-stage, phase II study of adavosertib (300 mg QDAY by mouth on days 1-5 and 8-12 of each 21-day cycle) in patients with solid tumor malignancies harboring a pathogenic SETD2 mutation. The primary endpoint was the objective response rate. Correlative assays evaluated the loss of H3K36me3 by IHC, a downstream consequence of SETD2 loss, in archival tumor tissue. Eighteen patients were enrolled (9/cohort). The median age was 60 years (range 45-74). The median duration of treatment was 1.28 months (range 0-24+). No objective responses were observed in either cohort; accrual was halted following stage 1. Minor tumor regressions were observed in 4/18 (22%) evaluable patients. Stable disease (SD) was the best overall response in 10/18 (56%) patients, including three patients with SD &gt; 4 months. One patient with ccRCC remains on treatment for &gt;24 months. The most common adverse events of any grade were nausea (59%), anemia (41%), diarrhea (41%), and neutropenia (41%). Nine patients (50%) experienced a Grade ≥3 adverse event. Of eight evaluable archival tissue samples, six (75%) had a loss of H3K36me3 by IHC. Adavosertib failed to exhibit objective responses in SETD2-altered ccRCC and other solid tumor malignancies although prolonged SD was observed in a subset of patients. Combination approaches may yield greater depth of tumor response. SIGNIFICANCE: WEE1 inhibition with adavosertib monotherapy demonstrated limited clinical activity in patients with SETD2-altered solid tumors despite compelling preclinical data indicating a synthetic lethal effect, which did not translate into robust tumor regression. Loss of the H3K36me3 trimethylation mark caused by SETD2-deficiency was confirmed in the majority of evaluable tumors. A subset of patients derived clinical benefit as manifested by minor tumor regressions and prolonged SD