Estudio de Factibilidad financiera de Bisutienda Masatepe, ubicada en el Municipio de Masatepe, Departamento de Masaya durante el año 2014

El proyecto BISUTIENDA MASATEPE consiste en comercializar material para la elaboración de prendas de bisutería, en el Municipio de Masatepe, Departamento de Masaya, durante el año 2014. La tienda estará ubicada en el mercado Municipal de Masatepe, en el barrio Macario Brenes, situado en la parte oeste de la ciudad, en un sector cercano al parque central y otras instituciones de importancia para el municipio, es de fácil acceso; la dirección exacta es de BANCENTRO ½ cuadra al oeste. Esta Mipyme cumpliendo con el carácter innovador ofrece al cliente productos como: pedrería de diversas variedades, herramientas para la elaboración de las prendas, artículos para el almacenamiento de las prendas y accesorios varios para la elaboración de bisutería. En cuanto al personal se realizara una selección del recurso humano con conocimiento sobre este mercado, que brinde amabilidad y asesoría a los clientes potenciales. La pequeña Empresa se dedica a vender materiales para la elaboración de bisutería, cabe señalar que la actividad principal es funcionar como minoristas, siendo los proveedores “Tienda Bella” y “Tienda El Rey”, ubicadas en el mercado oriental. Uno de los principales objetivos de la Mipyme es poder funcionar a un mediano plazo y tener una excelente aceptabilidad en la ciudadanía ya que no existe competencia alguna en el mercado que se pretende operar, el producto es altamente atractivo especialmente en el segmento femenino, contamos con una variedad de accesorios con los cuales se pueden elaborar diversas prendas de vesti

EL PROCESO DE ENSEÑANZA- APRENDIZAJE DE LAS RELACIONES PÚBLICAS EN LAS FACULTADES DE CIENCIAS DE LA COMUNICACIÓN EN TRUJILLO: PROPUESTA PARA UNA VISIÓN CIENTÍFICA

El presente trabajo de investigación fue desarrollado con el objetivo de conocer y comprender el fenómeno de la enseñanza- aprendizaje de las Relaciones Públicas a través del análisis de los currículos y la percepción de estudiantes y docentes de Ciencias de la Comunicación en Trujillo. La población y muestra de estudio fueron estudiantes, docentes y los currículos de las carreras profesionales. Se llegó a la conclusión principal de que la enseñanza- aprendizaje de las Relaciones Públicas realizada a través del análisis de los currículos y la percepción de estudiantes y docentes se manifiesta en el desarrollo de contenidos teóricos y poco prácticos sin ninguna incidencia en la solución de casos de nuestro contexto local, Además la falta de flexibilidad de los currículos que no permite que se desarrollen un mayor número de asignaturas de la especialidad hace que los estudiantes no estén preparados para gestionar una unidad de Relaciones Públicas en una empresa

Gestión de inventarios y su influencia en la productividad de la empresa Clorimax E. I. R. L. 2020

El presente trabajo de investigación tiene como objetivo determinar la influencia de la gestión de inventarios en la productividad de la empresa Clorimax. Para ello se utilizó la metodología de investigación de la hipótesis causal bivariado donde se plantea la relación causal (efecto) entre una variable independiente sobre una variable dependiente. Para comenzar se diagnosticó la situación actual de la empresa, luego se creó una base de datos que permitió analizarlos mediante gráficos estadísticos, luego se propuso la gestión de inventarios teniendo como criterio fundamental el modelo ABC Pareto, posteriormente se midió y comparó mediante indicadores la influencia de la propuesta de gestión de inventarios en la productividad, tomando en ella como sub dimensiones a la eficacia y eficiencia se demostró cómo es que mejora positivamente en 11% y 19% respectivamente con un margen positivo de dinero de S./ 33,992.48 de antes y después de ser implementada. Finalmente se procedió a realizar un análisis de factibilidad financiera del proyecto obteniendo como resultados una tasa interna de retorno de la inversión de 223% por cada unidad monetaria invertida, y con un Valor Actual Neto de S/. 86,866.87 nos indica que al regresar al año cero los flujos proyectados el proyecto es muy rentable y su periodo de recuperación es en el primer año.The present research work aims to determine the influence of inventory management on the productivity of the Clorimax company. For this, the research methodology of the bivariate causal hypothesis was used, where the causal relationship (effect) between an independent variable on a dependent variable is proposed. To begin with, the current situation of the company was diagnosed, then a database was created that allowed them to be analyzed using statistical graphics, then inventory management was proposed having the ABC Pareto model as a fundamental criterion, later the influence was measured and compared by indicators of the inventory management proposal in productivity, taking effectiveness and efficiency as a sub-dimension, it was shown how it improves positively by 11% and 19% respectively with a positive margin of money of S. / 33,992.48 from before and after being implemented. Finally, an analysis of the financial feasibility of the project was carried out, obtaining as results an internal rate of return of the investment of 223% for each monetary unit invested, and with a Net Present Value of S /. 86,866.87 indicates that when the projected flows return to year zero, the project is very profitable and its recovery period is in the first year

Improvement of cardiometabolic markers after fish oil intervention in young Mexican adults and the role of PPARα L162V and PPARγ2 P12A

Polyunsaturated fatty acids (PUFA) contained in fish oil (FO) are ligands for peroxisome proliferator-activated receptors (PPAR) that may induce changes in cardiometabolic markers. Variation in PPAR genes may influence the beneficial responses linked to FO supplementation in young adults. The study aimed to analyze the effect of FO supplementation on glucose metabolism, circulating lipids and inflammation according to PPARα L162V and PPARγ2 P12A genotypes in young Mexican adults. 191 young, non-smoking subjects between 18 and 40 years were included in a one-arm study. Participants were supplemented with 2.7 g/day of EPA+DHA, during six weeks. Dietary analysis, body composition measurements and indicators for glucose metabolism, circulating lipids, and markers for inflammation were analyzed before and after intervention. An overall decrease in triglycerides (TG) and an increase in HS-ω3 index were observed in all subjects [-4.1 mg/dL, (SD:±51.7), P=.02 and 2.6%, (SD:±1.2), P\u3c.001 respectively]. Mean fasting insulin and glycated hemoglobin (HbA1c%) were significantly decreased in all subjects [-0.547mlU/L, (SD:±10.29), P=.034 and-0.07%, (SD:±0.3), P\u3c.001 respectively], whereas there was no change in body composition, fasting glucose, adiponectin and inflammatory markers. Subjects carrying the minor alleles of PPARα L162V and PPARγ2 P12A had higher responses in reduction of TG and fasting insulin respectively. Interestingly, doses below 2.7 g/day (1.8 g/day) were sufficient to induce a significant reduction in fasting insulin and HbA1c% from baseline (P=.019 and P\u3c.001). The observed responses in triglycerides and fasting insulin in the Mexican population give further evidence of the importance of FO supplementation in young people as an early step towards the prevention of cardiometabolic disease. Trial registration: ClinicalTrials.gov NCT02296385

MANEJO ONCOLÓGICO Y TERAPÉUTICO EN EL HEPATOBLASTOMA

El Hepatoblastoma es el tumor hepático maligno más frecuente en la edad pediátrica. Es una neoplasia de origen embrionario que representa el 1-2% de todos los tumores infantiles. Predomina en el sexo masculino, en edades tempranas, lactantes y niños menores de 5 años de edad. Su etiología es incierta. La tasa de supervivencia a 5 años es del 70%, con resultados comparables en los recién nacidos. Puede ser asintomático en sus inicios o presentarse con una masa abdominal palpable en el cuadrante superior derecho del abdomen, dolor abdominal localizado o difuso, pérdida de peso, anorexia, náuseas y vómitos. La ictericia es infrecuente.  Este tipo de tumor puede asociarse con determinados síndromes. La realización de biopsia de la lesión tumoral, pruebas de imágenes, y marcadores tumorales como la alfafetoproteína y gonadotropina coriónica humana beta son de gran utilidad. En el momento del diagnóstico, aproximadamente el 40% de los pacientes presentan enfermedad hepática avanzada, por lo que resulta de vital importancia sospecharlo para realizar el diagnóstico oportuno y obtener un mejor pronóstico.  El tratamiento de elección de este tipo de tumor es la combinación de quimioterapia y cirugía, por la imposibilidad de ser resecados completamente. La radioterapia se reserva para tratar las metástasis pulmonares no resecables y como tratamiento paliativo en los casos de mal pronóstico

The evolution of lung cancer and impact of subclonal selection in TRACERx

Lung cancer is the leading cause of cancer-associated mortality worldwide. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource

The evolution of non-small cell lung cancer metastases in TRACERx

Metastatic disease is responsible for the majority of cancer-related deaths. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response