Diseño de un sistema de control de inventarios (método híbrido) para el Supermercado Totalhome Cía. Ltda., cantón Riobamba, provincia de Chimborazo

El presente Diseño de un Sistema de Control de Inventarios (Método Híbrido), para el Supermercado Totalhome Cía. Ltda., Cantón Riobamba, Provincia de Chimborazo, tiene como objeto mejorar la gestión de los inventarios, permitiendo optimizar sus costos, incrementar las utilidades y brindar un mejor servicio a los clientes. Previo a la elaboración de la propuesta, se realizó una visita preliminar a las instalaciones de la empresa, posteriormente se aplicó una encuesta al personal administrativo y operativo relacionado con el manejo de los inventarios; y, se complementó con la observación directa de los procesos que se ejecutan en el área de inventarios, técnicas de investigación con las cuales se evidenció un deficiente manejo y control de los productos a comercializarse, ocasionando el sobreabastecimiento y/o escasez de ciertos artículos como los de primera necesidad, elevados costos de mantenimiento del inventario, inadecuada gestión de stocks, pérdidas por obsolescencia o caducidad de los artículos, rotación constante del administrador de inventarios y disminución de ventas por clientes insatisfechos, todo lo cual tiene incidencia directa en los resultados del supermercado. Por consiguiente, en la elaboración del modelo de control de inventarios se tomó en consideración la cantidad económica de pedido, el punto de renovación de pedidos, la rotación de los inventarios y las políticas necesarias para mejorar la gestión de las existencias. Por ello, se recomienda a los directivos de la empresa implementar el Método Híbrido que facilitará la toma decisiones y ayudará a optimizar sus recursos.The present Design of an Inventory Control System (Hybrid Method) for the Totally Cía Supermarket. Ltda., Riobamba Canton, Chimborazo Province, the objective to improve the management of inventories, allowing to optimize their costs, increase profits and provide a better service to customers. Prior to the preparation of the proposal, it uses a preliminary visit to the company's facilities, it applied a survey to the administrative and operative personnel related to the handling of the inventories; and, it complemented with the direct observation of the processes that are carried out in the area of inventories, research techniques with which there is evidence of poor management and control of the products to be marketed, causing oversupply and/or shortage of certain items such as of first necessity, high costs of inventory maintenance, inadequate stock management, losses due to obsolescence or expiration of the items, constant rotation of the inventory manager and decrease of sales by dissatisfied customers, all of which have a direct impact on the results of the supermarket . Therefore, the preparation of the inventory control model, the economic order quantities, order renewal point, the rotation of inventories and the necessary policies to improve stock management were taken into account. Therefore, it is recommended that the company's executives implement the Hybrid Method that will facilitate decision-making and help optimize their resources

Dopaminergic metabolism in carotid bodies and high-altitude acclimatization in female rats

We tested the hypothesis that ovarian steroids stimulate breathing through a dopaminergic mechanism in the carotid bodies. In ovariectomized female rats raised at sea level, domperidone, a peripheral D 2-receptor antagonist, increased ventilation in normoxia (minute ventilation = +55%) and acute hypoxia (+32%). This effect disappeared after 10 daily injections of ovarian steroids (progesterone + estradiol). At high altitude (3,600 m, Bolivian Institute for High-Altitude Biology-IBBA, La Paz, Bolivia), neutered females had higher carotid body tyrosine hydroxylase activity (the rate-limiting enzyme for catecholamine synthesis: +129%) and dopamine utilization (+150%), lower minute ventilation (-30%) and hypoxic ventilatory response (-57%), and higher hematocrit (+18%) and Hb concentration (+21%) than intact female rats. Consistent signs of arterial pulmonary hypertension (right ventricular hypertrophy) also appeared in ovariectomized females. None of these parameters was affected by gonadectomy in males. Our results show that ovarian steroids stimulate breathing by lowering a peripheral dopaminergic inhibitory drive. This process may partially explain the deacclimatization of post-menopausal women at high altitude.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)