Diseño estructural del pavimento de la calle 45 en el centro poblado El Milagro - la Libertad

El presente trabajo de investigación tiene como objetivo elaborar el diseño estructural del pavimento de la Calle 45 en el Centro Poblado El Milagro – La Libertad, mediante una investigación descriptiva – tipo aplicada; el diseño se realizó mediante la metodología AASHTO 93. La vía de estudio, es una vía principal, donde, circulan vehículos en ambos sentidos, que tiene carencia de pavimento, esto hace dificultoso el pase de vehículos y de transeúntes. Se realizará dos propuestas: el diseño estructural del pavimento flexible y rígido, teniendo en cuenta la Norma Técnica Peruana (Manual de carreteras: suelos, geología, geotecnia y pavimentos,2013) del Ministerio de Transporte y Comunicaciones, para establecer los espesores de las capas de pavimento. Se realizó estudios básicos de ingeniería como: el estudio de mecánica de suelos, obteniendo un suelo de tipo Grava pobremente graduada con CBR de 21.5%; y el estudio de tráfico vehicular, donde el tráfico que se proyecta para 20 años es de 1’913,196 para el pavimento flexible y 2’357,216 para el pavimento rígido. Los resultados que se han obtenido para los espesores del pavimento flexible es una carpeta asfáltica de 5 cm, base de 22 cm y una sub base de 15 cm, con costo directo de cuatro millones ciento sesenta mil novecientos quince con 69/100 (s/ 4’160,915.69) y para el pavimento rígido: la losa de concreto es 20 cm y una base de 15 cm, con costo directo de seis millones ciento cincuenta y un mil seiscientos cuarenta y tres con 03/100 (s/ 6’151,643.03). Se concluye que le pavimento rígido es la alternativa más viable con respecto a su durabilidad, siendo menos vulnerable en una posible activación de la quebrada del leónThe objective of this research work is to elaborate the structural design of the pavement of Calle 45 in the Centro Poblado El Milagro - La Libertad, through descriptive research - applied type; The design was carried out using the AASHTO 93 methodology. The study road is a main road, where vehicles circulate in both directions, which has a lack of pavement, this makes it difficult for vehicles and pedestrians to pass. Two proposals will be made: the structural design of the flexible and rigid pavement, taking into account the Peruvian Technical Standard (Manual of highways: soils, geology, geotechnics and pavements, 2013) of the Ministry of Transport and Communications, to establish the thickness of the layers of pavement. Basic engineering studies were carried out such as: the study of soil mechanics, obtaining a poorly graded Gravel-type soil with CBR of 21.5%; and the vehicular traffic study, where the traffic projected for 20 years is 1,913,196 for flexible pavement and 2,357,216 for rigid pavement. The results that have been obtained for the thicknesses of the flexible pavement is an asphalt layer of 5 cm, a base of 22 cm and a sub-base of 15 cm, with a direct cost of four million one hundred sixty thousand nine hundred fifteen with 69/100 (s / 4'160,915.69) and for the rigid pavement: the concrete slab is 20 cm and a base of 15 cm, with a direct cost of six million one hundred fifty-one thousand six hundred forty-three with 03/100 (s / 6'151,643.03) . It is concluded that the rigid pavement is the most viable alternative with respect to its durability, being less vulnerable in a possible activation of the lion's gorge.Tesi

Evaluation of Nutritional Practices in the Critical Care Patient (The ENPIC Study): Does Nutrition Really Affect ICU Mortality?

Background & aims: The importance of artificial nutritional therapy is underrecognized, typically being considered an adjunctive rather than a primary therapy. We aimed to evaluate the influence of nutritional therapy on mortality in critically ill patients. Methods: This multicenter prospective observational study included adult patients needing artificial nutritional therapy for >48 h if they stayed in one of 38 participating intensive care units for >= 72 h between April and July 2018. Demographic data, comorbidities, diagnoses, nutritional status and therapy (type and details for <= 14 days), and outcomes were registered in a database. Confounders such as disease severity, patient type (e.g., medical, surgical or trauma), and type and duration of nutritional therapy were also included in a multivariate analysis, and hazard ratios (HRs) and 95% confidence intervals (95% CIs) were reported. Results: We included 639 patients among whom 448 (70.1%) and 191 (29.9%) received enteral and parenteral nutrition, respectively. Mortality was 25.6%, with non-survivors having the following char-acteristics: older age; more comorbidities; higher Sequential Organ Failure Assessment (SOFA) scores (6.6 +/- 3.3 vs 8.4 +/- 3.7; P < 0.001); greater nutritional risk (Nutrition Risk in the Critically Ill [NUTRIC] score: 3.8 +/- 2.1 vs 5.2 +/- 1.7; P < 0.001); more vasopressor requirements (70.4% vs 83.5%; P=0.001); and more renal replacement therapy (12.2% vs 23.2%; P=0.001). Multivariate analysis showed that older age (HR: 1.023; 95% CI: 1.008-1.038; P=0.003), higher SOFA score (HR: 1.096; 95% CI: 1.036-1.160; P=0.001), higher NUTRIC score (HR: 1.136; 95% CI: 1.025-1.259; P=0.015), requiring parenteral nutrition after starting enteral nutrition (HR: 2.368; 95% CI: 1.168-4.798; P=0.017), and a higher mean Kcal/Kg/day intake (HR: 1.057; 95% CI: 1.015-1.101; P=0.008) were associated with mortality. By contrast, a higher mean protein intake protected against mortality (HR: 0.507; 95% CI: 0.263-0.977; P=0.042). Conclusions: Old age, higher organ failure scores, and greater nutritional risk appear to be associated with higher mortality. Patients who need parenteral nutrition after starting enteral nutrition may represent a high-risk subgroup for mortality due to illness severity and problems receiving appropriate nutritional therapy. Mean calorie and protein delivery also appeared to influence outcomes. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism

Mendelian Randomization Analysis of the Relationship Between Native American Ancestry and Gallbladder Cancer Risk

Background A strong association between the proportion of Native American ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest Native American people in Chile. We set out to investigate the causal association between Native American Mapuche ancestry and GBC risk, and the possible mediating effects of gallstone disease and body mass index (BMI) on this association. Methods Markers of Mapuche ancestry were selected based on the informativeness for assignment measure and then used as instrumental variables in two-sample mendelian randomization (MR) analyses and complementary sensitivity analyses. Result We found evidence of a causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% for every 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.6×10-5). Mapuche ancestry was also causally linked to gallstone disease (IVW risk increase of 3.6% per 1% increase in Mapuche proportion, 95% CI 3.1% to 4.0%, p = 1.0×10-59), suggesting a mediating effect of gallstones in the relationship between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative causal effect on BMI (IVW estimate -0.006 kg/m2 per 1% increase in Mapuche proportion, 95% CI -0.009 to -0.003, p = 4.4×10-5). Conclusions The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between Mapuche ancestry and GBC risk previously noted in observational studies appears to be causal, primary and secondary prevention strategies that take into account the individual proportion of Mapuche ancestry could be particularly efficient

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Una mirada prospectiva de la industria Risaraldense camino a la industria 4.0 : plan tecnológico 2020–2030 Centro de Diseño e Innovación Tecnológico Industrial

Se presenta el plan tecnológico del Centro de Diseño e Innovación Tecnológico Industrial del SENA para la vigencia 2002 - 2030. Comprende el análisis y diagnóstico de la industria risaraldense, sus necesidades y tendencias, con enfoque a la industria 4.0. Se provee información para: identificar tecnologías y ocupaciones emergentes que permitan anticipar la definición de perfiles de instructores, determinar requerimientos de modernización de infraestructura física y tecnológica del Centro de formación, actualizar, crear o eliminar programas de formación, establecer el tipo de formación, servicios tecnológicos e innovación que el centro de formación ofrecerá en un horizonte de 10 años e identificar los proyectos y actores estratégicos para el centro de formación.The technological plan of the SENA Industrial Technological Design and Innovation Center for the period 2002-2030 is presented. It includes the analysis and diagnosis of the Risaralda industry, its needs and trends, with a focus on industry 4.0. Information is provided to: identify emerging technologies and occupations that allow anticipating the definition of instructor profiles, determine modernization requirements of the physical and technological infrastructure of the Training Center, update, create or eliminate training programs, establish the type of training, services technology and innovation that the training center will offer over a 10-year horizon and identify projects and strategic actors for the training center.Fase I: análisis y diagnóstico estratégico -- Análisis externo del centro de formación -- Análisis interno del centro de formación -- Seguimiento al plan tecnológico inmediatamente anterior -- Cruce DOFA -- Vigilancia científico -tecnológica y competitiva especialidad energía eléctrica -- Vigilancia científico -tecnológica y competitiva especialidad electrónica y automatización -- Vigilancia científico -tecnológica y competitiva especialidad Mecánica Industrial -- Vigilancia científico -tecnológica y competitiva especialidad Informática, diseño y desarrollo de software -- Vigilancia científico -tecnológica y competitiva especialidad materiales para la industria -- Vigilancia científico -tecnológica y competitiva especialidad Automotor -- Vigilancia científico -tecnológica y competitiva especialidad Textil, confección y diseño -- Vigilancia científico -tecnológica y competitiva especialidad construcción e infraestructura -- Vigilancia científico -tecnológica y competitiva servicios tecnológicos -- Fase II: formulación estratégica -- Mapa de trayectoria tecnológica -- Validación con expertos -- Construcción de escenarios -- Formulación estratégica -- Métodos prospectivos utilizados -- Formulación estratégica -- Fase III: recomendaciones estratégicas -- Recomendaciones estratégicas especialidad energía eléctrica -- Recomendaciones estratégicas especialidad electrónica y automatización -- Recomendaciones estratégicas especialidad mecánica industrial -- Recomendaciones estratégicas especialidad Informática, diseño y desarrollo de software -- Recomendaciones estratégicas especialidad materiales para la industria -- Recomendaciones estratégicas especialidad Automotor -- Recomendaciones estratégicas especialidad Textil, confección y diseño -- Recomendaciones estratégicas especialidad construcción e infraestructura -- Recomendaciones estratégicas Sennova -- Servicios tecnológicos -- Introducción e información general -- Planteamiento de la necesidad u oportunidad -- Objetivos -- Desarrollo de la vigilancia científico-tecnológica -- Resultados de vigilancia tecnológica con base en análisis de patentes -- Identificación de tecnologías y sublíneas tecnológicas -- Comportamiento de los aceros -- Vigilancia normativa y regulatoria -- Vigilancia tecnológica -- Vigilancia competitiva -- Vigilancia comercial -- Resultados -- Conclusiones y recomendacionesna556 página

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder