A Pharmacokinetic Model for Multiple-Dose Dynamics and Long-Term Treatment Effectiveness

This paper presents a novel pharmacokinetic model that utilizes Time Scale Calculus to analyze the dynamics of blood concentration resulting from multi-dose treatments. The proposed model offers a closed-form solution, termed the "Generalized Bateman function", which characterizes the blood concentration dynamics of orally administered multiple dosage regimens. We also investigate the asymptotic properties of this function to describe the long-term dynamics associated with specific dosage plans. Notably, we establish the ubiquitous existence of effective dosage schedules, meaning that a medical practitioner can always formulate a prescription ensuring that a patient's long-term blood concentration levels remain within a desired range. Furthermore, our framework highlights how different metabolisms can significantly influence long-term blood concentration dynamics in response to the same dosage. Lastly, we employ anecdotal treatment responses to Efavirenz as an illustrative example, demonstrating how individuals with distinct biological characteristics may require different dosage regimens to maintain effective drug blood concentrations over an extended period.Comment: 39 pages, 8 figure

Evaluacion y planificacion agroecologica de los suelos de la finca el eden

Gráficas de medición de las variables visuales del suelo; fotografías documentando la actividad; diagramas de consolidadosLa evaluación de suelos se realizó con el fin de lograr una recopilación de información referente a la salud actual del mismo, en la finca el Edén, de acuerdo con las características encontradas, se propone una planificación agroecológica. Inicialmente se realizó un reconocimiento de La finca, su estado, la cobertura vegetal o uso actual de sus suelos, luego se seleccionaron 5 lugares para realizar en cada uno muestras de suelos y aplicar la metodología denominada: Evaluación visual del suelo, la cual se basa en la observación en campo, de las principales propiedades presentes en este, sin utilizar ninguna otra tecnología, ni el análisis tradicional de laboratorio. Se determinaron de esta manera: la estructura, la textura, la porosidad, la consistencia, el color, la presencia de micro y macro organismos, de cada una de las muestras de suelos que se tomaron. Esto permitió, reconocer que en la finca, existen 4 tipos diferentes de suelo y realizar una zonificación de la finca con base en el uso potencial que se podría hacer se estos. Con estos resultados, finalmente se propusieron algunas prácticas de manejo y algunos sistemas productivos basados en los principios de la agroecología, acordes con el ambiente, con el abordaje de los problemas sociales y económicos del entorno y las características intrínsecas de la finca.The soil evaluation was performed in order to achieve a collection of information about the current health of it, on the grounds of Eden, according to the features found, an agro-ecological planning is proposed. Initially, a recognition of the property, its condition, vegetation cover or current use of the soils was performed, then 5 points for each soil sample and apply a methodology called were selected: Visual assessment of soil, which is based on field observations, the main properties present in this, without using any other technology or traditional laboratory analysis. Were determined as follows: the structure, texture, porosity, consistency, color, presence of micro and macro organisms, each of the soil samples that were taken. This allowed, to recognize that on the farm, there are 4 different types of soil and make a zoning of the property based on the potential use that could be made are these. With these results, finally some management practices and some production systems based on the principles of agroecology, consistent with the environment, in addressing social and economic problems of the environment and the inherent characteristics of the farm were proposed

Comparison of eight degree-days estimation methods in four agroecological regions in Colombia.

Eight methods were used to estimate degree-days in four Colombian localities. Four methods have been previously proposed in literature: Simple Sine, Double Sine, Simple Triangle, and Double Triangle methods. The other four methods are proposed in this research: Simple Logistic, Double Logistic, Simple Normal, and Double Normal. The estimation of the degree-days through hourly temperature values was used as the reference standard method, and the four localities from where the temperature values were taken were the municipalities of Cajicá (Cundinamarca), Santa Elena (Antioquia), Carepa (Urabá Antioqueño), and Ciudad Bolivar (Zona cafetera Antioqueña). Degree-days obtained by all methods under study were compared through linear regression to those obtained by the reference standard method. There were differences in the correlation of each method to the reference when compared within each region and among regions. The Simple Logistic and Double Logistic methods showed the best performance with acceptable R2 values and considerably lower bias than the other methods. The poorest fit was found in Cajicá, where the average R2 was 0.571. For the regions of Santa Elena and Carepa, the average R2 was 0.756 and 0.733. The best fit was found in Ciudad Bolivar, with an average R2 of 0.826

Sulfur fertilization technology in the Argentine Pampas region : a review

Sulfur (S) deficiencies in grain crops have become increasingly frequent worldwide, including the Argentine Pampas region, located in South America. The objective of this work is to review recent research literature regarding S fertilization in the Argentine Pampas region, with emphasis on technological issues. The S fertilization in this region has grown sharply over recent years and, simultaneously, more scientific literature has been generated. A knowledge gap is recognized on field research studies related to elemental sulfur (ES) fertilization and its relative agronomic effectiveness in comparison to soluble S sources. By far, solid sulfate fertilizers are the most widespread S sources applied by farmers in the Pampas region. Nonetheless, application of liquid sources has increased over recent times. Overall, similar agronomic performance among sulfate sources has been reported. Additionally, similar effectiveness was documented between micronized ES and sulfate sources for different crops, with the exception of some site-specific conditions where effectiveness of sulfate sources may outperform ES. This review manuscript contributes to synthesize current knowledge regarding S fertilization technology and identify research needs in this matter.La frecuencia de ocurrencia de deficiencias de azufre (S) en cultivos de grano se incrementó a nivel mundial, incluyendo la Región Pampeana argentina, localizada en Sudamérica. El objetivo del trabajo es realizar una revisión de la literatura científica sobre fertilización azufrada en la Región Pampeana, con énfasis en aspectos tecnológicos. La adopción de la fertilización azufrada creció marcadamente en ésta región y simultáneamente aumentó la cantidad de publicaciones científicas en el tema. Sin embargo, existe una brecha de conocimiento sobre la fertilización con azufre elemental (AE) y su efectividad agronómica relativa a fuentes azufradas solubles. Los fertilizantes sulfatados sólidos son, con creces, las fuentes de S más utilizadas en la Región Pampeana aunque la aplicación de fuentes líquidas se incrementó en los últimos tiempos. En términos generales, se ha reportado similar efectividad agronómica entre fuentes sulfatadas. Asimismo, se ha observado similar efectividad agronómica entre el AE micronizado y fuentes sulfatadas en diferentes cultivos, con la excepción de condiciones sitio-específicas donde las fuentes sulfatadas pueden presentar una mejor performance. Esta revisión contribuye a sintetizar el conocimiento vigente sobre tecnología de fertilización azufrada y puede resultar de interés para establecer necesidades de investigación en este tema.EEA PergaminoFil: Torres Duggan, Martín. Tecnoagro; ArgentinaFil: Melgar, Ricardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Pergamino. Departamento Suelo y Fertilidad; ArgentinaFil: Rodríguez, Monica Beatriz. Universidad de Buenos Aires. Facultad de Agronomía. Cátedra de Fertilidad y Fertilizantes; ArgentinaFil: Lavado, Raúl Silvio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Parque Centenario. Instituto de Investigaciones en Biociencias Agrícolas y Ambientales; ArgentinaFil: Ciampitti, Ignacio Antonio. Purdue University. Agronomy Department; Estados Unido

Scaling Equipment Effect on Technical–Tactical Actions in U-13 Basketball Players: A Maturity Study

The aim of this study was to analyse the performance of technical–tactical actions in two different types of tournaments and the influence of biological age on the performance of young basketball players. Thirty-seven under-13 male basketball players (age = 12.91 ± 0.57 years) were selected from four southeast Spanish teams to participate in two different tournaments on two consecutive days. The following technical–tactical variables were analysed: (a) Ball Obtained; (b) Ball Handler Player Actions; (c) Ball Handler Player Finished Actions; and (d) Ball Handler Shooting Performance. The results showed that reduced basket height and a closer three-point line promoted a higher number of balls obtained, 1 vs. 1 situations, finished ball player actions, shots, and the efficacy of offence phases. There was a significant increase in the number of balls obtained, 1 vs. 1 situations played, the number of plays finished with a lay-up or shot, number of received personal fouls, number of plays finished in 1 vs. 2, and those finished in equality and inferiority with a high defence opposition. The modified version presented a higher number of technical–tactical actions in Late Maturity players. The authors of this study believe that it is necessary to conduct more experimental studies and use bio-banding strategies in young basketball competitions.This research was funded by the Basket 2.0 project (No. 21076/PDC/19) granted by Fundación Séneca—Agencia de Ciencia y Tecnologia de la Región de Murcia and Consejo Superior de Deportes (19/UPB/21)

Methods of overcoming dormancy in seeds and initial development of Black Wattle

The objective of this work was to analyze the efficacy of different methods of dormancy break in seeds of Acacia mearnsii De Wild. The work was performed at the UFSM Botany Lab and Forest Nursery, in Frederico Westphalen, RS. The treatments were: (T1) control; (T2) immersion in hot water (90 °C) for 5 minutes, followed by rest; (T3) immersion in hot water (90 °C) for 10 minutes, followed by rest; (T4) chemical scarification with concentrated sulfuric acid for 3 minutes, followed by washing under running water; (T5) chiseling with concentrated sulfuric acid for 5 minutes, followed by washing under running water. The seeds were sown in plastic trays with Oxisol and vermiculite. The results were submitted to analysis of variance and data were differentiated by Test t with 5% of probability. The most efficient treatment to overcome dormancy was T2, presenting 81.29% of germinated seeds and IVG of 18.23 days for germination. This treatment was also the best for the variables of physical vigor and best performing root length and aerial part, and did not differ from improved treatments for diameter and green mass weight

Effect of a Fibrolytic Enzymatic Extract from Cellulomonas flavigena on In Vitro Degradation and In Vivo Digestibility and Productive Performance of Lambs

An enzymatic extract from Cellulomonas flavigena was evaluated at 0, 2.5, 7.5, 12.5 mL/kg DM of total mixed ration (TMR) on the in vitro degradation of DM, NDF and ADF and in vivo at 0, 5.0 and 7.5 mL of extract per kg DM of TMR to determine the digestibility and productive performance of lambs fed a TMR made up of 60% forage. Twenty four Pelibuey-Kathadin lambs were used in the trial. The in vitro degradation of ADF showed a linear (P<0.05) response from 6 to 72 h. There was no effect on DM intake, daily gain or feed conversion. The enzymatic dose tended to linearly decrease the apparent digestibility of DM (P=0.06), NDF (P=0.10) and ADF (P=0.06). The N-NH3 concentration showed a linear decrease (P=0.002) and total VFA concentration was linearly (P<0.001) increased. The incorporation of extract of Cellulomonas flavigena in the diet increased in vitro degradation of cellulose in terms of ADF but did not increase the digestion or productive performance of lambs

Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy

OBJECTIVE: The Notch pathway has been linked to pulmonary hypertension, but its role in systemic hypertension and, in particular in left ventricular hypertrophy (LVH), remains poorly understood. The main objective of this work was to analyse the effect of inhibiting the Notch pathway on the establishment and maintenance of angiotensin II (Ang-II)-induced arterial hypertension and LVH in adult mice with inducible genetic deletion of γ-secretase, and to test preclinically the therapeutic efficacy of γ-secretase inhibitors (GSIs). BASIC METHODS: We analysed Ang-II responses in primary cultures of vascular smooth muscle cells obtained from a novel mouse model with inducible genetic deletion of the γ-secretase complex, and the effects of GSI treatment on a mouse cardiac cell line. We also investigated Ang-II-induced hypertension and LVH in our novel mouse strain lacking the γ-secretase complex and in GSI-treated wild-type mice. Moreover, we analysed vascular tissue from hypertensive patients with and without LVH. MAIN RESULTS: Vascular smooth muscle cells activate the Notch pathway in response to Ang-II both 'in vitro' and 'in vivo'. Genetic deletion of γ-secretase in adult mice prevented Ang-II-induced hypertension and LVH without causing major adverse effects. Treatment with GSI reduced Ang-II-induced hypertrophy of a cardiac cell line 'in vitro' and LVH in wild-type mice challenged with Ang-II. We also report elevated expression of the Notch target HES5 in vascular tissue from hypertensive patients with LVH compared with those without LVH. CONCLUSION: The Notch pathway is activated in the vasculature of mice with hypertension and LVH, and its inhibition via inducible genetic γ-secretase deletion protects against both conditions. Preliminary observations in hypertensive patients with LVH support the translational potential of these findings. Moreover, GSI treatment protects wild-type mice from Ang-II-induced LVH without affecting blood pressure. Our results unveil the potential use of GSIs in the treatment of hypertensive patients with LVH.Juan de la Cierva postdoctoral contract from MINECO [JCI-2011-09663]; MINECO; ProCNIC Foundation; Spanish Ministry of Economy and Competitivity (MINECO) [SAF2013-46663-R]; Instituto de Salud Carlos III [RD12/0042/0028, RD12/0042/0009, MS-00151]; Inserm (jeune chercheur accueilli)S

Clinical Approach to Patients with Moderate-to-Severe Atopic Dermatitis: A Spanish Delphi Consensus

Despite emerging evidence and advances in the management of atopic dermatitis there a lack of consensus regarding the diagnostic criteria, therapeutic approach, method to assess severity, and patient follow-up for this condition. An expert consensus study was conducted to provide recommendations on the management of patients with moderate-to-severe atopic dermatitis. The study used Delphi-like methodology based on a literature review, a summary of the scientific evidence, and a 2-round survey. The agreement of 60 panellists on 21 statements was evaluated. Consensus was pre-defined as ≥ 80% agreement of all respondents. In the first round 6 statements reached consensus. Unanimous consensus was achieved regarding therapeutic goals and patient satisfaction (maintained in the long term and periodic goals reassessment recommended every 3-6 months). In the second round, half of the statements reached consensus, all related to patient follow-up, treatment goals, and atopic comorbidities. The statements that did not reach consensus were related to diagnosis (biomarkers, allergy, and food testing) and starting patients on conventional systemic treatment rather than advanced treatment. The study assessed expert opinion regarding a variety of topics related to the clinical approach to patients with moderate-to-severe atopic dermatitis, in order to provide guidance on the diagnosis and management of patients with atopic dermatitis

El Abuso de Poder Jerárquico (Power Harassment)

En este trabajo se va a realizar en primer lugar una revisión bibliográfica sobre aquella información que se ha recopilado sobre el Abuso de Poder Jerárquico (Power Harassment). En segundo lugar, se va a proceder a explicar un estudio piloto que se ha llevado a cabo en la población de trabajadores pertenecientes a la Universidad de Zaragoza, tanto en el campus de Zaragoza como en el de Teruel. Este estudio se llevó a cabo para conseguir los siguientes objetivos: -­‐ Estudiar y analizar la documentación sobre el Abuso de Poder Jerárquico. -­‐ Desarrollar un instrumento de medida para la evaluación del Abuso de Poder Jerárquico. -­‐ Estudiar las relaciones existentes entre las variables de Satisfacción Laboral y Mobbing con el Abuso de Poder Jerárquico. -­‐ Establecer líneas de investigación futuras en base a los resultados obtenidos