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Abstract Background Chronic pain is a major health issue and rapid population ageing exacerbates the burden to health systems in countries like Germany. Nonpharmacological interventions (NPIs) are essential in pain care and the prioritization of active NPIs is emphasized in guidelines. This paper examines the utilization of NPIs for chronic pain management in community-dwelling older adults with a certified need of care in Berlin, Germany. Methods Cross-sectional data was collected through standardized face-to-face surveys with older adults (≥65 years), using validated instruments (e.g., Brief Pain Inventory), and structured lists for NPI utilization. Categorization into active and passive NPIs was performed through a literature-based, iterative process by an interdisciplinary team. For not normally distributed data, non-parametric tests were used as appropriate. Logistic regression was conducted for multivariate analysis. Results In total, 250 participants were included in this analysis (aged 65-104, x̅ = 81.8, 68.8% female). Most (92%) use NPIs for chronic pain management: 85.6% use active NPIs, 50.4% active movement and only 5.6% use solely passive approaches. Most common NPIs are distraction, thermotherapy/compresses, and physiotherapy. The odds of utilizing physiotherapy are three times higher for those with high educational status when compared to those with low education while those with low educational status had higher odds of using thermotherapy/compresses. Conclusions In our sample, most community-dwelling older adults with a certified need of care use active NPIs for chronic pain management with about half using active movement approaches. Considering the high vulnerability of this population, physiotherapy (in the form of therapeutic exercise) is a particularly appropriate intervention, and it was the third most frequent NPI in our sample. However, there is a social gradient in the utilization of physiotherapy for chronic pain management which might be rooted in issues around awareness, appeal, and access to such measures. It is important to take socioeconomic differences into account when planning the care for older chronic pain patients but also when designing research or user-friendly guidelines for this target group. Trial registration Ethical approval from the Ethics Committee of Charité - Universitätsmedizin Berlin (EA1/368/14) and study registration with the Central Study Register (ZSR no. 20009093).

Indigenous peoples of Taiwan, the most disadvantaged of the minority groups, account for only about 2.4% of the total population. Within the Minnan dominant society of Taiwan, the Indigenous minority groups are confronted by critical language loss often attributed to cultural and structural assimilation factors. This study aims to investigate factors related with Austronesian language retention for indigenous peoples in Taiwan. Results reveal, Austronesian language fluency is reduced by education, but maintained by age, residing in an ethnic enclave during childhood, and practicing parental endogamy.

A field experiment was carried out to quantify the effect of a native bacterial inoculant on the growth, yield, and quality of the wheat crop, under different nitrogen (N) fertilizer rates in two agricultural seasons. Wheat was sown under field conditions at the Experimental Technology Transfer Center (CETT-910), as a representative wheat crop area from the Yaqui Valley, Sonora México. The experiment was conducted using different doses of nitrogen (0, 130, and 250 kg N ha−1) and a bacterial consortium (BC) (Bacillus subtilis TSO9, B. cabrialesii subsp. tritici TSO2T, B. subtilis TSO22, B. paralicheniformis TRQ65, and Priestia megaterium TRQ8). Results showed that the agricultural season affected chlorophyll content, spike size, grains per spike, protein content, and whole meal yellowness. The highest chlorophyll and Normalized Difference Vegetation Index (NDVI) values, as well as lower canopy temperature values, were observed in treatments under the application of 130 and 250 kg N ha−1 (the conventional Nitrogen dose). Wheat quality parameters such as yellow berry, protein content, Sodium dodecyl sulfate (SDS)-Sedimentation, and whole meal yellowness were affected by the N dose. Moreover, the application of the native bacterial consortium, under 130 kg N ha−1, resulted in a higher spike length and grain number per spike, which led to a higher yield (+1.0 ton ha−1 vs. un-inoculated treatment), without compromising the quality of grains. In conclusion, the use of this bacterial consortium has the potential to significantly enhance wheat growth, yield, and quality while reducing the nitrogen fertilizer application, thereby offering a promising agro-biotechnological alternative for improving wheat production.

El perfeccionamiento continuo en materia educacional que ocurre en los momentos actuales, demanda de profesionales y familias con una amplia preparación con la exigencia de contribuir a la formación educativa integral de la personalidad de los (las) niños (as), adolescentes y jóvenes que garantice calidad de vida y que les permita un desempeño activo en las diversas áreas del desarrollo social. Es por ello que la actividad comunicativa verbal, desde la expresión oral contextualizadas en la vida, constituye un elemento rector en los que se debe centrar la atención. Ello, sin duda se convierte en una de las problemáticas de mayor incidencia en la Educación Preescolar, en las últimas décadas. Los análisis realizados permiten corroborar que existen insuficiencias en la preparación de la familia de la primera infancia para contribuir con el desarrollo del lenguaje oral y la comprensión vivencial en los niños de cuarto año de vida, lo que implica que el vocabulario de los niños (as) en esta fase etaria evidencie limitación La investigación tiene como objetivo ofrecer sugerencias de actividades, a partir de vivencias cotidianas de la familia, de modo que puedan ser utilizados para el enriquecimiento del vocabulario y la comprensión oral. La validez de la propuesta se constata con el uso de diferentes métodos, procedimientos y alternativas a favor de la aplicación de talleres con la familia, lo que a su vez constituye una vía factible, viable y valida en la solución del problema planteado.

Undoubtedly, the term public space is common to all citizens, for several centuries these places have been central points in the development of both cities and entire civilizations. The patrimonial public space, built by human beings, with the city as the main paradigm is, above all, a space to be occupied, to serve and to be used, to fill and to empty with real or symbolic presence, to interact with other people in an environment and to interact with it. The current scenario in which cities develop and their increasing competitiveness has evidenced the existing limitations and shortcomings in the management of their public heritage spaces and, specifically, in the study of their identity. In response to this, the present research aims to propose a procedure for the evaluation of the identity of the public heritage spaces of a city, proposes, as a novelty, the design of the contextualized procedure, holistically addresses the problem of study from the systematization of the existing theoretical-methodological foundations in the management of public heritage spaces; in addition, the role and link between the marketing management of a city and the identity of these spaces are established. In this logic of analysis, pertinent methods and techniques are used and integrated in a coherent manner, which allow the study of the identity of public heritage spaces in order to contribute to increase the effectiveness of their management in the urban environment.

La presente investigación enfrenta una problemática relacionada con el tratamiento al desarrollo del lenguaje oral en la Primera Infancia. Derivada de las insuficiencias como: bajo nivel en el vocabulario básico, falta de coherencia y coordinación de las ideas, así como el uso de palabras aisladas que no conforman una oración corta, provocando contradicción entre el desarrollo del lenguaje oral de los niños del segundo año de vida en correspondencia con la edad cronológica y los objetivos básicos del año y los logros del desarrollo para estas edades. El tema seleccionado, tiene como punto de partida en un primer momento la observación fáctica de las relaciones comunicativas de los niños, concebida desde la relación progreso comunicacional - edad cronológica. A partir de un estudio de caso se incorporan un conjunto de acciones de intervención para atender el retraso en el desarrollo del lenguaje oral de un infante del salón de segundo año de vida del Círculo Infantil XX Aniversario, mediante la búsqueda de información y relaciones vivenciales que condicionan las limitaciones en el lenguaje oral. La experiencia de la autora como educadora motivo la realización de este estudio para dar tratamiento oportuno al retraso en el lenguaje. Los resultados obtenidos fueron sobre la base de la utilización del estudio de caso como método científico y técnicas investigativas tales como: métodos empíricos y el método descriptivo.

The tangible immovable cultural heritage is made concrete in the constructions or the set of them made by the man from the prehistory until the present time that represent the identity of the city. Matanzas is an example of city that possesses a high wealth as for cultural and patrimonial values that are sample of identity. As a result of the need for cities to adapt to the new changes existing worldwide, tourist destinations emerge, which must consolidate their identity in order to differentiate themselves from other cities and respond to the demands of the market. The purpose of this research is to identify the tangible immovable cultural heritage in terms of local tourism development. It is of an exploratory-descriptive type and uses theoretical and empirical methods that validate the procedure and its practical application in the city of Matanzas. Among the main results are: the application of the designed procedure in the case of the city of Matanzas, which allowed establishing the most identifying manifestations for its valorization and the integration of all the organizations that govern the immovable tangible cultural heritage in that city, which makes possible the modeling of the guidelines for the development of local tourism.

En la presente investigación se realiza un análisis de sensibilidad de cuatro parametrizaciones de Capa Límite Planetaria (PBL) utilizados en la simulación de un evento de niebla densa ocurrido el 4 de enero de 2019 en el Aeropuerto Internacional “José Martí” de La Habana. Para ello, en primer lugar, se evalúa el rendimiento de diferentes algoritmos que estiman la visibilidad horizontal para seleccionar el más óptimo para el área de estudio. En segundo lugar, se estudia el comportamiento de dicho algoritmo y un grupo de variables meteorológicas relacionadas con eventos de niebla/neblina con los diferentes esquemas de PBL. El análisis conduce a que los algoritmos relacionados con la depresión del punto de rocío, presentaron los mejores resultados, con índices de detección crítica de 0.75. Todos los esquemas de PBL en el horario de ocurrencia del evento subestimaron los valores de humedad relativa en aproximadamente 2 y 10 %, sobreestimaron la temperatura del punto de rocío y la temperatura del aire en rangos aproximados de 0.5-2.5 °C y de 0.5-3.5 °C respectivamente, así como la velocidad del viento entre 2 y 3 m/s. La parametrización de PBL más consistente con la realidad observada fue ACM2, presentando los menores errores estadísticos y un índice de detección crítica de 0.87. Esto sugiere una mejor representación de los procesos físicos que ocurren en la PBL y por tanto una mayor habilidad en la predicción y pronóstico de eventos de niebla/neblina en el área de estudio.

A sensitivity study is performed with Lin, Morrison 2-moment, WSM5, and WSM6 microphysics schemes for the numerical forecast of the low-level wind shear (LLWS) derived from storms at "José Martí" International Airport using the Weather Research and Forecasting (WRF) model. As case studies, we select four storms associated with synoptic patterns that cause dangerous conditions at this aerodrome. The simulations are made for several atmosphere low levels. The influence of obstacles of comparable height with the atmospheric low-levels was taken into account to obtain the wind fields with mass consistent correction. In this paper, the evaluation process of surface variables is focus on temperature, surface pressure, relative humidity, and precipitation. The schemes did not show bigger differences among themselves. From all of the variables, relative humidity exhibits the worst results. The best performance for precipitation forecast was obtained with WSM5 in rainy season (May-October) and Lin in dry season (November-April). For LLWS sensitivity, results indicate that each hydrometeor particle concentration predicted by tested microphysics has an influence on vertical wind profiles, particularly, for low-levels. WSM5 and Lin seems the best options for microphysics scheme, although that is not conclusive.

The study of above- and below-ground organ plant coordination is crucial for understanding the biophysical constraints and trade-offs involved in species’ performance under different environmental conditions. Environmental stress is expected to increase constraints on species trait combinations, resulting in stronger coordination among the organs involved in the acquisition and processing of the most limiting resource. To test this hypothesis, we compared the coordination of trait combinations in 94 tree seedling species from two tropical forest systems in Mexico: dry and moist. In general, we expected that the water limitation experienced by dry forest species would result in stronger leaf-stem-root coordination than light limitation experienced by moist forest species. Using multiple correlations analyses and tools derived from network theory, we found similar functional trait coordination between forests. However, the most important traits differed between the forest types. While in the dry forest the most central traits were all related to water storage (leaf and stem water content and root thickness), in the moist forest they were related to the capacity to store water in leaves (leaf water content), root efficiency to capture resources (specific root length), and stem toughness (wood density). Our findings indicate that there is a shift in the relative importance of mechanisms to face the most limiting resource in contrasting tropical forests.

En este estudio se evaluó la factibilidad de la aplicación de un esquema de relocalización de vórtice basado en un vórtice sintético en el sistema de pronóstico numérico de ciclones tropicales (CTs) NTHF (Numerical Tools for Hurricane Forecast), operativo en el Departamento de Meteorología del Instituto Superior de Tecnologías y Ciencias Aplicadas, Universidad de La Habana. Para ello, se seleccionaron como casos de estudios los huracanes Dorian y Lorenzo y la tormenta tropical Karen. La representación del vórtice sintético en toda la columna vertical se extrajo de las simulaciones de NTHF inicializado con los datos de 0.25 grados de resolución horizontal del GDAS (Global Data Asimilation System) del ciclo de 6 horas antes, y fue introducido en los campos de inicialización de NTHF obtenidos de las salidas pronóstico del modelo global GFS (Global Forcast System) con una resolución horizontal de 0.5 grados. En todos los casos las simulaciones se inicializaron a las 0000 UTC y las condiciones de frontera se actualizaron cada 6 horas. En los experimentos realizados se comprobó que el esquema de relocalización de vórtice representa un CT más estructurado aunque la inestabilidad dinámica causada por la introducción del vórtice sintético en el campo de fondo condicionó que el centro de los CTs se desarrollaran en un ambiente más seco y el centro del sistema fuera más frío, lo que propició un aumento de los errores medios en el pronóstico de trayectoria e intensidad, con respecto a los experimentos sin relocalización de vórtice.

Systemic therapies for pancreatic ductal adenocarcinoma (PDAC) remain unsatisfactory. Clinical prognosis is particularly poor for tumor subtypes with activating aberrations in the MYC pathway, creating an urgent need for novel therapeutic targets. To unbiasedly find MYC-associated epigenetic dependencies, we conducted a drug screen in pancreatic cancer cell lines. Here, we found that protein arginine N-methyltransferase 5 (PRMT5) inhibitors triggered an MYC-associated dependency. In human and murine PDACs, a robust connection of MYC and PRMT5 was detected. By the use of gain- and loss-of-function models, we confirmed the increased efficacy of PRMT5 inhibitors in MYC-deregulated PDACs. Although inhibition of PRMT5 was inducing DNA damage and arresting PDAC cells in the G2/M phase of the cell cycle, apoptotic cell death was executed predominantly in cells with high MYC expression. Experiments in primary patient-derived PDAC models demonstrated the existence of a highly PRMT5 inhibitor–sensitive subtype. Our work suggests developing PRMT5 inhibitor–based therapies for PDAC.

Abstract Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular‐informed therapy decisions in pancreatic ductal adenocarcinoma (PDAC) is currently neglectable. We present a longitudinal precision oncology platform based on functional model systems, including patient‐derived organoids, to identify chemotherapy‐induced vulnerabilities. We demonstrate that treatment‐induced tumor cell plasticity in vivo distinctly changes responsiveness to targeted therapies, without the presence of a selectable genetic marker, indicating that tumor cell plasticity can be functionalized. By adding a mechanistic layer to precision oncology, adaptive processes of tumors under therapy can be exploited, particularly in highly plastic tumors, such as pancreatic cancer.

Product information (PI) is a vital part of any medicinal product approved for use within the European Union and consists of a summary of products characteristics (SmPC) for healthcare professionals and package leaflet (PL) for patients, together with the product packaging. In this study, based on the English corpus of the EMA product information documents for all centrally approved medicinal products within the EU, a BERT sentence embedding model was used together with clustering and dimensional reduction techniques to identify sentence similarity clusters that could be candidates for standardization. A total of 1258 medicinal products were included in the study. From these, a total of 783 K sentences were extracted from SmPC and PL documents which were aggregated into a total of 284 and 129 semantic similarity clusters, respectively. The spread distribution among clusters shows separation into different cluster types. Examples of clusters with low spread include those with identical word embeddings due to current standardization, such as section headings and standard phrases. Others show minor linguistic variations, while the group with the largest variability contains variable wording but with significant semantic overlap. The sentence clusters identified could serve as candidates for further standardization of the PI. Moving from free text human wording to auto-generated text elements based on multiple-choice input for appropriate parts of the package leaflet and summary of product characteristics, could reduce both time and complexity for applicants as well as regulators, and ultimately provide patients and prescribers with documents that are easier to understand and better adapted for search availabilities.

Reseña de Arlett Cancino sobre Colombia y la guerra civil española. La voz de los intelectuales (Calambur, 2021) de Marta Ortiz Canseco (ed.). 550 p. ISBN: 9788483594872.

Purpose: There is increasing recognition of the importance of transparency and reproducibility in scientific research. This study aimed to quantify the extent to which programming code is publicly shared in pharmacoepidemiology, and to develop a set of recommendations on this topic., Methods: We conducted a literature review identifying all studies published in Pharmacoepidemiology and Drug Safety (PDS) between 2017 and 2022. Data were extracted on the frequency and types of programming code shared, and other key open science practices (clinical codelist sharing, data sharing, study preregistration, and stated use of reporting guidelines and preprinting). We developed six recommendations for investigators who choose to share code and gathered feedback from members of the International Society for Pharmacoepidemiology (ISPE)., Results: Programming code sharing by articles published in PDS ranged from 1.8% in 2017 to 9.5% in 2022. It was more prevalent among articles with a methodological focus, simulation studies, and papers which also shared record-level data., Conclusion: Programming code sharing is rare but increasing in pharmacoepidemiology studies published in PDS. We recommend improved reporting of whether code is shared and how available code can be accessed. When sharing programming code, we recommend the use of permanent digital identifiers, appropriate licenses, and, where possible, adherence to good software practices around the provision of metadata and documentation, computational reproducibility, and data privacy., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Studies using real-world data (RWD) can complement evidence from clinical trials and fill evidence gaps during different stages of a medicine's lifecycle. This review presents the experience resulting from the European Medicines Agency (EMA) pilot to generate RWE to support evaluations by EU regulators and down-stream decision makers from September 2021 to February 2023. A total of 61 research topics were identified for RWE generation during this period, covering a wide range of research questions, primarily generating evidence on medicines safety (22, 36%), followed by questions on the design and feasibility of clinical trials (11, 18%), drug utilization (10, 16%), clinical management (10, 16%), and disease epidemiology. A significant number of questions were related to the pediatric population and/or rare diseases. A total of 27 regulatory-led RWD studies have been conducted. Most studies were descriptive and aimed at estimating incidence and prevalence rates of clinical outcomes including adverse events or to evaluate medicines utilization. The review highlights key learnings to guide further efforts to enable the use and establish the value of real-world evidence (RWE) for regulatory decisions. For instance, there is a need to access additional fit-for-purpose and representative data, and to explore further means to provide timely evidence that meets regulatory timelines. The need for early interactions and close collaboration with study requesters, e.g., from the Agency's scientific Committees, to better understand the research question is equally important. Finally, the review provides our perspective on the way forward to maximize the potential of regulatory-led RWE generation., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Problem: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias., What We Did: The International Society for Pharmacoepidemiology (ISPE) and ISPOR-The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision-making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The overarching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision-making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility., Strategies to Disseminate and Facilitate Use: Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years., Conclusion: The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Product information (PI) is a vital part of any medicinal product approved for use within the European Union and consists of a summary of products characteristics (SmPC) for healthcare professionals and package leaflet (PL) for patients, together with the product packaging. In this study, based on the English corpus of the EMA product information documents for all centrally approved medicinal products within the EU, a BERT sentence embedding model was used together with clustering and dimensional reduction techniques to identify sentence similarity clusters that could be candidates for standardization. A total of 1258 medicinal products were included in the study. From these, a total of 783 K sentences were extracted from SmPC and PL documents which were aggregated into a total of 284 and 129 semantic similarity clusters, respectively. The spread distribution among clusters shows separation into different cluster types. Examples of clusters with low spread include those with identical word embeddings due to current standardization, such as section headings and standard phrases. Others show minor linguistic variations, while the group with the largest variability contains variable wording but with significant semantic overlap. The sentence clusters identified could serve as candidates for further standardization of the PI. Moving from free text human wording to auto-generated text elements based on multiple-choice input for appropriate parts of the package leaflet and summary of product characteristics, could reduce both time and complexity for applicants as well as regulators, and ultimately provide patients and prescribers with documents that are easier to understand and better adapted for search availabilities., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias., Methods: The International Society for Pharmacoepidemiology (ISPE) and ISPOR-The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision-making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The over-arching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision-making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility., Strategies to Disseminate and Facilitate Use: Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years., Conclusion: The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions., (Copyright © 2022. Published by Elsevier Inc.)