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BackgroundMusculoskeletal conditions account for 16% of global disability, resulting in a negative effect on patients and increasing demand for health care use. Triage directing patients to appropriate level intervention improving health outcomes and efficiency has been prioritized. We developed a musculoskeletal digital assessment routing tool (DART) mobile health (mHealth) system, which requires evaluation prior to implementation. Such innovations are rarely rigorously tested in clinical trials—considered the gold standard for evaluating safety and efficacy. This pilot study is a precursor to a trial assessing DART performance with a physiotherapist-led triage assessment. ObjectiveThe study aims to evaluate trial design, assess procedures, and collect exploratory data to establish the feasibility of delivering an adequately powered, definitive randomized trial, assessing DART safety and efficacy in an NHS primary care setting. MethodsA crossover, noninferiority pilot trial using an integrated knowledge translation approach within a National Health Service England primary care setting. Participants were patients seeking assessment for a musculoskeletal condition, completing a DART assessment and the history-taking element of a face-to-face physiotherapist-led triage in a randomized order. The primary outcome was agreement between DART and physiotherapist triage recommendation. Data allowed analysis of participant recruitment and retention, randomization, blinding, study burden, and potential barriers to intervention delivery. Participant satisfaction was measured using the System Usability Scale. ResultsOver 8 weeks, 129 patients were invited to participate. Of these, 92% (119/129) proceeded to eligibility assessment, with 60% (78/129) meeting the inclusion criteria and being randomized into each intervention arm (39/39). There were no dropouts and data were analyzed for all 78 participants. Agreement between physiotherapist and DART across all participants and all primary triage outcomes was 41% (32/78; 95% CI 22-45), intraclass correlation coefficient 0.37 (95% CI 0.16-0.55), indicating that the reliability of DART was poor to moderate. Feedback from the clinical service team led to an adjusted analysis yielding of 78% (61/78; 95% CI 47-78) and an intraclass correlation coefficient of 0.57 (95% CI 0.40-0.70). Participant satisfaction was measured quantitively using amalgamated System Usability Scale scores (n=78; mean score 84.0; 90% CI +2.94 to –2.94), equating to an “excellent” system. There were no study incidents, and the trial burden was acceptable. ConclusionsPhysiotherapist-DART agreement of 78%, with no adverse triage decisions and high patient satisfaction, was sufficient to conclude DART had the potential to improve the musculoskeletal pathway. Study validity was enhanced by the recruitment of real-world patients and using an integrated knowledge translation approach. Completion of a context-specific consensus process is recommended to provide definitive definitions of safety criteria, range of appropriateness, noninferiority margin, and sample size. This pilot demonstrated an adequately powered definitive trial is feasible, which would provide evidence of DART safety and efficacy, ultimately informing potential for DART implementation. Trial RegistrationClinicalTrials.gov NCT04904029; http://clinicaltrials.gov/ct2/show/NCT04904029 International Registered Report Identifier (IRRID)RR2-10.2196/31541

Alexander Sekita,1 Harald Unterweger,1 Sonja Berg,1 Sabine Ohlmeyer,2 Tobias Bäuerle,3 Kang H Zheng,4 Bram F Coolen,5 Aart J Nederveen,6 Claudia Cabella,7 Silvia Rossi,7 Erik SG Stroes,4 Christoph Alexiou,1 Stefan Lyer,1,* Iwona Cicha1,* 1ENT-Department, Section of Experimental Oncology Und Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, Universitätsklinikum Erlangen, Erlangen, Germany; 2Institute of Radiology, Universitätsklinikum Erlangen, Erlangen, Germany; 3Preclinical Imaging Platform Erlangen (PIPE), Universitätsklinikum Erlangen, Erlangen, Germany; 4Department of Vascular Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 5Department of Biomedical Engineering and Physics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 6Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands; 7Bracco Imaging SpA, Centro Ricerche Bracco, Colleretto Giacosa, Turin, Italy*These authors contributed equally to this workCorrespondence: Iwona Cicha, Universitätsklinikum Erlangen, Glückstr, 10a, Erlangen, 91054, Germany, Tel +49 9131 85 43953, Fax +49 9131 85 34828, Email Iwona.Cicha@uk-erlangen.dePurpose: In this study, a detailed characterization of a rabbit model of atherosclerosis was performed to assess the optimal time frame for evaluating plaque vulnerability using superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI).Methods: The progression of atherosclerosis induced by ballooning and a high-cholesterol diet was monitored using angiography, and the resulting plaques were characterized using immunohistochemistry and histology. Morphometric analyses were performed to evaluate plaque size and vulnerability features. The accumulation of SPIONs (novel dextran-coated SPIONDex and ferumoxytol) in atherosclerotic plaques was investigated by histology and MRI and correlated with plaque age and vulnerability. Toxicity of SPIONDex was evaluated in rats.Results: Weak positive correlations were detected between plaque age and intima thickness, and total macrophage load. A strong negative correlation was observed between the minimum fibrous cap thickness and plaque age as well as the mean macrophage load. The accumulation of SPION in the atherosclerotic plaques was detected by MRI 24 h after administration and was subsequently confirmed by Prussian blue staining of histological specimens. Positive correlations between Prussian blue signal in atherosclerotic plaques, plaque age, and macrophage load were detected. Very little iron was observed in the histological sections of the heart and kidney, whereas strong staining of SPIONDex and ferumoxytol was detected in the spleen and liver. In contrast to ferumoxytol, SPIONDex administration in rabbits was well tolerated without inducing hypersensitivity. The maximum tolerated dose in rat model was higher than 100 mg Fe/kg.Conclusion: Older atherosclerotic plaques with vulnerable features in rabbits are a useful tool for investigating iron oxide-based contrast agents for MRI. Based on the experimental data, SPIONDex particles constitute a promising candidate for further clinical translation as a safe formulation that offers the possibility of repeated administration free from the risks associated with other types of magnetic contrast agents.Keywords: atherosclerosis, plaque vulnerability, rabbit model, macrophages, histology, tissue iron, SPION-enhanced MRI

BackgroundHypertension is associated with working memory (WM) impairment. However, the benefits of Cogmed WM training for the hypertensive population are unknown. Therefore, we aimed to evaluate Cogmed’s effects on the WM performance of hypertensive individuals with executive function (EF) impairment.MethodsWe included 40 hypertensive patients (aged 40–70 years, 68% female) with EF impairment. They were randomized in a 1:1 ratio to receive 10 weeks of adaptive Cogmed training or a non-adaptive control training based on online games. The primary outcome was the WM performance. The secondary outcomes were verbal memory, visuospatial ability, executive function, global cognition, and the neuronal activity measured using functional magnetic resonance imaging (fMRI) under two WM task conditions: low (memorization of 4 spatial locations) and high (memorization of 6 spatial locations). An intention-to-treat (ITT) and per-protocol (PP) analysis were performed.ResultsCogmed did not show a significant effect on WM or any other cognitive outcome post-training. However, under the WM-low load and WM-high load conditions of the fMRI, respectively, the Cogmed group had an activation decrease in the right superior parietal lobe (ITT and PP analyses) and left inferior frontal lobe (PP analysis) in comparison to the control group.ConclusionThe Cogmed showed no effects on the WM performance of hypertensive individuals with EF impairment. However, activation decreases were observed in frontoparietal areas related to the WM network, suggesting a more efficient neuronal activity after training.

BackgroundMusculoskeletal disorders negatively affect millions of patients worldwide, placing significant demand on health care systems. Digital technologies that improve clinical outcomes and efficiency across the care pathway are development priorities. We developed the musculoskeletal Digital Assessment Routing Tool (DART) to enable self-assessment and immediate direction to the right care. ObjectiveWe aimed to assess and resolve all serious DART usability issues to create a positive user experience and enhance system adoption before conducting randomized controlled trials for the integration of DART into musculoskeletal management pathways. MethodsAn iterative, convergent mixed methods design was used, with 22 adult participants assessing 50 different clinical presentations over 5 testing rounds across 4 DART iterations. Participants were recruited using purposive sampling, with quotas for age, habitual internet use, and English-language ability. Quantitative data collection was defined by the constructs within the International Organization for Standardization 9241-210-2019 standard, with user satisfaction measured by the System Usability Scale. Study end points were resolution of all grade 1 and 2 usability problems and a mean System Usability Scale score of ≥80 across a minimum of 3 user group sessions. ResultsAll participants (mean age 48.6, SD 15.2; range 20-77 years) completed the study. Every assessment resulted in a recommendation with no DART system errors and a mean completion time of 5.2 (SD 4.44, range 1-18) minutes. Usability problems were reduced from 12 to 0, with trust and intention to act improving during the study. The relationship between eHealth literacy and age, as explored with a scatter plot and calculation of the Pearson correlation coefficient, was performed for all participants (r=–0.2; 20/22, 91%) and repeated with a potential outlier removed (r=–0.23), with no meaningful relationships observed or found for either. The mean satisfaction for daily internet users was highest (19/22, 86%; mean 86.5, SD 4.48; 90% confidence level [CL] 1.78 or –1.78), with nonnative English speakers (6/22, 27%; mean 78.1, SD 4.60; 90% CL 3.79 or –3.79) and infrequent internet users scoring the lowest (3/22, 14%; mean 70.8, SD 5.44; 90% CL 9.17 or –9.17), although the CIs overlap. The mean score across all groups was 84.3 (SD 4.67), corresponding to an excellent system, with qualitative data from all participants confirming that DART was simple to use. ConclusionsAll serious DART usability issues were resolved, and a good level of satisfaction, trust, and willingness to act on the DART recommendation was demonstrated, thus allowing progression to randomized controlled trials that assess safety and effectiveness against usual care comparators. The iterative, convergent mixed methods design proved highly effective in fully evaluating DART from a user perspective and could provide a blueprint for other researchers of mobile health systems. International Registered Report Identifier (IRRID)RR2-10.2196/27205

The therapeutic use of tyrosine kinase inhibitors (TKIs) represents one of the successful strategies for the treatment of glioblastoma (GBM). Pyrazolo[3,4-d]pyrimidines have already been reported as promising small molecules active as c-Src/Abl dual inhibitors. Herein, we present a series of pyrazolo[3,4-d]pyrimidine derivatives, selected from our in-house library, to identify a promising candidate active against GBM. The inhibitory activity against c-Src and Abl was investigated, and the antiproliferative profile against four GBM cell lines was studied. For the most active compounds endowed with antiproliferative efficacy in the low-micromolar range, the effects toward nontumoral, healthy cell lines (fibroblasts FIBRO 2-93 and keratinocytes HaCaT) was investigated. Lastly, the in silico and in vitro ADME properties of all compounds were also assessed. Among the tested compounds, the promising inhibitory activity against c-Src and Abl (Ki 3.14 µM and 0.44 µM, respectively), the irreversible, apoptotic-mediated death toward U-87, LN18, LN229, and DBTRG GBM cell lines (IC50 6.8 µM, 10.8 µM, 6.9 µM, and 8.5 µM, respectively), the significant reduction in GBM cell migration, the safe profile toward FIBRO 2-93 and HaCaT healthy cell lines (CC50 91.7 µM and 126.5 µM, respectively), the high metabolic stability, and the excellent passive permeability across gastrointestinal and blood–brain barriers led us to select compound 5 for further in vivo assays.

BackgroundMusculoskeletal conditions account for 16% of global disability, resulting in a negative effect on millions of patients and an increasing demand for health care use. Digital technologies to improve health care outcomes and efficiency are considered a priority; however, innovations are rarely tested with sufficient rigor in clinical trials, which is the gold standard for clinical proof of safety and efficacy. We have developed a new musculoskeletal digital assessment routing tool (DART) that allows users to self-assess and be directed to the right care. DART requires validation in a real-world setting before implementation. ObjectiveThis pilot study aims to assess the feasibility of a future trial by exploring the key aspects of trial methodology, assessing the procedures, and collecting exploratory data to inform the design of a definitive randomized crossover noninferiority trial to assess DART safety and effectiveness. MethodsWe will collect data from 76 adults with a musculoskeletal condition presenting to general practitioners within a National Health Service (NHS) in England. Participants will complete both a DART assessment and a physiotherapist-led triage, with the order determined by randomization. The primary analysis will involve an absolute agreement intraclass correlation (A,1) estimate with 95% CI between DART and the clinician for assessment outcomes signposting to condition management pathways. Data will be collected to allow the analysis of participant recruitment and retention, randomization, allocation concealment, blinding, data collection process, and bias. In addition, the impact of trial burden and potential barriers to intervention delivery will be considered. The DART user satisfaction will be measured using the system usability scale. ResultsA UK NHS ethics submission was done during June 2021 and is pending approval; recruitment will commence in early 2022, with data collection anticipated to last for 3 months. The results will be reported in a follow-up paper in 2022. ConclusionsThis study will inform the design of a randomized controlled crossover noninferiority study that will provide evidence concerning mobile health DART system clinical signposting in an NHS setting before real-world implementation. Success should produce evidence of a safe, effective system with good usability, potentially facilitating quicker and easier patient access to appropriate care while reducing the burden on primary and secondary care musculoskeletal services. This rigorous approach to mobile health system testing could be used as a guide for other developers of similar applications. Trial RegistrationClinicalTrials.gov NCT04904029; http://clinicaltrials.gov/ct2/show/NCT04904029 International Registered Report Identifier (IRRID)PRR1-10.2196/31541

BackgroundMusculoskeletal conditions account for 16% of global disability, resulting in a negative effect on millions of patients and an increasing burden on health care utilization. Digital technologies that improve health care outcomes and efficiency are considered a priority; however, innovations are often inadequately developed and poorly adopted. Further, they are rarely tested with sufficient rigor in clinical trials—the gold standard for clinical proof of efficacy. We have developed a new musculoskeletal Digital Assessment Routing Tool (DART) that allows users to self-assess and be directed to the right care. DART requires usability testing in preparation for clinical trials. ObjectiveThis study will use the iterative convergent mixed methods design to assess and mitigate all serious usability issues to optimize user experience and adoption. Using this methodology, we will provide justifiable confidence to progress to full-scale randomized controlled trials when DART is integrated into clinical management pathways. This study protocol will provide a blueprint for future usability studies of mobile health solutions. MethodsWe will collect qualitative and quantitative data from 20-30 participants aged 18 years and older for 4 months. The exact number of participants recruited will be dependent on the number of iterative cycles required to reach the study end points. Building on previous internal testing and stakeholder involvement, quantitative data collection is defined by the constructs within the ISO 9241-210-2019 standard and the system usability scale, providing a usability score for DART. Guided by the participant responses to quantitative questioning, the researcher will focus the qualitative data collection on specific usability problems. These will then be graded to provide the rationale for further DART system improvements throughout the iterative cycles. ResultsThis study received approval from the Queen Mary University of London Ethics of Research Committee (QMREC2018/48/048) on June 4, 2020. At manuscript submission, study recruitment was on-going, with data collection to be completed and results published in 2021. ConclusionsThis study will provide evidence concerning mobile health DART system usability and acceptance determining system improvements required to support user adoption and minimize suboptimal system usability as a potential confounder within subsequent noninferiority clinical trials. Success should produce a safe effective system with excellent usability, facilitating quicker and easier patient access to appropriate care while reducing the burden on primary and secondary care musculoskeletal services. This deliberately rigorous approach to mobile health innovation could be used as a guide for other developers of similar apps. International Registered Report Identifier (IRRID)DERR1-10.2196/27205

Resumen El objetivo de este trabajo es analizar la población de mujeres uruguayas que finalizan su vida reproductiva sin hijos. Además de cuantificar el fenómeno, se busca responder las siguientes preguntas: ¿qué rasgos socioeconómicos las caracterizan?; ¿cuáles son las trayectorias típicas que conducen a la nuliparidez?; ¿en qué medida es el resultado de aspiraciones reproductivas frustradas o de la voluntad de no tener hijos? Para responder estas preguntas, se utiliza una estrategia de métodos combinados que integra datos cuantitativos y cualitativos. Los resultados muestran que la proporción de nulíparas descendió aproximadamente de 25% a 10%, entre las nacidas entre 1900 y 1960, y que en los datos más recientes se detecta un incipiente incremento. Además, hay una mayor proporción de nulíparas entre las mujeres de nivel educativo alto. Finalmente, la tipologización de trayectorias hacia la nuliparidez definitiva reafirma la heterogeneidad de caminos y atributos: aunque se identificaron trayectorias guiadas por la intención de no tener hijos, un conjunto importante de mujeres llega a la nuliparidez como una consecuencia no buscada de la postergación de la maternidad.

PhotoAcoustic Imaging (PAI) is a biomedical imaging modality currently under evaluation in preclinical and clinical settings. In this work, ICG is coupled to an integrin binding vector (ICG-RGD) to combine the good photoacoustic properties of ICG and the favourable αvβ3-binding capabilities of a small RGD cyclic peptidomimetic. ICG-RGD is characterized in terms of physicochemical properties, biodistribution and imaging performance. Tumor uptake was assessed in subcutaneous xenograft mouse models of human glioblastoma (U-87MG, high αvβ3 expression) and epidermoid carcinoma (A431, low αvβ3 expression). ICG and ICG-RGD showed high PA signal in tumors already after 15 min post-injection. At later time points the signal of ICG rapidly decreased, while ICG-RGD showed sustained uptake in U-87MG but not in A431 tumors, likely due to the integrin-mediated retention of the probe. In conclusion, ICG-RGD is a novel targeted contrast agents for PAI with superior biodistribution, tumor uptake properties and diagnostic value compared to ICG. Keywords: Indocyanine green, Tumor targeting, Contrast agents, Photoacoustic imaging, αvβ3-Integrin, Optoacoustic imaging

BACKGROUND: In recent years, fertility rates have declined substantially in most Latin American countries. Uruguay has been at the forefront of this regional process, as the country's total fertility rate plummeted from 2 children per woman in 2015 to 1.37 in 2021 (and continued to drop to 1.28 in 2022, according to preliminary data). OBJECTIVE: We decompose fertility decline by age and birth order in Uruguay, and identify the probable mechanisms (e.g., postponement, stopping) behind this decline. METHODS: Combining census data and vital statistics, we estimate period fertility rates by age and conditional period fertility rates by birth order and age. We also decompose the relative contribution of decline in each age and birth order to total decline in TFR. RESULTS: Our findings suggest that the postponement of births, especially among adolescent and very young women, was the main driver of the big fertility decline. Additionally, the fall in higher-order births, mostly among middle-aged women, played a significant role in the overall decline. The findings also reveal an increase of nearly two years in age at first birth between 2016 and 2021. CONCLUSIONS: This unprecedented decline in fertility appears to be leveling off. Moreover, we expect that some of the births by adolescents and young women that were avoided during the big fertility decline will take place at some point in the future, probably generating a slight rebound in the total fertility rate. CONTRIBUTION: Our paper is the first to identify the demographic mechanisms leading to lowest-low fertility in Uruguay. It also contributes to discussions on the impact of the current adolescent fertility decline in short- and medium-term fertility trends. [ABSTRACT FROM AUTHOR]

This article makes a qualitative analysis of what constitutes the academic work in its overlapping elements and processes. There is a joint analysis of theory and facts based on discourse analysis theory to observe intrinsic aspects that put creativity as an essential product of academic work, and extrinsic aspects necessary to establish trust and dignity as necessary assumptions to achieve its goal. We hope this approach become an available tool to protect creativity against abuses of power and to show how one builds a balanced academic work within an ethical dimension, preventing the construction of a fallacious product.

In this work we analyze potential environmental drivers of malaria cases in Northwestern Argentina. We inspect causal links between malaria and climatic variables by means of the convergent cross mapping technique, which provides a causality criterion from the theory of dynamic systems. Analysis is based on 12 years of weekly malaria P. vivax cases in Tartagal, Salta, Argentina-at the southern fringe of malaria incidence in the Americas-together with humidity and temperature time-series spanning the same period. Our results show that there are causal links between malaria cases and both maximum temperature, with a delay of five weeks, and minimum temperature, with delays of zero and twenty two weeks. Humidity is also a driver of malaria cases, with thirteen weeks delay between cause and effect. Furthermore we also determined the sign and strength of the effects. Temperature has always a positive non-linear effect on cases, with maximum temperature effects more pronounced above 25°C and minimum above 17°C, while effects of humidity are more intricate: maximum humidity above 85% has a negative effect, whereas minimum humidity has a positive effect on cases. These results might be signaling processes operating at short (below 5 weeks) and long (over 12 weeks) time delays, corresponding to effects related to parasite cycle and mosquito population dynamics respectively. The non-linearities found for the strength of the effect of temperature on malaria cases make warmer areas more prone to higher increases in the disease incidence. Moreover, our results indicate that an increase of extreme weather events could enhance the risks of malaria spreading and re-emergence beyond the current distribution. Both situations, warmer climate and increase of extreme events, will be remarkably increased by the end of the century in this hot spot of climate change.

New images from Mars rover Curiosity display millimetric, elongate stick- like structures in the fluvio-lacustrine deposits of Vera Rubin Ridge, the depositional environment of which has been previously acknowledged as habitable. Morphology, size and topology of the structures are yet incompletely known and their biogenicity remains untested. Here we provide the first quantitative description of the Vera Rubin Ridge structures, showing that ichnofossils, i.e., the product of life-substrate interactions, are among their closest morphological analogues. Crystal growth and sedimentary cracking are plausible non-biological genetic processes for the structures, although crystals, desiccation and syneresis cracks do not typically present all the morphological and topological features of the Vera Rubin Ridge structures. Morphological analogy does not necessarily imply biogenicity but, given that none of the available observations falsifies the ichnofossil hypothesis, Vera Rubin Ridge and its sedimentary features are here recognized as a privileged target for astrobiological research.

Con la publicación del número 23 culmina nuestra etapa como editores de la Revista Latinoamericana de Población (relap), luego de cuatro años de trabajo. En marzo de 2015, sin experiencia pero con gran entusiasmo y el apoyo de las editoras del período anterior (Marcela Cerrutti y Georgina Binstock, del Centro de Estudios de Población, cenep, de Argentina), empezamos a trabajar en el número 16 de la revista, el primero publicado bajo nuestra responsabilidad. Es cierto que solo fueron ocho números: no parece una labor muy ajetreada para cuatro años, pero lo fue. Cuando comenzamos a trabajar en la revista, el equipo que nos precedió había publicado dos números anuales, logrando un objetivo clave para toda publicación periódica. Cumplir con el número de apariciones anuales preestablecido es un requisito para mantenerse en los índices de revistas científicas y continuar avanzando en los procesos de estandarización de calidad, por lo que nos complace haber mantenido la periodicidad semestral en el cuatrienio 2015-2018. A partir de 2015, tramitamos un gran cambio: la revista dejó de ser publicada en papel. No sin cierta nostalgia por el deleite de recibir, olfatear y hojear el objeto-revista, migramos al formato electrónico, lo que redujo de forma sustancial los costos de publicación y de distribución. Además, en este período la relap se integró a varios sistemas de indexación, incorporó el digital object identifier (doi) y con el número 22 inauguró la tecnología de marcación de artículos promovida por Redalyc. Todas estas acciones contribuyeron a mejorar la presencia de la relap entre las publicaciones científicas del área de las ciencias sociales y la Demografía, ampliaron su difusión y optimizaron la identificación de los trabajos publicados en la revista. A lo largo de estos años hemos ido incorporando otras novedades, entre ellas la aparición de «Conexiones demográficas», una sección dedicada a la difusión de diálogos cortos entre especialistas en temas de población. En 2017 agregamos una sección que recopila las referencias de las tesis de maestría y doctorado defendidas en los programas de posgrado de las universidades de América Latina y el Caribe. También hemos elaborado un banco de evaluadores para facilitar la tarea de identificación de revisores en cada especialidad temática. Por último, nos tocó celebrar la primera década de existencia de la relap. En el número correspondiente publicamos un informe con los artículos publicados por área y por país desde la aparición del primer número. El esfuerzo realizado fue gratificante y creemos que ha contribuido a consolidar la existencia de la relap. No obstante, somos conscientes de que es necesario trabajar mucho más para lograr el mejoramiento de la cantidad y calidad de los artículos que recibe la revista, para nombrar los problemas más evidentes. Una de las lecciones aprendidas en este período es que no alcanza con elevar los estándares formales de la revista y aumentar el número de indexaciones para volverla más visible. Se necesita mucho más trabajo de difusión, entre otros desafíos, para lograr un flujo más dinámico de recepción de manuscritos de calidad. Este reto queda en las manos de Irene Casique y Sonia Frías (Universidad Nacional Autónoma de México, unam), las nuevas editoras de la relap. Tenemos plena confianza en que lograrán superar con creces este reto y otros que se propongan para elevar los estándares editoriales de la revista. Antes de despedirnos, nos queda agradecer el trabajo del excelente equipo que nos acompañó en estos cuatro años. Nairí Aharonián tuvo a su cargo la corrección de estilo y la diagramación de todos los números y Maura Lacreu se incorporó en los dos últimos. No solo queremos reconocer su rigurosidad, buen tino, respeto por los autores y por el lenguaje, queremos agradecer también su enorme disposición para trabajar contrarreloj y sobre todo su inmejorable humor en las extenuantes jornadas de cierre, a menudo sobre el final del año. Lo mismo cabe decir de Teresa Morelli, quien gestionó el Open Journal System (ojs), la plataforma digital en la que se publica la relap. Queremos agradecerle en especial su gran generosidad y paciencia para introducirnos en el mundo editorial y en el funcionamiento del ojs, así como para guiarnos en los a veces intrincados procesos burocráticos. A Joice Melo Vieira queremos agradecerle su apoyo durante todo este tiempo en la ingrata tarea de gestionar los fondos entre países para que todo el equipo técnico, incluyendo traductores y correctores de inglés y portugués, recibieran sus remuneraciones. Al comité editorial de la revista, a las dos directivas de la Asociación Latinoamericana de Población que estuvieron en funciones en este cuatrienio, a sus presidentes, Enrique Peláez (2015-2016) y Verónica Montes de Oca (2017-2018), y a las secretarias generales de ambas administraciones, Joice Melo Vieira —nuevamente— y Sagrario Garay, también vaya nuestro agradecimiento. Para terminar, queremos saludar muy especialmente a nuestros lectores y agradecer y reconocer el trabajo de los autores y evaluadores que la revista ha tenido en este período.

Este número de la Revista Latinoamericana de Población (RELAP), el 21, da comienzo al undécimo año de vida de la revista. En esta ocasión, renovamos nuestros contenidos inaugurando una sección que recoge las tesis de maestría y doctorado producidas este año en América Latina y el Caribe. En adelante, es nuestra intención dar a conocer en cada número de diciembre las tesis que han sido defendidas en el correr del año. Confiamos en que la sección nos permita estar más cerca de los investigadores y mejorar la difusión de la investigación demográfica de nuestra región, una de nuestras principales tareas. Recuerden que relap recibe artículos originales de todas las áreas de conocimiento vinculadas a la población y a la Demografía. Los animamos a contribuir enviando vuestros trabajos y reseñas de libros. Esperamos que disfruten de este número de la revista y les deseamos un excelente 2018.

Atherosclerosis is a major cardiovascular disease worldwide, that could benefit from innovative nanomedicine imaging tools and treatments. In this perspective, we here studied, by fluorescence imaging in ApoE-/- mice, the biodistribution of non-functionalized and RXP470.1-targeted nanostructured lipid carriers (NLC) loaded with DiD dye. RXP470.1 specifically binds to MMP12, a metalloprotease that is over-expressed by macrophages residing in atherosclerotic plaques. Physico-chemical characterizations showed that RXP-NLC (about 105 RXP470.1 moieties/particle) displayed similar features as non-functionalized NLC in terms of particle diameter (about 60-65 nm), surface charge (about −5 — −10 mV), and colloidal stability. In vitro inhibition assays demonstrated that RXP-NLC conserved a selectivity and affinity profile, which favored MMP-12. In vivo data indicated that NLC and RXP-NLC presented prolonged blood circulation and accumulation in atherosclerotic lesions in a few hours. Twenty-four hours after injection, particle uptake in atherosclerotic plaques of the brachiocephalic artery was similar for both nanoparticles, as assessed by ex vivo imaging. This suggests that the RXP470.1 coating did not significantly induce an active targeting of the nanoparticles within the plaques. Overall, NLCs appeared to be very promising nanovectors to efficiently and specifically deliver imaging agents or drugs in atherosclerotic lesions, opening avenues for new nanomedicine strategies for cardiovascular diseases.

Superradiance describes the coherent collective radiation caused by the interaction between many emitters, mediated by a shared electromagnetic field. Recent experiments involving Bose−Einstein condensates coupled to high-finesse cavities and interacting quantum dots in condensed-matter have attracted attention to the superradiant regime as a fundamental step to create quantum technologies. Here, we consider a simplified description of superradiance that allows the evaluation of statistical moments. A correspondence with the classical birthday problem recovers the statistical moments for discrete time and an arbitrary number of emitters. In addition, the correspondence provides a way to calculate the degeneracy of the problem.

Cycles in population dynamics are abundant in nature and are understood as emerging from the interaction among coupled species. When sampling is conducted at a slow rate compared to the population cycle period (aliasing effect), one is prone to misinterpretations. However, aliasing has been poorly addressed in coupled population dynamics. To illustrate the aliasing effect, the Lotka−Volterra model oscillatory regime is numerically sampled, creating prey−predator cycles. We show that inadequate sampling rates may produce inversions in the cause-effect relationship among other artifacts. More generally, slow acquisition rates may distort data interpretation and produce deceptive patterns and eventually leading to misinterpretations, as predators becoming preys. Experiments in coupled population dynamics should be designed that address the eventual aliasing effect.

Con esta edición, la Revista Latinoamericana de Población (Relap) llega a su número 20, luego de una década de aparición semestral ininterrumpida y más de un centenar de trabajos publicados. La revista, contemporánea a la fundación de la Asociación Latinoamericana de Población (alap), fue editada inicialmente en México, para luego trasladarse a Argentina y recientemente a Uruguay. En estos veinte números no solo ha cambiado de sede y de editores, sino que incorporó nuevos contenidos, ingresó en un número creciente de bases de datos bibliográficos y modificó su formato, que pasó a ser exclusivamente digital.

Nos complace anunciar que la Revista Latinoamericana de Población (RELAP) ha comenzado una nueva etapa editorial. Durante la anterior gestión (2011-2014), conducida por Marcela Cerrutti y Georgina Binstock, la relap se consolidó como una de las principales revistas científicas dedicadas a la Demografía en América Latina y el Caribe y fue indexada en la Red de Revistas Científicas de América Latina y el Caribe, España y Portugal (Redalyc). En primer lugar, deseamos expresar nuestro reconocimiento al excelente trabajo realizado por las editoras salientes y agradecer su generosa colaboración en el actual proceso de transición.

El objetivo de este trabajo es analizar las trayectorias conyugales posruptura femeninas y masculinas con datos retrospectivos a partir de análisis de supervivencia y análisis multivariados. Se pretende responder a las siguientes preguntas: ¿con qué frecuencia y después de cuánto tiempo ocurren las uniones posruptura?; ¿hay diferencias de género en la probabilidad de recomposición?; ¿qué factores inciden sobre la probabilidad de recomponer la vida conyugal? La edad a la ruptura afecta muy especialmente a la recomposición en ambos sexos: pasados los treinta años decrece en forma sustantiva la probabilidad de volver a unirse. Contraintuitivamente, tener hijos no impone barreras a la formación de nuevas uniones. En consecuencia, los resultados no confirman la idea extendida de que los hijos son un obstáculo para iniciar otro vínculo conyugal. Este hallazgo, en combinación con los efectos positivos sobre la recomposición que ejercen tener orientación religiosa y haberse casado legalmente en la unión anterior, sugiere que, tanto entre los hombres como entre las mujeres, la formación de una nueva unión posruptura se vincula particularmente con orientaciones hacia la vida familiar.

Background: Musculoskeletal disorders negatively affect millions of patients worldwide, placing significant demand on health care systems. Digital technologies that improve clinical outcomes and efficiency across the care pathway are development priorities. We developed the musculoskeletal Digital Assessment Routing Tool (DART) to enable self-assessment and immediate direction to the right care. Objective: We aimed to assess and resolve all serious DART usability issues to create a positive user experience and enhance system adoption before conducting randomized controlled trials for the integration of DART into musculoskeletal management pathways. Methods: An iterative, convergent mixed methods design was used, with 22 adult participants assessing 50 different clinical presentations over 5 testing rounds across 4 DART iterations. Participants were recruited using purposive sampling, with quotas for age, habitual internet use, and English-language ability. Quantitative data collection was defined by the constructs within the International Organization for Standardization 9241-210-2019 standard, with user satisfaction measured by the System Usability Scale. Study end points were resolution of all grade 1 and 2 usability problems and a mean System Usability Scale score of ≥80 across a minimum of 3 user group sessions. Results: All participants (mean age 48.6, SD 15.2; range 20-77 years) completed the study. Every assessment resulted in a recommendation with no DART system errors and a mean completion time of 5.2 (SD 4.44, range 1-18) minutes. Usability problems were reduced from 12 to 0, with trust and intention to act improving during the study. The relationship between eHealth literacy and age, as explored with a scatter plot and calculation of the Pearson correlation coefficient, was performed for all participants (r=-0.2; 20/22, 91%) and repeated with a potential outlier removed (r=-0.23), with no meaningful relationships observed or found for either. The mean satisfaction for daily internet users was highest (19/22, 86%; mean 86.5, SD 4.48; 90% confidence level [CL] 1.78 or -1.78), with nonnative English speakers (6/22, 27%; mean 78.1, SD 4.60; 90% CL 3.79 or -3.79) and infrequent internet users scoring the lowest (3/22, 14%; mean 70.8, SD 5.44; 90% CL 9.17 or -9.17), although the CIs overlap. The mean score across all groups was 84.3 (SD 4.67), corresponding to an excellent system, with qualitative data from all participants confirming that DART was simple to use. Conclusions: All serious DART usability issues were resolved, and a good level of satisfaction, trust, and willingness to act on the DART recommendation was demonstrated, thus allowing progression to randomized controlled trials that assess safety and effectiveness against usual care comparators. The iterative, convergent mixed methods design proved highly effective in fully evaluating DART from a user perspective and could provide a blueprint for other researchers of mobile health systems. [ABSTRACT FROM AUTHOR]

Background: The total fertility rate (TFR) in Uruguay fell from 2.5 to 1.9 children per woman between 1996 and 2011. However, no study to date has examined the decline of the TFR by observing changes in fertility patterns by birth order. Objective: The main aim of this study is to analyze recent changes in fertility level and timing of childbearing by birth order in Uruguay. Methods: We estimate unconditional and conditional age- and birth-order-specific fertility rates for 1996-2011 using data from vital statistics, population census, and national population estimates. Additionally, three period summary measures of birth-order-specific fertility quantum are calculated: TFR, PATFR and TFRp*. Timing changes by birth order are examined with MAB and TMAB, focusing on MAB1 and its standard deviation and comparing their evolutions in Uruguay with those of selected countries. Results: Fertility decline fits a parity-specific stopping model with a moderate increase in the mean ages of first, second, and third births. The distribution of conditional fertility rates for first and second births depicts an asymmetric bimodal shape linked to the increasing heterogeneity of the timing of childbearing. Compared to countries with similar fertility trends, heterogeneity in the age at first birth in Uruguay is remarkably high. Conclusions: Previous studies suggest that heterogeneity in first and second birth timing is related to structural social inequalities, as women from lower social strata have not significantly changed the age at which they bear a first child, whereas women of middle to high social strata have started to postpone it. The new evidence reinforces the idea that postponement transition in Uruguay cannot be studied without considering this consolidation of social status polarization in fertility timing.

El objetivo de este trabajo es investigar los determinantes de la disolución de la primera unión en el Uruguay a partir del análisis de dos encuestas de carácter retrospectivo realizadas durante la década de 1990. A pesar de que la información presenta limitaciones, es importante resaltar que en el Uruguay y en la región en general son escasos los estudios de corte longitudinal sobre los factores que determinan las rupturas. Se consideraron tres grandes grupos de determinantes: 1) demográficos (edad a la primera unión, tipo de unión, hijos); 2) socioeconómicos (educación, área de residencia, actividad laboral); y 3) factores ideológicos (religión, ideología de género). Los resultados indican que las variables que dan cuenta de la historia del vínculo –más que las características sociales de los cónyuges– se perfilan como los principales determinantes de la mayor o menor estabilidad de las uniones. La relación entre el carácter consensual de las uniones y su mayor inestabilidad es uno de los más importantes predictores de ruptura. Aun controlando factores como la edad, la fecundidad, la educación y la orientación religiosa, las uniones libres tienen probabilidades significativamente mayores de disolverse. Asimismo, la presencia o ausencia de hijos en las parejas es una variable que muestra efectos significativos sobre la probabilidad de ruptura.

En los últimos quince años se registró un importante aumento de la incidencia del divorcio en Uruguay y el incumplimiento con las pensiones alimenticias a los hijos se ha vuelto un problema frecuentemente citado. El objetivo de este trabajo es estudiar los determinantes que conducen a la evasión en el pago de pensiones alimenticias a los hijos, así como presentar un análisis de los problemas que enfrenta el sistema judicial uruguayo en la aplicación de las herramientas legales previstas para su cumplimiento. Por un lado, se describe la normativa vigente en Uruguay sobre pensiones alimenticias y se analiza la opinión de actores del sistema judicial respecto a las dificultades para aplicarla. Por otro lado, se realiza una caracterización de los padres que no cumplen con las obligaciones económicas hacia sus hijos y se identifican los factores que se asocian al incumplimiento. El análisis empírico se basa en una encuesta del año 2001 específicamente diseñada para revelar este tipo de información.

Results of thermophysical investigations into the lavas of the island of Lipari (Southern Tyrrhenian Sea) are presented. Samples selected for laboratory measurements belong to four main magmatic cycles, which produced basaltic-andesitic, andesitic and rhyolitic lavas. The wet-bulk density and the thermal conductivity measured on 69 specimens range from 1900 to 2760 kg m-3 and from 1.02 to 2.88 W m-1 K-1, respectively. Porosity is never negligible and its influence on density is maximum in rhyolites of the third cycle. The thermal conductivity is also influenced by the amount of glass. Rhyolitic obsidians show values lower than other rhyolites, although the latter rocks have a larger average porosity. The radioactive heat production determined on 36 specimens varies with the rock type, depending on the amount of U, Th and K. In basic lavas of the first cycle its value is 0.95°± 0.30 mW m-3, while in rhyolites of the fourth cycle it attains 6.68°±0.61 mW m-3. A comparison between results of g-ray spectrometry and X-ray fluorescence points out that the assumption of equilibrium in the decay series of the isotopic elements seems fulfilled. The information obtained is useful not only for the interpretation of geophysical surveys but also for the understanding of the geochemical characteristics of lavas.

Resumen El artículo discute la pertinencia de los llamados indicadores refinados de fecundidad para evaluar el nivel de la fecundidad en los países de América Latina. La principal ventaja de estos indicadores es su capacidad de identificar cuánto del cambio en la tasa global de fecundidad se debe a cambios en la intensidad y cuánto a cambios en el calendario. Los países de muy baja fecundidad están culminando un proceso de postergación de la maternidad que solo pudo ser descrito adecuadamente una vez que surgieron estos indicadores. A pesar de que en América Latina hay indicios de que en algunos países se comienza a procesar la postergación de la fecundidad, es aún muy limitada la capacidad de elaborar indicadores refinados y no abunda la discusión sobre sus virtudes, desventajas y potencialidades. Con la intención de sistematizar la acumulación al respecto y fomentar el debate, en este artículo se presentan las principales características de estas medidas y se discute cuáles indicadores serían los más adecuados para evaluar las tendencias de la fecundidad en la región y cómo podrían difundirse de modo de evitar equívocos en su interpretación. Nuestra principal conclusión es que a corto plazo resulta más urgente contar con indicadores de intensidad y calendario por orden de nacimiento que apelar a medidas sintéticas refinadas.

Recent evidence confirms that the postponement transition has begun in some Latin American countries. As the mean age at first birth increases, dispersion around the mean value might also increase, reflecting a growing heterogeneity in the timing of transition to motherhood. In fact, in countries from the Southern Cone, recently available data suggest the emergence of a specific pattern that not only reflects heterogeneity, but also a polarization around two "crests;" the first one at the end of adolescence and the second one toward the end of the twenties. Using census data, vital statistics and household surveys from three countries, we study the extent to which this process consolidates a recognizable pattern in the timing of first birth in Argentina, Chile and Uruguay, visible through age-specific conditional rates of first births. [ABSTRACT FROM AUTHOR]