Universidad de Montevideo

Abstract Age-specific fertility rates (ASFRs) provide the most extensive record of reproductive change, but their aggregate nature obscures the individual-level behavioural mechanisms that drive fertility trends. To bridge this micro–macro divide, we introduce a simulation-based Bayesian framework that couples a demographically interpretable, individual-level simulation model of the reproductive process with sequential neural posterior estimation (SNPE). We show that this framework successfully recovers core behavioural parameters governing contemporary fertility, including preferences for family size, reproductive timing, and contraceptive failure, using only ASFRs. The framework’s effectiveness is validated on cohorts from four countries with diverse fertility regimes. Most compellingly, the model, estimated solely on aggregate data, successfully predicts out-of-sample distributions of individual-level outcomes, including age at first sex, desired family size, and birth intervals. Because our framework yields complete synthetic life histories, it significantly reduces the data requirements for building microsimulation models and enables behaviourally explicit demographic forecasts.

Multiple Myeloma (MM) is a haematological malignancy in which Interleukin-6 (IL-6) plays a crucial role in its growth and spread. The monoclonal antibody Tocilizumab binds strongly to IL-6 receptors, inhibiting their function. Our aim is to evaluate the potential of [177Lu]Lu-labeled Toclilzumab as a theranostic agent for MM. </P> Methods: Tocilizumab was derivatised with DOTA-NHS ester and radiolabeled with [177Lu]Lu. The stability of the radiochemical compound was evaluated, and in vitro binding and immunoreactive fraction assays were performed. Biodistribution was assessed at 24 and 48 h post-injection (n = 5) in normal and MM-bearing BALB/c nude mice. </P> Results: [177Lu]Lu-DOTA-Tocilizumab remained stable in all tested solutions. Epitope recognition was confirmed by cell-binding studies, and an immunoreactive fraction of 83.7% was observed. In vivo biodistribution studies revealed high tumor uptake over time, with tumor-to-muscle ratios of 11.66 ± 3.81 and 9.54 ± 1.75 at 24 and 48 h, respectively. </P> Discussion: This study focused on the synthesis and characterisation of a new radiolabeled theranostic agent against IL6R, [177Lu]Lu-DOTA-Tocilizumab. This agent demonstrated high radiochemical stability and strong binding to IL-6R in the MM cell line. Biodistribution studies indicated selective retention of the agent in tumor tissue, highlighting its potential for targeted imaging and therapy in IL-6R-positive cancers and paving the way for future research into its application in related diseases. </P> Conclusions: [177Lu]Lu-DOTA-Tocilizumab represents a potential theranostic agent for MM. Therefore, we expect this agent to open the way to new diagnostic and therapeutic strategies for this devastating disease.

En Argentina, la infertilidad afecta a 1 de cada 7 parejas, cifra que coincide con la estadística global. En este contexto, los avances científicos en tratamientos de reproducción asistida durante los últimos 40 años han transformado la perspectiva sobre la reproducción humana. Además, las investigaciones internacionales han revelado que quienes transitan por tratamientos de fertilidad experimentan diversas alteraciones emocionales. Objetivo: analizar el sentido en la vida y la percepción de felicidad en mujeres que se encuentran atravesando tratamientos de fertilidad de alta complejidad en Argentina. Metodología: la muestra estuvo compuesta por 73 mujeres, con una edad promedio de 37.8 años, que se encontraban en proceso de tratamientos de fertilidad asistida de alta complejidad. Se les administró el Pil test, para sentido en la vida y la Escala de felicidad subjetiva. Resultados: se encontró una correlación positiva y fuerte (R(73) = .81, p &lt; .05) entre las variables. Conclusión: el sentido en la vida se relaciona significativamente con la percepción de felicidad en mujeres que se encuentran transitando tratamientos de fertilidad de alta complejidad. Por lo tanto, fomentar el desarrollo de alguno de estos factores podría ser esencial en el contexto de la psicoterapia, ya que facilitaría un mejor afrontamiento y contribuiría al bienestar de las mujeres que atraviesan tratamientos de fertilidad.

Server-Guided Ad Insertion (SGAI) methodologies combine the best in both traditional approaches to dynamic advertisement (DAI), client-side and server-side. It is nearly as scalable as the client-side approach while being as robust and uniform and low-effort as the server-side approach. Unsurprisingly, lots of work is happening in the industry to support the approach.

This study aimed to estimate the association of udder health and herd management practices with bulk tank SCC (BTSCC) and the partial costs of subclinical mastitis (milk yield losses and penalties) on dairy farms in Uruguay. As part of a cross-sectional study, a survey on udder health and herd management practices was conducted on 190 randomly selected dairy farms stratified by region and milk shipment volume (MSV). Herd data comprising 13 mo of BTSCC and MSV were obtained from the dairy processing company, and BTSCC values exceeding 250 × 103 cells/mL (BTSCC >250) were identified. Multivariable regression models were developed to evaluate the association between udder health and herd management practices and 4 response variables on a monthly basis: BTSCC, BTSCC >250, milk yield losses, and penalties. In addition, we calculated the population attributable fraction (PAF) of practices associated with BTSCC >250 and their attributable cost. Postmilking teat disinfection (78%) and dry-cow therapy (80%) showed the highest adoption rates. Some practices such as culling of chronically infected cows based on records (11%), the use of automatic cluster removers (22%), the maintenance of calving areas (24%), monthly individual SCC (ISCC; 16%), and a monthly California Mastitis Test (CMT) on all cows (10%) showed low adoption rates. When adoption rates differed across MSV levels, small farms consistently had lower uptake. The lack of use of postmilking teat disinfection was associated with a higher BTSCC (30 ± 11 × 103 cells/mL), higher odds of BTSCC >250 (odds ratio = 2.45), and higher milk yield losses ($1.22 ± $0.45 per cow per month). Similarly, farms that manually removed clusters showed higher BTSCC (29 ± 13 × 103 cells/mL), higher odds of BTSCC >250 (odds ratio = 2.73), and higher penalties ($0.67 ± $0.28 per cow per month). For monthly ISCC, the odds of BTSCC >250 and the milk yield losses and penalties were lower, whereas on farms with maintenance of calving areas, the odds for BTSCC >250 and the penalties were lower. The partial cost of subclinical mastitis was $9.2 ± $3.9 per cow per month. Yield losses comprised 88% of the cost, and variability among farms was high. Practices associated with BTSCC >250 (postmilking teat disinfection, use of automatic cluster removers, monthly ISCC, and maintenance of calving areas) showed high PAF values. Our results highlight opportunities, some with a potential population effect, to reduce subclinical mastitis and increase overall farm profitability, particularly on smaller farms, and underscore the potential benefits of improved udder health management in Uruguay.

This study aims to identify the social and healthcare needs of patients with rare diseases (RD) and their physicians within a Universal Health Care System. It seeks to provide valuable insights for policymakers, patient organizations, and healthcare professionals while informing about these diseases, raising awareness, and designing strategies to improve access to quality, timely medical care, including therapies and medication at a local and regional level. Two semi-structured surveys were conducted between May 2023 and August 2024, targeting family members of patients with RD (N = 64) and physicians (N = 56) in Uruguay. Surveys were self-administered via email or conducted by an interviewer, and were disseminated through healthcare professionals, RD associations, and social media, using "snowball" methodology and word-of-mouth references. Uruguay faces significant deficiencies in access to diagnosis and treatment for rare diseases, leading to a prolonged "diagnostic odyssey" for families and multiple barriers for physicians, ranging from lack of training to limited access to specialized tools. The low reporting rate to the National Registry of Congenital Defects and Rare Diseases and the lack of updates to the Comprehensive Health Care Plan exacerbate inequities in access to diagnosis and treatment. A key finding is inequality in access to whole-exome sequencing (WES), despite its proven effectiveness in reducing diagnostic times and improving accuracy. Its use remains restricted due to high costs and lack of universal coverage, highlighting the need for a national genomic medicine strategy and medical training in molecular diagnosis. The survey results indicate that RDs have a significant physical, emotional, and economic impact on patients and families. The main concerns raised include diagnostic delays, partly due to difficulties accessing specific tests and treatments. The medical community also acknowledges these issues. The healthcare system needs to update its coverage to include genomic diagnostics, improve medical training, strengthen coordination, and ensure equitable treatment access. These results mimic what is seen in other countries in Latin America and the Southern Cone. They call for a comprehensive, formalized framework for diagnosis, treatment, and care of rare diseases at local and regional levels, accounting for family experiences and prioritizing family wellbeing.

Abstract Quantile regression is one of the most important methods to estimate heterogeneous effects on a variable of interest. In many applications there is a subset of covariates of interest, while the rest operate as controls in the regression equation. This work presents a straightforward empirical strategy for situations in which the control variables have a homogeneous effect on the conditional distribution. We develop the asymptotic theory for the proposed estimator and the corresponding inference procedures. An application using environmental pollution data illustrates the method by estimating the Environmental Kuznets Curve.