Time representation in reinforcement learning models of the basal ganglia

Reinforcement learning (RL) models have been influential in understanding many aspects of basal ganglia function, from reward prediction to action selection. Time plays an important role in these models, but there is still no theoretical consensus about what kind of time representation is used by the basal ganglia. We review several theoretical accounts and their supporting evidence. We then discuss the relationship between RL models and the timing mechanisms that have been attributed to the basal ganglia. We hypothesize that a single computational system may underlie both RL and interval timing—the perception of duration in the range of seconds to hours. This hypothesis, which extends earlier models by incorporating a time-sensitive action selection mechanism, may have important implications for understanding disorders like Parkinson's disease in which both decision making and timing are impaired

Comparative ergonomic workflow and user experience analysis of MRI versus fluoroscopy-guided vascular interventions:an iliac angioplasty exemplar case study

Purpose A methodological framework is introduced to assess and compare a conventional fluoroscopy protocol for peripheral angioplasty with a new magnetic resonant imaging (MRI)-guided protocol. Different scenarios were considered during interventions on a perfused arterial phantom with regard to time-based and cognitive task analysis, user experience and ergonomics. Methods Three clinicians with different expertise performed a total of 43 simulated common iliac angioplasties (9 fluoroscopic, 34 MRI-guided) in two blocks of sessions. Six different configurations for MRI guidance were tested in the first block. Four of them were evaluated in the second block and compared to the fluoroscopy protocol. Relevant stages’ durations were collected, and interventions were audio-visually recorded from different perspectives. A cued retrospective protocol analysis (CRPA) was undertaken, including personal interviews. In addition, ergonomic constraints in the MRI suite were evaluated. Results Significant differences were found when comparing the performance between MRI configurations versus fluoroscopy. Two configurations [with times of 8.56 (0.64) and 9.48 (1.13) min] led to reduce procedure time for MRI guidance, comparable to fluoroscopy [8.49 (0.75) min]. The CRPA pointed out the main influential factors for clinical procedure performance. The ergonomic analysis quantified musculoskeletal risks for interventional radiologists when utilising MRI. Several alternatives were suggested to prevent potential low-back injuries. Conclusions This work presents a step towards the implementation of efficient operational protocols for MRI-guided procedures based on an integral and multidisciplinary framework, applicable to the assessment of current vascular protocols. The use of first-user perspective raises the possibility of establishing new forms of clinical training and education

Endocrine disrupting potential of replacement flame retardants-Review of current knowledge for nuclear receptors associated with reproductive outcomes

Background and aim: Endocrine disrupting chemicals (EDCs) constitute a major public health concern because they can induce a large spectrum of adverse effects by interfering with the hormonal system. Rapid identification of potential EDCs using in vitro screenings is therefore critical, particularly for chemicals of emerging concerns such as replacement flame retardants (FRs). The review aimed at identifying (1) data gaps and research needs regarding endocrine disrupting (ED) properties of replacement FRs and (2) potential EDCs among these emerging chemicals. Methods: A systematic search was performed from open literature and ToxCast/Tox21 programs, and results from in vitro tests on the activities of 52 replacement FRs towards five hormone nuclear receptors (NRs) associated with reproductive outcomes (estrogen, androgen, glucocorticoid, progesterone, and aryl hydrocarbon receptors) were compiled and organized into tables. Findings were complemented with information from structure-based in silico model predictions and in vivo information when relevant. Results: For the majority of the 52 replacement FRs, experimental in vitro data on activities towards these five NRs were either incomplete (15 FRs) or not found (24 FRs). Within the replacement FRs for which effect data were found, some appeared as candidate EDCs, such as triphenyl phosphate (TPhP) and tris(1,3-dichloropropyl) phosphate (TDCIPP). The search also revealed shared ED profiles. For example, anti-androgenic activity was reported for 19 FRs and predicted for another 21 FRs. Discussion: This comprehensive review points to critical gaps in knowledge on ED potential for many replacement FRs, including chemicals to which the general population is likely exposed. Although this review does not cover all possible characteristics of ED, it allowed the identification of potential EDCs associated with reproductive outcomes, calling for deeper evaluation and possibly future regulation of these chemicals. By identifying shared ED profiles, this work also raises concerns for mixture effects since the population is co-exposed to several FRs and other chemicals

Human Exposure to Endocrine-Disrupting Chemicals and Prenatal Risk Factors for Cryptorchidism and Hypospadias: A Nested Case–Control Study

BACKGROUND: Exposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs. OBJECTIVE: In this study we aimed to determine whether the combined effect of environmental estrogens measured as total effective xenoestrogen burden (TEXB) is a risk factor for male urogenital malformations. METHODS: In a case-control study, nested in a mother-child cohort (n = 702) established at Granada University Hospital, we compared 50 newborns with diagnosis of cryptorchidism and/or hypospadias with 114 boys without malformations matched by gestational age, date of birth, and parity. Controls did not differ from the total cohort in confounding variables. TEXB and levels of 16 organochlorine pesticides were measured in placenta tissues. Characteristics of parents, pregnancy, and birth were gathered by questionnaire. We used conditional and unconditional regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: TEXB from organohalogenated compounds was detectable in 72% and 54% of case and control placentas, respectively. Compared with controls, cases had an OR for detectable versus non-detectable TEXB of 2.82 (95% CI, 1.10-7.24). More pesticides were detected in cases than in controls (9.34 +/- 3.19 vs. 6.97 +/- 3.93). ORs for cases with detectable levels of pesticides, after adjusting for potential confounders in the conditional regression analysis, were o,p'-DDT (OR = 2.25; 95% CI, 1.03-4.89), p,p'-DDT (OR = 2.63; 95% CI, 1.21-5.72), lindane (OR = 3.38; 95% CI, 1.36-8.38), mirex (OR = 2.85; 95% CI, 1.22-6.66), and endosulfan alpha (OR = 2.19; 95% CI, 0.99-4.82). Engagement of mothers in agriculture (OR = 3.47; 95% CI, 1.33-9.03), fathers' occupational exposure to xenoestrogens (OR = 2.98; 95% CI, 1.11-8.01), and history of previous stillbirths (OR = 4.20; 95% CI, 1.11-16.66) were also associated with risk of malformations. CONCLUSIONS: We found an increased risk for male urogenital malformations related to the combined effect of environmental estrogens in placenta

Disruptores endócrinos e metabólicos e desordens reprodutivas: perspectivas futuras

There is increasing evidence of the relation between environmental exposures [mainly to endocrine disrupting chemicals (EDC)] and human health impairment. These compounds include a wide assortment of chemicals used in agriculture (organophosphate and organochlorine compounds, fungicides, etc.) and industrial and commercial applications (bisphenol A, phthalates, perfluorinated compounds, etc.). Currently, the main research areas into this relation are related to neurodevelopmental disorders or cancer, and hormonal, metabolic or reproductive disorders or diseases. The incidence rates of metabolic disorders or conditions–obesity, metabolic syndrome or diabetes–and reproductive or infertility problems are on the rise in human populations. However, the already known risk factors do not fully explain the documented trends for these disorders and diseases. In general, it would be highly advisable to increase the number of epidemiological studies in humans and of mechanistic studies in preclinical and/or cellular models to better understand the links between environmental exposure to EDCs and metabolic disorders or conditions such as obesity, metabolic syndrome, diabetes or infertility, including epigenetic aspects as well.Es evidente la importancia que está adquiriendo la asociación entre exposiciones medioambientales (principalmente compuestos alteradores endocrinos) y la afectación de la salud humana. Estos compuestos incluyen una gran variedad de sustancias químicas, tanto de uso hortofrutícola (compuestos organoclorados y organofosforados, fungicidas, etc.), como industrial o comercial (bisfenol A, ftalatos, compuestos perfluorados, etc.). Actualmente, las principales líneas de investigación incluyen los desórdenes en el neurodesarrollo o el cáncer, junto con alteraciones o enfermedades hormonales, metabólicas o reproductivas. La incidencia de desórdenes metabólicos como la obesidad, el síndrome metabólico o la diabetes, y los problemas reproductivos o de infertilidad están incrementándose en poblaciones humanas. No obstante, los factores de riesgo establecidos no pueden explicar completamente las tendencias observadas para estos desórdenes. En general, sería extremadamente recomendable aumentar el número de estudios epidemiológicos en humanos y mecanísticos en modelos preclínicos o celulares que exploren las asociaciones entre exposición a alteradores endocrinos y desórdenes o enfermedades metabólicas como la obesidad, el síndrome metabólico, la diabetes o la infertilidad, incluyendo aspectos epigenéticos.É evidente a importância que tem sido dada à associação entre exposições ambientais (principalmente compostos disruptores endócrinos) e os efeitos na saúde humana. Estes compostos incluem uma variedade de produtos químicos, tanto para uso hortícola (organoclorados e organofosforados, fungicidas, etc.), como no uso industrial e/ou comercial (bisfenol A, ftalatos, compostos perfluorados, etc.). Atualmente, as principais linhas de investigação procuram desordens do desenvolvimento neurológico ou cancro, bem como as alterações hormonais ou doenças associadas à disfunção hormonal, metabólica ou reprodutiva. A incidência de distúrbios metabólicos, como obesidade, síndrome metabólica ou diabetes, e problemas reprodutivos ou infertilidade estão a aumentar em populações humanas. No entanto, os fatores de risco estabelecidos não conseguem explicar totalmente as tendências observadas nestas desordens. Em geral, seria altamente aconselhável aumentar o número de estudos epidemiológicos em humanos e modelos mecanísticos em pré-clínica e/ou celular, para explorar as associações entre a exposição aos disruptores endócrinos e distúrbios ou doenças metabólicas, tais como obesidade, síndrome metabólica, diabetes e infertilidade, incluindo aspetos epigenéticos

A Comprehensive Review

Funding: This project has received funding from the European Unions’ Horizon 2020 research and innovation Programme under grant agreement No 733032. HBM4EU.Polycyclic aromatic hydrocarbons (PAHs) are among the chemicals with proven impact on workers' health. The use of human biomonitoring (HBM) to assess occupational exposure to PAHs has become more common in recent years, but the data generated need an overall view to make them more usable by regulators and policymakers. This comprehensive review, developed under the Human Biomonitoring for Europe (HBM4EU) Initiative, was based on the literature available from 2008-2022, aiming to present and discuss the information on occupational exposure to PAHs, in order to identify the strengths and limitations of exposure and effect biomarkers and the knowledge needs for regulation in the workplace. The most frequently used exposure biomarker is urinary 1-hydroxypyrene (1-OH-PYR), a metabolite of pyrene. As effect biomarkers, those based on the measurement of oxidative stress (urinary 8-oxo-dG adducts) and genotoxicity (blood DNA strand-breaks) are the most common. Overall, a need to advance new harmonized approaches both in data and sample collection and in the use of appropriate biomarkers in occupational studies to obtain reliable and comparable data on PAH exposure in different industrial sectors, was noted. Moreover, the use of effect biomarkers can assist to identify work environments or activities of high risk, thus enabling preventive risk mitigation and management measures.publishersversionpublishe

Spatial and temporal variability of personal environmental exposure to radio frequency electromagnetic fields in children in Europe

Exposure to radiofrequency electromagnetic fields (RF-EMF) has rapidly increased and little is known about exposure levels in children. This study describes personal RF-EMF environmental exposure levels from handheld devices and fixed site transmitters in European children, the determinants of this, and the day-to-day and year-to-year repeatability of these exposure levels.; Personal environmental RF-EMF exposure (μW/m; 2; , power flux density) was measured in 529 children (ages 8-18 years) in Denmark, the Netherlands, Slovenia, Switzerland, and Spain using personal portable exposure meters for a period of up to three days between 2014 and 2016, and repeated in a subsample of 28 children one year later. The meters captured 16 frequency bands every 4 s and incorporated a GPS. Activity diaries and questionnaires were used to collect children's location, use of handheld devices, and presence of indoor RF-EMF sources. Six general frequency bands were defined: total, digital enhanced cordless telecommunications (DECT), television and radio antennas (broadcast), mobile phones (uplink), mobile phone base stations (downlink), and Wireless Fidelity (WiFi). We used adjusted mixed effects models with region random effects to estimate associations of handheld device use habits and indoor RF-EMF sources with personal RF-EMF exposure. Day-to-day and year-to-year repeatability of personal RF-EMF exposure were calculated through intraclass correlations (ICC).; Median total personal RF-EMF exposure was 75.5 μW/m; 2; . Downlink was the largest contributor to total exposure (median: 27.2 μW/m; 2; ) followed by broadcast (9.9 μW/m; 2; ). Exposure from uplink (4.7 μW/m; 2; ) was lower. WiFi and DECT contributed very little to exposure levels. Exposure was higher during day (94.2 μW/m; 2; ) than night (23.0 μW/m; 2; ), and slightly higher during weekends than weekdays, although varying across regions. Median exposures were highest while children were outside (157.0 μW/m; 2; ) or traveling (171.3 μW/m; 2; ), and much lower at home (33.0 μW/m; 2; ) or in school (35.1 μW/m; 2; ). Children living in urban environments had higher exposure than children in rural environments. Older children and users of mobile phones had higher uplink exposure but not total exposure, compared to younger children and those that did not use mobile phones. Day-to-day repeatability was moderate to high for most of the general frequency bands (ICCs between 0.43 and 0.85), as well as for total, broadcast, and downlink for the year-to-year repeatability (ICCs between 0.49 and 0.80) in a small subsample.; The largest contributors to total personal environmental RF-EMF exposure were downlink and broadcast, and these exposures showed high repeatability. Urbanicity was the most important determinant of total exposure and mobile phone use was the most important determinant of uplink exposure. It is important to continue evaluating RF-EMF exposure in children as device use habits, exposure levels, and main contributing sources may change

La variación en los parámetros de crecimiento de cepas Saccharomyces cerevisiae en respuesta a condiciones de estrés presentes durante el ciclo fenológico de la vid evidencia una aclimatación al nicho de viñedo

PosterLa producción de vid y la elaboración de vino constituyen dos actividades de amplia tradición e impacto económico en Mendoza, Argentina. La Zona Alta del Río Mendoza (ZARM) es la principal región vitícola donde se cultiva el Malbec, vino emblemático de Argentina. Saccharomyces cerevisiae es la principal responsable de la fermentación alcohólica del vino y en general, se acepta que el viñedo es el hábitat natural de las levaduras enológicas y que las uvas son la principal fuente de ellas. No obstante, la vid es una especie de hoja caduca y por ello necesita una secuencia específica de condiciones ambientales para renovar todos sus tejidos a través de un ciclo de crecimiento anual. Entonces, ¿qué sucede con las poblaciones de S. cerevisiae en los viñedos durante el ciclo de crecimiento anual de la vid? Esta pregunta plantea la posibilidad de que S. cerevisiae esté adaptada a hábitats ecológicos del viñedo distintos de las uvas, y que estos reservorios puedan constituir un refugio para las levaduras cuando la fruta no está disponible. Asimismo, dado que la tolerancia o resistencia al estrés ambiental tiene componentes tanto genéticos como ecológicos, es necesario estudiar el impacto de factores relacionados con las condiciones estacionales del ciclo anual de la vid para confirmar la adaptación de las cepas de S. cerevisiae a los nichos ecológicos del viñedo. El objetivo del presente estudio fue evaluar el efecto de los cambios estacionales del ciclo anual de la vid sobre el crecimiento de Saccharomyces cerevisiae. Se consideraron 10 condiciones de estrés subletal que reflejaran los cambios ambientales y del sustrato que se presentan en el viñedo. Se evaluó el efecto de: temperatura (7-40 °C), pH (2.5-8.0), concentración de glucosa (3-300 g. L-1), concentración de nitrógeno (0.008-8 g. L-1) y presencia de cobre (Cu2+,24 mg. L-1) sobre la cinética de crecimiento de un conjunto representativo de 30 cepas de S. cerevisiae, previamente aisladas de diferentes nichos ecológicos de un viñedo Malbec durante un ciclo completo de crecimiento de la vid. Los parámetros de crecimiento, fase de latencia, velocidad máxima y máximo asintótico de crecimiento, se estimaron a partir de las curvas de densidad óptica obtenidas con el espectrofotómetro Bioscreen C. El análisis estadístico se realizó mediante ANOVA multivariado (prueba de comparación post-hoc Fisher-LSD) y también se aplicó el Análisis Procrustes Generalizado para evaluar la interacción cepa-condiciones de crecimiento. Los resultados mostraron que el conjunto de cepas de S. cerevisiae caracterizadas fueron capaces de crecer cuando fueron sometidas a los tratamientos que simulaban los cambios ambientales estacionales en el ecosistema del viñedo. La limitación extrema de glucosa, la presencia de cobre y la baja temperatura fueron los factores con mayor impacto en el crecimiento de S. cerevisiae. Se verificaron respuestas de crecimiento homogéneas o variables según el estresor evaluado. Sin embargo, 10 cepas altamente aisladas en el viñedo fueron menos afectadas por todos los factores ensayados, lo que sugiere su aclimatación y capacidad para sobrevivir en las condiciones cambiantes del ciclo anual de la vid.EEA MendozaFil: Gonzalez, Magali Lucia Rosa. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza; ArgentinaFil: Chimeno, Selva Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza; ArgentinaFil: Valero, E. Universidad Pablo de Olavide. Departamento de Biología Molecular e Ingeniería Bioquímica; EspañaFil: Arroyo Lopez, F. N. Consejo Superior de Investigaciones Científicas (CSIC). Instituto de la Grasa; EspañaFil: Garrido Fernandez, A. Consejo Superior de Investigaciones Científicas (CSIC). Instituto de la Grasa; España. Universidad Pablo de Olavide. Departamento de Biotecnología de Alimentos; EspañaFil: Rodriguez Gomez, F. Consejo Superior de Investigaciones Científicas (CSIC). Instituto de la Grasa; España. Universidad Pablo de Olavide. Departamento de Biotecnología de Alimentos; EspañaFil: Sturm, Maria Elena. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza; ArgentinaFil: Rojo, Cecilia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza; ArgentinaFil: Combina, Mariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza; ArgentinaFil: Mercado, Laura Analia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mendoza; Argentin

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors