Macrophages modulate fibrosis during newt lens regeneration.

BACKGROUND: Previous studies have suggested that macrophages are present during lens regeneration in newts, but their role in the process is yet to be elucidated. METHODS: Here we generated a transgenic reporter line using the newt, Pleurodeles waltl, that traces macrophages during lens regeneration. Furthermore, we assessed early changes in gene expression during lens regeneration using two newt species, Notophthalmus viridescens and Pleurodeles waltl. Finally, we used clodronate liposomes to deplete macrophages during lens regeneration in both species and tested the effect of a subsequent secondary injury after macrophage recovery. RESULTS: Macrophage depletion abrogated lens regeneration, induced the formation of scar-like tissue, led to inflammation, decreased iris pigment epithelial cell (iPEC) proliferation, and increased rates of apoptosis in the eye. Some of these phenotypes persisted throughout the last observation period of 100 days and could be attenuated by exogenous FGF2 administration. A distinct transcript profile encoding acute inflammatory effectors was established for the dorsal iris. Reinjury of the newt eye alleviated the effects of macrophage depletion, including the resolution of scar-like tissue, and re-initiated the regeneration process. CONCLUSIONS: Together, our findings highlight the importance of macrophages for facilitating a pro-regenerative environment in the newt eye by regulating fibrotic responses, modulating the overall inflammatory landscape, and maintaining the proper balance of early proliferation and late apoptosis of the iPECs.

Macrophages modulate fibrosis during newt lens regeneration.

Background: Previous studies indicated that macrophages play a role during lens regeneration in newts, but their function has not been tested experimentally. Methods: Here we generated a transgenic newt reporter line in which macrophages can be visualized in vivo. Using this new tool, we analyzed the location of macrophages during lens regeneration. We uncovered early gene expression changes using bulk RNAseq in two newt species, Notophthalmus viridescens and Pleurodeles waltl. Next, we used clodronate liposomes to deplete macrophages, which inhibited lens regeneration in both newt species. Results: Macrophage depletion induced the formation of scar-like tissue, an increased and sustained inflammatory response, an early decrease in iris pigment epithelial cell (iPEC) proliferation and a late increase in apoptosis. Some of these phenotypes persisted for at least 100 days and could be rescued by exogenous FGF2. Re-injury alleviated the effects of macrophage depletion and re-started the regeneration process. Conclusions: Together, our findings highlight the importance of macrophages in facilitating a pro-regenerative environment in the newt eye, helping to resolve fibrosis, modulating the overall inflammatory landscape and maintaining the proper balance of early proliferation and late apoptosis.

Network efficiency of spatial systems with fractal morphology: a geometric graphs approach.

The functional features of spatial networks depend upon a non-trivial relationship between the topological and physical structure. Here, we explore that relationship for spatial networks with radial symmetry and disordered fractal morphology. Under a geometric graphs approach, we quantify the effectiveness of the exchange of information in the system from center to perimeter and over the entire network structure. We mainly consider two paradigmatic models of disordered fractal formation, the Ballistic Aggregation and Diffusion-Limited Aggregation models, and complementary, the Viscek and Hexaflake fractals, and Kagome and Hexagonal lattices. First, we show that complex tree morphologies provide important advantages over regular configurations, such as an invariant structural cost for different fractal dimensions. Furthermore, although these systems are known to be scale-free in space, they have bounded degree distributions for different values of an euclidean connectivity parameter and, therefore, do not represent ordinary scale-free networks. Finally, compared to regular structures, fractal trees are fragile and overall inefficient as expected, however, we show that this efficiency can become similar to that of a robust hexagonal lattice, at a similar cost, by just considering a very short euclidean connectivity beyond first neighbors.

DISTINCT METABOLIC STATES DIRECT RETINAL PIGMENT EPITHELIUM CELL FATE DECISIONS.

During tissue regeneration, proliferation, dedifferentiation, and reprogramming are necessary to restore lost structures. However, it is not fully understood how metabolism intersects with these processes. Chicken embryos can regenerate their retina through retinal pigment epithelium (RPE) reprogramming when treated with fibroblast factor 2 (FGF2). Using transcriptome profiling, we uncovered extensive regulation of gene sets pertaining to proliferation, neurogenesis, and glycolysis throughout RPE-to-neural retina reprogramming. By manipulating cell media composition, we determined that glucose, glutamine, or pyruvate are sufficient to support RPE reprogramming identifying glycolysis as a requisite. Conversely, the induction of oxidative metabolism by activation of pyruvate dehydrogenase induces Epithelial-to-mesenchymal transition (EMT), while simultaneously blocking the activation of neural retina fate. We also identify that EMT is partially driven by an oxidative environment. Our findings provide evidence that metabolism controls RPE cell fate decisions and provide insights into the metabolic state of RPE cells, which are prone to fate changes in regeneration and pathologies, such as proliferative vitreoretinopathy.

Freeform concentrator design for IR wireless-to-fiber link communications.

Airplanes use heavy wired harnesses to provide multimedia services to the seats. Optical wireless communications (OWC) are a natural choice to reduce the amount of weight, reduce the wiring complexity, and avoid possible spurious electromagnetic radiation that risks affecting the airplane's navigation systems. The light's dual use as lighting and optical communications functionalities allows for providing light and multimedia content through the reading lamp. Thus, an optical system using optical fibers to replace wires and a reading lamp can provide a cabin seat with lighting and onboard connectivity. However, changing shielded harnesses by optical fibers is-from an optical design point of view-a challenging task as the reading lamp must also meet the stringent requirements to link the optical wireless transmissions to the optical fiber. The difficulty up to now lies in injecting the light emitted from the passenger's device into the optical fiber using the reading lamp as the receiving antenna and light injector. Here, we describe a proof-of-concept device that experimentally allowed for establishing a link between a transmitter and a photodetector coupled to an optical fiber-end, i.e., the link consisted of an optical wireless communication and the launching of the light modulated signal into an optical fiber. Additionally, from the experimental experience, we will describe the optical design strategies permitting designing a compound freeform concentrator to allow optical free space-to-fiber links.

Macrophages modulate fibrosis during newt lens regeneration.

Previous studies indicated that macrophages play a role during lens regeneration in newts, but their function has not been tested experimentally. Here we generated a transgenic newt reporter line in which macrophages can be visualized in vivo. Using this new tool, we analyzed the location of macrophages during lens regeneration. We uncovered early gene expression changes using bulk RNAseq in two newt species, Notophthalmus viridescens and Pleurodeles waltl. Next, we used clodronate liposomes to deplete macrophages, which inhibited lens regeneration in both newt species. Macrophage depletion induced the formation of scar-like tissue, an increased and sustained inflammatory response, an early decrease in iris pigment epithelial cell (iPEC) proliferation and a late increase in apoptosis. Some of these phenotypes persisted for at least 100 days and could be rescued by exogenous FGF2. Re-injury alleviated the effects of macrophage depletion and re-started the regeneration process. Together, our findings highlight the importance of macrophages in facilitating a pro-regenerative environment in the newt eye, helping to resolve fibrosis, modulating the overall inflammatory landscape and maintaining the proper balance of early proliferation and late apoptosis.

Two-step crystallisation in a 2D active magnetic granular system confined by a parabolic potential.

We studied the two-step crystallisation process of a magnetic active 2D-granular system placed on different lens concaveness and under the action of an alternating magnetic field which controls its effective temperature. We have observed that the two-step features of the crystallisation process are more evident as the depth of the parabolic potential increases. At the initial formation of the nucleus, as a first step, in the central region of the lens an amorphous aggregate is formed. In an ulterior second step, this disordered aggregate, due to the effective temperature and the perturbations caused by the impacts of free particles moving in the surrounding region, evolves to an ordered crystalline structure. The nucleus size is larger for deeper concaveness of the parabolic potential. However, if the depth of the parabolic potential exceeds a certain value, the reordering process of the second step does not occur. The crystal growth occurs similarly; small disordered groups of particles join the nucleus, forming an amorphous shell of particles which experiments a rearranging while the aggregate grows. In the explored range of the depths of the parabolic potential, crystallisation generally occurs quicker as the deeper parabolic potential is. Also, aggregates are more clearly round-shaped as parabolic potential depth increases. On the contrary, the structures are more branched for a smaller depth of the parabolic potential. We studied the structural changes and features in the system by using the sixth orientational order parameter and the packing fraction.

Magnetized granular particles running and tumbling on the circle S

It has been shown that a nonvibrating magnetic granular system, when fed by an alternating magnetic field, behaves with most of the distinctive physical features of active matter systems. In this work, we focus on the simplest granular system composed of a single magnetized spherical particle allocated in a quasi-one-dimensional circular channel that receives energy from a magnetic field reservoir and transduces it into a running and tumbling motion. The theoretical analysis, based on the run-and-tumble model for a circle of radius R, forecasts the existence of a dynamical phase transition between an erratic motion (disordered phase) when the characteristic persistence length of the run-and-tumble motion, ℓ_{c}R/2. It is found that the limiting behaviors of these phases correspond to Brownian motion on the circle and a simple uniform circular motion, respectively. Furthermore, it is qualitatively shown that the smaller the magnetization of a particle, the larger the persistence length. It is so at least within the experimental limit of validity of our experiments. Our results show a very good agreement between theory and experiment.

Isolation and Characterization of Peritoneal Macrophages from Salamanders.

Salamanders have been used as research models for centuries. While they exhibit a wide range of biological features not seen in mammals, none has captivated scientists like their ability to regenerate. Interestingly, axolotl macrophages have emerged as an essential cell population for tissue regeneration. Whether the same is true in other salamanders such as newt species Notophthalmus viridescens, Cynops pyrrhogaster, or Pleurodeles waltl remains to be seen. Unfortunately, regardless of the species, molecular tools to study macrophage function in salamanders are lacking. We propose that the readily available, terminally differentiated peritoneal macrophages from newts or axolotls could be used to validate molecular reagents in the study of macrophage function during tissue regeneration in salamanders.

Cytogenetics of Chilean land plants (Embryophyta): state-of-the-art and prospects / CItogenética de plantas terrestres Chilenas (Embryophyta): estado del arte y perspectivas

ABSTRACT Chile is located in the south-western region of South America along the Pacific Ocean and contributes to the worldwide flora with ca. 6,120 species of Bryophyta, Pteridophyta, Pinophyta, Gnetophyta, and Magnoliophyta (1.9% of worldwide total species), exhibiting high endemism across all plant divisions. Little is known about the genetic diversity of Chilean land plants worldwide, including their cytogenetic and molecular characteristics. In 2012 we published the first state-of-the-art review in Cytogenetics of Chilean Angiosperms. The article gathered 78 publications from 1924 to 2010 accounting for approximately 139 species (2.8% of total Chilean species). The aim of this paper was to review the advances in cytogenetic studies of Chilean land plants, reporting additional cytogenetic data for species of four botanical divisions until 2020. Cytogenetic data were searched in the CPCD (Chilean Plants Cytogenetic Database). In total, we found 180 publications from both Chilean and foreign researchers. To date, cytogenetic data have been reported for 499 Chilean land plant species (8.2% of total) belonging to 244 genera and 117 families. In this context, the 2001-2020 period has been among the most productive regarding publications, with 74 available reports that include 163 additional species. Based on chromosome numbers, angiosperms and bryophytes registered the greatest diversity with 55 and 29 different 2n, respectively; both divisions having the greatest number of studied species. Given the importance of increasing information on Chilean land plants, it is expected that more publications will contribute to the knowledge of their cytogenetic diversity in the near future.

RESUMEN Chile está ubicado en la región suroeste de América del Sur a lo largo del Océano Pacífico y contribuye a la flora mundial con aproximadamente 6.120 especies de Bryophyta, Pteridophyta, Pinophyta, Gnetophyta y Magnoliophyta (1,9% del total de especies en todo el mundo), que presentan un alto endemismo en todas las divisiones de plantas. Poco se conoce sobre la diversidad genética de las plantas terrestres chilenas en todo el mundo, incluidas sus características citogenéticas y moleculares. En 2012 publicamos la primera revisión sobre el estado del arte en Citogenética de Angiospermas Chilenas. El artículo reunió 78 publicaciones desde 1924 hasta 2010, que representan aproximadamente 139 especies (2,8% del total de especies chilenas). El objetivo de este trabajo fue revisar los avances en estudios citogenéticos de plantas terrestres chilenas, reportando datos citogenéticos adicionales para especies de cuatro divisiones botánicas hasta el 2020. Los datos citogenéticos se buscaron en el CPCD (Base de Datos Citogenéticos de Plantas Chilenas). En total, encontramos 180 publicaciones sobre citogenética de plantas terrestres chilenas, con datos citogenéticos para 499 especies (8,2% del total) pertenecientes a 244 géneros y 117 familias. En este contexto, el período 2001-2020 ha sido uno de los más productivos en cuanto a publicaciones, con 74 artículos disponibles que incluyen 163 especies adicionales. Basado en los números cromosómicos, angiospermas y briófitos registran la mayor diversidad, con 55 y 29 2n diferentes, respectivamente; ambas divisiones tienen también el mayor número de especies estudiadas. Dada la importancia de incrementar la información sobre plantas terrestres chilenas, se espera que más publicaciones contribuyan al conocimiento de su diversidad citogenética en un futuro próximo.

Metas de logro 3x2 y mediadores psicológicos en estudiantes de educación física / 3x2 Achievement Goals and Psychological Mediators in Physical Education Students

Esta investigación examina la relación entre las metas de logro 3x2, las necesidades psicológicas básicas, la motivación autodeterminada, la intención de ser físicamente activo y la satisfacción con la vida. Participaron en el estudio 1706 estudiantes de Educación Física de 10 a 17 años (M = 13.75; DT = 2.98). Se realizaron análisis descriptivos y regresiones lineales. La validez y la consistencia interna fueron apropiadas. Los resultados señalaron la importancia de la satisfacción de la competencia y la relación, la motivación autodeterminada, y las metas de aproximación-tarea y aproximación-otro en la predicción de la intención de ser físicamente activo, así como de las metas basadas en la tarea y la satisfacción de las tres necesidades psicológicas básicas en la predicción de la satisfacción con la vida. El marco de metas de logro 3x2 supone una contribución relevante en la explicación de las consecuencias motivacionales y del bienestar del alumnado. (AU)

This research examines the relationship between 3x2 achievement goals, basic psychological needs, self-determined motivation, intention to be physically active, and satisfaction with life. The sample was comprised of 1706 Physical Education students with aged between 10 and 17 years old (M = 13.75; DT = 2.98). Descriptive analysis and linear regressions were performed. Validity and internal consistency were appropriate. The results pointed out the importance of competence and relationship satisfaction, self-determined motivation, and task-approach and other-approach goals in predicting the intention to be physically active, as well as task-based goals and satisfaction of the three basic psychological needs in predicting satisfaction with life. The 3x2 achievement goal framework is a relevant contribution in explaining the motivational and welfare consequences of the students. (AU)

New records of Triatoma huehuetenanguensis in an urban area of Southwest Mexico.

The recently described Triatoma huehuetenanguensis, has been reported in Mexico, Guatemala, Belize and Honduras. In Mexico, the species has been collected primarily in rural areas; it has the potential to colonize human dwellings, however, its contribution to Chagas outbreaks remains unclear. In 2021, T. huehuetenanguensis was first observed at Tuxtla Gutierrez city, Chiapas; then a collection for the species was performed. A total of 308 houses were inspected in the intra and peridomestic structures. Only 3 houses (0.97%) were infested. Triatoma huehuetenangensis was the only triatomine specie recorded and four males were collected. None of the bugs tested positive for Trypanosoma infection. We do not have evidence to suggest that urban human-vector contact still limited, and a possible domestication process is possible. The presence of reservoirs, the vector species and the parasite demonstrate that Tuxtla Gutierrez could be at risk of a Chagas disease outbreak.

A Stage-Specific OTX2 Regulatory Network and Maturation-Associated Gene Programs Are Inherent Barriers to RPE Neural Competency.

The retinal pigment epithelium (RPE) exhibits a diverse range of plasticity across vertebrates and is a potential source of cells for the regeneration of retinal neurons. Embryonic amniotes possess a transitory ability to regenerate neural retina through the reprogramming of RPE cells in an FGF-dependent manner. Chicken RPE can regenerate neural retina at embryonic day 4 (E4), but RPE neural competence is lost by embryonic day 5 (E5). To identify mechanisms that underlie loss of regenerative competence, we performed RNA and ATAC sequencing using E4 and E5 chicken RPE, as well as at both stages following retinectomy and FGF2 treatment. We find that genes associated with neural retina fate remain FGF2-inducible in the non-regenerative E5 RPE. Coinciding with fate restriction, RPE cells stably exit the cell cycle and dampen the expression of cell cycle progression genes normally expressed during regeneration, including E2F1. E5 RPE exhibits progressive activation of gene pathways associated with mature function independently of retinectomy or FGF2 treatment, including retinal metabolism, pigmentation synthesis, and ion transport. Moreover, the E5 RPE fails to efficiently repress OTX2 expression in response to FGF2. Predicted OTX2 binding motifs undergo robust accessibility increases in E5 RPE, many of which coincide with putative regulatory elements for genes known to facilitate RPE differentiation and maturation. Together, these results uncover widespread alterations in gene regulation that culminate in the loss of RPE neural competence and implicate OTX2 as a key determinant in solidifying the RPE fate. These results yield valuable insight to the basis of RPE lineage restriction during early development and will be of importance in understanding the varying capacities for RPE-derived retinal regeneration observed among vertebrates.

Effect of a multi-domain intervention on the quality of life in older adults with major neurocognitive disorder: A pilot study.

PURPOSE: Major neurocognitive disorders (MND) have multiple negative consequences on patients' lives and on their caregivers' health. Occupational therapy and cognitive stimulation have failed to show any significant efficacy on quality of life (QoL), cognitive functioning and behavioural symptoms. Bretonneau Hospital's Day Care Unit offers personalized and structured multi-domain interventions to cognitively impaired older patients on a weekly basis, for a 3-month period. OBJECTIVES: Our objective was to determine whether a specific rehabilitation day care unit (RDCU) could influence the QoL of cognitively impaired community-dwelling elderly patients. We also aimed to better understand the characteristics of patients who had the most benefited from the RDCU. METHODS: Retrospective study based on a sample of outpatients participating in RDCU during three months. All patients underwent a cognitive (MMS), functional (IADl, ADL) and behavioral (NPI) assessment. We compared QoL using the QoL-Alzheimer's Disease (QoL-AD) scale before and after RDCU. RESULTS: Overall, we included 60 outpatients in our study (mean age 83.3±5.8; women=70%). We found a statistically significant improvement of QoL-AD scores after RDCU (31.8±4.9 to 32.9±5.2, P=0.008). Patients who benefitted the most from RDCU were older (P=0.01) and had lower baseline QoL (P=0.04). We did not find any other characteristics associated with QoL-AD score improvement in our population. CONCLUSION: RDCU showed positive effects on QoL in this uncontrolled pilot study of older adults with MND. These findings should be confirmed in a future randomized controlled trial to corroborate the potential benefits of RDCU on QoL in older cognitively impaired patients.

Crystallisation in a two-dimensional granular system at constant temperature.

We study the crystallisation processes occurring in a nonvibrating two-dimensional magnetic granular system at various fixed values of the effective temperature. In this system, the energy loss due to dissipative effects is compensated by the continuous energy input coming into the system from a sinusoidal magnetic field. When this balance leads to high values of the effective temperature, no aggregates are formed, because particles' kinetic energy prevents them from aggregating. For lower effective temperatures, formation of small aggregates is observed. The smaller the values of the applied field's amplitude, the larger the number of these disordered aggregates. One also observes that when clusters form at a given effective temperature, the average effective diffusion coefficient decreases as time increases. For medium values of the effective temperature, formation of small crystals is observed. We find that the sixth bond-orientational order parameter and the number of bonds, when considering more than two, are very sensitive for exhibiting the order in the system, even when crystals are still very small.

Incidence, clinical patterns, and risk factors of postpartum uterine diseases in dairy cows from high-altitude tropical herds.

The cow's uterus sustains bacterial contamination and active inflammation after calving as part of the normal physiological process of uterine involution. Although the definition, incidence, and risk factors for postpartum uterine diseases (PUD) have been documented in annual calving systems with high-producing cows on total mixed ration, the literature contains little information for other production systems. The objective of this study was to quantify the incidence risk and factors associated with metritis, clinical endometritis, and cytological endometritis in high-altitude tropical dairy herds in a pasture-based system. A total of 248 cows from 5 commercial dairy herds in northern Antioquia, Colombia, were enrolled in this prospective observational longitudinal cohort study. Data collection and PUD diagnosis were performed at d 0, 3, 10, 17, 24, 31, 38, 45, and 52 (±1) after parturition. Between 60 and 70 d, cows were systematically enrolled in a synchronization protocol, and herds were visited monthly for pregnancy diagnosis until 180 ±15 d. The multivariable logistic regression model of variables associated with PUD occurrence included (a) parity, season of calving, transition diet, and body condition score at calving; (b) blood calcium, phosphorus, and magnesium concentrations, and milk urea nitrogen, ß-hydroxybutyrate and fat-to-protein ratio; and (c) dystocia, retained placenta, and delayed uterine involution. The incidences of puerperal metritis, clinical metritis (MET), clinical endometritis (CE), and cytological endometritis (CYTO) were 2.8, 25, 29, and 26%, respectively. Retained placenta and dystocia were associated with MET, and MET was associated with CE. Low blood calcium concentration at calving was associated with CYTO. Overall, 51.2% of the cows suffered at least 1 category of PUD during the first 60 d postpartum (DPP). However, cows also suffered from different consecutive clinical events of PUD (MET, CE, and CYTO) during the follow-up period (0 to 180 ±15 DPP). These events could be grouped into 4 types (which were referred to as "clinical patterns") based on interactions between MET, CE, and CYTO.

Chromosome number variation in part of the flora of protected wild areas in the Araucania region of southern Chile / Variación del número cromosómico en parte de la flora de áreas silvestres protegidas en la región de la Araucanía, sur de Chile

ABSTRACT An analysis was made of the correspondence between species diversity and chromosome number (CN) diversity across 13 Protected Wild Areas (PWA) in the Araucanía Region of southern Chile, encompassing 84 plant species with available cytogenetic data. Our aim was to establish whether higher species diversity within a PWA entails higher CN variation as based on the index of chromosome number heterogeneity (ICNH). The CN data were extracted from databases for Chilean plants, and the ICNH for the flora of each PWA was calculated. Results showed that in nine PWA the species diversity clearly correlates with CN diversity. However, four PWA do not fit this trend. The percentage of species with CN data varied between 9.6% and 24.5% among PWA, with 11 PWA presenting percentages higher than 11%. A 27.3% of the Chilean vascular plant species with available cytogenetic data were studied here for the 13 PWA. The results obtained by studying one part of the flora with available CN data suggest that the PWA could be an important reservoir of genetic diversity at a chromosome level, thus justifying the protective role of the PWA as biodiversity conservation sites.

RESUMEN Se realizó un análisis de la correspondencia entre la diversidad de especies y la diversidad de números cromosómicos (CN) en 13 Áreas Silvestres Protegidas (PWA) en la Región de La Araucanía en el sur de Chile, incluyendo 84 especies de plantas con datos citogenéticos disponibles. El objetivo fue establecer si una mayor diversidad de especies dentro de un PWA implica una mayor diversidad en CN expresado en base al Índice de Heterogeneidad Cromosómica (ICNH). Los CN de cada especie se extrajeron de bases de datos para plantas chilenas y se calculó el ICNH para la flora de cada PWA. Los resultados mostraron que en nueve PWA la diversidad de especies se correlaciona claramente con la diversidad de CN. Sin embargo, cuatro PWA no se ajustan a esta tendencia. El porcentaje de especies con datos de CN varió entre 9,6% y 24,5% entre PWA, con 11 PWA presentando porcentajes superiores al 11%. Un 27,3% de las especies de plantas vasculares chilenas con datos citogenéticos disponibles fueron estudiadas para las 13 PWA. Los resultados obtenidos al estudiar parte de la flora sugieren que las PWA serían un reservorio importante de diversidad genética a nivel cromosómico como se muestra aquí, justificando así el papel protector de las PWA como sitios de conservación de la biodiversidad.

Postpartum uterine diseases negatively impact the time to pregnancy in grazing dairy cows from high-altitude tropical herds.

Infertility is a common consequence of cows suffering from postpartum uterine diseases. Diseases from a uterine origin in early lactation affect both uterine and ovarian tissues decreasing the probability of pregnancy. The objective of the present study was to determine the impact of clinical metritis, clinical endometritis, and subclinical endometritis on days open in cows from high-altitude tropical dairy herds. A single cohort longitudinal study was conducted from January 2018 to February 2019, which included 248 cows enrolled from five commercial high-altitude tropical dairy herds in the northern region of the Department of Antioquia, Colombia. A directed acyclic graph was used to identify minimal sufficient adjustment sets for each exposure variable of interest. Based on the directed acyclic graph, three models (one for each of clinical metritis, clinical endometritis, and subclinical endometritis) were proposed to assess the impact of postpartum uterine diseases on days open. The time at risk was defined as the days elapsed from calving until pregnancy (event or censure). Observations were right-censored if cows were either culled, dead, were lost to follow up, suffered a systemic illness that required the use of parenteral drugs, or if they were not pregnant at 210 postpartum days. Three Cox proportional hazards models were proposed to estimate the Hazard Ratios (HR) at any point in the follow-up period for each exposure variable. The hazard of pregnancy was significantly lower for cows with metritis (40 %; HR = 0.60; 95 % CI: 0.43 - 0.86), clinical endometritis (69 %; HR = 0.31; 95 % CI: 0.22 - 0.45), and subclinical endometritis (76 %; HR = 0.24; 95 % CI: 0.16 - 0.36) compared to their herd mates without these conditions. These results provide evidence of the negative impact of postpartum uterine diseases on time to pregnancy in grazing lactating dairy cows from high-altitude tropical herds.

General formula to design a freeform singlet free of spherical aberration and astigmatism: comment.

In their paper [Appl. Opt.58, 1010 (2019)APOPAI0003-693510.1364/AO.58.001010] González-Acuña et al. claimed: "an analytical closed-form formula for the design of freeform lenses free of spherical aberration and astigmatism." However, as we show here, their formula can only be applied when the object and image are both real, and the image is inversed; additionally, the refractive index in the object and image media is the same. Here, we present the complete solution of this particular formula.

Results on Low-Mass Weakly Interacting Massive Particles from an 11 kg d Target Exposure of DAMIC at SNOLAB.

We present constraints on the existence of weakly interacting massive particles (WIMPs) from an 11 kg d target exposure of the DAMIC experiment at the SNOLAB underground laboratory. The observed energy spectrum and spatial distribution of ionization events with electron-equivalent energies >200 eV_{ee} in the DAMIC CCDs are consistent with backgrounds from natural radioactivity. An excess of ionization events is observed above the analysis threshold of 50 eV_{ee}. While the origin of this low-energy excess requires further investigation, our data exclude spin-independent WIMP-nucleon scattering cross sections σ_{χ-n} as low as 3×10^{-41} cm^{2} for WIMPs with masses m_{χ} from 7 to 10 GeV c^{-2}. These results are the strongest constraints from a silicon target on the existence of WIMPs with m_{χ}<9 GeV c^{-2} and are directly relevant to any dark matter interpretation of the excess of nuclear-recoil events observed by the CDMS silicon experiment in 2013.