Assessing nasal airway resistance and symmetry: An approach to global perspective through computational fluid dynamics.

This study aimed to explore the variability in nasal airflow patterns among different sexes and populations using computational fluid dynamics (CFD). We focused on evaluating the universality and applicability of dimensionless parameters R (bilateral nasal resistance) and ϕ (nasal flow asymmetry), initially established in a Caucasian Spanish cohort, across a broader spectrum of human populations to assess normal breathing function in healthy airways. In this retrospective study, CT scans from Cambodia (20 males, 20 females), Russia (20 males, 18 females), and Spain (19 males, 19 females) were analyzed. A standardized CFD workflow was implemented to calculate R-ϕ parameters from these scans. Statistical analyses were conducted to assess and compare these parameters across different sexes and populations, emphasizing their distribution and variances. Our results indicated no significant sex-based differences in the R parameter across the populations. However, moderate sexual dimorphism in the ϕ parameter was observed in the Cambodian group. Notably, no geographical differences were found in either R or ϕ parameters, suggesting consistent nasal airflow characteristics across the diverse human groups studied. The study also emphasized the importance of using dimensionless variables to effectively analyze the relationships between form and function in nasal airflow. The observed consistency of R-ϕ parameters across various populations highlights their potential as reliable indicators in both medical practice and further CFD research, particularly in diverse human populations. Our findings suggest the potential applicability of dimensionless CFD parameters in analyzing nasal airflow, highlighting their utility across diverse demographic and geographic contexts. This research advances our understanding of nasal airflow dynamics and underscores the need for additional studies to validate these parameters in broader population cohorts. The approach of employing dimensionless parameters paves the way for future research that eliminates confounding size effects, enabling more accurate comparisons across different populations and sexes. The implications of this study are significant for the advancement of personalized medicine and the development of diagnostic tools that accommodate individual variations in nasal airflow.

The influence of the land-to-sea macroevolutionary transition on vertebral column disparification in Pinnipedia.

The repeated returns of vertebrates to the marine ecosystems since the Triassic serve as an evolutionary model to understand macroevolutionary change. Here we investigate the effects of the land-to-sea transition on disparity and constraint of the vertebral column in aquatic carnivorans (Carnivora; Pinnipedia) to assess how their functional diversity and evolutionary innovations influenced major radiations of crown pinnipeds. We use three-dimensional geometric morphometrics and multivariate analysis for high-dimensional data under a phylogenetic framework to quantify vertebral size and shape in living and extinct pinnipeds. Our analysis demonstrates an important shift in vertebral column evolution by 10-12 million years ago, from an unconstrained to a constrained evolutionary scenario, a point of time that coincides with the major radiation of crown pinnipeds. Moreover, we also demonstrate that the axial skeleton of phocids and otariids followed a different path of morphological evolution that was probably driven by their specialized locomotor strategies. Despite this, we found a significant effect of habitat preference (coastal versus pelagic) on vertebral morphology of crown taxa regardless of the family they belong. In summary, our analysis provides insights into how the land-to-sea transition influenced the complex evolutionary history of pinniped vertebral morphology.

Beyond skeletal studies: A computational analysis of nasal airway function in climate adaptation.

OBJECTIVES: Ecogeographic variation in human nasal anatomy has historically been analyzed on skeletal morphology and interpreted in the context of climatic adaptations to respiratory air-conditioning. Only a few studies have analyzed nasal soft tissue morphology, actively involved in air-conditioning physiology. MATERIALS AND METHODS: We used in vivo computer tomographic scans of (N = 146) adult individuals from Cambodia, Chile, Russia, and Spain. We conducted (N = 438) airflow simulations during inspiration using computational fluid dynamics to analyze the air-conditioning capacities of the nasal soft tissue in the inflow, functional, and outflow tract, under three different environmental conditions: cold-dry; hot-dry; and hot-humid. We performed statistical comparisons between populations and sexes. RESULTS: Subjects from hot-humid regions showed significantly lower air-conditioning capacities than subjects from colder regions in all the three conditions, specifically within the isthmus region in the inflow tract, and the anterior part of the internal functional tract. Posterior to the functional tract, no differences were detected. No differences between sexes were found in any of the tracts and under any of the conditions. DISCUSSION: Our statistical analyses support models of climatic adaptations of anterior nasal soft tissue morphology that fit with, and complement, previous research on dry skulls. However, our results challenge a morpho-functional model that attributes air-conditioning capacities exclusively to the functional tract located within the nasal cavity. Instead, our findings support studies that have suggested that both, the external nose and the intra-facial soft tissue airways contribute to efficiently warming and humidifying air during inspiration. This supports functional interpretations in modern midfacial variation and evolution.

Efficacy and safety of systemic chemotherapy for radically resectable esophago-gastric adenocarcinoma in older patients: A systematic review and meta-analysis.

INTRODUCTION: A significant proportion of locally-advanced esophago-gastric adenocarcinoma (EGA) is diagnosed in patients ≥70 years old (y.o.) who are commonly underrepresented in clinical trials. MATERIALS AND METHODS: The PubMed database was searched for phase 2/3 clinical trials enrolling patients ≥70 y.o and reporting efficacy/safety information of chemotherapy for resectable EGA. The main outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS: Among 6,128 records, only seven studies reported these outcomes (three peri-operative, three adjuvant, and one neoadjuvant), including 1004 older patients, <20% of the overall population. No significant benefit in terms of OS and RFS was observed for perioperative or adjuvant chemotherapy vs surgery alone. No trial reported safety endpoints in this subgroup. DISCUSSION: This work did not show any significant benefit in OS or RFS for chemotherapy vs surgery alone or conventional vs de-escalated chemotherapy in the curative setting of EGA in ≥70 y.o patients. Specific ad hoc trials should be performed to derive reliable data.

[Numerical expression of the clinical course of the disease. Data management]. / Expresión numérica del curso clínico de la enfermedad. Manejo de datos.

Data management "behind the scenes" refers to collection, cleaning, imputation, and demarcation; and despite of being indispensable processes, they are usually neglected and thus, generate erroneous information. During the collection are errors: omission of covariates, deviation from the objective, and insufficient quality. The omission of covariates distorts the result attributed to the main manoeuvre. Deviation from the primary objective commonly occurs when the outcome is rare, delayed, or subjective and promotes substitution by non-equivalent surrogate variables. Moreover, insufficient quality occurs due to inadequate instruments, omission of the measurement procedure, or measurements out of context, such as attribution at the wrong time or equivalent. Furthermore, cleaning implies identifying erroneous, extreme, and missing values, which may or may not be imputed, depending on the percentage. The values of the manoeuvre or the outcome are never imputed, nor are patients eliminated due to a lack of values. Finally, the demarcation of each variable seeks to give it a clinical meaning about the outcome, for which a hierarchical sequence of criteria is followed: 1) previous clinical study, 2) expert agreement, 3) clinical judgment of the investigator/investigators, and 4) statistics. Acting without quality controls in data management frequently causes involuntary lies and confuses instead of clarifying.

El manejo de datos "tras bambalinas" se refiere a los procesos de recopilación, limpieza, imputación y demarcación; los cuales, aun siendo indispensables, usualmente suelen ser descuidados, por lo que generan información errónea. Durante la recopilación son errores: omisión de covariables, desvío del objetivo, y calidad insuficiente. La omisión de covariables distorsiona el resultado atribuido a la maniobra principal. El desvío del objetivo primario es común cuando el desenlace es raro, tardado o subjetivo y promueve la sustitución por variables subrogadas no equivalentes. Además, la calidad insuficiente, sucede por instrumentos inadecuados, omisión del procedimiento de medición, o medición fuera de contexto -como atribución a destiempo o equivalente-. Por otro lado, la limpieza implica identificar valores erróneos, extremos y faltantes, que podrán ser o no imputados, dependiendo del porcentaje se imputará comúnmente por la medida de resumen. Nunca se imputan los valores de la maniobra ni del desenlace, ni se eliminan pacientes por falta de valores. Finalmente, la demarcación de cada variable busca un significado clínico en referencia al desenlace, para ello se sigue una secuencia jerárquica de criterios: 1) estudio clínico previo, 2) acuerdo de expertos, 3) juicio clínico del investigador/investigadores y 4) estadística. Actuar sin controles de calidad en el manejo de datos provoca frecuentemente mentiras involuntarias y confunde en lugar de esclarecer.

The impact of the land-to-sea transition on evolutionary integration and modularity of the pinniped backbone.

In this study, we investigate how the terrestrial-aquatic transition influenced patterns of axial integration and modularity in response to the secondary adaptation to a marine lifestyle. We use 3D geometric morphometrics to quantify shape covariation among presacral vertebrae in pinnipeds (Carnivora; Pinnipedia) and to compare with patterns of axial integration and modularity in their close terrestrial relatives. Our results indicate that the vertebral column of pinnipeds has experienced a decrease in the strength of integration among all presacral vertebrae when compared to terrestrial carnivores (=fissipeds). However, separate integration analyses among the speciose Otariidae (i.e., sea lions and fur seals) and Phocidae (i.e., true seals) also suggests the presence of different axial organizations in these two groups of crown pinnipeds. While phocids present a set of integrated "thoracic" vertebrae, the presacral vertebrae of otariids are characterized by the absence of any set of vertebrae with high integration. We hypothesize that these differences could be linked to their specific modes of aquatic locomotion -i.e., pelvic vs pectoral oscillation. Our results provide evidence that the vertebral column of pinnipeds has been reorganized from the pattern observed in fissipeds but is more complex than a simple "homogenization" of the modular pattern of their close terrestrial relatives.

Signaling pathways governing the maintenance of breast cancer stem cells and their therapeutic implications.

Breast cancer stem cells (BCSCs) represent a distinct subpopulation of cells with the ability to self-renewal and differentiate into phenotypically diverse tumor cells. The involvement of CSC in treatment resistance and cancer recurrence has been well established. Numerous studies have provided compelling evidence that the self-renewal ability of cancer stem cells is tightly regulated by specific signaling pathways, which exert critical roles to maintain an undifferentiated phenotype and prevent the differentiation of CSCs. Signaling pathways such as Wnt/ß-catenin, NF-κB, Notch, Hedgehog, TGF-ß, and Hippo have been implicated in the promotion of self-renewal of many normal and cancer stem cells. Given the pivotal role of BCSCs in driving breast cancer aggressiveness, targeting self-renewal signaling pathways holds promise as a viable therapeutic strategy for combating this disease. In this review, we will discuss the main signaling pathways involved in the maintenance of the self-renewal ability of BCSC, while also highlighting current strategies employed to disrupt the signaling molecules associated with stemness.

Individual variability in diving behavior of the Black-vented Shearwater in an ever-changing habitat.

Oceanic mesoscale systems are characterized by inherent variability. Climatic change adds entropy to this system, making it a highly variable environment in which marine species live. Being at the higher levels of the food chain, predators maximize their performance through plastic foraging strategies. Individual variability within a population and the possible repeatability across time and space may provide stability in a population facing environmental changes. Therefore, variability and repeatability of behaviors, particularly diving behavior, could play an important role in understanding the adaptation pathway of a species. This study focuses on characterizing the frequency and timing of different dives (termed simple and complex) and how these are influenced by individual and environmental characteristics (sea surface temperature, chlorophyll a concentration, bathymetry, salinity, and Ekman transport). This study is based on GPS and accelerometer-recorded information from a breeding group of 59 Black-vented Shearwater and examine consistency in diving behavior at both individual and sex levels across four different breeding seasons. The species was found to be the best performing free diver in the Puffinus genus with a maximum dive duration of 88 s. Among the environmental variables assessed, a relationship was found with active upwelling conditions enhancing low energetic cost diving, on the contrary, reduced upwelling and warmer superficial waters induce more energetically demanding diving affecting diving performance and ultimately body conditions. The body conditions of Black-vented Shearwaters in 2016 were worse than in subsequent years, in 2016, deepest and longest complex dives were recorded, while simple dives were longer in 2017-2019. Nevertheless, the species' plasticity allows at least part of the population to breed and feed during warmer events. While carry-over effects have already been reported, the effect of more frequent warm events is still unknown.

Mitochondrial phosphatidylethanolamine modulates UCP1 to promote brown adipose thermogenesis.

Thermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms by which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in the inner mitochondrial membrane (IMM), where it dissipates membrane potential independent of adenosine triphosphate (ATP) synthase. Here, we provide evidence that phosphatidylethanolamine (PE) modulates UCP1-dependent proton conductance across the IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose abundance bidirectionally responds to changes in thermogenic burden. Reduction in mitochondrial PE by deletion of phosphatidylserine decarboxylase (PSD) made mice cold intolerant and insensitive to ß3 adrenergic receptor agonist-induced increase in whole-body oxygen consumption. High-resolution respirometry and fluorometry of BAT mitochondria showed that loss of mitochondrial PE specifically lowers UCP1-dependent respiration without compromising electron transfer efficiency or ATP synthesis. These findings were confirmed by a reduction in UCP1 proton current in PE-deficient mitoplasts. Thus, PE performs a previously unknown role as a temperature-responsive rheostat that regulates UCP1-dependent thermogenesis.

Elbow-joint morphology in the North American 'cheetah-like' cat Miracinonyx trumani.

The North American cheetah-like cat Miracinonyx trumani is an extinct species that roamed the Pleistocene prairies 13 000 years ago. Although M. trumani is more closely related to the cougar (Puma concolor) than to the living cheetah (Acinonyx jubatus), it is believed that both A. jubatus and M. trumani possess a highly specialized skeleton for fast-running, including limbs adapted for speed at the expense of restricting the ability of prey grappling. However, forelimb dexterity of M. trumani has not been yet investigated. Here, we quantify the 3D-shape of the humerus distal epiphysis as a proxy for elbow-joint morphology in a sample of living cats to determine whether the extinct M. trumani was specialized to kill open-country prey using predatory behaviour based on fast running across the prairies and steppe terrains of the North American Pleistocene. We show that M. trumani had an elbow morphology intermediate to that of P. concolor and A. jubatus, suggesting that M. trumani had a less specialized pursuit predatory behaviour than A. jubatus. We propose that M. trumani probably deployed a unique predatory behaviour without modern analogues. Our results bring into question the degree of ecomorphological convergence between M. trumani and its Old World vicar A. jubatus.

Intravertebral vs. intervertebral integration and modularity in the vertebral column of mammalian carnivorans.

The vertebral column is a multicomponent structure whose organization results from developmental and functional demands. According to their distinct somitic origins, individual vertebrae exhibit intravertebral modularity between the centrum and neural spine. However, vertebrae are also organized into larger units called intervertebral modules that result from integration between adjacent vertebrae due to locomotory demands or from common developmental origins due to resegmentation. A previous hypothesis suggested that the boundaries of intervertebral modules coincide with changes in the patterns of intravertebral integration. Here, we explicitly test whether the patterns of modularity and integration between the centrum and neural spine (i.e., intravertebral) in the boundary vertebrae among previously defined intervertebral modules change with respect to those in the vertebrae within intervertebral modules. We quantified intravertebral modularity patterns and quantified the strength of intravertebral integration for each vertebra of the presacral region in 41 species of carnivoran mammals using 3D geometric morphometrics. Our results demonstrate a significant intravertebral modular signal between the centrum and neural spine in all post-cervical vertebrae, including the boundary vertebrae among intervertebral modules. However, the strength of intravertebral integration decreases at the boundary vertebrae. We also found a significant correlation between the degree of intravertebral integration and intervertebral integration. Following our results, we hypothesize that natural selection does not override the integration between the centrum and neural spine at the boundary vertebrae, a pattern that should be influenced by their distinct somitic origins and separate ossification centers during early development. However, natural selection has probably influenced (albeit indirectly) the integration between the centrum and neural spine in the vertebrae that compose the intervertebral modules.

Bayesian inference for fitting cardiac models to experiments: estimating parameter distributions using Hamiltonian Monte Carlo and approximate Bayesian computation.

Customization of cardiac action potential models has become increasingly important with the recognition of patient-specific models and virtual patient cohorts as valuable predictive tools. Nevertheless, developing customized models by fitting parameters to data poses technical and methodological challenges: despite noise and variability associated with real-world datasets, traditional optimization methods produce a single "best-fit" set of parameter values. Bayesian estimation methods seek distributions of parameter values given the data by obtaining samples from the target distribution, but in practice widely known Bayesian algorithms like Markov chain Monte Carlo tend to be computationally inefficient and scale poorly with the dimensionality of parameter space. In this paper, we consider two computationally efficient Bayesian approaches: the Hamiltonian Monte Carlo (HMC) algorithm and the approximate Bayesian computation sequential Monte Carlo (ABC-SMC) algorithm. We find that both methods successfully identify distributions of model parameters for two cardiac action potential models using model-derived synthetic data and an experimental dataset from a zebrafish heart. Although both methods appear to converge to the same distribution family and are computationally efficient, HMC generally finds narrower marginal distributions, while ABC-SMC is less sensitive to the algorithmic settings including the prior distribution.

Advancements in veterinary medicine: the use of Flowgy for nasal airflow simulation and surgical predictions in big felids (a case study in lions).

Flowgy is a semi-automated tool designed to simulate airflow across the nasal passage and detect airflow alterations in humans. In this study, we tested the use and accuracy of Flowgy in non-human vertebrates, using large felids as the study group. Understanding the dynamics of nasal airflow in large felids such as lions (Panthera leo) is crucial for their health and conservation. Therefore, we simulated airflow during inspiration through the nasal passage in three lions (Panthera leo), two of which were siblings (specimens ZPB_PL_002 and ZPB_PL_003), without breathing obstructions. However, one of the specimens (ZPB_PL_001) exhibited a slight obstruction in the nasal vestibule, which precluded the specimen from breathing efficiently. Computed tomography (CT) scans of each specimen were obtained to create detailed three-dimensional models of the nasal passage. These models were then imported into Flowgy to simulate the airflow dynamics. Virtual surgery was performed on ZPB_PL_001 to remove the obstruction and re-simulate the airflow. In parallel, we simulated the respiration of the two sibling specimens and performed an obstructive operation followed by an operation to remove the obstruction at the same level and under the same conditions as the original specimen (ZPB_PL_001). Thus, we obtained a pattern of precision for the operation by having two comparable replicas with the obstructed and operated specimens. The simulations revealed consistent airflow patterns in the healthy specimens, demonstrating the accuracy of Flowgy. The originally obstructed specimen and two artificially obstructed specimens showed a significant reduction in airflow through the right nostril, which was restored after virtual surgery. Postoperative simulation indicated an improvement of >100% in respiratory function. Additionally, the temperature and humidity profiles within the nostrils showed marked improvements after surgery. These findings underscore the potential of Flowgy in simulating nasal airflow and predicting the outcomes of surgical interventions in large felids. This could aid in the early detection of respiratory diseases and inform clinical decision-making, contributing to improved veterinary care and conservation efforts. However, further research is needed to validate these findings in other species and explore the potential of integrating Flowgy with other diagnostic and treatment tools in veterinary medicine.

An Exploratory Comparison of Water-Tamped and -Untamped Explosive Breaches: Practical Applications for the Tactical Community via a Pilot Study.

BACKGROUND: Tamping explosive charges used by breachers is an increasingly common technique. The ability to increase the directional effectiveness of the charge used, combined with the potential to reduce experienced overpressure on breachers, makes tamping a desirable tool not only from an efficacy standpoint for breachers but also from a safety standpoint for operational personnel. The long-term consequences of blast exposure are an open question and may be associated with temporary performance deficits and negative health symptomatology. PURPOSE: This work evaluates breaches of varying charge weight, material breached, and tamping device used to determine the value of tamping during various scenarios by measuring actual breaches conducted during military and law enforcement training for efficacy and blast overpressure on Operators. METHODS: Three data collections across 18 charges of various construction were evaluated with blast overpressure sensors at various distances and locations where breachers would be located, to assess explosive forces on human personnel engaged in breaching activities. RESULTS AND CONCLUSIONS: Findings indicate that water tamping in general is a benefit on moderate and heavy charges but offers less benefit at a low charge with regard to mitigating blast overpressure on breachers. Reduced overpressure allows Operators to stage closer to explosives and lowers the potential for compromised reaction time. It also reduces the likelihood of negative consequences that can result from excessive overpressure exposure and allow Operators to "do more with less" in complex environments, where resource access may be limited by logistic or other limitations. However, tamping in all instances improved blast efficacy in creating successful breaches. Future studies are planned to investigate tamping mediums beyond water and environment changes, whether tamping can be used to mitigate acoustic insult, and other explosive types.

The evolution, form and function of the human respiratory system.

This paper presents an updated view on the morphological and functional significance of the human respiratory system in the context of human evolutionary anatomy. While usually the respiratory system is treated either from a craniofacial perspective, mostly in the context of nasal evolution and air-conditioning, or from a postcranial perspective featuring on overall thoracic shape changes, here we pursue a holistic perspective on the form, function, integration, and evolutionary change of the entire organismal system in hominins. We first present a brief review of the most important morphological structures, their function, and its potential integration and interaction with the nasal cavity and thoracic skeleton. This is followed by an overview of the most important improvements in methods for the comparative study in recent humans and fossil hominins. We then overview and list a compendium of hominin fossil material currently available for the study. We propose four functional categories of hominin respiratory system configurations that differ potentially with respect to size, shape, biomechanics and/or bioenergetics. Finally, we discuss these and speculate on possible ways for future research into an anatomical system that, despite its under-investigated status, is central to the understanding of the form and functions of the hominin organism and its paleobiology.

The brain of the North American cheetah-like cat Miracinonyx trumani.

The cheetah Acinonyx jubatus, the fastest living land mammal, is an atypical member of the family Felidae. The extinct feline Miracinonyx trumani, known as the North American cheetah, is thought to have convergently evolved with Acinonyx to pursue fast and open-country prey across prairies and steppe environments of the North American Pleistocene. The brain of Acinonyx is unique among the living felids, but it is unknown whether the brain of the extinct M. trumani is convergent to that of Acinonyx. Here, we investigate the brain of M. trumani from a cranium endocast, using a comparative sample of other big cats. We demonstrate that the brain of M. trumani was different from that of the living A. jubatus. Indeed, its brain shows a unique combination of traits among living cats. This suggests that the case of extreme convergence between Miracinonyx and its living Old World vicar should be reconsidered.

Keratinocyte Response to Infection with Sporothrix schenckii.

Sporotrichosis is a subacute, or chronic mycosis caused by traumatic inoculation of material contaminated with the fungus Sporothrix schenckii which is part of the Sporothrix spp. complex. The infection is limited to the skin, although its progression to more severe systemic or disseminated forms remains possible. Skin is the tissue that comes into contact with Sporothrix first, and the role of various cell lines has been described with regard to infection control. However, there is little information on the response of keratinocytes. In this study, we used the human keratinocyte cell line (HaCaT) and evaluated different aspects of infection from modifications in the cytoskeleton to the expression of molecules of the innate response during infection with conidia and yeast cells of Sporothrix schenckii. We found that during infection with both phases of the fungus, alterations of the actin cytoskeleton, formation of membrane protuberances, and loss of stress fibers were induced. We also observed an overexpression of the surface receptors MR, TLR6, CR3 and TLR2. Cytokine analysis showed that both phases of the fungus induced the production of elevated levels of the chemokines MCP-1 and IL-8, and proinflammatory cytokines IFN-α, IFN-γ and IL-6. In contrast, TNF-α production was significant only with conidial infection. In late post-infection, cytokine production was observed with immunoregulatory activity, IL-10, and growth factors, G-CSF and GM-CSF. In conclusion, infection of keratinocytes with conidia and yeast cells of Sporothrix schenckii induces an inflammatory response and rearrangements of the cytoskeleton.

Body-axis organization in tetrapods: a model-system to disentangle the developmental origins of convergent evolution in deep time.

Convergent evolution is a central concept in evolutionary theory but the underlying mechanism has been largely debated since On the Origin of Species. Previous hypotheses predict that developmental constraints make some morphologies more likely to arise than others and natural selection discards those of the lowest fitness. However, the quantification of the role and strength of natural selection and developmental constraint in shaping convergent phenotypes on macroevolutionary timescales is challenging because the information regarding performance and development is not directly available. Accordingly, current knowledge of how embryonic development and natural selection drive phenotypic evolution in vertebrates has been extended from studies performed at short temporal scales. We propose here the organization of the tetrapod body-axis as a model system to investigate the developmental origins of convergent evolution over hundreds of millions of years. The quantification of the primary developmental mechanisms driving body-axis organization (i.e. somitogenesis, homeotic effects and differential growth) can be inferred from vertebral counts, and recent techniques of three-dimensional computational biomechanics have the necessary potential to reveal organismal performance even in fossil forms. The combination of both approaches offers a novel and robust methodological framework to test competing hypotheses on the functional and developmental drivers of phenotypic evolution and evolutionary convergence.

Psychiatric beds and prison populations in 17 Latin American countries between 1991 and 2017: rates, trends and an inverse relationship between the two indicators.

BACKGROUND: In 1990, Latin American countries committed to psychiatric reforms including psychiatric bed removals. Aim of the study was to quantify changes in psychiatric bed numbers and prison population rates after the initiation of psychiatric reforms in Latin America. METHODS: We searched primary sources to collect numbers of psychiatric beds and prison population rates across Latin America between the years 1991 and 2017. Changes of psychiatric bed numbers were compared against trends of incarceration rates and tested for associations using fixed-effects regression of panel data. Economic variables were used as covariates. Reliable data were obtained from 17 Latin American countries: Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Honduras, Guatemala, Mexico, Nicaragua, Panama, Paraguay, Peru, El Salvador, Uruguay and Venezuela. RESULTS: The number of psychiatric beds decreased in 15 out of 17 Latin American countries (median -35%) since 1991. Our findings indicate the total removal of 69 415 psychiatric beds. The prison population increased in all countries (median +181%). Panel data regression analyses showed a significant inverse relationship -2.70 (95% CI -4.28 to -1.11; p = 0.002) indicating that prison populations increased more when and where more psychiatric beds were removed. This relationship held up when introducing per capita income and income inequality as covariates -2.37 (95% CI -3.95 to -0.8; p = 0.006). CONCLUSIONS: Important numbers of psychiatric beds have been removed in Latin America. Removals of psychiatric beds were related to increasing incarceration rates. Minimum numbers of psychiatric beds need to be defined and addressed in national policies.

SARS-CoV-2 Infection Rate in Patients With Cancer and Health Care Workers in a Chemoradiotherapy Unit During the Pandemic: A Prospective Cohort in Mexico.

PURPOSE: Cancer treatment during the COVID-19 pandemic represents a challenge. Hospital visits to receive treatment and interaction with health care workers (HCW) represent potential contagious events. We aimed to determine SARS-CoV-2 infection rate among patients with cancer and HCW of a chemoradiotherapy unit localized in a center designated as a COVID-19 priority facility in Mexico City. We also determined the diagnostic performance of a clinical questionnaire (CQ) as a screening tool and anti-SARS-CoV-2 antibody seroconversion rate. METHODS: HCW and patients with solid tumors attending the chemoradiotherapy unit signed informed consent. To determine SARS-CoV-2 infection rate prospectively, a nasopharyngeal swab for SARS-CoV-2 real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was performed every 2 weeks in asymptomatics. An electronic CQ interrogating COVID-19-related symptoms was sent daily. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies were measured at baseline and at the end of the study period. RESULTS: From June to September 2020, we included 130 asymptomatic participants, 44.6% HCW and 55.4% patients with cancer. During a median follow-up of 85 days, 634 nasopharyngeal swabs were performed. Average SARS-CoV-2 monthly incidence was 4.6% (3.15%-7.47%), and cumulative infection rate was 13.8% (18 of 130). Cases were mostly asymptomatic (66%), and no hospitalizations or deaths were recorded. The CQ as a screening tool provided a sensitivity of 27.7%, a positive predictive value of 26.3%, and a positive likelihood ratio of 12. SARS-CoV-2 IgG seroconversion rate was 27.7% among those with a positive RT-PCR. CONCLUSION: Patients with cancer on treatment can have uncomplicated COVID-19 outcomes. Biweekly RT-qPCR testing detects asymptomatic infections, prevents transmission, and should be implemented in units to increase patient safety. CQ increase RT-qPCR diagnostic yield and may prioritize testing in resource-deprived settings. Post-infection IgG seroconversion is unreliable.