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Abstract Reproduction, although absolutely essential to a species’ persistence, is in itself challenging. As anthropogenic change increasingly affects every landscape on Earth, it is critical to understand how specific pressures impact the reproductive efforts of individuals, which directly contribute to the success or failure of populations. However, organisms rarely encounter a single burden at a time, and the interactions of environmental challenges can have compounding effects. Understanding environmental and physiological pressures is difficult because they are often context‐dependent and not generalizable, but long‐term monitoring across variable landscapes and weather patterns can improve our understanding of these complex interactions. We tested the effects of urbanization, climate, and individual condition on the reproductive investment of wild side‐blotched lizards (Uta stansburiana) by measuring physiological/reproductive metrics from six populations in urban and rural areas over six consecutive years of variable precipitation. We observed that reproductive stage affected body condition, corticosterone concentration, and oxidative stress. We also observed that reproductive patterns differed between urban and rural populations depending on rainfall, with rural animals increasing reproductive investment during rainier years compared to urban conspecifics, and that reproductive decisions appeared to occur early in the reproductive process. These results demonstrate the plastic nature of a generalist species optimizing lifetime fitness under varying conditions.

Abstract Background Although mainly causing a respiratory syndrome, numerous neurological symptoms have been identified following of SARS-CoV-2 infection. However, how the virus affects the brain and how the mutations carried by the different variants modulate those neurological symptoms remain unclear. Methods We used primary human pericytes, foetal astrocytes, endothelial cells and a microglial cell line to investigate the effect of several SARS-CoV-2 variants of concern or interest on their functional activities. Cells and a 3D blood–brain barrier model were infected with the wild-type form of SARS-CoV-2, Alpha, Beta, Delta, Eta, or Omicron (BA.1) variants at various MOI. Cells and supernatant were used to evaluate cell susceptibility to the virus using a microscopic assay as well as effects of infection on (i) cell metabolic activity using a colorimetric MTS assay; (ii) viral cytopathogenicity using the xCELLigence system; (iii) extracellular glutamate concentration by fluorometric assay; and (iv) modulation of blood–brain barrier permeability. Results We demonstrate that productive infection of brain cells is SARS-CoV-2 variant dependent and that all the variants induce stress to CNS cells. The wild-type virus was cytopathic to all cell types except astrocytes, whilst Alpha and Beta variants were only cytopathic for pericytes, and the Omicron variant cytopathic for endothelial cells and pericytes. Lastly wild-type virus increases blood–brain barrier permeability and all variants, except Beta, modulate extracellular glutamate concentration, which can lead to excitotoxicity or altered neurotransmission. Conclusions These results suggest that SARS-CoV-2 is neurotropic, with deleterious consequences for the blood–brain barrier integrity and central nervous system cells, which could underlie neurological disorders following SARS-CoV-2 infection.

BackgroundSARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and viral loads over the course of COVID-19 infection with these sub-variants in otherwise-healthy, vaccinated, non-hospitalised adults, and compared data to infections with the preceding Delta variant of concern (VOC).MethodsIn a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive polymerase chain reaction (PCR) or lateral flow test, self-swabbed on alternate weekdays until day 10. We compared participant-reported symptoms and viral load trajectories between infections caused by VOCs Delta and Omicron (sub-variants BA.1, BA.2 or BA.4/5), and tested for relationships between vaccine dose, symptoms and PCR cycle threshold (Ct) as a proxy for viral load using Chi-squared (χ2) and Wilcoxon tests.Results563 infection episodes were reported among 491 participants. Across infection episodes, there was little variation in symptom burden (4 [IQR 3-5] symptoms) and duration (8 [IQR 6-11] days). Whilst symptom profiles differed among infections caused by Delta compared to Omicron sub-variants, symptom profiles were similar between Omicron sub-variants. Anosmia was reported more frequently in Delta infections after 2 doses compared with Omicron sub-variant infections after 3 doses, for example: 42% (25/60) of participants with Delta infection compared to 9% (6/67) with Omicron BA.4/5 (χ2 P < 0.001; OR 7.3 [95% CI 2.7-19.4]). Fever was less common with Delta (20/60 participants; 33%) than Omicron BA.4/5 (39/67; 58%; χ2 P = 0.008; OR 0.4 [CI 0.2-0.7]). Amongst infections with an Omicron sub-variants, symptoms of coryza, fatigue, cough and myalgia predominated. Viral load trajectories and peaks did not differ between Delta, and Omicron, irrespective of symptom severity (including asymptomatic participants), VOC or vaccination status. PCR Ct values were negatively associated with time since vaccination in participants infected with BA.1 (β = -0.05 (CI -0.10-0.01); P = 0.031); however, this trend was not observed in BA.2 or BA.4/5 infections.ConclusionOur study emphasises both the changing symptom profile of COVID-19 infections in the Omicron era, and ongoing transmission risk of Omicron sub-variants in vaccinated adults.Trial registrationNCT04750356.

The emergence of successive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) during 2020 to 2022, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics-such as varying levels of immunity-can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform Coronavirus Disease 2019 (COVID-19) planning and response and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both interindividual variation in Ct values and complex host characteristics-such as vaccination status, exposure history, and age-we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least 5 prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs. Trial Registration: The Legacy study is a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening for SARS-CoV-2 at University College London Hospitals or at the Francis Crick Institute (NCT04750356) (22,23). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469) and is sponsored by University College London Hospitals. Written consent was given by all participants.

The multi-objective optimization (MOO) of complex systems remains a challenging task in engineering domains. The methodological approach of applying MOO algorithms to simulation-enabled models has established itself as a standard. Despite increasing in computational power, the effectiveness and efficiency of such algorithms, i.e., their ability to identify as many Pareto-optimal solutions as possible with as few simulation samples as possible, plays a decisive role. However, the question of which class of MOO algorithms is most effective or efficient with respect to which class of problems has not yet been resolved. To tackle this performance problem, hybrid optimization algorithms that combine multiple elementary search strategies have been proposed. Despite their potential, no systematic approach for selecting and combining elementary Pareto search strategies has yet been suggested. In this paper, we propose an approach for designing hybrid MOO algorithms that uses reinforcement learning (RL) techniques to train an intelligent agent for dynamically selecting and combining elementary MOO search strategies. We present both the fundamental RL-Based Hybrid MOO (RLhybMOO) methodology and an exemplary implementation applied to mathematical test functions. The results indicate a significant performance gain of intelligent agents over elementary and static hybrid search strategies, highlighting their ability to effectively and efficiently select algorithms.

Background: To remove methylene blue (MB) from aqueous solutions, nanoscale zero-valent iron (nZVI) predicated on reduced expanded graphene oxide (rEGO) was used as the activator of persulfate. Methods: Scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS) analyses were used to investigate the surface morphology and to examine the surface elemental composition. X-ray diffraction (XRD) was used to determine the chemical compositions of the synthesized compound. In this study, the effects of pH (3-9), activator dose (0.4-1.6 g L-1), persulfate concentration (0.192-0.768 g L-1), and reaction time (0-60 minutes) on the removal of 10 mg L-1 MB were studied by nZVI -reduced expanded graphene oxide/persulfate (nZVI@rEGO/PS) process. Results: The maximum removal efficiencies of MB at optimum operational conditions (pH 3, activator dose = 1.2 g L-1, persulfate concentration = 0.576 g L-1, and reaction time = 20 minutes) by nZVI@rEGO/PS process was 96%. The chemical method was used to prepare expanded graphene. The volume of natural flake graphite increased about 25 times after the process. SEM image of the nZVI@rEGO showed the presence of nZVI placed on the EGO surface in chain structure with a diameter about 100 nm. The EDS analysis of the activator indicated the existence of Fe element to an amount greater than 50%. Conclusion: According to the results, nZVI@rEGO is considered as a promising activator of persulfate.

Climate change and anthropogenic modifications to the landscape can have both positive and negative effects on an animal. Linking landscape change to physiological stress and fitness of an animal is a fundamental tenet to be examined in applied ecology. Cortisol is a glucocorticoid hormone that can be used to indicate an animal's physiological stress response. In the Sierra Nevada Mountains of California, fishers (Pekania pennanti) are a threatened mesocarnivore that have been subjected to rapid landscape changes due to anthropogenic modifications and tree mortality related to a 4-year drought. We measured cortisol concentrations in the hair of 64 fishers (41 females, 23 males) captured and radio-collared in the Sierra National Forest, California. We addressed two main questions: (1) Is the physiological stress response of fishers influenced by anthropogenic factors, habitat type, canopy cover, and tree mortality due to drought in their home range? (2) Does the physiological stress response influence survival, reproduction, or body condition? We examined these factors within a fisher home range at 3 scales (30, 60, 95% isopleths). Using model selection, we found that tree mortality was the principle driver influencing stress levels among individual fishers with female and male fishers having increasing cortisol levels in home ranges with increasing tree mortality. Most importantly, we also found a link between physiological stress and demography where female fishers with low cortisol levels had the highest annual survival rate (0.94), whereas females with medium and high cortisol had lower annual survival rates, 0.78 and 0.81, respectively. We found no significant relationships between cortisol levels and body condition, male survival, or litter size. We concluded that tree mortality related to a 4-year drought has created a "landscape of stress" for this small, isolated fisher population.

Background: Asynchronous telepsychiatry (ATP) consultations are a novel form of psychiatric consultation. Studies comparing patient and provider satisfaction for ATP with that for synchronous telepsychiatry (STP) do not exist. Methods: This mixed-methods study is a secondary analysis of patients' and primary care providers' (PCPs) satisfaction from a randomized clinical trial of ATP compared with STP. Patients and their PCPs completed satisfaction surveys, and provided unstructured feedback about their experiences with either ATP or STP. Differences in patient satisfaction were assessed using mixed-effects logistic regression models, and the qualitative data were analyzed using thematic analysis with an inductive coding framework. Results: Patient satisfaction overall was high with 84% and 97% of respondents at 6 months reported being somewhat or completely satisfied with ATP and STP, respectively. Patients in the STP group were more likely to report being completely satisfied, to recommend the program to a friend, and to report being comfortable with their care compared with ATP (all p < 0.05). However, there was no difference between the patients in ATP and STP in perceived change in clinical outcomes (p = 0.51). The PCP quantitative data were small, and thus only summarized descriptively. Conclusions: Patients expressed their overall satisfaction with both STP and ATP. Patients in ATP reported more concerns about the process, likely because feedback after ATP was slower than that after STP consultations. PCPs had no apparent preference for STP or ATP, and reported implementing the psychiatrists' recommendations for both groups when such recommendations were made, which supports our previous findings. Trial Registration: ClinicalTrials.gov NCT02084979; https://clinicaltrials.gov/ct2/show/NCT02084979.

In recent years many research studies have been carried out to use a vertical planting system for production of some plants. Although saffron is one of the most expensive spices in the word, there is no investigation about saffron production in a vertical planting system. Therefore, the growth and production of saffron plant in two different systems (vertical and horizontal) were studied in the agricultural research field of the Tarbiat Modares University during the 2013-2014 growing seasons. In the vertical system, saffron corms were planted in fabric bags containing potting soil. The fabric bags were hanged on a cube of metal with an area of each side of the cube being equal to 2.25 square meters. In the horizontal system, the corms were planted in three plots with the area of each plots being 2.25 square meters. The results showed that in the vertical planting system, the number of flowers, flower dry weight and dry weight of stigma per unit area of land (10 flower, 347.34 and 0.56 mg respectively) were significantly higher than those obtained in the horizontal culture (They were almost three times higher) .In contrast, the numbers and dry weight of lateral corms (2.4 corm and 0.36 g respectively) and the dry weight of apical corm (0.88 g) in the horizontal system were significantly greater than those obtained in the vertical system. Dry weight of leaf and root were significantly greater in the vertical system. The total number of buds and leaves were more in the horizontal culture. However, the maximum leaf length of the vertical planting system was higher than those of the horizontal system.

Critics suggest that youth lack basic civic knowledge and are disengaging from civic action, particularly political action. The validity of these criticisms depends on how civic knowledge and civic engagement are defined. The results of four studies of civic education, conducted by the IEA over a period of almost 50 years, are examined in terms of the definition of these concepts. Five questions are addressed: (1) What are the goals of civic education? (2) What is civic knowledge? (3) What is civic engagement? (4) What are civic attitudes and values? (5) What do we know about teaching civics in schools? The results suggest that (1) there is disagreement on the goals of civic education; (2) civic knowledge is often equated with the memorization of facts about government and politics; (3) civic engagement is different from political engagement, with today's youth more interested in civic engagement; (4) civic attitudes and values may be more important than civic knowledge or engagement for preparing informed, productive citizens; and (5) there is limited time for teaching civics in schools, and the ways in which civics is currently taught are inconsistent with the kind of teaching needed.