Adaptive differentiation in functional traits and their underlying loci can occur across a small geographic area if natural selection is stronger than the countervailing effects of gene flow and drift. We investigated this hypothesis in a long-lived, wind-pollinated species, Quercus rubra, across a fine spatial scale with a steep climate gradient. We examined phenotypic differentiation in a common garden study with eight populations sampled 0-160 km from the coast of Lake Superior. We estimated genomic differentiation for these and 22 additional populations from the same region, along with two populations of a congener, Quercus ellipsoidalis, using RAD-seq. We found a strong signal of population differentiation associated with climate in the common garden study, and differentiation was significantly associated with at least one climate factor for nine of ten measured traits. At the genomic level, we discovered widespread introgression from Q. ellipsoidalis into Q. rubra that increased with distance from the lake. Pairwise FST among Q. rubra populations was low, but both distance-based and environmental association analyses identified loci under selection, with one locus in common across all analyses (CalS10/GSL8). This locus was associated with the precipitation of the driest month, a climate factor that was also significant in the common garden analyses. In sum, this study reveals signatures of selection at the phenotypic and genomic level consistent with climate adaptation, a pattern that is usually seen across a much broader geographic scale.

Intestinal microbial communities are influenced by a confluence of ecological forces. Understanding the dynamics between environment, microbiota and host is essential to gain insights into microbial community assembly processes. However, few studies systematically assess the contribution of different environmental sources to gut microbial community composition. We used a common garden experiment to determine the roles of biotic, abiotic and stochastic processes shaping gut microbial communities in Atlantic salmon (Salmo salar) in a natural river during a simulated 10-month farm escape scenario. Most of the taxa found in the salmon intestine originated from macroinvertebrates (the potential food source) rather than the water column, indicating that diet is an important factor in community assembly. The contribution of food sources to the fish gut community was lowest in winter and increased over March and May, reflecting seasonality in fish appetite. Previous work in salmon has hinted at a role for maternal effects in driving inter-generational sharing of microbial taxa. Our results suggest a possible host and/or maternal genetic effect affecting inter-individual differences in gut microbial community composition, whereby distinct assemblages were noted between farmed, wild and hybrid fish. Neutral modelling estimated that the majority (86%) of taxa present in the gut are transient. Overall, our data highlight the significance of both deterministic and stochastic drivers influencing the seasonal fluctuations of gut microbial communities in young Atlantic Salmon and hint at potential genetic or maternal effects on fish microbiota. These findings greatly enhance our understanding of the complex interactions between hosts, their living environment and associated microbiota.

In this paper, we provide a systematic and constructive way to build a Lyapunov-Krasovskii functional for time-delay systems whose stability can be established through the Razumikhin or the Halanay approaches. The constructed Lyapunov-Krasovskii functional turns out to be coercive, meaning sandwiched between functions of the state history norm, and to dissipate in terms of the whole history norm. We present these results in the framework of input-to-state stability (ISS) in order to further account for the influence of input disturbances. A special emphasis is also given on exponential stability and exponential ISS. We illustrate our findings though the study of a coupled ODE-PDE model of a chemical reactor, and show that, unlike most results in that area, our approach happens to ensure ISS in terms of the supremum norm of the state.

Background and Aims: Although it is known that hepatitis B virus (HBV) can be transmitted through sexual behavior, limited research has been conducted on the specific types of sexual behavior that facilitate transmission. The purpose of the research was to analyze the association of sexual behavior with HBV infection in US adults. Method: Four cycles (2009-2016) of National Health and Nutrition Examination Surveys (NHANES) were collected, and 16569 participants were finally included. HBV infection was determined by a positive HBV core antibody and participants were categorized into two groups: “yes” and “no” group. Data pertaining to sexual behaviors were gathered. The sexual identity group comprised individuals with no sex, heterosexual, homosexual, bisexual, or unclear. The sexual type group consisted of individuals with no sex, heterosexual vaginal sex, heterosexual oral sex, heterosexual anal sex, heterosexual multiple types, bisexual sex, male homosexual sex, female homosexual sex, or unclear. Multivariable logistic regression was used to analyze the association of sexual identity/type with HBV infection by adjusting different covariates. Results: The present study comprised a sample of 16,569 individuals between the ages of 18 and 69. Participants with HBV infection were more likely to be 40-69 years predominant, men, non-Hispanic Black. Additionally, these individuals were more likely to have co-infections with HIV or HCV, engage in drug use or current smoking, identify as homosexual or bisexual. After full adjustment, it was found that homosexual men were associated with a higher risk of HBV infection (odds ratio [OR]: 4.00, 95% confidence interval [CI]: 2.09-7.64) compared to men without sexual behavior. Bisexual men (OR: 5.65, 95% CI: 2.13-15) and men with heterosexual anal sex (OR: 4.52, 95% CI: 1.12-18.2) were associated with a higher risk of HBV infection. Notably, women engaging in any type of sexual behavior with men or women did not have a significantly higher risk of HBV infection compared to women without sexual behavior. Conclusion: The study showed that homosexual men, bisexual men, and men with heterosexual anal sex were found to be correlated with a higher risk of HBV infection. These results may offer valuable insights for the pursuit of HBV elimination.

Human adenovirus (HAdV) type 40 in species F (HAdV-F40) and HAdV-F41 represent the third most prevalent causative agents of non-bacterial acute gastroenteritis in infants and young children, following norovirus and rotavirus. Despite their significant contribution to global child morbidity, vaccines to preemptively combat these viruses remain elusive. In this study, we scrutinize the potential for cross-neutralization between HAdV-F40 and HAdV-F41 using the knob protein of the fiber-2 protein immunized sera. To this end, we immunized female BALB/c mice with synthetically produced knob proteins of the fiber-2 protein from HAdV-F40 and HAdV-F41. Subsequently, we implemented a series of assays to evaluate the results, including enzyme-linked immunosorbent, micro-neutralization, immunofluorescence, and quantitative polymerase chain reaction. We found that HAdV-F40-knob and HAdV-F41-knob immunized sera could effectively neutralize HAdV-F40 and HAdV-F41, indicating a mutual cross-neutralizing effect. Notably, the serum immunized with HAdV-F40-knob demonstrated a stronger neutralization effect, suggesting the potential to develop a subunit vaccine that can simultaneously counteract both viruses. Our findings underscore the potential of knob protein immunization in evoking a cross-neutralizing antibody response between HAdV-F40 and HAdV-F41. This suggests a promising avenue for developing subunit vaccines against HAdV-F40 and HAdV-F41 and provides a novel perspective on the potential of neutralizing antibodies to protect against these two types of HAdV.

Background Global COVID-19 vaccination programs effectively contain the fast spread of the SARS-CoV-2. Characteristic the immunity status of returned populations will favor for understanding the achievement of herd immunity and long-term management of COVID-19 in China. Methods Returning travellers were recruited from 7 quarantine stations in Guangzhou, China. The immunity statuses of participants were determined through Competitive ELISA, Micro-Neutralization Assay and Enzyme-Linked FluoroSpot Assay. Results A total of 272 subjects were involved in questionnaire survey, in which 235 (86.4%) were returning ex-patriot Chinese and 37 (13.6%) were foreigners. Blood and throat swabs specimens were collected from each of 108 returning ex-patriot Chinese. The neutralizing antibody against SARS-CoV-2 was detected in ~90% of returning ex-patriot Chinese, either in the primary or the homologous and heterologous booster vaccination group. The serum NAb titers of them were significantly decreased against SARS-CoV-2 Omicron BA.5, BF.7, BQ.1 and XBB.1 compare with prototype virus. However, memory T cell responses including specific IFN-γ and IL-2 were no differences in either group. Smoking, drinking, SARS-CoV-2 infection, COVID-19 vaccination, and the time interval between last vaccination and the sampling were independent influencing factors for NAb titers against prototype SARS-CoV-2 and variants of concerns. The dose of vaccination was the unique common influencing factor for Omicron variants. Conclusions The herd immunity was established in returning ex-patriot Chinese who exposure to the complicated infection and vaccination circumstance. Domestic residents will benefit from booster of COVID-19 vaccines either in homologous and heterologous vaccination after re-opening of China, as well as breakthrough infection.

Protists are major actors of soil communities and play key roles in shaping food webs, community assembly, and ecosystem processes, yet their functional diversity is understudied. High-throughput sequencing data have revealed their ubiquity and diversity, but lack of standardized traits has hampered the integration of functional information, limiting our understanding of soil ecosystems. Here we propose a framework for soil protists, identify a set of common traits to characterize their functional diversity, and apply the framework on a broad-scale, real-world dataset. We reviewed studies on soil protists to identify the traits used in the literature, and define a framework based on 10 key traits that satisfy two criteria: availability of information, and applicability to most taxa. The framework was tested on a dataset of environmental DNA metabarcoding data from 1123 soil samples collected in 48 glacier forelands worldwide. Traits were assigned to all the 570 Molecular Operational Taxonomic Units (MOTUs) detected in our dataset, leading to the production of a global trait-based dataset from glacier forelands. We estimated the functional space of protist communities and evaluated if the selected traits were effective in describing protist diversity. The functional space of protist communities showed that the MOTUs are clustered in three regions, mainly reflecting different nutritional and habitat preferences. The proposed framework is appropriate for multiple applications, including estimation of functional diversity and food web analyses, and provides a basis for ecological studies on soil protists, enabling the functional characterization of this essential but often neglected component of soil biodiversity.

The KEAP1-NRF2 system plays a central role in cytoprotection and defense mechanisms against oxidative stress. Because KEAP1 serves as a biosensor for electrophiles by using its reactive thiols and because NRF2 is a transcriptional factor regulating genes involved in the sulfur-mediated redox reactions, the KEAP1-NRF2 system has been regarded as a sulfur-utilizing cytoprotective mechanism. NRF2 is a key regulator of cytoprotective genes, such as antioxidant and detoxification genes, and also to possess potent anti-inflammatory activity. NRF2 has been recently focused as a great modifier/regulator for the cellular metabolism and mitochondrial function. Particularly, the NRF2-mediated regulatory mechanisms of metabolites and mitochondria has been considered diverse, but has not been fully-clarified yet. This review article provides an overview of the molecular mechanisms that regulate NRF2 signaling and its cytoprotective roles, and also highlights NRF2 contribution to the cellular metabolism, particularly in the context of mitochondrial function and newly found sulfur metabolism.

CLINICAL PROBLEM: A 43-year-old lady with no evidence of structural heart disease underwent an electrophysiological study for the evaluation of recurrent episodes of palpitations. A narrow complex regular tachycardia was documented, which was not reverted with intravenous adenosine administration. There was no basal pre-excitation. The AH and HV intervals during sinus rhythm were 70ms and 48ms respectively. A regular narrow complex long RP tachycardia with concentric atrial activation was induced which was incessant in nature. Ventricular overdrive pacing from RV septum during tachycardia at 20 ms earlier than tachycardia cycle length showed pseudo-V-A-A-V response with VA linking on cessation of pacing. A His refractory ventricular premature beat (VPB) was delivered during the tachycardia (Figure 1). A spontaneous catheter induced VPB was noted after 2 beats. What are the observations and mechanisms?

A retrospective observational study was conducted among healthcare workers (HCWs) in a tertiary paediatric hospital. The study covered the period before and after implementation of the vaccination programme and evaluated the incidence of new SARS-CoV-2 infections in both periods. Risk factors of the new SARS-CoV-2 infection and COVID-19 vaccine effectiveness was also assessed in a real-world setting. The overall incidence of SARS-CoV-2 infections among HCWs in the study period was 19.4% with a high proportion of asymptomatic individuals (45.1%). The incidence before vaccination was 16.6% and nurses had a higher risk of infection, while physicians had a reduced risk (OR 1.80, 95% CI 1.29–2.52; and OR 0.45, 95% CI 0.30–0.68). Within two months of implementation, the programme achieved a high (88.9%) vaccination coverage in our cohort, although some disparities in vaccination rates were observed. In particular, older individuals, physicians, those working in clinical settings, and those previously uninfected were more likely to be vaccinated. The overall incidence of SARS-CoV-2 infection after vaccination deployment was 6.3% (40.0% in unvaccinated individuals and 3.2% in individuals vaccinated with at least one dose). The estimated vaccine efficacy was high (95.0%) in fully vaccinated HCWs and similar to those observed previously in clinical trials and real-world settings.

Objective: Based on the Montreux definition, we aim to develop and validate a predictive model for the early diagnosis of neonatal acute respiratory distress syndrome. Methods: A retrospective analysis of clinical data on 198 neonates with respiratory distress from January 2018 to January 2022 was conducted. Neonates meeting Montreux definition were classified as ARDS group (n=79), while the rest were controls (n=119). Univariate analysis identified indicators for neonatal ARDS, followed by logistic regression to construct a predictive model for early diagnosis. The ability of predictors and models to predict neonatal ARDS was evaluated using AUC, and model performance was estimated through bootstrap resampling. Results: Maternal prenatal fever, abnormal fetal heart beat, meconium-stained amniotic fluid (MSAF), white blood cell (WBC)，absolute neutrophil count (ANC) , neutrophil percentage (NE%), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), creatine kinase (CK), activated partial thromboplastin time (APTT), serum calcium (S-Ca) and sodium（S-Na）exhibited significant differences between the ARDS group and the control group ( P<0.05). MSAF (OR=5.037; 95%CI: 1.523~16.657; P<0.05), ANC (OR=1.324; 95%CI: 1.172~1.495; P<0.05), PLT (OR=0.979; 95%CI: 0.971~0.986; P<0.05), S-Ca (OR=0.020; 95%CI: 0.004~0.088; P<0.05) emerged as independent risk factors for the development of ARDS. The respective area under the curve (AUC) values for MSAF, ANC, PLT, S-Ca, and the combined prediction models were 0.606, 0.691, 0.808, 0.761 and 0.931. Internal validation showed that the C-index for the model was 0.931. Conclusions: The predictive model that incorporates MSAF, ANC, PLT, and S-Ca demonstrates significant efficacy in predicting the early diagnosis of neonatal ARDS.

Background and Aim To assess the outcomes of children born with esophageal atresia/tracheoesophageal fistula (EA-TEF) with concomitant SARS-CoV-2 infection. Methods An international survey was circulated to the International Network of Esophageal Atresia (INoEA) members from April 2020 to May 2022. Information on demography, type of EA-TEF, co-morbidities, complications, hospitalization, and therapies administered for SARS-CoV-2 infection was collected for all patients. Results Forty-two patients from April 2020-May 2022, with a mean age of 6.8 years were reported from Argentina, Switzerland, Netherlands, Canada, France, Italy, Australia and Turkey. 34 patients (81%) had a type C, EA-TEF. 30 had respiratory comorbidities, 14 had associated cardiac malformations and 14 had a history of recurrent anastomotic stricture. Reported medications included proton-pump inhibitors (n=14), inhaled bronchodilators (n=3) and inhaled corticosteroids (n=4). Six patients (14%) were hospitalised. Three required respiratory support and one required extra-corporal membranous oxygenation. There were no deaths. Respiratory, cardiac and gastrointestinal comorbidities were not associated with increased risk of hospitalization. Concomitant medication at time of infection was associated with increased risk for hospitalization with SARS-CoV-2 infection (p=0.0035), however PPI alone was not significantly associated with increased risk for hospitalization (p=0.16). Conclusion Rates of hospitalization with SARS-CoV-2 are higher for patients with EA-TEF than the general pediatric population, with increased risk in those on medication in patients. 67% of those admitted required respiratory support. Infection likely does not represent a risk for severe respiratory complications or severe outcome.

Safety behaviors are core cognitive and behavioral components involved in the onset, maintenance, and treatment of anxiety-related disorders. Yet, these behaviors remain understudied in the context of posttraumatic stress disorder (PTSD). This may be due, in part, to the lack of psychometrically valid instruments designed to evaluate safety behaviors, particularly those relevant to the diagnosis of PTSD. Furthermore, there is an absence of PTSD-related safety behavior measures with the brevity necessary for continuous measurement-based care during treatment. Our research aims to investigate the psychometric characteristics of the newly formed PTSD scale of the Safety Behavior Assessment form (SBAF-PTSD) through three studies. The first study examined SBAF-PTSD factorial validity via confirmatory factor analyses (CFA), along with other psychometric properties. Results identified a 10-item bi-factor model that reflects a primary Safety Behavior scale and a secondary, latent construct labeled SBAF-PTSD Social Index. The newly revised SBAF-PTSD scale was then used in an effectiveness study to investigate its clinical utility in the context of PTSD treatment. The third study sought to generalize our results to non-clinical samples. The results of the studies are discussed in terms of their implications for the use of the new PTSD-SBAF measure.

Postpartum depression refers to depression that occurs in the postpartum period. It threatens the life of the neonatal mother as well as the infant. The study aims to explore the influence of several risk factors and social support on postpartum depressed mothers. A cross-sectional, mixed-method study was conducted and a total of 273 women between one and 4 months postpartum were screened for depressive symptoms by the Edinburgh Post-Natal Depression Scale. Women scoring Thirteen or more (indicating potential depressive disorder) (n = 232) were interviewed regarding depressive symptoms, risk factors associated with postpartum depression, availability and necessity of social support. The response rate is 84.98%. The location of living and occupational difference has strong significance of post-partum depression. Again, women feel depressed for the unavoidable physical chance and previous depressive symptoms. They used to face barrier in their career as well as social comments results in post-partum depression. In spite of having emotional support, women need to get further instrumental support from family. There is an insufficiency of cognitive knowledge and institutional support in the study area. This study aimed to examine the situation of the mothers of newborn that quest for the solution in social support as well as explore the availability of emotional and behavioral support to mitigate the possible risk. By investigating risk factors among the new mothers would guide the policy makers of government and non-government organizations to mitigate the problem by providing accessible concealing centers, creating awareness and enhancing hospital facilities.

Background: GINA guidelines suggest to use PEFR monitoring to assess response to treatment, to identify triggers for exacerbation and to have a baseline value for action plan (especially for the poor perceivers). In comparison to adults, there are less evidence in support of the routine use of PEFR recording for the diagnosis and monitoring level of control of asthma in children. Objective: This study was conducted with objective to assess the effect of PEFR monitoring on numbers of exacerbations in comparison to monitoring by symptoms in asthma. Material and Methods: This was a prospective cohort study done for a in Department of Pediatrics and Respiratory medicine, of a tertiary care hospital, North India. Prior to recruitment ethical approval and informed consent/assent was taken. Study subjects were children with partial and uncontrolled asthma aged 5-12 years of age. Patients were divided into two groups on their first visit by using random allocation number. In Group “A” monitoring was done with symptoms only, while in Group “B” monitoring was done by symptoms and PEFR. Number of exacerbations during study period was noted. At baseline and follow up, CACT score was calculated. Spirometry was done at the end of 3 months. Result: Group B had statistically significant lesser exacerbation during study period as compared to Group A (OR=0.11; 95%CI=0.01-0.57; p value=0.003). Conclusion: PEFR based monitoring can be used as a potential tool for aborting or decreasing the severity of episodes of exacerbations of asthma especially in resource limited areas.

A document by Alexandre Barboni. Click on the document to view its contents.

ABSTRACT Maternal hyperoxygenation (MH) has been studied as a diagnostic tool to evaluate pulmonary vasculature and as a treatment option to improve the growth of fetal left heart in fetuses with left-sided cardiac defects. Chronic maternal hyperoxygenation (CMH) therapy leads to an improvement in fetal pulmonary blood flow resulting in an enhanced venous return to the left heart with increased gestational age. With this manipulation it is anticipated to augment blood flow directed remodeling of the left heart structures and to improve left heart growth spanning from the mitral valve to the aortic isthmus. However, there are concerns about CMH therapy with regard to fetal complications with growth restriction and fetal brain development. Now, with two successful cases we try to discuss this fetal treatment option and related concerns.

The knife-edge diffraction model (KED) and the uniform geometrical theory of diffraction (UTD) have been widely used to predict the shadowing effect at millimetre-wave (mmWave) bands. This letter proposes a mathematical derivation to rigorously prove that, for an absorbing screen, UTD applying the narrow-angle Fresnel approximation is equivalent to KED. The simulation scenarios are designed to validate the proposal by comparing KED with UTD in the narrow-angle (less than 20○) and wide-angle (over 20○) regions at mmWave bands (20 GHz - 100 GHz). Simulated results agree with the proposal that KED is identical to UTD with a low error of less than 0.1 dB in the narrow-angle region, while they have a difference with an error of over 1 dB in the wide-angle region. In addition, the average computational time is measured and results in both UTD and KED taking approximately 8.0 ms for one test. From the proposal, it can be theoretically explained the differences and similarities between KED and UTD for an absorbing screen.

The black phosphorus (BP) crystals and two-dimensional black phosphorus (2D BP) are prepared from amorphous red phosphorus by mechanical ball milling- liquid exfoliation method. The spectrophotometric analysis shows that a few layers of 2D BP have been successfully prepared. Aiming at the characteristics of 2D BP that was easily degraded in the natural environment, a low-cost solvothermal method was used, and 2D BP and nickel chloride are used as raw materials to prepare a green and pollution-free transition metal phosphide (TMPs) heterojunction was prepared. Metal ions are preferentially deposited on the defects of 2D BP such as edges and unsaturated sites, forming a 2D BP / P-rich TMPs in-plane heterojunction (BP / NiP3). It occupies the defects of BP nanosheet to enhance its stability.

Background: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative therapy for Alzheimer’s disease (AD) due to its ability to modulate neural networks and enhance cognitive function. This treatment offers the unique advantage of enabling real-time monitoring of immediate cognitive effects and dynamic brain changes through electroencephalography (EEG). Objective: This study focused on exploring the effects of left parietal rTMS stimulation on visual evoked potentials (VEP) and visual event-related potentials (VERP) in AD patients. Methods: Sixteen AD patients were recruited for this longitudinal study. EEG data were collected within a Faraday cage both pre and post-rTMS to evaluate its impact on potentials. Results: Significant alterations were found in both VEP and VERP oscillations. Specifically, delta power in VEP decreased while theta power in VERP increased post-rTMS, indicating a modulation of brain activities. Discussion: These findings confirm the positive modulatory impact of rTMS on brain activities in AD, evidenced by improved cognitive scores. They align with previous studies highlighting the potential of rTMS in managing hyperexcitability and oscillatory disturbances in the AD cortex. Conclusion: Cognitive improvements post-rTMS endorse its potential as a promising neuromodulatory treatment for cognitive enhancement in AD, thereby providing critical insights into the neurophysiological anomalies in AD and possible therapeutic avenues.

Plant reproductive ecology is one of the research hotspots in ecology. With the increasing attention paid to the conservation of plant diversity, the research on reproductive characteristics and flowering biological characteristics of more species has attracted more attention. However, plant reproduction is affected by multiple interacting factors such as pollen limitation and resource availability. Vitex negundo var. heterophylla (Franch.) Rehder (Lamiaceae) is a significant species for water and soil conservation. Previous studies have revealed its mating system by the biological characteristics of flowering and SSR markers, but its reproductive strategies remain to be further studied. We evaluated reproductive success through artificial pollination to explore the reproductive characteristics of V. negundo var. heterophylla for the first time. From the results of fruit set, there is a mixed mating system dominated by outcrossing in V. negundo var. heterophylla accompanied by self-compatibility, and it cannot carry out autonomous selfing. Our data shows the pollinator-mediated interaction in the success of reproduction, whereas the effect of anemophily is very weak. And the seed germination rate of inbred line progenies was lower than that of hybrid progenies, which is suspected to be caused by inbreeding depression. The research will provide scientific information for the protection and conservation of V. negundo var. heterophylla from the point of view of reproduction. In sum, the results are necessary to protect animal vectors in the background of insect decline.

COMMENTARY

Background: Vancomycin is a glycopeptide antibiotic used for gram-positive infections. Several vancomycin population pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed to compare published pharmacokinetics models and (ii) to summarise and explore identified covariates influencing the vancomycin pharmacokinetics models. Methods: A search of publications for population pharmacokinetic analyses of vancomycin in critically ill obese patients from inception to October 2022 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analyses were excluded. Data on study characteristics, patient demographics, clinical parameters, pharmacokinetic parameters, and outcomes were collected. Results: Six studies were included in this review. Vancomycin pharmacokinetics was described as one-compartment in most of the studies. Significant interindividual variations of vancomycin pharmacokinetic parameters were found in most of the included studies. Age, sex, body weight, fibrinogen, aspartate aminotransferase, blood urea nitrogen, cystatin, and concomitant nephrotoxic drugs were the most commonly identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models. Conclusions. Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors, such as metabolic factors and significant drug-drug interactions in a well-designed population pharmacokinetic model in the future, taking into account the incorporation of a larger sample size and a more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.

The effect of mixing litter on decomposition has received considerable attention in terrestrial and aquatic (but rarely in both) ecosystems, with a striking lack of consensus in the obtained results. We studied the decomposition of a mixture of poplar and alder in three terrestrial:aquatic exposures to determine (1) if the effect of mixing litter on mass loss, associated decomposers and detritivores differs between the stream (fully aquatic exposure) and when litter is exposed to a period of terrestrial exposure prior to immersion and (2) the global effect of the mixture across exposure scenarios. The effect of the mixture was additive on mass loss and synergistic on decomposers and detritivores across exposure scenarios. Within scenarios, mass loss and decomposers showed synergistic effects only in the fully aquatic exposure, detritivores showed synergistic effects only when the period of terrestrial was shorter than the period of aquatic exposure, and when the period of terrestrial was equal to the period of aquatic exposure the effect of the mixture was additive on mass loss, decomposers, and detritivores. The species-specific effects also differed among exposure scenarios. Alder affected poplar only when there was a period of terrestrial exposure, with increased sporulation rates and fungal richness in exposure 25:75, and increased mass loss in exposure 50:50. Poplar affected alder only under fully aquatic exposure, with increased mass loss. In conclusion, the synergistic effects of the mixture changed with a period of terrestrial exposure prior to immersion. These results provide a cross-boundary perspective on the effect of mixing litter, showing a legacy effect of exposure to terrestrial decomposition on the fate of plant litter in aquatic ecosystems and highlighting the importance of assessing the effect of mixing litter on the associated biota and not only on mass loss.