Recent Experience Affects Delay Discounting: Evidence across Temporal Framing, Signs, and Magnitudes.

Delay discounting, the decrease in outcome value as a function of delay to receipt, is an extensive area of research. How delays are framed (i.e., temporal framing), as well as the sign and magnitude of an outcome, produce important effects on the degree to which outcomes are discounted. Here, we examined how recent experience (i.e., order of presentation) modifies these well-known findings. Experiment 1 examined the effects of temporal framing across gains and losses. Regardless of outcome sign, the order of task presentation affected the effect of temporal framing. In particular, when typical delay frames (e.g., 1 week) preceded delays framed as actual dates (e.g., February 15), discounting was less in the date-framed task. However, when dates were followed by the delay frame, there was no difference in the degree of discounting. The experience of date-framed delays persisted or carried over to the delay-framed task. Experiment 2 examined recent experience and the magnitude effect. In particular, $10 and $100 were discounted similarly between-subjects when it was the first task completed. However, once participants completed the second magnitude task, the magnitude effect was present both within-subjects and across subjects. Furthermore, $10 was discounted more steeply when it followed $100, and $100 was discounted less steeply when it followed $10. The impact of recent experience on delay discounting has important implications for understanding mechanisms that may contribute to delay discounting. Recent experience should be considered when designing delay discounting experiments as well as when implementing interventions to reduce steep delay discounting.

Winter Tracking Data Suggest that Migratory Seabirds Transport Per- and Polyfluoroalkyl Substances to Their Arctic Nesting Site.

Seabirds are often considered sentinel species of marine ecosystems, and their blood and eggs utilized to monitor local environmental contaminations. Most seabirds breeding in the Arctic are migratory and thus are exposed to geographically distinct sources of contamination throughout the year, including per- and polyfluoroalkyl substances (PFAS). Despite the abundance and high toxicity of PFAS, little is known about whether blood concentrations at breeding sites reliably reflect local contamination or exposure in distant wintering areas. We tested this by combining movement tracking data and PFAS analysis (nine compounds) from the blood of prelaying black-legged kittiwakes (Rissa tridactyla) nesting in Arctic Norway (Svalbard). PFAS burden before egg laying varied with the latitude of the wintering area and was negatively associated with time upon return of individuals at the Arctic nesting site. Kittiwakes (n = 64) wintering farther south carried lighter burdens of shorter-chain perfluoroalkyl carboxylates (PFCAs, C9-C12) and heavier burdens of longer chain PFCAs (C13-C14) and perfluorooctanesulfonic acid compared to those wintering farther north. Thus, blood concentrations prior to egg laying still reflected the uptake during the previous wintering stage, suggesting that migratory seabirds can act as biovectors of PFAS to Arctic nesting sites.

Optimizing carry-over in automated dissolution system dissoBOT for paracetamol and diclofenac sodium analysis.

In this work, an automated dissolution system (dissoBOT) was used for dissolution testing for the first time. Carry-over (CO) of the dissoBOT was determined for paracetamol (PA) and diclofenac sodium (DS), which are active pharmaceutical ingredients (APIs). Initially, partial method validation of the UV-VIS spectrophotometry method for PA and DS determination was performed by defining the limit of detection (LOD), the limit of quantification (LOQ), linear concentration range, accuracy, and precision. The LODs and LOQs were less than 0.01 mg/L for both APIs. The determined linear concentration ranges were from 1.00 mg/L to 30.00 mg/L for PA and from 0.50 mg/L to 3.50 mg/L for DS (the square of the correlation coefficient was greater than 0.9990, and the quality coefficient was less than 1.00 % for both APIs). The accuracy of the method was evaluated by calculating the recovery (Re) of the solutions of standards with known concentrations. The method for both APIs was deemed to be accurate (the average Re for PA and DS were 99.81 % and 101.43 %, respectively). Precision was evaluated by calculating the relative standard deviation (RSD). The method for PA and DS was deemed to be precise, as the RSD value for PA was 0.13 %, and for DS was 0.38 %. The volume (V) of the washing medium in both cleaning cycles performed by the dissoBOT system, as well as the medium dispensing V, were established, where the medium dispensing V was in accordance with the United States Pharmacopeia requirements. The CO of the dissoBOT system, using tap water as the washing medium, was determined to be less than 1.00 % for both APIs. The CO values for one cleaning cycle of the sampling station with a V of 2 mL was in the range of 1.24-1.54 %, for V of 5 mL was in the range of 0.78-0.93 %, and for V of 10 mL was in the range of 0.27-0.36 %. In addition, the CO of the dissoBOT, when employing two cleaning cycles of the sampling station (each V of 10 mL) was reduced (CO <0.20 %). Finally, the dissoBOT was successfully employed for the dissolution PA and DS tables.

Influence of global/local processing on perceived colour transparency.

Our cognitive processing is flexible and affected by global/local dominance in prior cognitive tasks. Similar to cognitive processing, perceptual processing, especially colour perception related to global/local processing, may be affected by prior global/local dominance; however, this possibility has not yet been assessed. Here, we examined whether prior tasks involving global/local processing influenced colour perception related to global/local processing. As colour perception is related to global/local processing, we focused on perceived colour transparency, in which a transparent layer is perceived in front of a background layer, even though these stimuli are physically in the same layer. When viewing the colour transparency stimulus, we expected that the perceived colour of a specific region, when focusing on only the local region, would differ from that when focusing on the whole image. In our study, the participants completed a global or local Navon task, followed by a colour-matching task that assessed how they saw colours using colour transparency stimuli. The degree of optical illusion (i.e., perceived colour transparency) after the global Navon task was greater than that after the local Navon task. Thus, prior global/local processing, a flexible mode of cognitive processing, influenced colour perception. This study provides new insight into perceptual flexibility, especially in colour perception.

Quinolizidine alkaloids and phomopsin A in animal feed containing lupins: co-occurrence and carry-over into veal products.

Lupins are used in animal feed because of their excellent nutritional composition. Australian and European Lupinus angustifolius seeds are incorporated in compound feed of calves for veal production in Belgium. To investigate the co-occurrence of quinolizidine alkaloids (QAs) and phomopsin A (PHO A) in lupin seeds and lupin-containing feed, and the potential transfer to animal-derived foods, representative samples were obtained from various actors in the chain. A UHPLC-MS/MS method was validated for the simultaneous quantification of seven QAs and PHO A in relevant matrices. Results indicate highly consistent total QA (TQA) levels in Australian lupins (173 ± 24 mg/kg) (n = 25), while European samples showed a high variability (1442 ± 1497 mg/kg) (n = 15). PHO A was detected in 7 of 40 samples. Lupin-containing feed had a mean TQA content of 42 ± 28 mg/kg (n = 20). An in vivo feeding trial demonstrated the transfer of QAs to muscle and liver of calves that were fed the lupin-containing feed. Highest concentrations were found for lupanine in liver tissue samples (67 ± 46 µg/kg). PHO A concentrations were below the LOD in all feed and tissue samples. These results indicate that animal-derived foods (veal meat/liver) are a potential route for QAs to enter the food chain.

Noise accelerates embryonic development in a key crab species: Morphological and physiological carryover effects on early life stages.

Anthropogenic noise is considered one important global pollutant. The impact of noise on marine invertebrates has been less assessed. The present study evaluated the chronic effect of the motorboat noise obtained from a lagoon's soundscape, the natural habitat of the key crab Neohelice granulata, on its whole embryonic development, considering morphological and physiological carryover effects on embryos and hatched larvae. Results demonstrated that embryonic development was shortened under noise exposure. The effects on advanced embryos, larvae and adult females were: increased heartbeats and non-viable eggs, and decreased fecundity. Biochemical responses showed lipid peroxidation in embryos while antioxidant enzymes were activated in larvae and adults, indicating a counteracting effect related to the life stage. The negative effects on fitness offspring may imply ecological consequences at the population level. Results are discussed in terms of the ecosystem engineer species studied and the habitat, a MAB UNESCO Reserve lagoon, suggesting the urgent need to develop mitigation plans.

Formation Mechanisms, Interrelationships, and Effects of Cognitive Factors on Diet and Physical Activity During the Post-Bariatric Surgery Period: A Cross-Sectional Study Based on Compensatory Carry-Over Action Model.

Background: Diet and physical activity (PA) are pivotal behaviors for managing energy balance post-bariatric surgery. Given the need for dual behavioral management, understanding the interplay of cognitive factors influencing these behaviors is crucial. This study applied the compensatory carry-over action model (CCAM) to explore the impact of cognitive factors on behaviors and their subsequent effects on subjective health outcomes. Methods: This cross-sectional study was conducted among patients at the third month after bariatric surgery in China. Data on diet and PA status, behavioral cognitive factors (intention, self-efficacy, compensatory belief, transfer cognition), and subjective health outcomes (perceived stress, well-being, quality of life) were collected. Structural equation model (SEM) was employed to test hypotheses in CCAM and assess mediation relationships. Results: Analysis of data from 239 patients revealed the following: (1) Among antecedent cognitive factors, only compensatory belief significantly influenced diet (P<0.001). (2) Intention and self-efficacy directly correlated with their respective behaviors, while compensatory belief affected intention, and transfer cognition impacted self-efficacy (P<0.05), aligning with CCAM hypotheses. (3) PA demonstrated significant influence only on perceived stress (P=0.004), whereas diet significantly affected all subjective health outcomes (P<0.05). (4) Mediation analysis indicated intention partially mediated the relationship between compensatory belief and diet and fully mediated the relationship between compensatory belief and PA. Self-efficacy completely mediated the relationship between transfer cognition and diet and PA. Conclusion: Transfer cognition's carry-over effect did not directly influence behaviors among antecedent cognitions. Interventions should primarily target improving diet by mitigating compensatory belief. Moreover, diet exhibited a more pronounced impact on overall health compared to PA. Consequently, prioritizing dietary intervention over PA intervention is warranted based on the analysis of CCAM and the aim of promoting joint behaviors post-bariatric surgery.

Prevalence and concentration of mycotoxins in bovine feed and feed components: A global systematic review and meta-analysis.

Mycotoxins are secondary metabolites produced by fungi and identified as contaminants in animal feed. They have potentially harmful effects, including carcinogenicity, mutagenicity, and repro-toxicity in animals and humans. As a result of climate change, there is the potential for a change in the prevalence and concentration of mycotoxins in animal feed components. This necessitates an assessment of the present and emerging threats to the food supply chain from mycotoxins. This systematic review and meta-analysis study synthesised studies on mycotoxin contamination and prevalence in cattle feed components. The studies were collected from scientific databases Web of Knowledge, Scopus, and Embase between 2011 and 2022. The meta-analysis synthesised 97 studies on the prevalence and the concentration of aflatoxins, ochratoxin A, deoxynivalenol, zearalenone, fumonisin and T-2/HT-2 toxins in feed components. Aflatoxin was highly prevalent (59 %), with a concentration of 2.58-3.92 µg kg-1 in feed components. Ochratoxin A had a global prevalence of 31 % with a concentration of 5.56-12.41 µg kg-1. Deoxynivalenol had a global concentration of 233.17-327.73 µg kg-1 and a prevalence of 74 %. Zearalenone had a prevalence of 70 % and a concentration of 42.47-66.19 µg kg-1. The concentration and prevalence of fumonisins was 232.19-393.07 µg kg-1 and 65 %, respectively. The prevalence and concentration of T-2/HT-2 toxins were 45 % and 23.54-35.12 µg kg-1, respectively. The synthesised concentration of the mycotoxins in the overall feed components was lower than the regulated and guidance values set by the European Union. However, in a few cases, the 95th percentile exceeded these concentration values due to high levels of uncertainty attributed to lower sample size, and thus, need to be considered while conducting risk assessments. The study highlights climates and regions likely to be conducive to the emergence of mycotoxin risk, especially considering the potential influences of climate change.

Cellular mechanisms underlying carry-over effects after magnetic stimulation.

Magnetic fields are widely used for neuromodulation in clinical settings. The intended effect of magnetic stimulation is that neural activity resumes its pre-stimulation state right after stimulation. Many theoretical and experimental works have focused on the cellular and molecular basis of the acute neural response to magnetic field. However, effects of magnetic stimulation can still last after the termination of the magnetic stimulation (named "carry-over effects"), which could generate profound effects to the outcome of the stimulation. However, the cellular and molecular mechanisms of carry-over effects are largely unknown, which renders the neural modulation practice using magnetic stimulation unpredictable. Here, we investigated carry-over effects at the cellular level, using the combination of micro-magnetic stimulation (µMS), electrophysiology, and computation modeling. We found that high frequency magnetic stimulation could lead to immediate neural inhibition in ganglion neurons from Aplysia californica, as well as persistent, carry-over inhibition after withdrawing the magnetic stimulus. Carry-over effects were found in the neurons that fired action potentials under a variety of conditions. The carry-over effects were also observed in the neurons when the magnetic field was applied across the ganglion sheath. The state of the neuron, specifically synaptic input and membrane potential fluctuation, plays a significant role in generating the carry-over effects after magnetic stimulation. To elucidate the cellular mechanisms of such carry-over effects under magnetic stimulation, we simulated a single neuron under magnetic stimulation with multi-compartment modeling. The model successfully replicated the carry-over effects in the neuron, and revealed that the carry-over effect was due to the dysfunction of the ion channel dynamics that were responsible for the initiation and sustaining of membrane excitability. A virtual voltage-clamp experiment revealed a compromised Na conductance and enhanced K conductance post magnetic stimulation, rendering the neurons incapable of generating action potentials and, therefore, leading to the carry over effects. Finally, both simulation and experimental results demonstrated that the carry-over effects could be controlled by disturbing the membrane potential during the post-stimulus inhibition period. Delineating the cellular and ion channel mechanisms underlying carry-over effects could provide insights to the clinical outcomes in brain stimulation using TMS and other modalities. This research incentivizes the development of novel neural engineering or pharmacological approaches to better control the carry-over effects for optimized clinical outcomes.

Synchronous timing of return to breeding sites in a long-distance migratory seabird with ocean-scale variation in migration schedules.

BACKGROUND: Migratory birds generally have tightly scheduled annual cycles, in which delays can have carry-over effects on the timing of later events, ultimately impacting reproductive output. Whether temporal carry-over effects are more pronounced among migrations over larger distances, with tighter schedules, is a largely unexplored question. METHODS: We tracked individual Arctic Skuas Stercorarius parasiticus, a long-distance migratory seabird, from eight breeding populations between Greenland and Siberia using light-level geolocators. We tested whether migration schedules among breeding populations differ as a function of their use of seven widely divergent wintering areas across the Atlantic Ocean, Mediterranean Sea and Indian Ocean. RESULTS: Breeding at higher latitudes led not only to later reproduction and migration, but also faster spring migration and shorter time between return to the breeding area and clutch initiation. Wintering area was consistent within individuals among years; and more distant areas were associated with more time spent on migration and less time in the wintering areas. Skuas adjusted the period spent in the wintering area, regardless of migration distance, which buffered the variation in timing of autumn migration. Choice of wintering area had only minor effects on timing of return at the breeding area and timing of breeding and these effects were not consistent between breeding populations. CONCLUSION: The lack of a consistent effect of wintering area on timing of return between breeding areas indicates that individuals synchronize their arrival with others in their population despite extensive individual differences in migration strategies.

Electrostatic Repulsion Hydrophilic Interaction Liquid Chromatography (ERLIC) for the Quantitative Analysis of Polyamines.

Highly polar low molecular weight organic molecules are still very challenging to analyze by liquid chromatography. Yet, with the steadily increasing application of metabolomics and similar approaches in chemical analysis, separating polar compounds might be even more important. However, almost all established liquid chromatography techniques (i.e., normal and reversed phase, hydrophilic interaction liquid chromatography (HILIC), ion chromatography) struggle with either carry-over, low sensitivity, or a lack of retention. For improving these shortcomings, electrostatic repulsion hydrophilic interaction chromatography (ERLIC) might be an alternative. By combining a HILIC mobile phase, that is highly organic with a low water content, and an ion exchange column, a distinct layer system develops. When the analyte's charge is of the same direction as the stationary phase, retention and elution are determined by two antagonistic forces: electrostatic repulsion and hydrophilicity. One prominent group of challenging polar analytes are the polyamines cadaverine, putrescine, spermidine, and spermine. Carrying charges from +2 to +4 at physiological pH, these compounds are essential cell constituents and found in all living organisms. However, they are still notoriously challenging to analyze via the established liquid chromatography methods. In the present work, an ERLIC tandem mass spectrometry method has been exemplarily developed, optimized, and validated for the quantitative determination of cadaverine, putrescine, spermidine, and spermine. This method enables symmetrical peak shapes and good separation of analytes with different charges while simultaneously selectively detecting the co-eluting diamines by MS/MS. Furthermore, high linearity (R > 0.998) and sensitivity (LODs ≤ 2 ng/mL) have been proven. Thus, ERLIC may be interesting for both targeted and untargeted analysis approaches of highly charged low molecular weight organic molecules.

Natal legacies cause social and spatial marginalization during dispersal.

Early-life experiences can drive subsequent variation in social behaviours, but how differences among individuals emerge remains unknown. We combined experimental manipulations with GPS-tracking to investigate the pathways through which developmental conditions affect social network position during the early dispersal of wild red kites (Milvus milvus). Across 211 juveniles from 140 broods, last-hatched chicks-the least competitive-had the fewest number of peer encounters after fledging. However, when food supplemented, they had more encounters than all others. Using 4425 bird-days of GPS data, we revealed that this was driven by differential responses to competition, with less competitive individuals naturally spreading out into marginal areas, and clustering in central foraging areas when food supplemented. Our results suggest that early-life adversities can cause significant natal legacies on individual behaviour beyond independence, with potentially far-reaching consequences on the social and spatial structure of animal populations.

Effects of pre-winter cortisol exposure on condition, diet, and morphology of wild juvenile brown trout (Salmo trutta).

Winter is an energetically challenging period for many animals in temperate regions because of the relatively harsh environmental conditions and reduction in food availability during this season. Moreover, stressors experienced by individuals in the fall can affect their subsequent foraging strategy and energy stores after exposure has ended, referred to as carryover effects. We used exogenous cortisol manipulation of wild juvenile brown trout (Salmo trutta) in the fall to simulate a physiological stress response and then investigated short-term (2 weeks) and long-term (4 months) effects on condition metrics (hepatosomatic index and water muscle content), diet (stomach contents and stable isotopes), and morphology during growth in freshwater. We revealed some short-term impacts, likely due to handling stress, and long-term (seasonal) changes in diet, likely reflecting prey availability. Unfortunately, we had very few recaptures of cortisol-treated fish at long-term sampling, limiting detailed analysis about cortisol effects at that time point. Nonetheless, the fish that were sampled showed elevated stable isotopes, suggestive of a cortisol effect long after exposure. This is one of few studies to investigate whether cortisol influences foraging and morphology during juvenile growth, thus extending the knowledge of proximate mechanisms influencing ecologically-relevant phenotypes.

Variations of salinity during reproduction and development affect ontogenetic trajectories in a coastal amphibian.

Although coastal ecosystems are naturally submitted to temporal variations of salinity, salinization has been increasing over time threatening coastal biodiversity. Species that exploit such habitats can thus be exposed to brackish water at different life stages. However, the impacts of variations of salinity on wildlife remain poorly understood. This is particularly true for coastal amphibians, due to the strong dependency of early life stages (embryos and larvae) on aquatic environments. In order to investigate the effect of salinity during egg laying and embryonic and larval development of coastal amphibians, we used a full-factorial design to expose reproductive adults, eggs, and larvae of coastal spined toads (Bufo spinosus) to fresh (0 g.l-1) or brackish water (4 g.l-1). At egg laying, we evaluated parental investment in reproduction. During embryonic and larval development, we assessed effects on survival, development, and growth. We highlighted strong effects of environmental salinity on reproduction (reduced egg laying time, marginally reduced egg size, and reduced investment in reproduction). Responses to salinity were highly dependent on the developmental stages of exposure (stronger effects when individuals were exposed during embryonic development). These effects carried over when exposure occurred at egg laying or during embryonic development, highlighting the importance of the environmental conditions during early life on ontogenetic trajectories. We also highlighted partial compensation when individuals were transferred back to freshwater. Whether the magnitude of these responses can allow coastal biodiversity to overcome the observed detrimental effects of salinization remain to be assessed.

The embryonic thermal environment has positive but weak effects on thermal tolerance later in life in the aquatic invertebrate Gammarus chevreuxi.

Recent evidence suggests that the adult phenotype is influenced by temperatures experienced in early life. However, our understanding of the extent to which the embryonic environment can modulate thermal tolerance later in life is limited, owing to the paucity of studies with appropriate experimental designs to test for this form of developmental plasticity. We investigated whether the thermal environment experienced during embryonic development affects thermal limits in later life. Embryos of the estuarine amphipod Gammarus chevreuxi were incubated until hatching to 15 °C, 20 °C and 25 °C, then reared under a common temperature. Using thermal ramping assays, we determined upper thermal limits in juveniles, four weeks post-hatch. Individuals exposed to higher temperatures during embryonic development displayed greater thermal tolerance as juveniles (acclimation response ratio ≈ 0.10-0.25 for upper lethal temperature). However, we suggest that the degree of developmental plasticity observed is limited, and will provide little benefit under future climate change scenarios.

A Systematic Review of the Long-Term Effects of Using Smartphone- and Tablet-Based Rehabilitation Technology for Balance and Gait Training and Exercise Programs.

Recent advances in wearable motion sensors, mobile devices, the Internet of Things, and telecommunications have created new potential for telerehabilitation. Recognizing that there is no systematic review of smartphone- or tablet-based balance and gait telerehabilitation technology for long-term use (i.e., four weeks or more), this systematic review summarizes the effects of smartphone- or tablet-based rehabilitation technology on balance and gait exercise and training in balance and gait disorders. The review examined studies written in English published from 2013 to 2023 in Web of Science, Pubmed, Scopus, and Google Scholar. Of the 806 studies identified, 14 were selected, and the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-sectional Studies was applied to evaluate methodological quality. The systematic review concluded that all 14 studies found balance and gait performance improvement after four weeks or more of balance and gait telerehabilitation. Ten of the 14 studies found that carry-over effects (improved functional movements, muscle strength, motor capacity, cognition, and reduced fear of falling and anxiety levels) were maintained for weeks to months. The results of the systematic review have positive technical and clinical implications for the next-generation design of rehabilitation technology in balance and gait training and exercise programs.

Interpopulation differences and temporal synchrony in rates of adult survival between two seabird colonies that differ in population size and distance to foraging grounds.

Understanding the processes that drive interpopulation differences in demography and population dynamics is central to metapopulation ecology. In colonial species, populations are limited by local resource availability. However, individuals from larger colonies will travel greater distances to overcome density-dependent competition. Consequently, these individuals may also experience greater carry-over effects and interpopulation differences in demography. To test this prediction, we use mark-recapture data collected over four decades from two breeding colonies of a seabird, the Manx shearwater (Puffinus puffinus), that exhibit strong spatial overlap throughout the annual cycle but differ in population size and maximum foraging distances. We quantify interpopulation differences and synchrony in rates of survival and assess whether local mean wind speeds act to strengthen or disrupt synchrony. In addition, we examine whether the imputed interpopulation differences in survival can generate population-level consequences. The colony where individuals travel further during the breeding season had slightly lower and more variable rates of survival, indicative of individuals experiencing greater carry-over effects. Fluctuations in survival were highly synchronous between the colonies, but neither synchronous, nor asynchronous, variation could be strongly attributed to fluctuations in local mean wind speeds. Finally, we demonstrate that the imputed interpopulation differences in rates of survival could lead to considerable differences in population growth. We hypothesise that the observed interpopulation differences in rates of adult survival reflect carry-over effects associated with foraging distances during the breeding season. More broadly, our results highlight that breeding season processes can be important for understanding interpopulation differences in the demographic rates and population dynamics of long-lived species, such as seabirds.

An LC-ESI-MS/MS method for determination of ondansetron in low-volume plasma and cerebrospinal fluid: Method development, validation, and clinical application.

Ondansetron is used in clinical settings as an antiemetic drug. Although the animal studies showed its potential effectiveness also in treating neuropathic pain, the results from humans are inconclusive. The lack of efficacy of ondansetron in a subset of patients might be due to the overexpression of P-glycoprotein, which could result in low concentrations of ondansetron in the central nervous system (CNS). A surrogate of the CNS exposure might be drug concentration in the cerebrospinal fluid (CSF), especially in humans, as assessing the drug disposition directly in the patient's brain would be challenging. The study aimed to develop a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine concentrations of ondansetron in human K3EDTA plasma and CSF. Ondansetron was extracted from biological matrices by liquid-liquid extraction. The quantification was performed on a Sciex QTRAP 6500+ mass spectrometer with labeled ondansetron as an internal standard. The calibration range was 0.25-350 ng/mL in plasma and 0.025-100 ng/mL in CSF; for both matrices, 25 µL of samples was required for the assays. The method was validated according to the FDA and EMA guidelines and showed acceptable results. A pilot study confirmed its suitability for clinical samples: after 4-16 mg of intravenous ondansetron, the determined concentrations in plasma were 1.22-235.90 ng/mL, while in CSF - 0.018-11.93 ng/mL. In conclusion, the developed method fulfilled all validation requirements and can be applied to pharmacokinetic studies assessing the CNS ondansetron exposure in humans. The method's advantages, such as a low volume of matrix and a wide calibration range, support its use in a study in which rich sampling and various drug doses are expected.

Large offspring have enhanced lifetime reproductive success: Long-term carry-over effects of weaning size in gray seals (Halichoerus grypus).

An individual's size in early stages of life may be an important source of individual variation in lifetime reproductive performance, as size effects on ontogenetic development can have cascading physiological and behavioral consequences throughout life. Here, we explored how size-at-young influences subsequent reproductive performance in gray seals (Halichoerus grypus) using repeated encounter and reproductive data on a marked sample of 363 females that were measured for length after weaning, at ~4 weeks of age, and eventually recruited to the Sable Island breeding colony. Two reproductive traits were considered: provisioning performance (mass of weaned offspring), modeled using linear mixed effects models; and reproductive frequency (rate at which a female returns to breed), modeled using mixed effects multistate mark-recapture models. Mothers with the longest weaning lengths produced pups 8 kg heavier and were 20% more likely to breed in a given year than mothers with the shortest lengths. Correlation in body lengths between weaning and adult life stages, however, is weak: Longer pups do not grow to be longer than average adults. Thus, covariation between weaning length and future reproductive performance appears to be a carry-over effect, where the size advantages afforded in early juvenile stages may allow enhanced long-term performance in adulthood.

Spring arrival of the common cuckoo at breeding grounds is strongly determined by environmental conditions in tropical Africa.

Failure to adapt migration timing to changes in environmental conditions along migration routes and at breeding locations can result in mismatches across trophic levels, as occurs between the brood parasitic common cuckoo Cuculus canorus and its hosts. Using satellite tracking data from 87 male cuckoos across 11 years, we evaluate why the cuckoo has not advanced its arrival to the UK. Across years, breeding ground arrival was primarily determined by timing of departure from stopover in West Africa before northward crossing of the Sahara. Together with high population synchrony and low apparent endogenous control of this event, this suggests that a seasonal ecological constraint operating here limits overall variation in breeding grounds arrival, although this event was itself influenced by carry-over from timing of arrival into tropical Africa. Between-year variation within individuals was, in contrast, mostly determined by northward migration through Europe, probably due to weather conditions. We find evidence of increased mortality risk for (a) early birds following migration periods positively impacting breeding grounds arrival, and (b) late birds, possibly suffering energy limitation, after departure from the breeding grounds. These results help identify areas where demands of responding to global change can potentially be alleviated by improving stopover quality.