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Molecular monitoring of tumor-derived alterations has an established role in the surveillance of leukemias, and emerging nucleic acid sequencing technologies are likely to similarly transform the clinical management of lymphomas. Lymphomas are well suited for molecular surveillance due to relatively high cell-free DNA and circulating tumor DNA concentrations, high somatic mutational burden, and the existence of stereotyped variants enabling focused interrogation of recurrently altered regions. Here, we review the clinical scenarios and key technologies applicable for the molecular monitoring of lymphomas, summarizing current evidence in the literature regarding molecular subtyping and classification, evaluation of treatment response, the surveillance of active cellular therapies, and emerging clinical trial strategies. Expected final online publication date for the

Repeated social interactions with conspecifics and/or heterospecifics during early development may drive the differentiation of behavior among individuals. Competition is a major form of social interaction and its impacts can depend on whether interactions occur between conspecifics or heterospecifics and the directionality of a response could be specific to the ecological context that they are measured in. To test this, we reared tungara frog tadpoles (Engystomops pustulosus) either in isolation, with a conspecific tadpole or with an aggressive heterospecific tadpole, the whistling frog tadpole (Leptodactylus fuscus). In each treatment, we measured the body size and distance focal E. pustulosus tadpoles swam in familiar, novel and predator risk contexts six times during development. We used univariate and multivariate hierarchical mixed effect models to investigate the effect of treatment on mean behavior, variance among and within individuals, behavioral repeatability and covariance among individuals in their behavior between contexts. There was a strong effect of competition on behavior, with different population and individual level responses across social treatments. Within a familiar context, the variance in the distance swam within individuals decreased under conspecific competition but heterospecific competition caused more variance in the average distance swam among individuals. Behavioral responses were also context specific as conspecific competition caused an increase in the distance swam within individuals in novel and predator risk contexts. The results highlight that the impact of competition on among and within individual variance in behavior is dependent on both competitor species identity and context.

Species that hibernate generally live longer than would be expected based solely on their body size. Hibernation is characterized by long periods of metabolic suppression (torpor) interspersed by short periods of increased metabolism (arousal). The torpor–arousal cycles occur multiple times during hibernation, and it has been suggested that processes controlling the transition between torpor and arousal states cause ageing suppression. Metabolic rate is also a known correlate of longevity; we thus proposed the ‘hibernation–ageing hypothesis’ whereby ageing is suspended during hibernation. We tested this hypothesis in a well-studied population of yellow-bellied marmots (Marmota flaviventer), which spend 7–8 months per year hibernating. We used two approaches to estimate epigenetic age: the epigenetic clock and the epigenetic pacemaker. Variation in epigenetic age of 149 samples collected throughout the life of 73 females was modelled using generalized additive mixed models (GAMM), where season (cyclic cubic spline) and chronological age (cubic spline) were fixed effects. As expected, the GAMM using epigenetic ages calculated from the epigenetic pacemaker was better able to detect nonlinear patterns in epigenetic ageing over time. We observed a logarithmic curve of epigenetic age with time, where the epigenetic age increased at a higher rate until females reached sexual maturity (two years old). With respect to circannual patterns, the epigenetic age increased during the active season and essentially stalled during the hibernation period. Taken together, our results are consistent with the hibernation–ageing hypothesis and may explain the enhanced longevity in hibernators.

Nanocomposites based on graphene oxide (GO) or reduced graphene oxide (rGO) grafted with hollow gold nanoshells (HGNs) were developed as enhanced photothermal agents with improved biocompatibility. Infrared and Raman spectroscopy allowed determining that graphene was highly oxidized due to the presence of oxygenated groups that allowed further functionalization and provided anchor points for the grafting of HGNs. Using HRTEM and STEM, good dispersion of the HGN on the surface of the graphitic materials was observed. Meanwhile, using UV–Vis spectroscopy, an increase of absorbance in the near-infrared region was appreciated, resulting in an enhancement of the photothermal properties of the nanocomposites in contrast to the materials separately. Remarkable temperature increases were obtained in short periods of irradiation using a low-power laser. Moreover, a decrease in the cytotoxicity of GO and rGO was observed in the human neuronal line hNS1 under the presence of the plasmonic nanoparticles on the surface.

To obtain a deeper understanding of poor responses to COVID-19 vaccination in patients with lymphoma, we assessed blocking antibodies, total anti-spike IgG, and spike-specific memory B cells in the peripheral blood of 126 patients with lymphoma and 20 age-matched healthy controls 1 and 4 months after COVID-19 vaccination. Fifty-five percent of patients developed blocking antibodies postvaccination, compared with 100% of controls. When evaluating patients last treated from days to nearly 18 years prior to vaccination, time since last anti-CD20 was a significant independent predictor of vaccine response. None of 31 patients who had received anti-CD20 treatment within 6 months prior to vaccination developed blocking antibodies. In contrast, patients who initiated anti-CD20 treatment shortly after achieving a vaccine-induced antibody response tended to retain that response during treatment, suggesting a policy of immunizing prior to treatment whenever possible. Significance: In a large cohort of patients with B-cell lymphoma, time since anti-CD20 treatment was an independent predictor of neutralizing antibody response to COVID-19 vaccination. Comparing patients who received anti-CD20 treatment before or after vaccination, we demonstrate that vaccinating first can generate an antibody response that endures through anti-CD20–containing treatment. This article is highlighted in the In This Issue feature, p. 85

Follicular lymphomas (FL) are characterized by BCL2 translocations, often detectable in blood years before FL diagnosis, but also observed in aging healthy individuals, suggesting additional lesions are required for lymphomagenesis. We directly characterized early cooperating mutations by ultradeep sequencing of prediagnostic blood and tissue specimens from 48 subjects who ultimately developed FL. Strikingly, CREBBP lysine acetyltransferase (KAT) domain mutations were the most commonly observed precursor lesions, and largely distinguished patients developing FL (14/48, 29%) from healthy adults with or without detected BCL2 rearrangements (0/13, P = 0.03 and 0/20, P = 0.007, respectively). CREBBP variants were detectable a median of 5.8 years before FL diagnosis, were clonally selected in FL tumors, and appeared restricted to the committed B-cell lineage. These results suggest that mutations affecting the CREBBP KAT domain are common lesions in FL cancer precursor cells (CPC), with the potential for discriminating subjects at risk of developing FL or monitoring residual disease.Significance:Our study provides direct evidence for recurrent genetic aberrations preceding FL diagnosis, revealing the combination of BCL2 translocation with CREBBP KAT domain mutations as characteristic committed lesions of FL CPCs. Such prediagnostic mutations are detectable years before clinical diagnosis and may help discriminate individuals at risk for lymphoma development.

Supplementary Methods and Figures S1-S5

This paper explores how claims for transformative adaptation toward more equitable and sustainable societies can be assessed. We build on a theoretical framework describing transformative adaptation as it manifests across four core elements of the public-sector adaptation lifecycle: vision, planning, institutional frameworks, and interventions. For each element, we identify characteristics that can help track adaptation as transformative. Our purpose is to identify how governance systems can constrain or support transformative choices and thus enable targeted interventions. We demonstrate and test the usefulness of the framework with reference to three government-led adaptation projects of nature-based solutions (NBS): river restoration (Germany), forest conservation (China), and landslide risk reduction (Italy). Building on a desktop study and open-ended interviews, our analysis adds evidence to the view that transformation is not an abrupt system change, but a dynamic complex process that evolves over time. While each of the NBS cases fails to fulfill all the transformation characteristics, there are important transformative elements in their visions, planning, and interventions. There is a deficit, however, in the transformation of institutional frameworks. The cases show institutional commonalities in multi-scale and cross-sectoral (polycentric) collaboration as well as innovative processes for inclusive stakeholder engagement; yet, these arrangements are ad hoc, short-term, dependent on local champions, and lacking the permanency needed for upscaling. For the public sector, this result highlights the potential for establishing cross-competing priorities among agencies, cross-sectoral formal mechanisms, new dedicated institutions, and programmatic and regulatory mainstreaming.

To obtain a deeper understanding of poor responses to COVID-19 vaccination in patients with lymphoma, we assessed blocking antibodies, total anti-spike IgG, and spike-specific memory B cells in the peripheral blood of 126 patients with lymphoma and 20 age-matched healthy controls 1 and 4 months after COVID-19 vaccination. Fifty-five percent of patients developed blocking antibodies postvaccination, compared with 100% of controls. When evaluating patients last treated from days to nearly 18 years prior to vaccination, time since last anti-CD20 was a significant independent predictor of vaccine response. None of 31 patients who had received anti-CD20 treatment within 6 months prior to vaccination developed blocking antibodies. In contrast, patients who initiated anti-CD20 treatment shortly after achieving a vaccine-induced antibody response tended to retain that response during treatment, suggesting a policy of immunizing prior to treatment whenever possible.Significance:In a large cohort of patients with B-cell lymphoma, time since anti-CD20 treatment was an independent predictor of neutralizing antibody response to COVID-19 vaccination. Comparing patients who received anti-CD20 treatment before or after vaccination, we demonstrate that vaccinating first can generate an antibody response that endures through anti-CD20–containing treatment.This article is highlighted in the In This Issue feature, p. 85

Supplementary Data from CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Preestablished Immunity

In order to assess user and policy needs related to biodiversity monitoring and data, the EuropaBON project invited national experts to fill in this survey in August 2021. The survey was tailored to the national level and aimed at identifying current monitoring efforts, data flows from collection to reporting, data uptake by policymaking, challenges and roadblocks, as well as biodiversity variables and indicators for a desirable future. On behalf of the European Commission (DG Environment) and EuropaBON, the surveys were sent out to all national focal points of the European Environment Information and Observation Network (Eionet) as well as key national agencies. Eionet is a partnership network of the European Environment Agency (EEA) and its 38 member and cooperating countries to gather and develop data, knowledge, and advice to policy makers about Europe's environment. The results of our surveys form the basis for the analysis of the EuropaBON User and Policy Needs Assessment (DOI) and inform the design of the Europa Biodiversity Observation Network and its work programme. We published the original responses of survey sections A and B in the annex of the User and Policy Needs Assessment. Responses of section C were synthesised in the assessment.

Supplementary Figure from CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Preestablished Immunity

In order to assess user and policy needs related to biodiversity monitoring and data, the EuropaBON project invited European experts to fill in this survey in August 2021. The survey was tailored to the European level and aimed at identifying current monitoring efforts, data flows from collection to reporting, data uptake by policymaking, challenges and roadblocks, as well as biodiversity variables and indicators for a desirable future. On behalf of the European Commission (DG Environment) and EuropaBON, the surveys were sent out to key European agencies (e.g., DG ENV, DG AGRI, DG CLIMA, EEA, Eurostat, Biodiversa+). The results of our surveys form the basis for the analysis of the EuropaBON User and Policy Needs Assessment (DOI) and inform the design of the Europa Biodiversity Observation Network and its work programme. We published the original responses of survey sections A and B in the annex of the User and Policy Needs Assessment. Responses of section C were synthesised in the assessment.

This review provides examples of the utilisation of plant bioactivity to mitigate enteric methane (CH4) emissions from the Australian ruminant production systems. Potential plant-based mitigation strategies that reduce CH4 without major impacts on forage digestibility include the following: (i) low methanogenic tropical and temperate grass, legume and shrub forage species, which offer renewable and sustainable solutions and are easy to adopt, but may have restricted geographical distribution or relatively high costs of establishment and maintenance; (ii) plant-based agricultural by-products including grape marc, olive leaves and fruit, and distiller’s grains that can mitigate CH4 and provide relatively cheap high-nutrient supplements, while offsetting the impact of agricultural waste, but their use may be limited due to unfavourable characteristics such as high protein and water content or cost of transport; (iii) plant extracts, essential oils and pure compounds that are abundant in Australian flora and offer exciting opportunities on the basis of in vitro findings, but require verification in ruminant production systems. The greatest CH4 mitigation potential based on in vitro assays come from the Australian shrubs Eremophila species, Jasminum didymium and Lotus australis (>80% CH4 reduction), tropical forages Desmanthus leptophyllus, Hetropogon contortus and Leucaena leucocephala (~40% CH4 reduction), temperate forages Biserrula pelecinus (70–90% CH4 reduction), perennial ryegrass and white clover (~20% CH4 reduction), and plant extracts or essential oils from Melaleuca ericifolia, B. pelecinus and Leptospermum petersonii (up to 80% CH4 reduction). Further research is required to confirm effectiveness of these plant-based strategies in vivo, determine optimal doses, practical modes of delivery to livestock, analyse benefit–cost ratios and develop pathways to adoption.

The availability of food during early life has been proposed as a key proximate mechanism for the development of variation in behaviour among and within individuals.Individuals can vary amongst each other in their personality, plasticity and predictability and if an individual’s behaviour is correlated across contexts this can lead to behavioural, plasticity and predictability syndromes.In this study, we used a split brood design to raise African clawed frog tadpoles (Xenopus laevis) on a high or low diet in food availability and measured the distance they swam in a familiar and unfamiliar context eight times during their development.In a familiar context, we found that there was an increase in among individual variance in plasticity and predictability in the high food treatment. This shows that when resources are not restricted, individuals are not constrained in the expression of their behaviour at certain phenotypic levels.In an unfamiliar context, we found a different response, with an increase in individual variance in personality in the low but not the high feed tadpoles. As unfamiliar contexts may be riskier, our results highlight that individuals receiving less food may take greater foraging risks in novel contexts.Across contexts, we found a predictability syndrome in the high but not the low feed tadpoles, highlighting that cross-context behaviours can become decoupled in some developmental conditions but remain intact in others.Together our findings show that early life conditions contribute to among individual variation in behaviour but that these may only impact the phenotype at specific phenotypic levels and are context specific.We emphasise that having a fundamental understanding of how early development may promote or constrain individual variation can provide a greater understanding of how individuals and populations may respond to novel conditions brought about by anthropogenic activity.

The timing of life events (phenology) can be influenced by climate. Studies from around the world tell us that climate cues and species' responses can vary greatly. If variation in climate effects on phenology is strong within a single ecosystem, climate change could lead to ecological disruption, but detailed data from diverse taxa within a single ecosystem are rare. We collated first sighting and median activity within a high-elevation environment for plants, insects, birds, mammals and an amphibian across 45 years (1975–2020). We related 10 812 phenological events to climate data to determine the relative importance of climate effects on species’ phenologies. We demonstrate significant variation in climate-phenology linkage across taxa in a single ecosystem. Both current and prior climate predicted changes in phenology. Taxa responded to some cues similarly, such as snowmelt date and spring temperatures; other cues affected phenology differently. For example, prior summer precipitation had no effect on most plants, delayed first activity of some insects, but advanced activity of the amphibian, some mammals, and birds. Comparing phenological responses of taxa at a single location, we find that important cues often differ among taxa, suggesting that changes to climate may disrupt synchrony of timing among taxa.

This dataset is supplementary to the study on the Lower Jurassic fossiliferous interbeds in the Karoo continental flood basalts of southern Africa, and contains: a) Supplementary Material Figure A, an illustration of the measured ichnological morphometric parameters of the Batrachopus trackway at Ralikhomo (compare to Fig 10). b) Supplementary Material Figure B (I–VII), several illustrations of the vertebrate tracks in the sandstone interbeds of the Lower Jurassic Drakensberg Group in Lesotho identified by Ellenberger (1970) and in his unpublished data. c) Supplementary Material Text 1, a translation of excerpts from Ellenberger (1975). d) Supplementary Material Table 1, inventory of the Drakensberg fossil biota. e) Photogrammetric data: photographs used in the photogrammetric models of the Drakensberg fossils in this study (including Supplementary Material), and the cleaned and aligned 3D models as recommended by Falkingham et al. (2018).

Background Heart failure (HF) is a leading cause of hospital admission. However, prompt identification of worsening HF using implantable device data and proactive intervention may reduce hospitalizations. The validated TriageHF algorithm in enabled ICD/CRT devices uses sensor data to risk stratify patients for HF hospitalization in the next 30 days. TriageHF Plus is a novel device-based HF care pathway (DHFP) that uses “high” risk status as the trigger for remote intervention (see Figure 1 for pathway overview). Outcomes after DHFP implementation in a clinical setting have not been examined. Purpose To evaluate the impact of TriageHF Plus clinical pathway on hospitalisation rates. Methods A prospective, multi-center evaluation comparing monthly hospitalization rates for patients enrolled in a DHFP with a concurrent standard of care (SoC) cohort and characterizing staffing resources necessary to implement the DHFP. The DHFP cohort received telephonic assessment and guideline-directed clinical care upon transition to high-risk status. Propensity scores (PS) were applied to DHFP and SoC cohorts to allow unbiased comparison. A negative binomial model was fitted to the monthly number of all-cause hospitalizations with treatment group (DHFP vs. SoC) as a covariate, using PS as weights. Results Between 09/11/2019 and 06/24/2021, 758 patients were included in the study (443 DHFP, 315 SoC). Proportion CRT 76%/ 89% and LVEF 196 high risk transmissions prompted telephone assessment, with successful contact in 182; of which, 79 (43%) identified an explanatory acute medical issue. A secondary intervention was undertaken in 44/79 (56%). High risk transmissions took on average 19 minutes per clinical assessment (initial telephone triage and 30 day follow up). The rate of hospitalizations was 58% lower in the DHFP group, compared with SoC, after PS adjustment (IRR 0.42, 95% CI: 0.23, 0.76, p=0.004), see Figure 2. Sensitivity analyses showed Covid-19 had little effect on results. Conclusions This is the first prospective, real-world evaluation of a device-based HF care pathway to report a reduction in hospitalizations and does so with minimal staffing time. Integrated into existing HF services, device-based remote monitoring of HF patients can improve outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic

Aim The purpose of this work is to elucidate if low cumulative doxorubicin doses has a differential cardiac impact in pigs with or without pre-existing LV pressure overload. Impact of interventions on LV anatomy, function and tissue composition was evaluated by serial cardiac magnetic resonance (CMR). At the end of the in vivo protocol, hearts were processed to evaluate differential molecular pathways in both groups. Methods A total of 95 pigs were included. 52 animals underwent supravalvular aortic banding to generate LV hypertrophy, while another did not. 4 months after banding (a time where LV hypertrophy is prominent), animals in both groups were randomized to receive intravenous doxorubicin (1 mg/kg once per week, for 5 weeks) or saline. Thus, 4 study groups (N=15–22 per group) comprised the study population (banding yes/no, doxorubicin yes/no). All individuals underwent to serial Cardiac Magnetic Resonance exams every month and were sacrificed fo ex vivo analysisat 4 months after doxorubicin injections. To discriminate between doxorubicin effect in banding/no banding groups but also the effect of banding in doxorubicin protocols, t-test was used for two-group comparisons after two-way ANOVA test. Differences were considered statistically significant at p Results Pigs receiving doxorubicin after cardiac pressure overload showed an increased mortality compared with the other groups (p=0.006). Only this group developed a progressive cardiotoxicity phenotype, characterized as a significant decline in cardiac function compared with control operated animals (49.7% ± 8.1 vs 79.6% ± 6.7, p Conclusion(s) We demonstrated that a very low dosage of doxorubicin is enough to exert cardiotoxicity in a pressure overload scenario. Characterized as a deterioration in cardiac function, myocardial edema, classical histological lesions and mitochondrial damage. Providing preclinical evidence that modest anthracycline protocols may be harmful for patients with cardiac comorbidities. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): ERC MATRIX

Circulating tumor DNA (ctDNA) is an emerging biomarker for many cancers, but the limited sensitivity of current detection methods reduces its utility for diagnosing minimal residual disease. Here we describe phased variant enrichment and detection sequencing (PhasED-Seq), a method that uses multiple somatic mutations in individual DNA fragments to improve the sensitivity of ctDNA detection. Leveraging whole-genome sequences from 2,538 tumors, we identify phased variants and their associations with mutational signatures. We show that even without molecular barcodes, the limits of detection of PhasED-Seq outperform prior methods, including duplex barcoding, allowing ctDNA detection in the parts-per-million range in patient samples. We profiled 678 specimens from 213 patients with B-cell lymphomas, including serial cell-free DNA samples before and during therapy for diffuse large B-cell lymphoma. In patients with undetectable ctDNA by CAPP-Seq after two cycles of therapy, an additional 25% have ctDNA detectable by PhasED-Seq and have worse outcomes. Finally, we demonstrate the application of PhasED-Seq to solid tumors., Editorial summary The sensitivity of circulating tumor DNA detection is improved by identifying sequences with two or more mutations.

Switched Reluctance Motor (SRM) is an electrical motor which operates by a reluctance torque that has stator and rotor salient poles. It also has a simple configuration and reasonable power electronics necessity for both AC and DC machines within adjustable-speed drives. The problem working on it is, SRM with doubly salient poles introduce a torque ripple in its output which leads to deteriorated performance on speed control. In this proposed work, torque ripple reduction and speed control of SRM is implemented, utilizing an asymmetrical converter with PI-PWM controller with the aid of Bio-inspired algorithms. By utilizing the best value of flux, torque ripple and integral square error of speed and settling times, controller design is performed. The proposed research work compares three optimization algorithms namely Crow Search Algorithm, an Improved Ant Lion Optimization Algorithm and Modified Chaotic Starling Particle Swarm technique to control the speed and torque reduction of SRM in aerospace applications. To obtain the optimal parameter values, optimization techniques are introduced and the optimized controller results are compared with other conventional controller results. In normal operation, the engine operates with two phases simultaneously, but it is modelled to meet the load specification, which is single and double phase faulty. Detection of fault gives a great outcome in control of an electrical drive system. Reduction of faulty operation time leads to better motor lifetime that is obtained by early detection of a fault. This paper presents how the five-phase switched reluctance motor is designed to meet the needs of flap actuators in mid-sized aircraft. Electrical systems are modelled to provide the right functionality at the right time in advanced aircraft. However, requirement of power for the landing gear and secondary flight control only a short duration. The system is powered on and off as required, thus preserving power. Control performance and fault analysis were verified by the results of the MATLAB simulation. Experiments have been carried out more effectively to compare the results obtained with those of simulations.

Limited information is available regarding youth-onset diabetes in Mali. We investigated demographic, clinical, biochemical, and genetic features in new diabetes cases in children and adolescents.The study was conducted at Hôpital du Mali in Bamako. A total of 132 recently-diagnosed cases21 years were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, glutamic acid decarboxylase-65 (GAD-65) and islet antigen-2 (IA2) autoantibodies) were assessed. DNA was genotyped for HLA-DRB1 using high-resolution genotyping technology.A total of 130 cases were clinically diagnosed as type 1 diabetes (T1D), one with type 2 diabetes (T2D), and one with secondary diabetes. A total of 66 (50.8%) T1D cases were males and 64 (49.2%) females, with a mean age at diagnosis of 13.8 ± 4.4 years (range 0.8-20.7 years) peak onset of 15 years. 58 (44.6%) presented in diabetic ketoacidosis; with 28 (21.5%) IA2 positive, 76 (58.5%) GAD-65 positive, and 15 (11.5%) positive for both autoantibodies. HLA was also genotyped in 195 controls without diabetes. HLA-DRB1 genotyping of controls and 98 T1D cases revealed that DRB1*03:01, DRB1*04:05, and DRB1*09:01 alleles were predisposing for T1D (odds ratios [ORs]: 2.82, 14.76, and 3.48, p-values: 9.68E-5, 2.26E-10, and 8.36E-4, respectively), while DRB1*15:03 was protective (OR = 0.27; p-value = 1.73E-3). No significant differences were observed between T1D cases with and without GAD-65 and IA2 autoantibodies. Interestingly, mean C-peptide was 3.6 ± 2.7 ng/ml (1.2 ± 0.9 nmol/L) in T1D cases at diagnosis.C-peptide values were higher than expected in those diagnosed as T1D and autoantibody rates lower than in European populations. It is quite possible that some cases have an atypical form of T1D, ketosis-prone T2D, or youth-onset T2D. This study will help guide assessment and individual management of Malian diabetes cases, potentially enabling healthier outcomes.

Image-guided percutaneous ablation is an accepted treatment modality for common adult cancers. Unfortunately, its use in patients younger than 18 years is rare. This retrospective review presents our series of pediatric patients treated with ablation at our institution. From January 2002 to December 2021, a total of 14 patients (17 lesions) younger than 18 years were treated with percutaneous image-guided ablation. Estimated overall survival at 5 years was 58%; median survival of this group was not reached. Estimated local tumor progression-free survival at 5 years was 62%. One major complication was recorded.

Repeated social interactions with conspecifics and/or heterospecifics during early development may drive the differentiation of behaviour among individuals. This behavioural differentiation may occur through individuals behaving more different from each other on average and/or individuals behaving more consistently. Competition is a major form of social interaction and its impacts can depend on whether interactions occur between conspecifics or heterospecifics and the directionality of a response could be specific to different behavioural traits. To test this, we reared tungara frog tadpoles (Engystomops pustulosus) either in isolation, with a conspecific tadpole or with an aggressive heterospecific tadpole, the whistling frog tadpole, Leptodactylus fuscus. In each treatment, we measured the body size, activity, exploration and risk taking in the presence of a predator in focal E. pustulosus tadpoles six times during development. We used univariate and multivariate hierarchical mixed effect models to investigate the effect of treatment on mean behaviour and on among individual variance between and within individuals across behavioural traits. There was a strong effect of competition on behaviour, with different population and individual level responses across social treatments. Within their home tank, individuals were more consistent in their movements under conspecific competition but heterospecific competition caused more variance in the average movement among individuals. Behavioural responses were also trait specific as conspecific competition caused greater variability in movements among individuals in a novel environment. The results highlight that the impact of competition on inter-individual differences in behaviour is dependent on competitor species identity and is trait specific.

The blood-brain barrier (BBB) consists of a tight network of blood capillaries in the brain that separate the circulatory system from the central nervous system. Its particular properties are based on the dynamic interaction between cerebral endothelial cells and other surrounding cells, especially astrocytes. We have designed and synthesized a three-dimensional scaffold that recapitulates the main hallmarks of the BBB extracellular matrix and serves as a platform to co-culture human brain microvascular endothelial cells and human cortical astrocytes. The scaffold can be exposed to flow, thereby allowing the study of flow-mediated pathways at the BBB.