Functional Variation Research Articles

Divergent selection in a Mediterranean pine on local spatial scales

Abstract The effects of selection on an organism's genome are hard to detect on small spatial scales, as gene flow can swamp signatures of local adaptation. Therefore, most genome scans to detect signatures of environmental selection are performed on large spatial scales; however, divergent selection on the local scale (e.g. between contrasting soil conditions) has also been demonstrated, in particular for herbaceous plants. Here, we hypothesised that in topographically complex landscapes, microenvironment variability is strong enough to leave a selective footprint in the genomes of long‐lived organisms. To test this, we investigated paired south‐ versus north‐facing Pinus pinaster stands on the local scale, with trees growing in close vicinity (≤820 m distance between paired south‐ and north‐facing stands), in a Mediterranean mountain area. While trees on north‐facing slopes experience less radiation, trees on south‐facing slopes suffer from especially harsh conditions, particularly during the dry summer season. Two outlier analyses consistently revealed five putatively adaptive loci (out of 4034), in candidate genes two of which encoded non‐synonymous substitutions. Additionally, one locus showed consistent allele frequency differences in all three stand pairs indicating divergent selection despite high gene flow on the local scale. Permutation tests demonstrated that our findings were robust. Functional annotation of these candidate genes revealed biological functions related to abiotic stress response, such as water availability, in other plant species. Synthesis. Our study highlights how divergent selection in heterogeneous microenvironments shapes and maintains the functional genetic variation within populations of long‐lived forest tree species, being the first to focus on adaptive genetic divergence between south‐ and north‐facing slopes within continuous forest stands. This is especially relevant in the current context of climate change, as this variation is at the base of plant population responses to future climate.

Revealing associations between spatial time series trends of COVID-19 incidence and human mobility: an analysis of bidirectionality and spatiotemporal heterogeneity

BackgroundUsing human mobility as a proxy for social interaction, previous studies revealed bidirectional associations between COVID-19 incidence and human mobility. For example, while an increase in COVID-19 cases may affect mobility to decrease due to lockdowns or fear, conversely, an increase in mobility can potentially amplify social interactions, thereby contributing to an upsurge in COVID-19 cases. Nevertheless, these bidirectional relationships exhibit variations in their nature, evolve over time, and lack generalizability across different geographical contexts. Consequently, a systematic approach is required to detect functional, spatial, and temporal variations within the intricate relationship between disease incidence and mobility.MethodsWe introduce a spatial time series workflow to investigate the bidirectional associations between human mobility and disease incidence, examining how these associations differ across geographic space and throughout different waves of a pandemic. By utilizing daily COVID-19 cases and mobility flows at the county level during three pandemic waves in the US, we conduct bidirectional Granger causality tests for each county and wave. Furthermore, we employ dynamic time warping to quantify the similarity between the trends of disease incidence and mobility, enabling us to map the spatial distribution of trends that are either similar or dissimilar.ResultsOur analysis reveals significant bidirectional associations between COVID-19 incidence and mobility, and we develop a typology to explain the variations in these associations across waves and counties. Overall, COVID-19 incidence exerts a greater influence on mobility than vice versa, but the correlation between the two variables exhibits a stronger connection during the initial wave and weakens over time. Additionally, the relationship between COVID-19 incidence and mobility undergoes changes in direction and significance for certain counties across different waves. These shifts can be attributed to alterations in disease control measures and the presence of evolving confounding factors that differ both spatially and temporally.ConclusionsThis study provides insights into the spatial and temporal dynamics of the relationship between COVID-19 incidence and human mobility across different waves. Understanding these variations is crucial for informing the development of more targeted and effective healthcare policies and interventions, particularly at the city or county level where such policies must be implemented. Although we study the association between mobility and COVID-19 incidence, our workflow can be applied to investigate the associations between the time series trends of various infectious diseases and relevant contributing factors, which play a role in disease transmission.

A novel viscoelastic fractional damage model of thermosetting polymers for dynamic responses

Thermosets-polymeric materials play a key role in the modern plastics and polymers composites, which are increasingly used in the areas subject to dynamic loading condition. The materials will experience an amount of micro-damage under such circumstances, while the damage softening behaviors cannot be well captured by viscoelastic or elasto-viscoplastic constitutive models. In this paper, a viscoelastic fractional damage model depended on strain rate is formulated to depict the dynamic responses of thermosetting polymers. A dynamic damage evolution law related to strain and strain rate is developed by means of the fractional calculus. The relationship between fractional order and damage evolution for materials is theoretically investigated. It is observed that the fractional order can be able to characterize the intensity of damage evolution, and the variation of order function is in line with the evolution with damage of material properties. The model applicability is verified by the compressive loading experimental data under different strain rates and temperatures of thermosets. The influences of temperatures on the proposed model and the damage evolution are analyzed by the fitting results. Furthermore, a corresponding thermo-viscoelastic model is developed by considering the temperature effect, of which the predictive ability is tested and the comparisons with the existing model are also presented. The results indicate the proposed model can better capture the stress-strain responses over a wider range of strain.

Plant functional composition as an effective surrogate for biodiversity conservation

In biodiversity conservation frameworks, determining surrogates for biodiversity is crucial for improving the effectiveness of biodiversity conservation and management. As plant functional composition can indicate variations in ecosystem functions and services, it could be used as an effective surrogate in biodiversity conservation planning. However, to the best of our knowledge, this metric has been rarely used in biodiversity conservation planning. To explore whether plant functional composition can be used as an effective surrogate for biodiversity conservation, we used a linear mixed regression model to investigate the relationships between plant functional composition (i.e., community-weighted means (CWMs) from the sPlot database) and the species richness of birds, mammals, and amphibians, and between plant functional composition and terrestrial conservation priority ranks (considering biodiversity conservation alone, or biodiversity, carbon, and water conservation together). Thereafter, we quantified the changing trends in these relationships across biomes using the least square method. We found that CWMs significantly affected species richness and terrestrial conservation priority ranks, based on the marginal R2 and conditional R2 values from the linear mixed regression model. Further, CWMs significantly affected species richness and terrestrial conservation priority ranks across different biomes of forests and shrublands. However, the nature of these effects (i.e., positive or negative) was dependent on biome type. These results suggest that functional composition can be considered as a biodiversity surrogate for conservation planning, and that biome-specific relationships should be considered.

Resilience among children in foster care: Variability in adaptive functioning and associated factors

ObjectiveVariability in adaptation is common among children exposed to early adversity, with a proportion of this group demonstrating adaptive functioning or resilience. The present study aimed to explore variability in adaptive functioning in social competence, mental health, and school adjustment in a sample of children in foster care, and to assess which factors differentiated resilient children (i.e., showing adaptive functioning across domains) from those who were not resilient. MethodWe assessed 45 children in foster care aged between 4 and 9 years. The analysis was conducted from a multi-method, multi-informant perspective and included domains of functioning or competence (social competence, mental health, and school adjustment), distal factors (adversity and placement factors), and proximal psychological factors (behavioral regulation, emotion understanding, and attachment representations). Following a threshold approach, children were categorized as showing positive or negative outcomes in each domain. Results17 (37.8 %) foster children were found to have positive outcomes in all three domains, whereas 14 (31.1 %) had only one or no positive outcomes. Resilient foster children displayed greater behavioral regulation than the rest of the foster children. ConclusionsThere is great heterogeneity in adjustment among foster children, with a substantial proportion well-adjusted across domains and almost one-third displaying difficulties in two domains or more. Consequently, the available support and interventions for foster families should correspond to this varying level of needs. Behavioral regulation seems a promising intervention target for promoting resilience among children in foster care.

Bounded variation of functions defined on a convex and compact set in the plane

In this paper, the variation of functions has been defined, whose domain is a convex and compact set in the plane. Furthermore, in addition to presenting properties that satisfy this variation, the vector space formed by functions with finite variation is studied, demonstrating that it is a Banach space and its elements can be expressed as the difference of non-decreasing functions.

Cardiac human bitter taste receptors contain naturally occurring variants that alter function

Bitter taste receptors (T2R) are a subfamily of G protein-coupled receptors that enable humans to detect aversive and toxic substances. The ability to discern bitter compounds varies between individuals and is attributed mainly to naturally occurring T2R polymorphisms. T2Rs are also expressed in numerous non-gustatory tissues, including the heart, indicating potential contributions to cardiovascular physiology. In this study. T2Rs that have previously been identified in human cardiac tissues (T2Rs – 10, 14, 30, 31, 46 and 50) and their naturally occurring polymorphisms were functionally characterised. The ligand-dependent signaling responses of some T2R variants were completely abolished (T2R30 Leu252 and T2R46 Met228), whereas other receptor variants had moderate changes in their maximal response, but not potency, relative to wild type. Using a cAMP fluorescent biosensor, we reveal the productive coupling of T2R14, but not the T2R14 Phe201 variant, to endogenous Gαi. Modeling revealed that these variants resulted in altered interactions that generally affected ligand binding (T2R30 Leu252) or Gα protein interactions (T2R46 Met228 and T2R14 Phe201), rather than receptor structural stability. Interestingly, this study is the first to show a difference in signaling for T2R50 Tyr203 (rs1376251) which has been associated with cardiovascular disease. The observation of naturally occurring functional variation in the T2Rs with the greatest expression in the heart is important, as their discovery should prove useful in deciphering the role of T2Rs within the cardiovascular system.

Variationally mimetic operator networks

In recent years operator networks have emerged as promising deep learning tools for approximating the solution to partial differential equations (PDEs). These networks map input functions that describe material properties, forcing functions, and boundary data to the solution of a PDE. This work describes a new architecture for operator networks, called the variationally mimetic operator network (VarMiON ), that mimics the form of the numerical solution obtained from an approximate variational or weak formulation of the problem. Like the conventional Deep Operator Network (DeepONet) the VarMiON is also composed of a sub-network that constructs the basis functions for the output and another that constructs the coefficients for these basis functions. However, in contrast to the DeepONet, the architecture of these sub-networks in the VarMiON is precisely determined. An analysis of the error in the VarMiON solution reveals that it contains contributions from the error in the training data, the training error, the quadrature error in sampling input and output functions, and a “covering error” that measures the distance between the test input functions and the nearest functions in the training dataset. It also depends on the stability constants for the exact solution operator and its VarMiON approximation. The application of the VarMiON to a canonical elliptic PDE and a nonlinear PDE reveals that for approximately the same number of network parameters, on average the VarMiON incurs smaller errors than a standard DeepONet and a recently proposed multiple-input operator network (MIONet). Further, its performance is more robust to variations in input functions, the techniques used to sample the input and output functions, the techniques used to construct the basis functions, and the number of input functions. Moreover, it consistently outperforms baseline methods at various dataset sizes. The data and code accompanying this manuscript are publicly available at https://github.com/dhruvpatel108/VarMiON.

Response of soil health index to untreated wastewater irrigation in selected farms under different vegetable types

Crop irrigation with wastewater has drawn global attention in water-scarce areas as a strategy to offset water scarcity. However, the response of soil ecosystem functioning and soil health to long-term and continuous wastewater (WW) irrigation has not been well-understood. A total of 12 vegetable farms irrigated with WW and fresh water (FW) were analyzed to assess WW irrigation impacts on soil health using the minimum data set (MDS) and soil health index (SHI) framework. We determined the combination of soil physicochemical, nutritional, and biological indicators (22 soil indicators) along with linear SHI (L- SHI) and nonlinear SHI (NL- SHI) quantification approaches in the WW-irrigated fields versus the FW-irrigated fields. Significant changes were observed in most soil attributes in the WW-irrigated farms versus the FW-irrigated farms. These changes could mostly improve soil health (e.g., soil stability index, exchangeable cations, organic matter (OM), total N, and available P), but some of them have a degrading effect on soil health (e.g., electrical conductivity (EC), sodium absorption ratio (SAR), and heavy metals). Soil health indicators identified through the MDS approach were clay, EC, OM, exchangeable K, Pb, and soil microbial respiration, contributing to the SHI value by 40.6%, 40.6%, 23.8%, 23.8%, 20.8%, and 14.9%, respectively. The SHI values computed through the non-linear scoring technique were more sensitive to WW irrigation than those computed through the linear scoring technique, suggesting that NL- SHI would outperform L- SHI in representing variations in soil functions. The L- SHI and NL- SHI values were 17–31% and 21–32% higher in the WW-irrigated farms than in the FW-irrigated farms, respectively, suggesting a good improvement in soil capacity and functions after WW irrigation. To conclude, our results revealed that an integrated SHI, particularly NL- SHI, would be more instrumental for evaluating post-WW irrigation soil functions and soil health in the WW-affected croplands than single soil indicators.

The Impact of the Free-floating Planet Mass Function on the Event Rate for Accurate Microlensing Parallax Determination: Application to Euclid and Roman Parallax Observation

A microlensing event is mainly used to search for free-floating planets (FFPs). To estimate the FFP mass and distance via the microlensing effect, a microlensing parallax is one of the key parameters. A short duration of FFP microlensing makes it difficult to yield a parallax by the observer’s motion at a recognizable level, so the FFP microlensing parallax is expected on the simultaneous observation by multiple telescopes. Here, we approach the FFP detection by considering a variation in the FFP mass functions and the event rate of accurately measured microlensing parallaxes. We used our FFP microlensing simulator assuming a parallax observation between upcoming space-based missions (Euclid and Roman) with full kinematics. As a result, we confirmed that the event rate of accurately measured microlensing parallaxes (i.e., within a factor of 2 uncertainty) does not simply follow the number of FFPs at a given mass but the ratio of the FFP population per star. This is because the population ratio determines the optical depth for a given mass and potential sources. In addition, we found that the probability of the event that can estimate the FFP mass and distance within a factor of 2 is not so high: ∼40% of Earth-mass, ∼16% of Neptune-mass, and ∼4% of Jupiter-mass FFP events under our criteria. The probability can be improved by some technical approach such as using high cadence and observation in parallax of more than two observers.

Divergences in stem and leaf traits between lianas and coexisting trees in a subtropical montane forest

Abstract Patterns in functional trait variation associated with the ecological strategies of lianas and trees in subtropical montane forests remain poorly understood due to lack of trait comparisons. Here, we filled this gap by investigating trait divergence between lianas and trees with different leaf habits for 13 traits of 33 species (7 deciduous and 4 evergreen liana species, and 10 deciduous and 12 evergreen tree species) in a subtropical montane forest in southwestern China. We found that lianas had significantly larger stem xylem vessel diameter, higher theoretical hydraulic conductivity, specific leaf area, leaf nitrogen, and phosphorus concentrations, but lower leaf dry-matter content and N/P ratio than sympatric trees, indicating that lianas employ an acquisitive ecological strategy, with a more efficient stem hydraulic system and more productive leaves. In contrast to trees, lianas exhibited a larger variation in vessel diameter, with a few wide and many narrow vessels in the xylem, indicating a greater vessel dimorphism. Growth form explained 48.7% of the total trait variation, while leaf habit only explained 3.8% of trait variation, without significant interaction between growth form and leaf habit. In addition, significant stem–leaf trait relationships were only found in trees, but not in lianas, indicating decoupling of stem hydraulic function and leaf traits in subtropical lianas. These results suggest that subtropical montane lianas and trees differ strikingly in stem and leaf functional traits. Further studies are warranted to strengthen our understanding of the mechanisms underlying the strong divergence in ecological strategies between lianas and trees in subtropical forest ecosystems.

A Universal Heat Semigroup Characterisation of Sobolev and BV Spaces in Carnot Groups

Abstract In sub-Riemannian geometry there exist, in general, no known explicit representations of the heat kernels, and these functions fail to have any symmetry whatsoever. In particular, they are not a function of the control distance, nor they are for instance spherically symmetric in any of the layers of the Lie algebra. Despite these unfavourable aspects, in this paper we establish a new heat semigroup characterisation of the Sobolev and $BV$ spaces in a Carnot group by means of an integral decoupling property of the heat kernel.

Normal Variations in Upper Esophageal Sphincter Function During Deglutition: A Secondary Analysis of Videofluoroscopic Data.

Cricopharyngeal dysfunction is a common potential cause of pharyngoesophageal dysphagia. Contextual factors (i.e., personal demographics and bolus properties) appear to impact upper esophageal sphincter (UES) function but have yet to be assessed collectively in a large-scale study using psychometrically sound swallow task procedures. Using a standardized and validated videofluoroscopic approach, we investigated the collective effects of age, sex, and swallow task on UES opening duration (UESOdur) and UES maximum distension (UESmax) in a large sample of healthy adults. UESOdur and UESmax data were analyzed from existing videofluoroscopic images of 195 healthy adults (21-89 years old) across seven swallow tasks (thin liquid to viscous liquids, puree, and a solid). Generalized estimating equation modeling captured the effects of the aforementioned contextual factors (α = 0.05). UESOdur significantly increased with age, while UESmax had an inverse relationship. Females had significantly wider UESmax. UESOdur of 5 mL thin liquid was significantly shorter than all other liquid swallow tasks, while solid had an inverse effect. Compared to 5 mL thin liquid, all other swallow tasks resulted in significantly wider UESmax. Mildly and moderately thick liquid significantly increased UESOdur when isolating viscosity. UESmax was significantly wider with mildly and moderately thick liquid and puree than thin liquid. When isolating volume, cup sip thin liquid increased both measures significantly relative to 5 mL. Age, sex, and swallow task can influence the normal timing and extent of UES movement. These collective effects contribute to normal variability in UES function and should be considered for clinical decision-making. 4 Laryngoscope, 134:2306-2315, 2024.

Convergence in Total Variation for nonlinear functionals of random hyperspherical harmonics

Random hyperspherical harmonics are Gaussian Laplace eigenfunctions on the unit d-dimensional sphere (d≥2). We study the convergence in Total Variation distance for their nonlinear statistics in the high energy limit, i.e., for diverging sequences of Laplace eigenvalues. Our approach takes advantage of a recent result by Bally, Caramellino and Poly (2020): combining the Central Limit Theorem in Wasserstein distance obtained by Marinucci and Rossi (2015) for Hermite-rank 2 functionals with new results on the asymptotic behavior of their Malliavin-Sobolev norms, we are able to establish second order Gaussian fluctuations in this stronger probability metric as soon as the functional is regular enough. Our argument requires some novel estimates on moments of products of Gegenbauer polynomials that may be of independent interest, which we prove via the link between graph theory and diagram formulas.

Despite genetic isolation in sympatry, post-copulatory reproductive barriers have not evolved between bat- and human-associated common bedbugs (Cimex lectularius L.)

BackgroundThe common bedbug Cimex lectularius is a widespread ectoparasite on humans and bats. Two genetically isolated lineages, parasitizing either human (HL) or bat (BL) hosts, have been suggested to differentiate because of their distinct ecology. The distribution range of BL is within that of HL and bedbugs live mostly on synanthropic bat hosts. This sympatric co-occurrence predicts strong reproductive isolation at the post-copulatory level.ResultsWe tested the post-copulatory barrier in three BL and three HL populations in reciprocal crosses, using a common-garden blood diet that was novel to both lineages. We excluded pre-copulation isolation mechanisms and studied egg-laying rates after a single mating until the depletion of sperm, and the fitness of the resulting offspring. We found a higher sperm storage capability in BL, likely reflecting the different seasonal availability of HL and BL hosts. We also observed a notable variation in sperm function at the population level within lineages and significant differences in fecundity and offspring fitness between lineages. However, no difference in egg numbers or offspring fitness was observed between within- and between-lineage crosses.ConclusionsDifferences in sperm storage or egg-laying rates between HL and BL that we found did not affect reproductive isolation. Neither did the population-specific variation in sperm function. Overall, our results show no post-copulatory reproductive isolation between the lineages. How genetic differentiation in sympatry is maintained in the absence of a post-copulatory barrier between BL and HL remains to be investigated.

Genetic analysis of pericarp pigmentation variation in Corn Belt dent maize.

The US standard for maize commercially grown for grain specifies that yellow corn can contain at maximum 5% corn of other colors. Inbred parents of commercial hybrids typically have clear pericarp, but transgressive segregants in breeding populations can display variation in pericarp pigmentation. We identified 10 doubled haploid biparental populations segregating for pigmented pericarp and evaluated qualitative genetic models using chi-square tests of observed and expected frequencies. Pigmentation ranged from light to dark brown color, and pigmentation intensity was quantitatively measured across 1,327 inbred lines using hue calculated from RGB pixel values. Genetic mapping was used to identify loci associated with pigmentation intensity. For 9 populations, pigmentation inheritance best fit a hypothesis of a 2- or 3-gene epistatic model. Significant differences in pigment intensity were observed across populations. W606S-derived inbred lines with the darkest pericarp often had clear glumes, suggesting the presence of a novel P1-rw allele, a hypothesis supported by a significant quantitative trait locus peak at P1. A separate quantitative trait locus region on chromosome 2 between 221.64 and 226.66 Mbp was identified in LH82-derived populations, and the peak near p1 was absent. A genome-wide association study using 416 inbred lines from the Wisconsin Diversity panel with full genome resequencing revealed 4 significant associations including the region near P1. This study supports that pericarp pigmentation among dent maize inbreds can arise by transgressive segregation when pigmentation in the parental generation is absent and is partially explained by functional allelic variation at the P1 locus.

Interactional metadiscourse in expert and student disciplinary writing: Exploring intrageneric and functional variation

Recent critical inquiries in metadiscourse research call into question the functional inadequacy of a word-based lexical approach. To account more fully the functional affordances of metadiscoursal features in academic writing, this paper examines the Interactional Metadiscourse, namely hedges, boosters, attitude markers and self-mentions based on a 2.64-million-word corpus of L1-English expert and L1-Chinese student writing in Agricultural Science. Through an intra-generic lens, we found a significant effect of part-genre on the use of all four target categories for both writer groups; and L1-English experts employed significantly more hedges than L2 students while L2 students used significantly more boosters and attitude markers. Functionally, both groups shared a largely similar deployment of functional subtypes across part-genres with L1-English experts outperforming L2 students only in one function: ‘stating a goal or purpose’ in self-mentions. Subsequent qualitative discourse-functional analyses at part-genre level between two writer groups explained some student-produced discipline-inappropriate metadiscoursal choices. This paper concludes with resources for a rigorous coding development, and implications for teaching metadiscourse to disciplinary writers with an emphasis on using available discipline-specific corpora to understand how functional taxonomizations of IM interface with socio-rhetorical contexts in disciplinary writing.

Longitudinal assessment of coronary microvascular dysfunction in an all-comer patient population detects the highly dynamic natural history of this condition

Abstract Introduction Coronary microvascular dysfunction (CMD) is a common condition contributing to heterogenous cardiac diseases, such as myocardial ischemia and heart failure. However, little is known regarding the natural history of CMD, as most studies assessing this condition were performed cross-sectionally. Therefore, we investigated the evolution over time of microvascular function in an all-comer population, to assess the natural history of CMD. Methods 273 patients undergoing elective coronary angiography at two timepoints at least 6 months apart were included; average time between the two coronary angiographies was 34±21 months. Microvascular function was measured retrospectively by means of angiography-based index of microvascular resistance (aIMR) at both timepoints in the same vessel (LAD in 93.4% of cases, LCx in 1.5%, RCA in 4.8%), in order to assess variation of microvascular function over time. An aIMR ≥25 was considered indicative of CMD. Results Of the included 273 patients, 107 presented CMD at inclusion (39.2%); average aIMR at baseline was 23.2±8.0. At the second timepoint, after an average of 34±21 months, average aIMR was significantly increased compared to baseline (24.4±8.6, p=0.013). Interestingly, in spite of an overall increased average aIMR expressing a tendentially worsening microvascular function over time, of the 107 patients with CMD at inclusion only 61 (22.3% of the total population) still presented CMD at follow-up. On the contrary, 46 patients with CMD at inclusion (16.8%) showed an improved coronary microvascular function with an aIMR<25. On the other hand, 60 patients (22.0%) with initially normal aIMR developed de novo CMD at control angiography. Conclusion In our study longitudinally assessing CMD in an all-comer population, we could show that average microvascular function shows a mild overall worsening over time. However, our data show that CMD is a highly dynamic condition with high rates of improvement and worsening over time. The assessment of the clinical predictors of these variations may shed further light on the still incompletely understood pathogenesis of CMD and mainly on its natural history.

Long-term efficacy of tailored prolonged immunosuppressive therapy in biopsy-proven virus- negative myocarditis: a single center propensity weighted study

Abstract Background The efficacy of immunosuppressive therapy (IT) in biopsy-proven (BP) myocarditis was proved by small trials in lymphocytic myocarditis with heart failure (HF) presentation. Aim To evaluate the efficacy of IT in a single center cohort of BP myocarditis patients, irrespective of histological type and clinical presentation. Methods Consecutive BP myocarditis patients were included and, in the absence of contraindications, were treated with IT according to current guidelines on top of standard care. IT patients were compared with a propensity score-weighted control group of non-IT patients, considering age, gender, ejection fraction (EF), NYHA class and histological type (Fig. 1A). The primary outcome was a composite of death or heart transplant (HTx), and the secondary outcome a composite of variation of biventricular function, NYHA class and myocarditis relapse. Results 87 IT patients were compared with 265 without IT. IT patients were older (44 vs 39 years, p=0.035), and more frequently had a systemic immune-mediated disease (34% vs 10%, p<0.001), and HF (59% vs 46%, p=0.048) or fulminant presentation (9% vs 2 %, p=0.002). IT patients had lower baseline left ventricular (LV) EF both on echocardiography (35±15% vs 43±15%, p=0.001) and cardiac magnetic resonance (26±16 % vs 45.5±15 %, p=0.0013), lower right ventricular (RV) fractional area change (FAC: 34±11 % vs 41±11 %, p<0.001) and higher frequency of lymphocytic, eosinophilic and giant cell myocarditis (71% vs 58%, 11% vs 1 %, and 7% vs 2%, p<0.001 respectively) compared to non IT patients. IT was indicated because of unremitting HF (62%) and recurrent chest pain (14%), and mainly involved prednisone (PDN) and azathioprine as first-line (61%) and PDN and mycophenolate mofetil as second-line therapy (62%). IT lasted on average 24 months. No difference was observed in the primary outcome between the two groups (5 years survival 88% in IT vs 91% in non-IT patients, p=0.8, Fig. 1B), while relapse incidence was higher in IT patients (p<0.001, Fig.2B). At long-term follow up (54 months, IQR 21.4-96.45), LVEF and RV FAC were within the normal range in both groups, and propensity score weighting analysis showed that IT patients presented LVEF values of only 3% lower than non-IT (p=0.013, Fig. 2). In addition, IT patients had a similar probability of presenting the same NYHA class as non-IT patients at last follow up (p=0.46). Conclusions Our study shows for the first time the efficacy of prolonged tailored IT in BP lymphocytic and non lymphocytic autoimmune myocarditis, with or without HF and with or without RV dysfunction. IT patients, despite having lower biventricular function and a higher risk profile at baseline as well as a higher frequency of relapses, at long-term follow up showed normalized biventricular function and a similar survival compared to their propensity-score weighted controls. Thus, autoimmune myocarditis responds to IT, even when the disease relapses.Figure 1.Figure 2.

AF in the AFternoon: The circadian pattern of incident atrial fibrillation in a loop recorder population

Abstract Introduction Loop recorders have provided the opportunity to systematically screen individuals for arrhythmias, and in doing so provide new appreciated mechanistic insights to arrhythmia pathophysiology. Atrial fibrillation (AF) is a complex arrhythmia with a multitude of precipitants and substrates. Previous studies looking at the circadian rhythm of AF, have required patient symptoms to define onset. All studies on the circadian rhythm of AF suggest that AF does not occur randomly. It has been suggested that the circadian variation in autonomic function may provide an underlying substrate for AF initiation. This is the largest study to utilise loop recorder detected AF to explore the circadian pattern of AF. Purpose We sought to ascertain how the detection of incident AF varied throughout the day, in patients monitored with a loop recorder Methods This was a single-centre retrospective observational study. Consecutive adult patients referred for ILR implantation between March 2009 and November 2019, without prevalent AF or atrial flutter, were included. Demographic and anthropometric data was identified from the individuals medical notes. The time of incident AF episodes was identified from loop recorder reports. Results A total of 1168 AF episodes of any duration were identified by the ILR, of which onset time was available for 1118 episodes. Onset of AF episodes in our data for the entire population demonstrated a monophasic distribution (figure 1a). The OR for developing AF between 13.00-14.59 compared to 03.00-04.59 was 4.89 (95% CI 3.47-6.90). Amongst the ESUS population time of onset distribution showed multiple daytime peaks (figure 1b). The OR for developing AF between 10.00-11.59 compared to 03.00-04.59 was 4.39 (95% CI 2.68-7.20). Amongst the non- ESUS population time of onset distribution (figure 1c) shows a monophasic pattern with the peak at time blocks 12.00-14.59. The OR for developing AF between 13.00-14.59 compared to 02.00-03.59 was 6.75 (95% CI 4.17-10.93). Conclusion(s) Our study demonstrated that there is a diurnal variation for incident AF detection using a loop recorder. There is a general propensity for episodes to occur in the afternoon, with a nadir at night. This is in contrast to previous reports which have suggested that the nocturnal and morning peaks are more apparent. Moreover, different cohorts appear to show different temporal patterns, with ESUS patients having multiple time peaks, whereas the non-stroke cohort had a solitary peak period. Understanding the diurnal variation of AF may help to shed more light on the complex pathogenesis of AF, and whether different AF phenotypes are associated with stroke risk. Moreover, the finding of a day-time propensity for AF, adds weight to the utilisation of consumer facing non-invasive monitoring tools during the day for AF identification in high-risk populations.