Biology subjects

Martin, C.

Publications and source records attributed to Martin, C..

126 records · Page 7Linked to original sources

bioRxiv2018

Speed breeding in growth chambers and glasshouses for crop breeding and model plant research

1.To meet the challenge of feeding a growing population, breeders and scientists are continuously looking for ways to increase genetic gain in crop breeding. One way this can be achieved is through \"speed breeding\" (SB), which shortens the breeding cycle and accelerates research studies through rapid generation advancement. The SB method can be carried out in a number of ways, one of which involves extending the duration of a plants daily exposure to light (photoperiod) combined with early seed harvest in order to cycle quickly from seed to seed, thereby reducing the generation times for some long-day (LD) or day-neutral crops. Here we present glasshouse and growth chamber-based SB protocols with supporting data from experimentation with several crop species. These protocols describe the growing conditions, including soil media composition, lighting, temperature and spacing, which promote rapid growth of spring and winter bread wheat, durum wheat, barley, oat, various members of the Brassica family, chickpea, pea, grasspea, quinoa and the model grass Brachypodium distachyon. Points of flexibility within the protocols are highlighted, including how plant density can be increased to efficiently scale-up plant numbers for single seed descent (SSD) purposes. Conversely, instructions on how to perform SB on a small-scale by creating a benchtop SB growth cabinet that enables optimization of parameters at a low cost are provided. We also outline the procedure for harvesting and germinating premature wheat, barley and pea seed to reduce generation time. Finally, we provide troubleshooting suggestions to avoid potential pitfalls.

plant biology↗

bioRxiv2018

Mammalian vesicular glutamate transporter VGLUT1 reduces synaptic vesicle superpool size and spontaneous release frequency.

Glutamate secretion at excitatory synapses is tightly regulated to allow for the precise tuning of synaptic strength. Vesicular Glutamate Transporters (VGLUT) accumulate glutamate into synaptic vesicles (SV) and thereby regulate quantal size. Further, the number of release sites and the release probability of SVs maybe regulated by the organization of active zone proteins and SV clusters. In the present work, we uncover a mechanism mediating an increased SV clustering through a tripartite interaction of VGLUT1, endophilinA1 and intersectin1. This strengthening of SV clusters results in a combined reduction of axonal SV super-pool size and miniature excitatory events frequency. Our findings support a model in which clustered vesicles are held together through multiple weak interactions between SH3 domains and proline rich sequences of synaptic proteins. In mammals, VGLUT1 gained a poly-proline sequence that recruits endophilinA1 and turns the transporter into a dual regulator of quantal release parameters at excitatory synapses.

neuroscience↗

bioRxiv2018

Can we obtain in vivo transmural mean hoop stress of the aortic wall without knowing patient-specific material properties and residual deformations?

It is well known that residual deformations/stresses alter the mechanical behavior of arteries, e.g. the pressure-diameter curves. In an effort to enable personalized analysis of the aortic wall stress, approaches have been developed to incorporate experimentally-derived residual deformations into in vivo loaded geometries in finite element simulations using thick-walled models. Solid elements are typically used to account for \"bending-like\" residual deformations. Yet, the difficulty in obtaining patient-specific residual deformations and material properties has become one of the biggest challenges of these thick-walled models. In thin-walled models, fortunately, static determinacy offers an appealing prospect that allows for the calculation of the thin-walled membrane stress without patient-specific material properties. The membrane stress can be computed using forward analysis by enforcing an extremely stiff material property as penalty treatment, which is referred to as the forward penalty approach. However, thin-walled membrane elements, which have zero bending stiffness, are incompatible with the residual deformations, and therefore, it is often stated as a limitation of thin-walled models. In this paper, by comparing the predicted stresses from thin-walled models and thick-walled models, we demonstrate that the transmural mean hoop stress is the same for the two models and can be readily obtained from in vivo clinical images without knowing the patient-specific material properties and residual deformations. Computation of patient-specific mean hoop stress can be greatly simplified by using membrane model and the forward penalty approach, which may be clinically valuable.

bioengineering↗

bioRxiv2018

Testing Darwin’s hypothesis about the most wonderful plant in the world: The Venus flytrap’s marginal spikes are a ‘horrid prison’ for moderate-sized insect prey

Botanical carnivory is a novel feeding strategy associated with numerous physiological and morphological adaptations. However, the benefits of these novel carnivorous traits are rarely tested. Here, we used field observations and lab experiments to test the prey capture function of the marginal spikes on snap traps of the Venus flytrap (Dionaea muscipula). Our field and laboratory results suggested surprisingly inefficient capture success: fewer than 1 in 4 prey encounters led to prey capture. Removing the marginal spikes decreased the rate of prey capture success for moderate-sized cricket prey by 90%, but this effect disappeared for larger prey. The nonlinear benefit of spikes suggests that they provide a better cage for capturing more abundant insects of moderate and small sizes, but may also provide a foothold for rare large prey to escape. Our observations support Darwins hypothesis that the marginal spikes form a horrid prison that increases prey capture success for moderate-sized prey, but the decreasing benefit for larger prey is unexpected and previously undocumented. Thus, we find surprising complexity in the adaptive landscape for one of the most wonderful evolutionary innovations among all plants. These findings further enrich our understanding of the evolution and diversification of novel trap morphology in carnivorous plants.

evolutionary biology↗

bioRxiv2018

Animacy and real world size shape object representations in the human medial temporal lobes

Identifying what an object is, and whether an object has been encountered before, is a crucial aspect of human behavior. Despite this importance, we do not have a complete understanding of the neural basis of these abilities. Investigations into the neural organization of human object representations have revealed category specific organization in the ventral visual stream in perceptual tasks. Interestingly, these categories fall within broader domains of organization, with distinctions between animate, inanimate large, and inanimate small objects. While there is some evidence for category specific effects in the medial temporal lobe (MTL), it is currently unclear whether domain level organization is also present across these structures. To this end, we used fMRI with a continuous recognition memory task. Stimuli were images of objects from several different categories, which were either animate or inanimate, or large or small within the inanimate domain. We employed representational similarity analysis (RSA) to test the hypothesis that object-evoked responses in MTL structures during recognition-memory judgments also show evidence for domain-level organization along both dimensions. Our data support this hypothesis. Specifically, object representations were shaped by either animacy, real-world size, or both, in perirhinal and parahippocampal cortex, as well as the hippocampus. While sensitivity to these dimensions differed when structures when probed individually, hinting at interesting links to functional differentiation, similarities in organization across MTL structures were more prominent overall. These results argue for continuity in the organization of object representations in the ventral visual stream and the MTL.

neuroscience↗

bioRxiv2018

A catalog of microbial genes from the bovine rumen reveals the determinants of herbivory

BackgroundThe rumen microbiota provides essential services to its host and, through its role in ruminant production, contributes to human nutrition and food security. A thorough knowledge of the genetic potential of rumen microbes will provide opportunities for improving the sustainability of ruminant production systems. The availability of gene reference catalogs from gut microbiomes has advanced the understanding of the role of the microbiota in health and disease in humans and other mammals. In this work, we established a catalog of reference prokaryote genes from the bovine rumen.\n\nResultsUsing deep metagenome sequencing we identified 13,825,880 non-redundant prokaryote genes from the bovine rumen. Compared to human, pig and mouse gut metagenome catalogs, the rumen is larger and richer in functions and microbial species associated with the degradation of plant cell wall material and production of methane. Genes encoding enzymes catalyzing the breakdown of plant polysaccharides showed a particularly high richness that is otherwise impossible to infer from available genomes or shallow metagenomics sequencing. The catalog expands by several folds the dataset of carbohydrate-degrading enzymes described in the rumen. Using an independent dataset from a group of 77 cattle fed 4 common dietary regimes, we found that only <0.1% of genes were shared by all animals, which contrast with a large overlap for functions, i.e. 63% for KEGG functions. Different diets induced differences in the relative abundance rather than the presence or absence of genes explaining the great adaptability of cattle to rapidly adjust to dietary changes.\n\nConclusionsThese data bring new insights into functions, carbohydrate-degrading enzymes and microbes of the rumen that is complementing the available information on microbial genomes. The catalog is a significant biological resource enabling deeper understanding of phenotypes and biological processes and will be expanded as new data is made available.

microbiology↗

bioRxiv2018

Proper chromosome alignment depends on BRCA2 phosphorylation by PLK1

The BRCA2 tumor suppressor protein is involved in the maintenance of genome integrity through its role in homologous recombination. In mitosis, BRCA2 is phosphorylated by Polo-like kinase 1 (PLK1). Here we describe how this phosphorylation contributes to the control of mitosis. We identified two highly conserved phosphorylation sites at S193 and T207 of BRCA2. Phosphorylated-T207 is a bona fide docking site for PLK1 as illustrated by the crystal structure of the BRCA2 peptide bound to PLK1 Polo-box domain. We found that BRCA2 bound to PLK1 forms a complex with the phosphatase PP2A and phosphorylated-BUBR1. Reducing BRCA2 binding to PLK1, as observed in BRCA2 breast cancer variants S206C and T207A, alters the tetrameric complex resulting in misaligned chromosomes, faulty chromosome segregation and aneuploidy. We thus reveal a direct role of BRCA2 in the alignment of chromosomes, distinct from its DNA repair function, with important consequences on chromosome stability. These findings may explain in part the aneuploidy observed in BRCA2-mutated tumors.

cell biology↗

bioRxiv2018

Design principles for TB vaccines’ clinical trials based on spreading dynamics

Tuberculosis (TB) is one of the most complex diseases from the perspective of mathematical epidemiology. Individuals recently infected with the bacillus Mycobacterium tuberculosis can either develop TB directly in a matter of several weeks, or enter into an asymptomatic latent TB infection state (LTBI) that only occasionally derives into active disease, sometimes even decades after the infection event. The possible interruptions that a vaccine might provoke on these two mechanisms are indistinguishable in phase II clinical trials. In this work, we present a new methodology that allows differentiating vaccines that slow down the progression to disease from vaccines that prevent it. By introducing a stochastic framework for simulating synthetic clinical trials based on transmission models, we show how the method proposed here contributes both to reduce uncertainty in vaccine characterization and impact forecasts as well as to assist the design of clinical trials, improving their probabilities of success.

epidemiology↗

bioRxiv2017

A complex performance landscape for suction-feeding reveals constraints and adaptations in a population of reef damselfish

The ability to predict how multiple traits interact in determining performance is key to understanding the evolution of complex functional systems. Similar to Simpsons adaptive landscape, which describes the fitness consequences of varying morphological traits, performance landscapes depict the performance consequences of varying morphological traits. Mapping the populations location with respect to the topographic features of the landscape could inform us on the selective forces operating on the traits that underlie performance. Here, we used a mechanistic model derived from first principles of hydrodynamics to construct a hypothetical performance landscape for zooplankton prey capture using suction feeding. We then used the landscape to test whether a population of Chromis viridis, a coral reef zooplanktivore, is located on a performance peak or ridge based on measurements of kinematic variables recorded in-situ during undisturbed foraging. Observed trait combinations in the wild population closely matched regions of high feeding performance in the landscape, however the population was not located on a local performance peak. This sub-optimal performance was not due to constraints stemming from the observed trait correlations. The predominant directions of variation of the phenotypic traits was tangent to the path of steepest ascent that points towards the local peak, indicating that the population does not reside on a \"performance ridge\". Rather, our analysis suggests that feeding performance is constrained by stabilizing selection, possibly reflecting a balance between selection on feeding performance and mechanical or genetic constraints.

evolutionary biology↗

bioRxiv2017

Sequential Super-Resolution Imaging using DNA Strand Displacement

Sequential labeling and imaging in fluorescence microscopy allows the imaging of multiple structures in the same cell using a single fluorophore species. In super-resolution applications, the optimal dye suited to the method can be chosen, the optical setup can be simpler and there are no chromatic aberrations between images of different structures. We describe a method based on DNA strand displacement that can be used to quickly and easily perform the labeling and removal of the fluorophores during each sequence. Site-specific tags are conjugated with unique and orthogonal single stranded DNA. Labeling for a particular structure is achieved by hybridization of antibody-bound DNA with a complimentary dye-labeled strand. After imaging, the dye is removed using toehold-mediated strand displacement, in which an invader strand competes off the dye-labeled strand than can be subsequently washed away. Labeling and removal of each DNA-species requires only a few minutes. We demonstrate the concept using sequential dSTORM super-resolution for multiplex imaging of subcellular structures.

bioengineering↗

bioRxiv2017

Speciation in sympatry with ongoing secondary gene flow and an olfactory trigger in a radiation of Cameroon cichlids

Whether speciation can happen in the absence of geographical barriers and if so, under which conditions, is a fundamental question in our understanding of the evolution of new species. Among candidates for sympatric speciation, Cameroon crater lake cichlid radiations have been considered the most compelling. However, it was recently shown that a more complex scenario than a single colonization followed by isolation underlies these radiations. Here, we perform a detailed investigation of the speciation history of a radiation of Coptodon cichlids from Lake Ejagham using whole-genome sequencing data. The existence of the Lake Ejagham Coptodon radiation is remarkable since this 0.5 km2 lake offers limited scope for divergence across a shallow depth gradient, disruptive selection is weak, the species are sexually monochromatic, yet assortative mating is strong. We infer that Lake Ejagham was colonized by Coptodon cichlids almost as soon as it came into existence 9,000 years ago, yet speciation events occurred only in the last 1,000-2,000 years. We show that secondary gene flow from a nearby riverine species has been ongoing, into ancestral as well as extant Lake Ejagham lineages, and we identify and date river-to-lake admixture blocks. One of these contains a cluster of olfactory receptor genes that introgressed close to the time of the first speciation event and coincides with a higher overall rate of admixture into the recipient lineages. Olfactory signaling is a key component of mate choice and species recognition in cichlids. A functional role for this introgression event is consistent with previous findings that assortative mating appears much stronger than ecological divergence in Ejagham Coptodon. We conclude that speciation in this radiation took place in sympatry, yet may have benefited from ongoing riverine gene flow.\n\nAuthor SummaryDespite an active search for empirical examples and much theoretical work, sympatric speciation remains one of the most controversial ideas in evolutionary biology. While a host of examples have been described in the last few decades, more recent results have shown that several of the most convincing systems have not evolved in complete isolation from allopatric populations after all. By itself, documenting the occurrence of secondary gene flow is not sufficient to reject the hypothesis of sympatric speciation, since speciation can still be considered sympatric if gene flow did not contribute significantly to the build-up of reproductive isolation. One way forward is to use genomic data to infer where, when and into which lineages gene flow occurred, and identify the regions of the genome that experienced admixture. In this study, we use whole-genome sequencing to examine one of the cichlid radiations from a small isolated Cameroon lake, which have long been the flagship example of sympatric speciation. We show that gene flow from a riverine species into the lake has been ongoing during the history of the radiation. In line with this, we infer that the lake was colonized very soon after it was formed, and argue that Lake Ejagham is not as isolated as previously assumed. The magnitude of secondary gene flow was relatively even across Lake Ejagham lineages, yet with some evidence for differential admixture, most notably before the first speciation event into the C. deckerti and C. ejagham lineage. Among the sequences that were introgressed into this lineage is a cluster of olfactory receptor genes, which may have facilitated speciation by promoting sexual isolation between incipient species, consistent with previous findings that sexual isolation appears to be stronger than ecological isolation in Ejagham Coptodon. We conclude that speciation in this radiation took place in sympatry, yet may have benefited from ongoing riverine gene flow.

evolutionary biology↗

bioRxiv2017

Don’t throw out the sympatric species with the crater lake water: fine-scale investigation of introgression provides weak support for functional role of secondary gene flow in one of the clearest examples of sympatric speciation

Genomic data has revealed complex histories of colonization and repeated gene flow previously unrecognized in some of the most celebrated examples of sympatric speciation and radiation. However, much of the evidence for secondary gene flow into these radiations comes from genome-wide tests, which tells us little about how gene flow potentially influenced sympatric diversification. Here we investigated whole genomes of Barombi Mbo crater lake cichlids for fine-scale patterns of introgression between species with neighboring riverine cichlid populations. We did find evidence of secondary gene flow into the radiation scattered across < 0.24% of the genome; however, the functional and genetic diversity in these regions paint no clear picture of how that variation could have contributed to the ecological and morphological diversity found in the lake. Our results suggest that either variation in novel genetic pathways introduced during secondary gene flow contributed to the radiation, or that secondary gene flow was predominantly neutral with respect to the diversification processes. We also found evidence for differential assortment of ancestral polymorphism found in riverine populations between sympatric sister species, suggesting the presence of a hybrid swarm in the past. While the history of gene flow and colonization appears to be more complicated than once thought, the lack of compelling evidence for secondary gene flow influencing diversification suggests that we should not yet rule out one of the most celebrated examples of sympatric speciation in nature.

evolutionary biology↗

bioRxiv2017

Physiological and pathological brain activation in the anesthetized rat produces hemodynamic-dependent cortical temperature increases that can confound the BOLD fMRI signal.

Anesthetized rodent models are ubiquitous in pre-clinical neuroimaging studies. However, because the associated cerebral morphology and experimental methodology results in a profound negative brain-core temperature differential, cerebral temperature changes during functional activation are likely to be principally driven by local inflow of fresh, core-temperature, blood. This presents a confound to the interpretation of blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data acquired from such models, since this signal is also critically temperature-dependent. Nevertheless, previous investigation on the subject is surprisingly sparse. Here, we address this issue through use of a novel multi-modal methodology in the urethane anesthetized rat. We reveal that sensory stimulation, hypercapnia and recurrent acute seizures induce significant increases in cortical temperature that are preferentially correlated to changes in total hemoglobin concentration, relative to cerebral blood flow and oxidative metabolism. Furthermore, using a phantom-based evaluation of the effect of such temperature changes on the BOLD fMRI signal, we demonstrate a robust inverse relationship between the two. These findings indicate that temperature increases, due to functional hyperemia, should be accounted for to ensure accurate interpretation of BOLD fMRI signals in pre-clinical neuroimaging studies.

neuroscience↗

bioRxiv2017

Seizure epicenter depth and translaminar field potential synchrony underlie complex variations in tissue oxygenation during ictal initiation.

Whether functional hyperemia during epileptic activity is adequate to meet the heightened metabolic demand of such events is controversial. Whereas some studies have demonstrated hyperoxia during ictal onsets, other work has reported transient hypoxic episodes that are spatially dependent on local surface microvasculature. Crucially, how laminar differences in ictal evolution can affect subsequent cerebrovascular responses has not been thus far investigated, and is likely significant in view of possible laminar-dependent neurovascular mechanisms and angioarchitecture. We addressed this open question using a novel multi-modal methodology enabling concurrent measurement of cortical tissue oxygenation, blood flow and hemoglobin concentration, alongside laminar recordings of neural activity, in a urethane anesthetized rat model of recurrent seizures induced by 4-aminopyridine. We reveal there to be a close relationship between seizure epicenter depth, translaminar LFP synchrony and tissue oxygenation during the early stages of recurrent seizures, whereby deep layer seizures are associated with decreased cross laminar synchrony and prolonged periods of hypoxia, and middle layer seizures are accompanied by increased cross-laminar synchrony and hyperoxia. Through comparison with functional activation by somatosensory stimulation and graded hypercapnia, we show that these seizure-related cerebrovascular responses occur in the presence of conserved neural-hemodynamic and blood flow-volume coupling. Our data provide new insights into the laminar dependency of seizure-related neurovascular responses, which may reconcile inconsistent observations of seizure-related hypoxia in the literature, and highlight a potential layer-dependent vulnerability that may contribute to the harmful effects of clinical recurrent seizures. The relevance of our findings to perfusion-related functional neuroimaging techniques in epilepsy are also discussed.

neuroscience↗

bioRxiv2017

Novel Repolarisation Metric Predicts Arrhythmia Origin And Clinical Events In ARVC And Brugada Syndrome

Structured abstractO_ST_ABSBackgroundC_ST_ABSInitiation of re-entrant ventricular tachycardia (VT) involves complex interactions between activation (AT) and repolarization times (RT). The re-entry vulnerability index (RVI) is a recently proposed activation-repolarization metric designed to quantify tissue susceptibility to re-entry.\n\nObjectivesThe study aimed to test the feasibility of an RVI-based algorithm to predict the exit site of VT and occurrence of clinical events.\n\nMethodsPatients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n=11), Brugada Syndrome (BrS) (n=13) and focal RV outflow tract VT (n=9) underwent programmed stimulation with unipolar electrograms recorded from a non-contact array. The distance between region of lowest RVI and site of VT breakout (Dmin), and global minimum RVI (RVIG) were computed to assess prediction of site of VT breakout and occurrence of clinical events, respectively.\n\nResultsLowest values of RVI, representing sites of highest susceptibility to re-entry, co-localised with site of VT breakout in ARVC/BrS but not in focal VT and Dmin values were lower in ARVC/BrS. ARVC/BrS patients with inducible VT had lower RVIG than those who were non-inducible or those with focal VT. Patients were followed up for 112 {+/-} 19 months; those with clinical VT events had lower RVIg than those without VT or those with focal VT.\n\nConclusionsThe proposed methodology based on RVI localises the origin of re-entrant but not focal ventricular arrhythmias and predicts clinical events. This index could be applied to target ablation for arrhythmias which are difficult to induce or are haemodynamically unstable and also risk stratify patients for ICD prophylaxis.\n\nAbbreviations list

physiology↗

bioRxiv2017

Improved Outcome And Cost Effectiveness In Ablation Of Persistent Atrial Fibrillation Under General Anaesthetic

AimsOutcome of persistent atrial fibrillation (AF) ablation remains suboptimal. Techniques employed to reduce arrhythmia recurrence rate are more likely to be embraced if cost-effectiveness can be demonstrated. A single-centre observational study assessed whether use of general anaesthesia (GA) in persistent AF ablation improved outcome and was cost-effective.\n\nMethods292 patients undergoing first ablation procedures for persistent AF under conscious sedation or GA were followed. End points were freedom from listing for repeat ablation at 18 months and freedom from recurrence of atrial arrhythmia at one year.\n\nResultsFreedom from atrial arrhythmia was higher in patients who underwent ablation under GA rather than sedation (63.9% vs 42.3%, HR 1.87, 95% CI: 1.23 to 2.86, p = 0.002). Significantly fewer GA patients were listed for repeat procedures (29.2% vs 42.7%, HR 1.62, 95% CI: 1.01 to 2.60, p = 0.044). Despite GA procedures costing slightly more, a saving of {pound}177 can be made per patient in our centre for a maximum of 2 procedures if all persistent AF ablations are performed under GA.\n\nConclusionsIn patients with persistent AF, it is both clinical and economically more effective to perform ablation under GA rather than sedation.\n\nWhats New?O_LIThere is very little known regarding the clinical outcome of catheter ablation of AF under GA compared with sedation; to our knowledge there is one study only in paroxysmal AF and no studies examining cost effectiveness.\nC_LIO_LIThis study shows that in patients with persistent AF, it is both clinical and economically more effective to perform ablation under GA rather than sedation.\nC_LIO_LIThis study leads us to recommend the use of GA for the ablation of persistent AF. As PAF ablation is now increasingly being undertaken by single shot techniques which do not have the same requirements for analgesia and immobility, GA resources may be allocated for persistent AF ablation.\nC_LI

systems biology↗

bioRxiv2017

Ablation Of Complex Fractionated Electrograms Improves Outcome In Long Standing Persistent Atrial Fibrillation

PurposeThere is controversy and sparse data on whether substrate based techniques in addition to pulmonary vein isolation (PVI) confer benefit in the catheter ablation of persistent atrial fibrillation (AF), especially if long standing. We performed an observational study to assess whether substrate based ablation improved freedom from atrial arrhythmia.\n\nMethods286 patients undergoing first ablation procedures for persistent AF with PVI only, PVI plus linear ablation, or PVI plus complex fractionated electrogram (CFAE) and linear ablation were followed. Primary end point was freedom from atrial arrhythmia at one year.\n\nResultsMean duration of pre-procedure time in AF was 28+/-27 months. Freedom from atrial arrhythmia was higher with a PVI+CFAE+lines strategy then for PVI alone (HR 1.56, 95% CI: 1.04-2.34, p=0.032) but was not higher with PVI+lines. Benefit of substrate modification was conferred for pre-procedure times in AF of over 30 months. The occurrence of atrial tachycardia was higher when lines were added to the ablation strategy (HR 0.08, 95% CI: 0.01-0.59, p=0.014). Freedom from atrial arrhythmia at 1 year was higher with lower patient age, use of general anaesthetic (GA), normal or mildly dilated left atrium and decreasing time in AF.\n\nConclusionsIn patients with long standing persistent AF of over 30 months duration, CFAE ablation resulted in improved freedom from atrial arrhythmia. Increased freedom from atrial arrhythmia occurs in patients who are younger and have smaller atria, and with GA procedures. Linear ablation did not improve outcome and resulted in a higher incidence of atrial tachycardia.

systems biology↗

bioRxiv2017

A data-driven model for the assessment of age-dependent patterns of Tuberculosis burden and impact evaluation of novel vaccines.

In the case of tuberculosis (TB), the capabilities of epidemic models to produce quantitatively robust forecasts are limited by multiple hindrances. Among these, understanding the complex relationship between disease epidemiology and populations' age structure has been highlighted as one of the most relevant. TB dynamics depends on age in multiple ways, some of which are traditionally simplified in the literature. That is the case of the heterogeneities in contact intensity among different age-strata that are common to all air-borne diseases, but still typically neglected in the TB case. Furthermore, whilst demographic structures of many countries are rapidly aging, demographic dynamics is pervasively ignored when modeling TB spreading. In this work, we present a TB transmission model that incorporates country-specific demographic prospects and empirical contact data around a data-driven description of TB dynamics. Using our model, we find that the inclusion of demographic dynamics is followed by an increase in the burden levels prospected for the next decades in the areas of the world that are most hit by the disease nowadays. Similarly, we show that considering realistic patterns of contacts among individuals in different age-strata reshapes the transmission patterns reproduced by the models, a result with potential implications for the design of age-focused epidemiological interventions.\n\nSignificance StatementEven though tuberculosis (TB) is acknowledged as a strongly age-dependent disease, it remains unclear how TB epidemics would react, in the following decades, to the generalized aging that human populations are experiencing worldwide. This situation is partly caused by the limitations of current transmission models at describing the relationship between demography and TB transmission. Here, we present a data-driven epidemiological model that, unlike previous approaches, explicitly contemplates relevant aspects of the coupling between agestructure and TB dynamics, such as demographic evolution and contact heterogeneities. Using our model, we identify substantial biases in epidemiological forecasts rooted in an inadequate description of these aspects, both at the level of aggregated incidence and mortality rates and their distribution across age-strata.

epidemiology↗