EXACT PHYLODYNAMIC LIKELIHOOD VIA STRUCTURED MARKOV GENEALOGY PROCESSES.

We consider genealogies arising from a Markov population process in which individuals are categorized into a discrete collection of compartments, with the requirement that individuals within the same compartment are statistically exchangeable. When equipped with a sampling process, each such population process induces a time-evolving tree-valued process defined as the genealogy of all sampled individuals. We provide a construction of this genealogy process and derive exact expressions for the likelihood of an observed genealogy in terms of filter equations. These filter equations can be numerically solved using standard Monte Carlo integration methods. Thus, we obtain statistically efficient likelihood-based inference for essentially arbitrary compartment models based on an observed genealogy of individuals sampled from the population.

Reversion to sensitivity explains limited transmission of resistance in a hospital pathogen.

Bacterial pathogens that are successful in hospital environments must survive times of intense antibiotic exposure and times of no antibiotic exposure. When these organisms are closely associated with human hosts, they must also transmit from one patient to another for the resistance to spread. The resulting evolutionary dynamics have, in some settings, led to rising levels of resistance in hospitals. Here, we focus on an important but understudied aspect of this dynamic: the loss of resistance when the resistant organisms evolve in environments where the antibiotic pressure is removed. Based on prior data, we hypothesize that resistance arising in the context of strong selection may carry a high cost and revert to sensitivity quickly once the selective pressure is removed. Conversely, resistant isolates that persist through times of no antibiotic pressure should carry a lower cost and revert less quickly. To test this hypothesis, we utilize a genetically diverse set of patient-derived, daptomycin-resistant Enterococcus faecium isolates that include cases of both de novo emergence of resistance within patients and putatively transmitted resistance. Both of these sets of strains have survived periods of antibiotic exposure, but only putatively transmitted resistant strains have survived extended periods without antibiotic exposure. These strains were then allowed to evolve in antibiotic free laboratory conditions. We find that putatively transmitted resistant strains tended to have lower level resistance but that evolution in antibiotic-free conditions resulted in minimal loss of resistance. In contrast, resistance that arose de novo within patients was higher level but exhibited greater declines in resistance in vitro. Sequencing of the experimentally evolved isolates revealed that reversal of high level resistance resulted from evolutionary pathways that were frequently genetically associated with the unique resistance mutations of that strain. Thus, the rapid reversal of high-level resistance was associated with accessible evolutionary pathways where an increase in fitness is associated with decreased resistance. We describe how this rapid loss of resistance may limit the spread of resistance within the hospital and shape the diversity of resistance phenotypes across patients.

The Number and Pattern of Viral Genomic Reassortments are not Necessarily Identifiable from Segment Trees.

Reassortment is an evolutionary process common in viruses with segmented genomes. These viruses can swap whole genomic segments during cellular co-infection, giving rise to novel progeny formed from the mixture of parental segments. Since large-scale genome rearrangements have the potential to generate new phenotypes, reassortment is important to both evolutionary biology and public health research. However, statistical inference of the pattern of reassortment events from phylogenetic data is exceptionally difficult, potentially involving inference of general graphs in which individual segment trees are embedded. In this paper, we argue that, in general, the number and pattern of reassortment events are not identifiable from segment trees alone, even with theoretically ideal data. We call this fact the fundamental problem of reassortment, which we illustrate using the concept of the "first-infection tree," a potentially counterfactual genealogy that would have been observed in the segment trees had no reassortment occurred. Further, we illustrate four additional problems that can arise logically in the inference of reassortment events and show, using simulated data, that these problems are not rare and can potentially distort our observation of reassortment even in small data sets. Finally, we discuss how existing methods can be augmented or adapted to account for not only the fundamental problem of reassortment, but also the four additional situations that can complicate the inference of reassortment.

The contradictory role of febuxostat in ABCG2 expression and potentiating hypericin-mediated photodynamic therapy in colorectal cancers.

Photodynamic Therapy (PDT) is an emerging method to treat colorectal cancers (CRC). Hypericin (HYP) is an effective mediator of PDT and the ABCG2 inhibitor, Febuxostat (FBX) could augment PDT. HT29 and HEK293 cells showed light dependant cytotoxic response to PDT in both 2D and 3D cell models. FBX co-treatment was not found to improve PDT cytotoxicity. Next, ABCG2 protein expression was observed in HT29 but not in HEK293 cells. However, ABCG2 gene expression analysis did not support protein expression results as ABCG2 gene expression results were found to be higher in HEK293 cells. Although HYP treatment was found to significantly reduce ABCG2 gene expression levels in both cell lines, FBX treatment partially restored ABCG2 gene expression. Our findings indicate that FBX co-treatment may not be suitable for augmenting HYP-mediated PDT in CRC but could potentially be useful for other applications.

The effect of experts on attitude change in public-facing political science: Scientific communication on term limits in the United States.

How can scientists best inform the public and change attitudes? Does the message or the messenger matter more? We test the effect of scientific expert messengers and messages in a preregistered, nationally representative survey experiment in the United States. Consistent with our hypotheses, scientists can move public attitudes in areas where knowledge is based on a non-ideological misperception to a greater extent than the same science-based message from another source. Although we focus on political science as a field and Congressional term limits in the United States as a topic area, our findings have broader implications for science communication with policymaking relevance given the persistence of misperceptions among the public across all natural and social science research fields.

Ligand Centered Reactivity of a Transition Metal Bound Geometrically Constrained Phosphine.

The electronic properties, coordination chemistry and reactivity of metal complexes of a planar (C2v symmetric) acridane-derived geometrically constrained phosphine, P(NNN), are described. On complexation to metal centers, the phosphine was found to adopt a distorted trigonal pyramidal structure with a high barrier to pyramidal inversion (22.3 kcal/mol at 298 K for Au[P(NNN)]Cl). Spectroscopic data and theoretical calculations carried out at the density functional level of theory indicate that P(NNN) is a moderate σ-donor, with significant π-acceptor properties. Despite the distortion undergone by the phosphorus atom on coordination to metal centers, the P(NNN) ligand retains its ability to react with small molecule substrates with polar E-H bonds (MeOH, NH2Ph, NH3). It does so in a concerted fashion across one of the P-N bonds, and reversibly in the case of amine substrates. This cooperative bond activation chemistry may ultimately prove beneficial in catalysis.

Real-World Effectiveness of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists (OW GLP-1RAs) in Comparison with Dipeptidyl Peptidase-4 Inhibitors (DPP-4is) for Glycemic Control and Weight Outcomes in Type 2 Diabetes Mellitus (RELATE).

BACKGROUND: The efficacy of once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1RAs) has been established in several trials in people with type 2 diabetes mellitus (T2DM); however, real-world evidence on their effectiveness is limited. This study evaluated the effectiveness of OW GLP-1RA regarding glycemic and weight outcomes, and relative to DPP-4i in a comparator analysis. METHODS: This observational cohort study evaluated glycated hemoglobin (HbA1c) and weight outcomes in people with T2DM with two or more prescription claims for the same OW GLP-1RA using a pre-post study design (including for a semaglutide OW T2DM subgroup, hereafter referred to as semaglutide). Comparator analysis for the same outcome was performed for OW GLP-1RAs versus DPP-4i and semaglutide subgroup versus DPP-4i. A linked patient population from the IQVIA PharMetrics® Plus database and the Ambulatory Electronic Medical Records (AEMR) database was analyzed using data from January 2017 to April 2022. HbA1c and weight were assessed at baseline and at the end of the 12-month post-index period. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances in baseline patient characteristics in the comparator analysis. RESULTS: In the pre-post analysis, a greater numerical reduction in HbA1c and weight was observed for the semaglutide subgroup (N = 354) relative to the OW GLP-1RA cohort (N = 921). In the semaglutide subgroup, 52.5% and 34.2% of patients achieved HbA1c of < 7.0% and ≥ 5% weight loss, respectively. For the comparator analysis, the OW GLP-1RAs (N = 651) were significantly more effective (p < 0.001) in reducing HbA1c (- 1.5% vs. -  1.0%) and weight (- 3.2 kg vs. -  1.0 kg) than the DPP-4is (N = 431). Similarly, the semaglutide cohort (N = 251) also displayed more effectiveness (p < 0.001) in reducing HbA1c (- 1.7% vs. -  0.9%) and weight (- 4.1 kg vs. -  1.3 kg) than the respective DPP-4i cohort (N = 417). Patients initiating OW GLP-1RAs, including the semaglutide cohort, were at least twice as likely to achieve HbA1c and weight outcomes as well as composite outcomes compared with those initiating DPP-4is. CONCLUSION: The study reinforces that OW GLP-1RAs are more effective in glycemic control and weight reduction compared with DPP-4is in people with T2DM in the real-world setting. These findings align with the recommendation in the current guidelines for utilizing glucose-lowering treatment regimens that support weight-management goals in people with T2DM.

In type 2 diabetes mellitus (T2DM), glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for managing blood sugar levels and major adverse cardiovascular event risk reduction. In clinical trials, once-weekly (OW) GLP-1RAs showed better control of blood sugar levels and body weight than those administered daily, as well as another class of daily T2DM medications called dipeptidyl peptidase-4 inhibitors (DPP-4is). However, there is limited evidence of OW GLP-1RAs-based routine care to confirm these findings. This study gathered prescription and outcomes data for people with T2DM (January 2017­April 2022) from two linked US databases. Body weight measurements and glycated hemoglobin (HbA_1c) test results (measuring average blood sugar levels) were used to evaluate the effectiveness of OW GLP-1RAs (exenatide, dulaglutide, and semaglutide) via a pre-post analysis, and compare OW GLP-1RAs with DPP-4is. We found that treatment with semaglutide lowered body weight and blood sugar levels to a greater extent than OW GLP-1RAs in the pre-post analysis. In the comparator analysis, people receiving OW GLP-1RAs, including semaglutide, were at least twice as likely to achieve reduced HbA_1c levels and body weight compared with those receiving DPP-4is. People receiving OW GLP-1RAs were three times more likely than those on DPP-4is to achieve the recommended target of HbA_1c < 7.0% and weight loss ≥ 5%, while treatment with semaglutide increased this likelihood by > 4.6 times. This study shows clear benefits of OW GLP-1RAs, building on current evidence for integration of this treatment into overall management of T2DM.

Red blood cell dynamics during malaria infection violate the assumptions of mathematical models of infection dynamics.

For decades, mathematical models have been used to understand the course and outcome of malaria infections (i.e., infection dynamics) and the evolutionary dynamics of the parasites that cause them. A key conclusion of these models is that red blood cell (RBC) availability is a fundamental driver of infection dynamics and parasite trait evolution. The extent to which this conclusion holds will in part depend on model assumptions about the host-mediated processes that regulate RBC availability i.e., removal of uninfected RBCs and supply of RBCs. Diverse mathematical functions have been used to describe host-mediated RBC supply and clearance, but it remains unclear whether they adequately capture the dynamics of RBC supply and clearance during infection. Here, we use a unique dataset, comprising time-series measurements of erythrocyte (i.e., mature RBC) and reticulocyte (i.e., newly supplied RBC) densities during Plasmodium chabaudi malaria infection, and a quantitative data-transformation scheme to elucidate whether RBC dynamics conform to common model assumptions. We found that RBC clearance and supply are not well described by mathematical functions commonly used to model these processes. Furthermore, the temporal dynamics of both processes vary with parasite growth rate in a manner again not captured by existing models. Together, these finding suggest that new model formulations are required if we are to explain and ultimately predict the within-host population dynamics and evolution of malaria parasites.

Durability of Effectiveness Between Users of Once-Weekly Semaglutide and Dipeptidyl Peptidase 4 Inhibitors (DPP-4i) in US Adults with Type 2 Diabetes.

INTRODUCTION: Long-term effectiveness and durability of glucose-lowering medications are important considerations in managing type 2 diabetes (T2D). This study aimed to compare durability of treatment efficacy of once-weekly (OW) semaglutide for T2D with that of the dipeptidyl peptidase 4 inhibitor (DPP-4i) class. METHODS: This observational cohort study used 2017-2022 data from the Optum® Clinformatics® Data Mart to compare long-term clinical outcomes associated with semaglutide or DPP-4i in US adults with T2D. The primary outcomes were HbA1c at 2-year follow-up, change in HbA1c from baseline, and the odds of achieving HbA1c targets. BMI at 2-year follow-up, change in BMI from baseline, odds of reducing BMI category, and the need for treatment augmentation were exploratory outcomes. Bivariate and multivariate analyses were conducted using inverse probability of treatment weighting (IPTW) weighted descriptive statistics. RESULTS: Weighted HbA1c and BMI cohorts included 865 and 642 semaglutide users and 779 and 537 DPP-4i users, respectively. In the weighted HbA1c cohort, semaglutide and DPP-4i users had an average age of 60 years and similar baseline characteristics including HbA1c level and comorbidity status. Two-year follow-up HbA1c with semaglutide was 0.56% lower than with DPP-4i; reduction in HbA1c from baseline was 0.61% greater. Odds of achieving HbA1c level < 7% were 2.16 times greater after covariate adjustment (all, p < 0.001). Semaglutide was associated with 1.03 kg/m2 greater reduction in BMI and 2.27 times greater odds of reducing BMI category vs DPP-4i (p < 0.001). Semaglutide users were less likely to add new glucose-lowering treatment (hazard ratio [HR] 0.57; p < 0.001) or initiate insulin (HR 0.49; p < 0.001) vs DPP-4i users. CONCLUSION: Compared with DPP-4i, semaglutide was associated with lower follow-up HbA1c and BMI, greater reduction in HbA1c and BMI from baseline, and reduced likelihood of requiring treatment augmentation or insulin initiation to manage T2D in US adults, suggesting better durability of semaglutide vs DPP-4i. INFOGRAPHIC.

Type 2 diabetes (T2D) is a progressive disease. Over time, many patients with T2D will need multiple drugs to manage their disease. Long-term efficacy is important for achieving treatment goals, such as blood sugar control and weight loss. The amount of time that different types of diabetes drugs remain effective varies. This study used real-world data to compare two distinct types of diabetes drugs, semaglutide and dipeptidyl peptidase 4 inhibitors (DPP­4is). We looked at how blood sugar control and body weight changed with each drug after 2 years of use. We also compared how many patients needed to start using new drugs to meet their treatment goals and the odds that a patient would need to start using new drugs. Semaglutide was better than DPP­4i in reducing both blood sugar levels and body weight. Patients had over two times the odds of meeting target blood sugar levels with semaglutide. Fewer patients needed to start using new drugs with semaglutide, and patients were 43% less likely to start using new drugs to lower blood sugar than patients taking DPP­4is.

Modeling the evolution of segment trees reveals deficiencies in current inferential methods for genomic reassortment.

Reassortment is an evolutionary process common in viruses with segmented genomes. These viruses can swap whole genomic segments during cellular co-infection, giving rise to new viral variants. Large-scale genome rearrangements, such as reassortment, have the potential to quickly generate new phenotypes, making the understanding of viral reassortment important to both evolutionary biology and public health research. In this paper, we argue that reassortment cannot be reliably inferred from incongruities between segment phylogenies using the established remove-and-rejoin or coalescent approaches. We instead show that reassortment must be considered in the context of a broader population process that includes the dynamics of the infected hosts. Using illustrative examples and simulation we identify four types of evolutionary events that are difficult or impossible to reconstruct with incongruence-based methods. Further, we show that these specific situations are very common and will likely occur even in small samples. Finally, we argue that existing methods can be augmented or modified to account for all the problematic situations that we identify in this paper. Robust assessment of the role of reassortment in viral evolution is difficult, and we hope to provide conceptual clarity on some important methodological issues that can arise in the development of the next generation of tools for studying reassortment.

Magnetically driven preparation of 1-D nano-necklaces capable of MRI relaxation enhancement.

We report a novel magnetically-facilitated approach to produce 1-D 'nano-necklace' arrays composed of 0-D magnetic nanoparticles, which are assembled and coated with an oxide layer to produce semi-flexible core@shell type structures. These 'nano-necklaces' demonstrate good MRI relaxation properties despite their coating and permanent alignment, with low field enhancement due to structural and magnetocrystalline anisotropy.

Bagged filters for partially observed interacting systems.

Bagging (i.e., bootstrap aggregating) involves combining an ensemble of bootstrap estimators. We consider bagging for inference from noisy or incomplete measurements on a collection of interacting stochastic dynamic systems. Each system is called a unit, and each unit is associated with a spatial location. A motivating example arises in epidemiology, where each unit is a city: the majority of transmission occurs within a city, with smaller yet epidemiologically important interactions arising from disease transmission between cities. Monte Carlo filtering methods used for inference on nonlinear non-Gaussian systems can suffer from a curse of dimensionality as the number of units increases. We introduce bagged filter (BF) methodology which combines an ensemble of Monte Carlo filters, using spatiotemporally localized weights to select successful filters at each unit and time. We obtain conditions under which likelihood evaluation using a BF algorithm can beat a curse of dimensionality, and we demonstrate applicability even when these conditions do not hold. BF can out-perform an ensemble Kalman filter on a coupled population dynamics model describing infectious disease transmission. A block particle filter also performs well on this task, though the bagged filter respects smoothness and conservation laws that a block particle filter can violate.

Strategic outline of interventions targeting extracellular matrix for promoting healthy longevity.

The extracellular matrix (ECM), composed of interlinked proteins outside of cells, is an important component of the human body that helps maintain tissue architecture and cellular homeostasis. As people age, the ECM undergoes changes that can lead to age-related morbidity and mortality. Despite its importance, ECM aging remains understudied in the field of geroscience. In this review, we discuss the core concepts of ECM integrity, outline the age-related challenges and subsequent pathologies and diseases, summarize diagnostic methods detecting a faulty ECM, and provide strategies targeting ECM homeostasis. To conceptualize this, we built a technology research tree to hierarchically visualize possible research sequences for studying ECM aging. This strategic framework will hopefully facilitate the development of future research on interventions to restore ECM integrity, which could potentially lead to the development of new drugs or therapeutic interventions promoting health during aging.

Glucagon-Like Peptide 1 Receptor Agonists Have the Potential to Revolutionize the Attainment of Target A1C Levels in Type 2 Diabetes-So Why Is Their Uptake So Low?

A target A1C of <7% is the recommended goal for most people with type 2 diabetes. However, many are not achieving this target with their current treatment. Glucagon-like peptide 1 (GLP-1) receptor agonists are highly efficacious in achieving glycemic control and could aid primary care providers (PCPs) in getting patients to their A1C target. However, despite their potential, use of GLP-1 receptor agonists in the primary care setting is limited. This review provides guidance for PCPs on how to help patients achieve their glycemic target and overcome perceived barriers of GLP-1 receptor agonist use, with the overall goal of improving PCP confidence in prescribing these agents.

Reactivity of a Strictly T-Shaped Phosphine Ligated by an Acridane Derived NNN Pincer Ligand.

The steric tuning of a tridentate acridane-derived NNN pincer ligand allows for the isolation of a strictly T-shaped phosphine that exhibits ambiphilic reactivity. Well-defined phosphorus-centered reactivity towards nucleophiles and electrophiles is reported, contrasting with prior reports on this class of compounds. Reactions towards oxidants are also described. The latter result in the two-electron oxidation of the phosphorus atom from +III to +V and are accompanied by a strong geometric distortion of the NNN pincer ligand. By contrast, cooperative activation of E-H (HCl, HBcat, HOMe) bonds proceeds with retention of the phosphorus redox state. When using H2 O as a substrate, the reaction results in the full disassembly of H2 O to its constituent atoms, highlighting the potential of this platform for small molecule activation reactions.

Disentangling the causes of mumps reemergence in the United States.

Over the past two decades, multiple countries with high vaccine coverage have experienced resurgent outbreaks of mumps. Worryingly, in these countries, a high proportion of cases have been among those who have completed the recommended vaccination schedule, raising alarm about the effectiveness of existing vaccines. Two putative mechanisms of vaccine failure have been proposed as driving observed trends: 1) gradual waning of vaccine-derived immunity (necessitating additional booster doses) and 2) the introduction of novel viral genotypes capable of evading vaccinal immunity. Focusing on the United States, we conduct statistical likelihood-based hypothesis testing using a mechanistic transmission model on age-structured epidemiological, demographic, and vaccine uptake time series data. We find that the data are most consistent with the waning hypothesis and estimate that 32.8% (32%, 33.5%) of individuals lose vaccine-derived immunity by age 18 y. Furthermore, we show using our transmission model how waning vaccine immunity reproduces qualitative and quantitatively consistent features of epidemiological data, namely 1) the shift in mumps incidence toward older individuals, 2) the recent recurrence of mumps outbreaks, and 3) the high proportion of mumps cases among previously vaccinated individuals.

Separation of Neodymium (III) and Lanthanum (III) via a Flat Sheet-Supported Liquid Membrane with Different Extractant-Acid Systems.

The increasing demand for neodymium (Nd) permanent magnets in electric motors has revived research interest of Nd recovery and separation from other rare earth elements (REEs). Typically, Nd/La separation is necessary for Nd recovery from primary ores and secondary resource recycling. This research used a flat sheet-supported liquid membrane (FSSLM) with different extractant-acid systems to extract Nd from a Nd/La mixture. The recovery and separation of Nd/La with 204P-H2SO4, 507P-HCl, and TBP-HNO3 were discussed. The results showed effective Nd recovery and promising Nd/La selectivity could be achieved in the 507P-HCl system, compared to 204P-H2SO4 and TBP-HNO3. The addition of citric acid to the feed solution was effective for pH buffering but did not improve the Nd transport or Nd/La selectivity. Long-term stability of the 507P-HCl extractant system was demonstrated by extending the processing time from 6 h to 6 days.

Impact of cardiovascular disease on health care economic burden and resource utilization: a retrospective cohort study in adults in the United States with type 2 diabetes with or without stroke, myocardial infarction, and peripheral arterial disease.

OBJECTIVES: To evaluate incidence of stroke, myocardial infarction (MI), and peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM) and assess associated health care resource utilization (HCRU) and costs in the United States. METHODS: Patients ≥18 years of age with a T2DM diagnosis, with or without incident stroke/MI/PAD, were indexed between 1 January 2012 and 31 December 2020, from the deidentified Optum Clinformatics Data Mart claims database. Incidence of stroke, MI, and PAD was evaluated in the year following T2DM. HCRU and costs were measured in the 12 months following study entry in patients with T2DM + stroke, T2DM + MI, and T2DM + PAD (experimental cohorts) and compared to HCRU and costs in patients with T2DM alone (control cohorts). RESULTS: Incidence of stroke, MI, and PAD in patients with T2DM was 0.9% (n = 16,034), 0.7% (n = 13,681), and 4.1% (n = 68,479), respectively. Compared to matched patients with T2DM alone, patients with T2DM + stroke/MI/PAD had significantly higher total healthcare costs in the year post-index date (T2DM + stroke: +$5962 per patient per month [PPPM]; T2DM + MI: +$7932 PPPM; T2DM + PAD: +$2652 PPPM; p < .05). Patients with T2DM + stroke/MI/PAD had significantly higher mean HCRU than patients without stroke/MI/PAD in all categories measured. CONCLUSION: Having stroke, MI, or PAD was associated with increases in HCRU and costs in patients with T2DM. Although PAD was associated with smaller per patient increases in total healthcare costs than patients with T2DM + stroke/MI, the higher frequency of incident PAD may make it more costly than MI or stroke in a large population of patients with T2DM.

Compared to patients without type 2 diabetes (T2D), patients with T2D have a greater chance of having a stroke, heart attack, and narrowing of blood vessels in the arms and legs (peripheral artery disease [PAD]). A stroke, heart attack, or PAD may lead to hospitalization or death. We sought to understand healthcare usage (hospital visits, emergency room visits, office visits, etc.) and costs associated with stroke, heart attack, and PAD in patients with T2D in the United States. Healthcare resource usage and costs were estimated by using data from health insurance claims to compare healthcare usage and costs among patients with T2D, some of whom had a stroke, heart attack, or PAD, and some who did not. Compared to patients with T2D without stroke/heart attack/PAD, patients with T2D and stroke/heart attack/PAD had more overnight hospital visits, doctors' office visits, and emergency room visits. Patients with T2D and stroke/heart attack/PAD also had longer hospital stays. Patients with T2D and stroke/heart attack/PAD all had higher total healthcare costs in the year following their diagnoses, compared to patients with T2D without stroke/heart attack/PAD. By highlighting the greater costs and use of healthcare associated with stroke, heart attack, and PAD in patients with T2D, we hope to encourage more preventative management of stroke, heart attack, and PAD in patients with T2D.

Fine-scale heterogeneity in population density predicts wave dynamics in dengue epidemics.

The spread of dengue and other arboviruses constitutes an expanding global health threat. The extensive heterogeneity in population distribution and potential complexity of movement in megacities of low and middle-income countries challenges predictive modeling, even as its importance to disease spread is clearer than ever. Using surveillance data at fine resolution from Rio de Janeiro, we document a scale-invariant pattern in the size of successive epidemics following DENV4 emergence. Using surveillance data at fine resolution following the emergence of the DENV4 dengue serotype in Rio de Janeiro, we document a pattern in the size of successive epidemics that is invariant to the scale of spatial aggregation. This pattern emerges from the combined effect of herd immunity and seasonal transmission, and is strongly driven by variation in population density at sub-kilometer scales. It is apparent only when the landscape is stratified by population density and not by spatial proximity as has been common practice. Models that exploit this emergent simplicity should afford improved predictions of the local size of successive epidemic waves.