The effect of cooperator recognition on competition among clones in spatially structured microbial communities.

In spatially structured microbial communities, clonal growth of stationary cells passively generates clusters of related individuals. This can lead to stable cooperation without the need for recognition mechanisms. However, recent research suggests that some biofilm-forming microbes may have mechanisms of kin recognition. To explore this unexpected observation, we studied the effects of different types of cooperation in a microbial colony using spatially explicit, agent-based simulations of two interacting strains. We found scenarios that favor a form of kin recognition in spatially structured microbial communities. In the presence of a "cheater" strain, a strain with greenbeard cooperation was able to increase in frequency more than a strain with obligate cooperation. This effect was most noticeable in high density colonies and when the cooperators were not as abundant as the cheaters. We also studied whether a polychromatic greenbeard, in which cells only cooperate with their own type, could provide a numerical benefit beyond a simple, binary greenbeard. We found the greatest benefit to a polychromatic greenbeard when cooperation is highly effective. These results suggest that in some ecological scenarios, recognition mechanisms may be beneficial even in spatially structured communities.

Müllerian-Type Clear Cell Carcinoma of Donor Origin in a Male Patient with a Kidney Transplant: Ascertained by Molecular Testing.

Clear cell carcinomas of Müllerian origin have a strong female predominance and only extremely rarely will arise within the kidney, presumably due to ectopic Müllerian embryogenesis. Herein, we report a unique case of metastatic Müllerian type clear cell carcinoma in a 37-year-old patient who had previously received a transplanted kidney from his father at age 11 (due to severe bilateral vesicoureteral reflux) and remained on chronic immunosuppression. The tumor was highly aggressive and demonstrated somatic mutations in NF2 and SETD2. Imaging of the transplanted kidney did not reveal any clear evidence of malignancy. However, targeted multigene sequencing and short tandem repeat testing revealed that the cancer was of donor origin, presumably from ectopic Müllerian tissue transplanted to the patient along with the kidney graft. The tumor was resistant to first-line therapy with a triple combination of carboplatin plus paclitaxel plus bevacizumab, as well as to second-line immunotherapy with nivolumab plus ipilimumab after tapering down the patient's immunosuppression. Despite the tumor being genetically distinct from the host, the use of immune checkpoint therapy with nivolumab plus ipilimumab did not yield a response. This unique case showcases the value of molecular testing in determining the tumor origin in patients with solid organ transplants who present with cancers of unknown primary. This can prompt the potential investigation of other recipients from the same donor.

Hepatitis C Virus Reinfection in a Real-World Cohort of Homeless-Experienced Individuals in Boston.

BACKGROUND: People experiencing homelessness are disproportionately affected by hepatitis C virus (HCV) infection compared with housed populations. Surveillance for HCV reinfection after successful treatment is a critical step in the care cascade, but limited data on reinfection are available among this highly marginalized group. This study assessed posttreatment reinfection risk in a real-world cohort of homeless-experienced individuals in Boston. METHODS: Individuals receiving HCV direct-acting antiviral treatment through Boston Health Care for the Homeless Program during 2014-2020 with posttreatment follow-up assessment were included. Reinfection was identified based on recurrent HCV RNA at 12 weeks posttreatment with HCV genotype switch or any recurrent HCV RNA following sustain virologic response. RESULTS: A total of 535 individuals were included (81% male, median age 49 years, 70% unstably housed or homeless at treatment initiation). Seventy-four HCV reinfections were detected, including 5 second reinfections. HCV reinfection rate was 12.0/100 person-years (95% confidence interval [CI]: 9.5-15.1) overall, 18.9/100 person-years (95% CI: 13.3-26.7) among individuals with unstable housing and 14.6/100 person-years (95% CI: 10.0-21.3) among those experiencing homelessness. In adjusted analysis, experiencing homelessness (vs stable housing, adjusted hazard ratio, 2.14; 95% CI: 1.09-4.20; P = .026) and drug use within 6 months before treatment (adjusted hazard ratio, 5.23; 95% CI: 2.25-12.13; P < .001) were associated with increased reinfection risk. CONCLUSIONS: We found high HCV reinfection rates in a homeless-experienced population, with increased risk among those homeless at treatment. Tailored strategies to address the individual and systems factors impacting marginalized populations are required to prevent HCV reinfection and to enhance engagement in posttreatment HCV care.

PrEP disclosure and discussions within social networks of people who inject drugs experiencing homelessness: a brief report.

BACKGROUND: In the context of increasing injection-related HIV outbreaks across the United States, particularly among people who inject drugs (PWID) experiencing homelessness, there is an urgent need to expand access to pre-exposure prophylaxis (PrEP) for HIV prevention. Peer-based interventions for PrEP could be helpful for promoting PrEP uptake, yet the social experiences of using PrEP among PWID experiencing homelessness have not been thoroughly explored. METHODS: To better understand social experiences surrounding PrEP use among PWID experiencing homelessness, we conducted qualitative interviews from March-December 2020 with current and former PrEP patients of an innovative, low-threshold program implemented by Boston Health Care for the Homeless Program (BHCHP) in Boston, MA. Thematic analysis of coded interview data explored participants' perspectives and experiences with PrEP disclosure and discussions within their social networks. RESULTS: Among interviews with 21 participants, we identified the following four interrelated aspects of their social experiences using PrEP: (1) participants' were aware of increasing HIV transmission within their social networks, which motivated their PrEP use and disclosure; (2)  participants generally avoided disclosing their PrEP use within public spaces or casual conversations; (3)  participants expressed greater willingness to discuss PrEP with their close social contacts; and (4)  some participants self-identified as leaders or expressed interest in leading the dissemination of PrEP information within their social networks. CONCLUSIONS: Findings highlight the significance of PrEP disclosure and discussions within the social networks of PWID experiencing homelessness, suggesting a need for continued social network and intervention research-particularly to establish the feasibility and acceptability of peer-based interventions for promoting PrEP-with this marginalized population.

Patient and Provider Perspectives on a Novel, Low-Threshold HIV PrEP Program for People Who Inject Drugs Experiencing Homelessness.

BACKGROUND: HIV outbreaks among people who inject drugs (PWID) and experience homelessness are increasing across the USA. Despite high levels of need, multilevel barriers to accessing antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention persist for this population. The Boston Health Care for the Homeless Program (BHCHP) initiated a low-threshold, outreach-based program to support engagement in PrEP services among PWID experiencing homelessness. METHODS: To inform dissemination efforts, we explored patient and provider perspectives on key program components. From March to December 2020, we conducted semi-structured qualitative interviews with current and former BHCHP PrEP program participants and prescribers, patient navigators, and outreach workers (i.e., providers). Thematic analysis explored perspectives on key program components. RESULTS: Participants (n = 21) and providers (n = 11) identified the following five key components of BHCHP's PrEP program that they perceived to be particularly helpful for supporting patient engagement in PrEP services: (1) community-driven PrEP education; (2) low-threshold, accessible programming including same-day PrEP prescribing; (3) tailored prescribing supports (e.g., on-site pharmacy, short-term prescriptions, medication storage); (4) intensive outreach and navigation; and (5) trusting, respectful patient-provider relationships. DISCUSSION: Findings suggest that more patient-centered services formed the basis of BHCHP's innovative, successful PrEP program. While contextual challenges including competing public health emergencies and homeless encampment "sweeps" necessitate ongoing programmatic adaptations, lessons from BHCHP's PrEP program can inform PrEP delivery in a range of community-based settings serving this population, including syringe service programs and shelters.

Factors Associated with Sustained Virologic Response to Hepatitis C Treatment in a Homeless-Experienced Cohort in Boston, 2014-2020.

BACKGROUND: Engaging people experiencing homelessness or unstable housing in hepatitis C virus (HCV) treatment is critical to achieving HCV elimination. OBJECTIVE: To describe HCV treatment outcomes, including factors associated with retention through the treatment cascade, for a cohort of individuals treated in a homeless health center in Boston. DESIGN: Retrospective cohort study. PARTICIPANTS: All individuals who initiated HCV treatment with Boston Health Care for the Homeless Program's HCV treatment program between January 2014 and March 2020 (N = 867). OUTCOME MEASURES: The primary outcome was sustained virologic response (SVR), defined as an HCV ribonucleic acid (RNA) level ≤ 15 IU/mL at least 12 weeks after treatment completion. We used multivariable logistic regression to examine the association between baseline variables and SVR. Process-oriented outcomes included treatment completion, assessment for SVR, and achievement of SVR. RESULTS: Of 867 individuals who started HCV treatment, 796 (91.8%) completed treatment, 678 (78.2%) were assessed for SVR, and 607 (70.0%) achieved SVR. In adjusted analysis, residing in stable housing (OR 3.83, 95% CI 1.85-7.90) and age > 45 years old (OR 1.53, 95% CI 1.04-2.26) were associated with a greater likelihood of achieving SVR. Recent drug use (OR 0.63, 95% CI 0.41-0.95) was associated with a lower likelihood of SVR. Age, housing status, and drug use status impacted retention at every step in the treatment cascade. CONCLUSION: A large proportion of homeless-experienced individuals engaging in HCV treatment in a homeless health center achieved SVR, but enhanced approaches are needed to engage and retain younger individuals, those with recent or ongoing substance use, or those experiencing homelessness or unstable housing. Efforts to achieve HCV elimination in this population should consider the complex and overlapping challenges experienced by this population and aim to address the fundamental harm of homelessness itself.

Pattern formation in marsh ecosystems modeled through the interaction of marsh vegetation, mussels and sediment.

Spatial self-organization, a common feature of multi-species communities, can provide important insights into ecosystem structure and resilience. As environmental conditions gradually worsen (e.g., resource depletion, erosion intensified by storms, drought), some ecological systems collapse to an irreversible state once a tipping point is reached. Spatial patterning may be one way for them to cope with such changes. We use a mathematical model to describe self-organization of an eroding marsh shoreline based on three-way interactions between sediment volume and two ecosystem engineers - smooth cordgrass Spartina alterniflora and ribbed mussels Geukensia demissa. Our model indicates that scale-dependent interactions between multiple ecosystem engineers drive the self-organization of eroding marsh edges and regulate the spatial scale of shoreline morphology. Spatial self-organization of the marsh edge increases the system's productivity, allows it to withstand erosion, and delays degradation that otherwise would occur in the absence of strong species interactions. Further, changes in wavelength and variance of the spatial patterns give insight into marsh recession. Finally, we find that the presence of mussels in the system modulates the spatial scale of the patterns, generates patterns with shorter wavelengths, and allows the system to tolerate a greater level of erosion. Although previous studies suggest that self-organization can emerge from local interactions and can result in increased ecosystem persistence and stability in various ecosystems, our findings extend these concepts to coastal salt marshes, emphasizing the importance of the ecosystem engineers, smooth cordgrass and ribbed mussels, and demonstrating the potential value of self-organization for ecosystem management and restoration.

Evaluation of Technology-Enabled Monitoring of Patient-Reported Outcomes to Detect and Treat Toxic Effects Linked to Immune Checkpoint Inhibitors.

Importance: Immune checkpoint inhibitors can produce distinct toxic effects that require prompt recognition and timely management. Objective: To develop a technology-enabled, dynamically adaptive protocol that can provide the accurate information needed to inform specific remedies for immune toxic effects in patients treated with immune checkpoint inhibitors. Design, Setting, and Participants: An open-label cohort study was conducted at a single tertiary referral center from September 6, 2019, to September 3, 2020. The median follow-up duration was 63 (interquartile range, 35.5-122) days. Fifty patients with genitourinary cancers treated with immune checkpoint inhibitors were enrolled. Interventions: A fit-for-purpose electronic platform was developed to enable active patient and care team participation. A smartphone application downloaded onto patients' personal mobile devices prompted them to report their symptoms at least 3 times per week. The set of symptoms and associated queries were paired with alert thresholds for symptoms requiring clinical action. Main Outcomes and Measures: The primary end point of this interim analysis was feasibility, as measured by patient and care team adherence, and lack of increase in care team staffing. Operating characteristics were estimated for each symptom alert and used to dynamically adapt the alert thresholds to ensure sensitivity while reducing unnecessary alerts. Results: Of the 50 patients enrolled, 47 had at least 1 follow-up visit and were included in the analysis. Median age was 65 years (range, 37-86), 39 patients (83%) were men, and 39 patients (83%) had metastatic cancer, with the most common being urothelial cell carcinoma and renal cell carcinoma (22 [47%] patients each). After initial onboarding, no further care team training or additional care team staffing was required. Patients had a median study adherence rate of 74% (interquartile range, 60%-86%) and 73% of automated alerts were reviewed within 3 days by the clinic team. Symptoms with the highest positive predictive value for adverse events requiring acute intervention included dizziness (21%), nausea/vomiting (26%), and shortness of breath (14%). The symptoms most likely to result in unnecessary alerts were arthralgia and myalgia, fatigue, and cough. Conclusions and Relevance: The findings of this cohort study suggest an acceptable and fiscally sound method can be developed to create a dynamic learning system to detect and manage immune-related toxic effects.

Delivering Preexposure Prophylaxis to People Who Use Drugs and Experience Homelessness, Boston, MA, 2018-2020.

Despite high need, HIV preexposure prophylaxis (PrEP) utilization among people who use drugs (PWUD) remains low. Boston Health Care for the Homeless Program implemented an innovative "low-threshold" PrEP Program for PWUD experiencing homelessness in Boston, Massachusetts. From October 1, 2018 to February 29, 2020, 239 clients were linked to PrEP services, and 152 were prescribed PrEP (mean = 8.9/month), over twice the number of PrEP prescriptions over the previous 12 months (n = 48; mean = 4/month). The cumulative probability of remaining on PrEP for 6 months was 44% (95% confidence interval = 36%, 52%).

Corrigendum to "Bistability in a differential equation model of oyster reef height and sediment accumulation" [J. Theor. Biol. 289 (2011) 1-11].

There was a mistake in the Matlab code we used to generate time series solutions of our model, Eqs. (16)-(18). The corrected text below replaces one paragraph on p. 7, and the figures below replace Figs. 4-5 on p. 8. There is no qualitative change to our results. However, there is a quantitative change in the initial dead oyster shell volume B(0) needed for reef survival. The corrected threshold B(0), about 0.40 m3 per m2 of sea floor, is more consistent with a recently experimentally estimated threshold of 0.30 m (Colden, Latour, and Lipcius, Mar Ecol Prog Ser 582: 1-13, 2017) than was our old incorrect threshold of about 0.12 m3.

Population Estimates of GFR and Risk Factors for CKD in Guatemala.

INTRODUCTION: Chronic kidney disease (CKD) is an emerging public health priority in Central America. However, data on the prevalence of CKD in Guatemala, Central America's most populous country, are limited, especially for rural communities. METHODS: We conducted a population-representative survey of 2 rural agricultural municipalities in Guatemala. We collected anthropometric data, blood pressure, serum and urine creatinine, glycosylated hemoglobin, and urine albumin. Sociodemographic, health, and exposure data were self-reported. RESULTS: We enrolled 807 individuals (63% of all eligible, 35% male, mean age 39.5 years). An estimated 4.0% (95% confidence interval [CI] 2.4-6.6) had CKD, defined as an estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m2. Most individuals with an eGFR below 60 ml/min per 1.73 m2 had diabetes or hypertension. In multivariable analysis, the important factors associated with risk for an eGFR less than 60 ml/min per 1.73 m2 included a history of diabetes or hypertension (adjusted odds ratio [aOR] 11.21; 95% CI 3.28-38.24), underweight (body mass index [BMI] <18.5) (aOR 21.09; 95% CI 2.05-217.0), and an interaction between sugar cane agriculture and poverty (aOR 1.10; 95% CI 1.01-1.19). CONCLUSIONS: In this population-based survey, most observed CKD was associated with diabetes and hypertension. These results emphasize the urgent public health need to address the emerging epidemic of diabetes, hypertension, and CKD in rural Guatemala. In addition, the association between CKD and sugar cane in individuals living in poverty provides some circumstantial evidence for existence of CKD of unknown etiology in the study communities, which requires further investigation.

Safe and effective use of nivolumab plus ipilimumab in a patient with metastatic clear-cell renal cell carcinoma with sarcomatoid dedifferentiation and end stage renal disease on hemodialysis.

Targeting the programmed cell death protein-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4) pathways using the combination immune checkpoint inhibitors (ICI) nivolumab and ipilimumab is an approved frontline therapy for patients with metastatic clear-cell renal cell carcinoma (mccRCC). Certain populations pose clinical challenges due to exclusion from large clinical trials that established the safety and efficacy of these treatments, including patients with end stage renal disease (ESRD). While there are reports successfully administering single-agent ICI in patients with ESRD, we present herein a case of safe and effective use of combination nivolumab plus ipilimumab in a 53-year-old man with mccRCC with sarcomatoid dedifferentiation and ESRD on hemodialysis.

Feasibility of satellite image and GIS sampling for population representative surveys: a case study from rural Guatemala.

BACKGROUND: Population-representative household survey methods require up-to-date sampling frames and sample designs that minimize time and cost of fieldwork especially in low- and middle-income countries. Traditional methods such as multi-stage cluster sampling, random-walk, or spatial sampling can be cumbersome, costly or inaccurate, leading to well-known biases. However, a new tool, Epicentre's Geo-Sampler program, allows simple random sampling of structures, which can eliminate some of these biases. We describe the study design process, experiences and lessons learned using Geo-Sampler for selection of a population representative sample for a kidney disease survey in two sites in Guatemala. RESULTS: We successfully used Epicentre's Geo-sampler tool to sample 650 structures in two semi-urban Guatemalan communities. Overall, 82% of sampled structures were residential and could be approached for recruitment. Sample selection could be conducted by one person after 30 min of training. The process from sample selection to creating field maps took approximately 40 h. CONCLUSION: In combination with our design protocols, the Epicentre Geo-Sampler tool provided a feasible, rapid and lower-cost alternative to select a representative population sample for a prevalence survey in our semi-urban Guatemalan setting. The tool may work less well in settings with heavy arboreal cover or densely populated urban settings with multiple living units per structure. Similarly, while the method is an efficient step forward for including non-traditional living arrangements (people residing permanently or temporarily in businesses, religious institutions or other structures), it does not account for some of the most marginalized and vulnerable people in a population-the unhoused, street dwellers or people living in vehicles.

Hospitalization outcomes of people who use drugs: One size does not fit all.

People with opioid use disorder (OUD) have worse hospital outcomes and higher healthcare costs. There are rising reports of people with OUD also using other classes of drugs, however patterns of substance use have not been evaluated for differential effects on hospital outcomes. We performed a data-analysis of the Healthcare Utilization Project's National Readmissions Database, examining the effects of patterns of substance use, age, gender, and diagnosis on the outcomes of Against Medical Advice (AMA) discharges and 30-day readmissions. About one-third of the patients with OUD who were admitted to the hospital had at least one additional substance use disorder (SUD). Thirteen percent of persons with OUD were discharged AMA, and 12% were readmitted to the hospital within 30 days of discharge. Compared to people with OUD alone, people who used stimulants had increased odds of AMA discharge (aOR 1.83 (CI 1.73, 1.96)) and 30-day readmission (aOR 1.30 (95% CI 1.23, 1.37)). Multiple concomitant substance use disorders were associated with increased odds of AMA discharge and 30-day readmission. Conclusions: People with OUD have high rates of both AMA discharges and 30 day-readmissions, and there is a layered effect of increasing co-occurring SUDs leading to worse hospitalization outcomes. The heterogeneity of drug use patterns needs to be considered when developing strategies to improve health care outcomes for people with substance use disorder.

Model of pattern formation in marsh ecosystems with nonlocal interactions.

Smooth cordgrass Spartina alterniflora is a grass species commonly found in tidal marshes. It is an ecosystem engineer, capable of modifying the structure of its surrounding environment through various feedbacks. The scale-dependent feedback between marsh grass and sediment volume is particularly of interest. Locally, the marsh vegetation attenuates hydrodynamic energy, enhancing sediment accretion and promoting further vegetation growth. In turn, the diverted water flow promotes the formation of erosion troughs over longer distances. This scale-dependent feedback may explain the characteristic spatially varying marsh shoreline, commonly observed in nature. We propose a mathematical framework to model grass-sediment dynamics as a system of reaction-diffusion equations with an additional nonlocal term quantifying the short-range positive and long-range negative grass-sediment interactions. We use a Mexican-hat kernel function to model this scale-dependent feedback. We perform a steady state biharmonic approximation of our system and derive conditions for the emergence of spatial patterns, corresponding to a spatially varying marsh shoreline. We find that the emergence of such patterns depends on the spatial scale and strength of the scale-dependent feedback, specified by the width and amplitude of the Mexican-hat kernel function.

Botulinum Toxin for Side-Effect Management and Prevention of Surgical Complications in Patients Treated for Head and Neck Cancers and Esophageal Cancer.

The management of head and neck cancers (HNC) and esophageal cancer (EC) is complex and often involves multiple modalities of treatment, including chemotherapy, radiation therapy, and surgery. The side effects associated with these therapies and disease processes are extensive. A literature review was performed to evaluate the use of botulinum toxin as an intervention for side-effect management in patients with HNC and EC. Specific adverse events reviewed included salivary function (hypersalivation, fistula, hyposalivation) and gastrointestinal motility (esophageal stricture, delayed gastric emptying after esophagectomy). Published results demonstrate an improvement in hypersalivation and, when botulinum toxin was used as an adjunct to treatment, a reduction in symptoms associated with salivary fistula, or an inappropriate communication between the salivary gland and the skin that causes the leakage of saliva through the skin. Positive effects were also demonstrated in regard to esophageal stricture and equivalent effects in the management of gastric emptying to prevent complications after esophagectomy when compared to currently available interventions. However, the potential for increased symptoms associated with botulinum toxin injection related to its use in the management of gastric secretions was noted in one of the studies reviewed.

Enhancement of large fluctuations to extinction in adaptive networks.

During an epidemic, individual nodes in a network may adapt their connections to reduce the chance of infection. A common form of adaption is avoidance rewiring, where a noninfected node breaks a connection to an infected neighbor and forms a new connection to another noninfected node. Here we explore the effects of such adaptivity on stochastic fluctuations in the susceptible-infected-susceptible model, focusing on the largest fluctuations that result in extinction of infection. Using techniques from large-deviation theory, combined with a measurement of heterogeneity in the susceptible degree distribution at the endemic state, we are able to predict and analyze large fluctuations and extinction in adaptive networks. We find that in the limit of small rewiring there is a sharp exponential reduction in mean extinction times compared to the case of zero adaption. Furthermore, we find an exponential enhancement in the probability of large fluctuations with increased rewiring rate, even when holding the average number of infected nodes constant.

A Framework for Inferring Unobserved Multistrain Epidemic Subpopulations Using Synchronization Dynamics.

A new method is proposed to infer unobserved epidemic subpopulations by exploiting the synchronization properties of multistrain epidemic models. A model for dengue fever is driven by simulated data from secondary infective populations. Primary infective populations in the driven system synchronize to the correct values from the driver system. Most hospital cases of dengue are secondary infections, so this method provides a way to deduce unobserved primary infection levels. We derive center manifold equations that relate the driven system to the driver system and thus motivate the use of synchronization to predict unobserved primary infectives. Synchronization stability between primary and secondary infections is demonstrated through numerical measurements of conditional Lyapunov exponents and through time series simulations.

Epidemics with temporary link deactivation in scale-free networks.

During an epidemic, people may adapt or alter their social contacts to avoid infection. Various adaptation mechanisms have been studied previously. Recently, a new adaptation mechanism was presented in [1], where susceptible nodes temporarily deactivate their links to infected neighbors and reactivate when their neighbors recover. Considering the same adaptation mechanism on a scale-free network, we find that the topology of the subnetwork consisting of active links is fundamentally different from the original network topology. We predict the scaling exponent of the active degree distribution and derive mean-field equations by using improved moment closure approximations based on the conditional distribution of active degree given the total degree. These mean field equations show better agreement with numerical simulation results than the standard mean field equations based on a homogeneity assumption.

Effects of community structure on epidemic spread in an adaptive network.

When an epidemic spreads in a population, individuals may adaptively change the structure of their social contact network to reduce risk of infection. Here we study the spread of an epidemic on an adaptive network with community structure. We model two communities with different average degrees. The disease model is susceptible-infected-susceptible (SIS), and adaptation is rewiring of links between susceptibles and infectives. Locations of rewired links are selected so that the community structure will be preserved if susceptible-infective links are homogeneously distributed. The bifurcation structure is obtained, and a mean field model is developed that accurately predicts the steady-state behavior of the system. In a static network, weakly connected heterogeneous communities can have significantly different infection levels. In contrast, adaptation promotes similar infection levels and alters the network structure so that communities have more similar average degrees. We estimate the time for network restructuring to allow infection incursion from one community to another and show that it is inversely proportional to the number of cross-links between communities. In extremely heterogeneous systems, periodic oscillations in infection level can occur due to repeated infection incursions.