Asymptotic Relative Risk Results from a Simplified Armitage and Doll Model of Carcinogenesis.

We examine basic asymptotic properties of relative risk for two families of generalized Erlang processes (where each one is based off of a simplified Armitage and Doll multistage model) in order to predict relative risk data from cancer. The main theorems that we are able to prove are all corroborated by large clinical studies involving relative risk for former smokers and transplant recipients. We then show that at least some of these theorems do not extend to other Armitage and Doll multistage models. We conclude with suggestions for lifelong increased cancer screening for both former smoker and transplant recipient subpopulations of individuals and possible future directions of research.

Corrigendum to "Silent circulation of poliovirus in small populations" [Infectious Disease Modeling 2 (2017) 431-440].

[This corrects the article DOI: 10.1016/j.idm.2017.11.001.].

Efficacies of prevention and control measures applied during an outbreak in Southwest Madrid, Spain.

Leishmaniasis is a vector-borne disease of worldwide distribution, currently present in 98 countries. Since late 2010, an unusual increase of human visceral and cutaneous leishmaniasis cases has been observed in the south-western Madrid region, totaling more than 600 cases until 2015. Some hosts, such as human, domestic dog and cat, rabbit (Oryctolagus cuniculus), and hare (Lepus granatensis), were found infected by the parasite of this disease in the area. Hares were described as the most important reservoir due to their higher prevalence, capacity to infect the vector, and presence of the same strains as in humans. Various measures were adopted to prevent and control the disease, and since 2013 there was a slight decline in the human sickness. We used a mathematical model to evaluate the efficacy of each measure in reducing the number of infected hosts. We identified in the present model that culling both hares and rabbits, without immediate reposition of the animals, was the best measure adopted, decreasing the proportion of all infected hosts. Particularly, culling hares was more efficacious than culling rabbits to reduce the proportion of infected individuals of all hosts. Likewise, lowering vector contact with hares highly influenced the reduction of the proportion of infected hosts. The reduction of the vector density per host in the park decreased the leishmaniasis incidence of hosts in the park and the urban areas. On the other hand, the reduction of the vector density per host of the urban area (humans, dogs and cats) decreased only their affected population, albeit at a higher proportion. The use of insecticide-impregnated collar and vaccination in dogs affected only the infected dogs' population. The parameters related to the vector contact with dog, cat or human do not present a high impact on the other hosts infected by Leishmania. In conclusion, the efficacy of each control strategy was determined, in order to direct future actions in this and in other similar outbreaks. The present mathematical model was able to reproduce the leishmaniasis dynamics in the Madrid outbreak, providing theoretical support based on successful experiences, such as the reduction of human cases in Southwest Madrid, Spain.

Silent circulation of poliovirus in small populations.

BACKGROUND: Small populations that have been isolated by conflict make vaccination and surveillance difficult, threatening polio eradication. Silent circulation is caused by asymptomatic infections. It is currently not clear whether the dynamics of waning immunity also influence the risk of silent circulation in the absence of vaccination. Such circulation can, nevertheless, be present following a declaration of elimination as a result of inadequate acute flaccid paralysis surveillance (AFPS) or environmental surveillance (ES). METHODS: We have constructed a stochastic model to understand how stochastic effects alter the ability of small populations to sustain virus circulation in the absence of vaccination. We analyzed how the stochastic process determinants of the duration of silent circulation that could have been detected by ES were affected by R0 , waning dynamics, population size, and AFPS sensitivity in a discrete individual stochastic model with homogeneous contagiousness and random mixing. We measured the duration of silent circulation both by the interval between detected acute flaccid paralysis (AFP) cases and the duration of circulation until elimination. RESULTS: As R0 increased and population size increased, the interval between detected AFP cases and the duration of circulation until elimination increased. As AFPS detection rates decreased, the interval between detected AFP cases increased. There was up to a 22 % chance of silent circulation lasting for more than 3 years with 100 % AFP detection. The duration of silent circulation was not affected by the waning immunity dynamics. CONCLUSION: We demonstrated that small populations have the potential to sustain prolonged silent circulation. Surveillance in these areas should be intensified before declaring elimination. To further validate these conclusions, it is necessary to realistically relax the simplifying assumptions about mixing and waning.

Characteristic patterns of cancer incidence: Epidemiological data, biological theories, and multistage models.

We investigate and classify several patterns in cancer incidence and relative risk data which persist across different countries and multiple published studies. We then explore biological hypotheses as well as many mathematical models in the literature that attempt to explain these patterns. A general modeling framework is presented which is general enough to model most of observed behaviors. It is our belief that this model has sufficient flexibility to be adapted to new information as it is discovered. As one application of this framework, we give a model for the effect of aging on the process of carcinogenesis.

Asymptomatic spread of huanglongbing and implications for disease control.

Huanglongbing (HLB) is a bacterial infection of citrus trees transmitted by the Asian citrus psyllid Diaphorina citri. Mitigation of HLB has focused on spraying of insecticides to reduce the psyllid population and removal of trees when they first show symptoms of the disease. These interventions have been only marginally effective, because symptoms of HLB do not appear on leaves for months to years after initial infection. Limited knowledge about disease spread during the asymptomatic phase is exemplified by the heretofore unknown length of time from initial infection of newly developing cluster of young leaves, called flush, by adult psyllids until the flush become infectious. We present experimental evidence showing that young flush become infectious within 15 d after receiving an inoculum of Candidatus Liberibacter asiaticus (bacteria). Using this critical fact, we specify a microsimulation model of asymptomatic disease spread and intensity in a grove of citrus trees. We apply a range of psyllid introduction scenarios to show that entire groves can become infected with up to 12,000 psyllids per tree in less than 1 y, before most of the trees show any symptoms. We also show that intervention strategies that reduce the psyllid population by 75% during the flushing periods can delay infection of a full grove, and thereby reduce the amount of insecticide used throughout a year. This result implies that psyllid surveillance and control, using a variety of recently available technologies, should be used from the initial detection of invasion and throughout the asymptomatic period.

A flexible simulation platform to quantify and manage emergency department crowding.

BACKGROUND: Hospital-based Emergency Departments are struggling to provide timely care to a steadily increasing number of unscheduled ED visits. Dwindling compensation and rising ED closures dictate that meeting this challenge demands greater operational efficiency. METHODS: Using techniques from operations research theory, as well as a novel event-driven algorithm for processing priority queues, we developed a flexible simulation platform for hospital-based EDs. We tuned the parameters of the system to mimic U.S. nationally average and average academic hospital-based ED performance metrics and are able to assess a variety of patient flow outcomes including patient door-to-event times, propensity to leave without being seen, ED occupancy level, and dynamic staffing and resource use. RESULTS: The causes of ED crowding are variable and require site-specific solutions. For example, in a nationally average ED environment, provider availability is a surprising, but persistent bottleneck in patient flow. As a result, resources expended in reducing boarding times may not have the expected impact on patient throughput. On the other hand, reallocating resources into alternate care pathways can dramatically expedite care for lower acuity patients without delaying care for higher acuity patients. In an average academic ED environment, bed availability is the primary bottleneck in patient flow. Consequently, adjustments to provider scheduling have a limited effect on the timeliness of care delivery, while shorter boarding times significantly reduce crowding. An online version of the simulation platform is available at http://spark.rstudio.com/klopiano/EDsimulation/. CONCLUSION: In building this robust simulation framework, we have created a novel decision-support tool that ED and hospital managers can use to quantify the impact of proposed changes to patient flow prior to implementation.

A Mathematic Model That Describes Modes of MdSGHV Transmission within House Fly Populations.

In this paper it is proposed that one potential component by which the Musca domestica salivary gland hypertrophy virus (MdSGHV) infects individual flies is through cuticular damage. Breaks in the cuticle allow entry of the virus into the hemocoel causing the infection. Male flies typically have a higher rate of infection and a higher rate of cuticular damage than females. A model for the transmission of MdSGHV was formulated assuming several potential and recognized means of transmission. The model yields results that are in agreement with field data that measured the infection rate in house flies on dairy farms in Florida. The results from this model indicate that MdSGHV will be maintained at a stable rate within house fly populations and support the future use of MdSGHV as a birth control agent in house fly management.

Muscavirus (MdSGHV) disease dynamics in house fly populations--how is this virus transmitted and has it potential as a biological control agent?

The newly classified family Hytrosaviridae comprises several double-stranded DNA viruses that have been isolated from various dipteran species. These viruses cause characteristic salivary gland hypertrophy and suppress gonad development in their hosts. One member, Muscavirus or MdSGHV, exclusively infects adult house flies (Musca domestica) and, owing to its massive reproduction in and release from the salivary glands, is believed to be transmitted orally among feeding flies. However, results from recent experiments suggest that additional transmission routes likely are involved in the maintenance of MdSGHV in field populations of its host. Firstly, several hours before newly emerged feral flies begin feeding activities, the fully formed peritrophic matrix (PM) constitutes an effective barrier against oral infection. Secondly, flies are highly susceptible to topical virus treatments and intrahemocoelic injections. Thirdly, disease transmission is higher when flies are maintained in groups with infected conspecifics than when flies have access to virus-contaminated food. We hypothesize that interactions between flies may lead to cuticular damage, thereby providing an avenue to viral particles for direct access to the hemocoel. Based on our current knowledge, two options seem plausible for developing Muscavirus as a sterilizing agent to control house fly populations: The virus may either be formulated with PM-disrupting materials to facilitate oral infection from a feeding bait system, or amended with abrasive materials to enhance infection through a damaged cuticle after topical aerosol applications.