Assessing the Role of Patient Generation Techniques in Virtual Clinical Trial Outcomes.

Virtual clinical trials (VCTs) are growing in popularity as a tool for quantitatively predicting heterogeneous treatment responses across a population. In the context of a VCT, a plausible patient is an instance of a mathematical model with parameter (or attribute) values chosen to reflect features of the disease and response to treatment for that particular patient. A number of techniques have been introduced to determine the set of model parametrizations to include in a virtual patient cohort.

Predicting the impact of placing an overdose prevention site in Philadelphia: a mathematical modeling approach.

Background: Fatal overdoses from opioid use and substance disorders are increasing at an alarming rate. One proposed harm reduction strategy for reducing overdose fatalities is to place overdose prevention sites-commonly known as safe injection facilities-in proximity of locations with the highest rates of overdose. As urban centers in the USA are tackling legal hurdles and community skepticism around the introduction and location of these sites, it becomes increasingly important to assess the magnitude of the effect that these services might have on public health.

Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections.

Mathematical models of biological systems must strike a balance between being sufficiently complex to capture important biological features, while being simple enough that they remain tractable through analysis or simulation. In this work, we rigorously explore how to balance these competing interests when modeling murine melanoma treatment with oncolytic viruses and dendritic cell injections. Previously, we developed a system of six ordinary differential equations containing fourteen parameters that well describes experimental data on the efficacy of these treatments.

Distinction in EEG slow oscillations between chronic mild traumatic brain injury and PTSD.

Spectral information from resting state EEG is altered in acute mild traumatic brain injury (mTBI) and in disorders of consciousness, but there is disagreement about whether mTBI can elicit long term changes in the spectral profile. Even when identified, any long-term changes attributed to TBI can be confounded by psychiatric comorbidities such as PTSD, particularly for combat-related mTBI where postdeployment distress is commonplace. To address this question, we measured spectral power during the resting state in a large sample of service members and Veterans varying in mTBI history and active PTSD diagnosis but matched for having had combat blast exposure.

Evaluating Infection Prevention Strategies in Out-Patient Dialysis Units Using Agent-Based Modeling.

Patients receiving chronic hemodialysis (CHD) are among the most vulnerable to infections caused by multidrug-resistant organisms (MDRO), which are associated with high rates of morbidity and mortality. Current guidelines to reduce transmission of MDRO in the out-patient dialysis unit are targeted at patients considered to be high-risk for transmitting these organisms: those with infected skin wounds not contained by a dressing, or those with fecal incontinence or uncontrolled diarrhea. Here, we hypothesize that targeting patients receiving antimicrobial treatment would more effectively reduce transmission and acquisition of MDRO.

Treatment strategies for combining immunostimulatory oncolytic virus therapeutics with dendritic cell injections.

Oncolytic viruses (OVs) are used to treat cancer, as they selectively replicate inside of and lyse tumor cells. The efficacy of this process is limited and new OVs are being designed to mediate tumor cell release of cytokines and co-stimulatory molecules, which attract cytotoxic T cells to target tumor cells, thus increasing the tumor-killing effects of OVs. To further promote treatment efficacy, OVs can be combined with other treatments, such as was done by Huang et al.

Characterizing effects of mild traumatic brain injury and posttraumatic stress disorder on balance impairments in blast-exposed servicemembers and Veterans using computerized posturography.

The high rate of blast exposures experienced by U.S. servicemembers (SMs) during the recent conflicts in Iraq and Afghanistan has resulted in frequent combat-related mild traumatic brain injuries (mTBIs).

Quantitative impact of immunomodulation versus oncolysis with cytokine-expressing virus therapeutics.

The past century's description of oncolytic virotherapy as a cancer treatment involving specially-engineered viruses that exploit immune deficiencies to selectively lyse cancer cells is no longer adequate. Some of the most promising therapeutic candidates are now being engineered to produce immunostimulatory factors, such as cytokines and co-stimulatory molecules, which, in addition to viral oncolysis, initiate a cytotoxic immune attack against the tumor. This study addresses the combined effects of viral oncolysis and T-cell-mediated oncolysis.

Effects of hyperbaric oxygen on eye tracking abnormalities in males after mild traumatic brain injury.

The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (TBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA).

Differential eye movements in mild traumatic brain injury versus normal controls.

Objectives: Objective measures to diagnose and to monitor improvement of symptoms following mild traumatic brain injury (mTBI) are lacking. Computerized eye tracking has been advocated as a rapid, user friendly, and field-ready technique to meet this need.

Design: Eye-tracking data collected via a head-mounted, video-based binocular eye tracker was used to examine saccades, fixations, and smooth pursuit movement in military Service Members with postconcussive syndrome (PCS) and asymptomatic control subjects in an effort to determine if eye movement differences could be found and quantified.

A mathematical model for cell cycle-specific cancer virotherapy.

Oncolytic viruses preferentially infect and replicate in cancerous cells, leading to elimination of tumour populations, while sparing most healthy cells. Here, we study the cell cycle-specific activity of viruses such as vesicular stomatitis virus (VSV). In spite of its capacity as a robust cytolytic agent, VSV cannot effectively attack certain tumour cell types during the quiescent, or resting, phase of the cell cycle.

Efficacy of infection control interventions in reducing the spread of multidrug-resistant organisms in the hospital setting.

Multidrug-resistant organisms (MDRO) continue to spread in hospitals globally, but the population-level impact of recommended preventive strategies and the relative benefit of individual strategies targeting all MDRO in the hospital setting are unclear. To explore the dynamics of MDRO transmission in the hospital, we develop a model extending data from clinical individual-level studies to quantify the impact of hand hygiene, contact precautions, reducing antimicrobial exposure and screening surveillance cultures in decreasing the prevalence of MDRO colonization and infection. The effect of an ongoing increase in the influx of patients colonized with MDRO into the hospital setting is also quantified.