Coevolutionary immune system dynamics driving pathogen speciation

We introduce and analyze a within-host dynamical model of the coevolution between rapidly mutating pathogens and the adaptive immune response. Pathogen mutation and a homeostatic constraint on lymphocytes both play a role in allowing the development of chronic infection, rather than quick pathogen clearance. The dynamics of these chronic infections display emergent structure, including branching patterns corresponding to asexual pathogen speciation, which is fundamentally driven by the coevolutionary interaction. Over time, continued branching creates an increasingly fragile immune system, and leads to the eventual catastrophic loss of immune control.Comment: main article: 16 pages, 5 figures; supporting information: 3 page

Optimal vaccination in a stochastic epidemic model of two non-interacting populations

Developing robust, quantitative methods to optimize resource allocations in response to epidemics has the potential to save lives and minimize health care costs. In this paper, we develop and apply a computationally efficient algorithm that enables us to calculate the complete probability distribution for the final epidemic size in a stochastic Susceptible-Infected-Recovered (SIR) model. Based on these results, we determine the optimal allocations of a limited quantity of vaccine between two non-interacting populations. We compare the stochastic solution to results obtained for the traditional, deterministic SIR model. For intermediate quantities of vaccine, the deterministic model is a poor estimate of the optimal strategy for the more realistic, stochastic case.Comment: 21 pages, 7 figure

Using The Balanced Scorecard To Reform University Policing: An Illustrative Example

Since the death of George Floyd, protestors nationwide have called for police reform, including on college campuses. This paper provides an illustrative example of how a balanced scorecard approach was utilized in the strategic reform of a campus police department. The study highlights how decision-makers can integrate the balanced scorecard’s use to successfully reform the campus police department and to create buy-in throughout the process

Comparing the Effects of Tissue Flossing and Instrument Assisted Soft Tissue Mobilization on Ankle Dorsiflexion

Purpose: The purpose of this study is to evaluate the claimed effects of a new technique called Tissue Flossing and compare those effects with Instrument Assisted Soft Tissue Mobilization, or IASTM. Background: Tissue flossing is a relatively new technique that utilizes a large rubber band that is wrapped around the involved joint. Once applied, range of motion exercises are completed, and the band is removed. The goal is to increase joint range of motion. IASTM involves using a specialized tool to scrape an effected muscle or tendon of the body. The goal is to reduce any adhesions or scar tissue in the muscle and bring blood flow to the area to encourage healing and increase range of motion. Design: The design for this study is a multi-group pre-test post-test study with three groups of participants. there was a significant effect of time. Results: Therefore, for the participants as a whole, ROM significantly improved over time (p value = 0.023). However, there was no significant difference in ROM between groups over the different time periods. Discussion: Conclusions can be made, at the very least, that stretching protocol done at a minimum of two times a week, can increase ankle dorsiflexion. We are unable to determine if IASTM or tissue flossing would be beneficial for increasing flexibility. However, we can draw that it is not detrimental to ankle dorsiflexion

The Suppression of Immune System Disorders by Passive Attrition

Exposure to infectious diseases has an unexpected benefit of inhibiting autoimmune diseases and allergies. This is one of many fundamental fitness tradeoffs associated with immune system architecture. The immune system attacks pathogens, but also may (inappropriately) attack the host. Exposure to pathogens can suppress the deleterious response, at the price of illness and the decay of immunity to previous diseases. This “hygiene hypothesis” has been associated with several possible underlying biological mechanisms. This study focuses on physiological constraints that lead to competition for survival between immune system cell types. Competition maintains a relatively constant total number of cells within each niche. The constraint implies that adding cells conferring new immunity requires loss (passive attrition) of some cells conferring previous immunities. We consider passive attrition as a mechanism to prevent the initial proliferation of autoreactive cells, thus preventing autoimmune disease. We see that this protection is a general property of homeostatic regulation and we look specifically at both the IL-15 and IL-7 regulated niches to make quantitative predictions using a mathematical model. This mathematical model yields insight into the dynamics of the “Hygiene Hypothesis,” and makes quantitative predictions for experiments testing the ability of passive attrition to suppress immune system disorders. The model also makes a prediction of an anti-correlation between prevalence of immune system disorders and passive attrition rates

Razonamiento covariacional aplicado a la modelación de eventos dinámicos: un marco conceptual y un estudio

Se desarrolla la noción de razonamiento covariacional y se propone un marco conceptual para describir las acciones mentales involucradas al aplicar razonamiento covariacional cuando se interpretan y representan funciones asociadas a eventos dinámicos. Se reporta la habilidad para razonar sobre cantidades covariantes en situaciones dinámicas, de estudiantes de alto desempeño en un curso de cálculo. El estudio reveló que ellos eran capaces de construir imágenes de la variable dependiente de una función que cambia simultáneamente con el cambio imaginado de la variable independiente, y en algunas ocasiones eran capaces de construir imágenes de la razón de cambio para intervalos contiguos del dominio de una función. Sin embargo, al parecer, tuvieron dificultad para formar imágenes de una razón cambiante de manera continua y no pudieron representar con exactitud o interpretar los puntos de inflexión ni la razón creciente y decreciente para funciones asociadas a situaciones dinámicas. Estos hallazgos sugieren que el currículo y la instrucción deberían aumentar el énfasis en el cambio que debe darse en los alumnos de una imagen coordinada de dos variables que cambian simultáneamente a una imagen coordinada de razón de cambio instantánea con cambios continuos en la variable independiente para funciones asociadas a situaciones dinámicas

Economic Evaluation of Tocilizumab Monotherapy Compared to Adalimumab Monotherapy in the Treatment of Severe Active Rheumatoid Arthritis

AbstractObjectivesTo estimate the cost-effectiveness of tocilizumab (TCZ) monotherapy (Mono) versus adalimumab (ADA) Mono from the US payer perspective in patients with rheumatoid arthritis for whom methotrexate is inappropriate.MethodsWe compared TCZ Mono (8 mg/kg monthly) with ADA Mono (40 mg every other week), using efficacy results from a head-to-head study, ADalimumab ACTemrA (ADACTA). We calculated the incremental cost per responder (achievement of American College of Rheumatology [ACR] 20% improvement criteria, ACR 50% improvement criteria, ACR 70% improvement criteria, or low disease activity score) for TCZ versus ADA at 6 months. A patient-level simulation was used to estimate the lifetime incremental cost per quality-adjusted life-year (QALY) of initiating treatment with TCZ Mono versus ADA Mono. Both drugs are followed by an etanercept-certolizumab-palliative care sequence. Nonresponders discontinue at 6 months; responders experience a constant probability of discontinuation. Discontinuers move to the next treatment. ACR responses produce changes in the Health Assessment Questionnaire (HAQ) score. We mapped the HAQ score to utility to estimate QALYs. Costs include those related to hospitalization and those related to treatment (drug acquisition, administration, and monitoring). Probabilistic and one-way sensitivity analyses were conducted, along with several scenario analyses.ResultsCompared with ADA, TCZ was more effective, with an estimated 6-month incremental cost ranging from $6,570 per additional low disease activity score achiever to$14,265 per additional ACR 70% improvement criteria responder. The lifetime incremental cost-effectiveness ratio was $36,944/QALY.ConclusionsTCZ Mono is projected to be cost-effective compared with ADA Mono in patients with severe rheumatoid arthritis for whom methotrexate is not appropriate, from a US payer perspective

Robustness and Fragility in Immunosenescence

We construct a model to study tradeoffs associated with aging in the adaptive immune system, focusing on cumulative effects of replacing naive cells with memory cells. Binding affinities are characterized by a stochastic shape space model. System loss arising from an individual infection is associated with disease severity, as measured by the total antigen population over the course of an infection. We monitor evolution of cell populations on the shape space over a string of infections, and find that the distribution of losses becomes increasingly heavy-tailed with time. Initially this lowers the average loss: the memory cell population becomes tuned to the history of past exposures, reducing the loss of the system when subjected to a second, similar infection. This is accompanied by a corresponding increase in vulnerability to novel infections, which ultimately causes the expected loss to increase due to overspecialization, leading to increasing fragility with age (i.e., immunosenescence). In our model, immunosenescence is not the result of a performance degradation of some specific lymphocyte, but rather a natural consequence of the built-in mechanisms for system adaptation. This “robust, yet fragile” behavior is a key signature of Highly Optimized Tolerance