Optimal control of a vectored plant disease model for a crop with continuous replanting.

Vector-transmitted diseases of plants have had devastating effects on agricultural production worldwide, resulting in drastic reductions in yield for crops such as cotton, soybean, tomato, and cassava. Plant-vector-virus models with continuous replanting are investigated in terms of the effects of selection of cuttings, roguing, and insecticide use on disease prevalence in plants. Previous models are extended to include two replanting strategies: frequencyreplanting and abundance-replanting. In frequency-replanting, replanting of infected cuttings depends on the selection frequency parameter ε, whereas in abundance-replanting, replanting depends on plant abundance via a selection rate parameter also denoted as ε. The two models are analysed and new thresholds for disease elimination are defined for each model. Parameter values for cassava, whiteflies, and African cassava mosaic virus serve as a case study. A numerical sensitivity analysis illustrates how the equilibrium densities of healthy and infected plants vary with parameter values. Optimal control theory is used to investigate the effects of roguing and insecticide use with a goal of maximizing the healthy plants that are harvested. Differences in the control strategies in the two models are seen for large values of ε. Also, the combined strategy of roguing and insecticide use performs better than a single control.

Immune therapeutic strategies using optimal controls with L1 and L2 type objectives.

Therapeutic strategies to correct an excessive immune response to pathogenic infection is investigated as an optimal control problem. The control problem is formulated around a four dimensional mathematical model describing the inflammatory response to a pathogenic insult with two therapeutic control inputs which have either a direct pro- or anti-inflammatory effect in the given system. We use Pontryagin's maximum principle and discuss necessary optimality conditions. We consider both an L1 type objective functional as well as an L2 type objective. For the former, the presence of singular control will be addressed. For each case, numerical simulations using a nonlinear programming optimization solver to acquire different drug treatment strategies are presented and discussed. The results provide insight for possible treatment strategies and the methods could be a relevant tool for future practice to assist in better prediction of clinical outcomes and subsequently better treatment for patients.

Optimization and Control of Agent-Based Models in Biology: A Perspective.

Agent-based models (ABMs) have become an increasingly important mode of inquiry for the life sciences. They are particularly valuable for systems that are not understood well enough to build an equation-based model. These advantages, however, are counterbalanced by the difficulty of analyzing and using ABMs, due to the lack of the type of mathematical tools available for more traditional models, which leaves simulation as the primary approach. As models become large, simulation becomes challenging. This paper proposes a novel approach to two mathematical aspects of ABMs, optimization and control, and it presents a few first steps outlining how one might carry out this approach. Rather than viewing the ABM as a model, it is to be viewed as a surrogate for the actual system. For a given optimization or control problem (which may change over time), the surrogate system is modeled instead, using data from the ABM and a modeling framework for which ready-made mathematical tools exist, such as differential equations, or for which control strategies can explored more easily. Once the optimization problem is solved for the model of the surrogate, it is then lifted to the surrogate and tested. The final step is to lift the optimization solution from the surrogate system to the actual system. This program is illustrated with published work, using two relatively simple ABMs as a demonstration, Sugarscape and a consumer-resource ABM. Specific techniques discussed include dimension reduction and approximation of an ABM by difference equations as well systems of PDEs, related to certain specific control objectives. This demonstration illustrates the very challenging mathematical problems that need to be solved before this approach can be realistically applied to complex and large ABMs, current and future. The paper outlines a research program to address them.

BLADE Sequences in Transverse T2-weighted MR Imaging of the Cervical Spine. Cut-off for Artefacts?

PURPOSE: The BLADE (PROPELLER) technique reduces artefacts in imaging of the cervical spine in sagittal orientation, but till now failed to do so in axial orientation, because here it increased through plane CSF-flow artefacts, which spoiled the benefit of BLADE artefact reduction "in plane". The aim of this study was to compare a BLADE sequence with optimised measurement parameters in axial orientation to T2-TSE. MATERIALS AND METHODS: Both sequences were compared in 58 patients with 31 discal, 16 bony and 11 spinal cord lesions. Image sharpness, reliability of spinal cord depiction, CSF flow artefacts and lesion detection were evaluated by 3 independent observers. Additionally the observers were asked which sequence they would prefer for diagnostic workup. Statistical evaluations were performed using sign and χ2 test. RESULTS: BLADE was significantly superior concerning image sharpness, spinal cord depiction and overall lesion detection. BLADE was rated better for most pathologies, for bony lesions the differences compared with TSE were statistically significant. Regarding CSF-flow artefacts both sequences showed no difference. All readers preferred BLADE in side by side reading. CONCLUSION: An optimised axial T2 BLADE sequence decreases the problems of increased through plane CSF-flow artefacts in this orientation. By reducing various other artefacts it yields better image quality and has the potential to reduce the number of non-diagnostic examinations especially in uncooperative patients. KEY POINTS: T2 BLADE/PROPELLER sequences proofed to reduce artefacts in sagittal spine imaging. BLADE/PROPELLER improve image quality, but can aggravate CSF flow artefacts in axial orientation. Optimised parameter setting for axial T2 BLADE reduces "through-plane" CSF artefacts aggravation. Optimised axial T2 BLADE reduces non-diagnostic examinations especially in uncooperative patients.

BLADE sequences in transverse T2-weighted MR imaging of the cervical spine. Cut-off for Artefacts?

PURPOSE: The BLADE (PROPELLER) technique reduces artefacts in imaging of the cervical spine in sagittal orientation, but till now failed to do so in axial orientation, because here it increased through plane CSF-flow artefacts, which spoiled the benefit of BLADE artefact reduction "in plane". The aim of this study was to compare a BLADE sequence with optimised measurement parameters in axial orientation to T2-TSE. MATERIALS AND METHODS: Both sequences were compared in 58 patients with 31 discal, 16 bony and 11 spinal cord lesions. Image sharpness, reliability of spinal cord depiction, CSF flow artefacts and lesion detection were evaluated by 3 independent observers. Additionally the observers were asked which sequence they would prefer for diagnostic workup. Statistical evaluations were performed using sign and χ2 test. RESULTS: BLADE was significantly superior concerning image sharpness, spinal cord depiction and overall lesion detection. BLADE was rated better for most pathologies, for bony lesions the differences compared with TSE were statistically significant. Regarding CSF-flow artefacts both sequences showed no difference. All readers preferred BLADE in side by side reading. CONCLUSION: An optimised axial T2 BLADE sequence decreases the problems of increased through plane CSF-flow artefacts in this orientation. By reducing various other artefacts it yields better image quality and has the potential to reduce the number of non-diagnostic examinations especially in uncooperative patients.

Optimal control of the transient behavior of coupled solid-state lasers.

We apply optimal control theory to substantially reduce transient times for transitions between in-phase and out-of-phase states in coupled solid-state lasers. The control is a time-varying optical field that is injected into the cavities of each laser. We have analytically derived the optimal control and numerically solved the optimality system. Numerical simulations indicate that transient times can be significantly reduced upon increasing the injection strength very briefly.

Treatment of insomnia in hospitalized patients.

OBJECTIVE: To provide recommendations for the short-term management of insomnia in hospitalized patients and review patient assessment, nonpharmacologic treatment modalities, and selection of hypnotic medications. DATA SOURCES: Review articles and primary literature representative of current knowledge regarding the treatment of insomnia were identified by MEDLINE search (1966-January 2001). Search terms included insomnia (sleep initiation and maintenance disorders), benzodiazepines, zaleplon, zolpidem, and trazodone. DATA SYNTHESIS: Literature regarding the management of insomnia in hospitalized patients is limited; therefore, data pertinent to the treatment of ambulatory patients must be extrapolated to the inpatient setting. When evaluating insomnia in hospitalized patients, it seems reasonable to obtain a thorough history and physical examination to identify potential underlying etiologies. Treatment of these underlying etiologies should be considered. When the use of a sedative-hypnotic agent is necessary, medication and dose selection should be based on the pharmacokinetic and adverse effect profiles of each agent. Patent-specific characteristics should also be considered to provide effective treatment while minimizing adverse effects. CONCLUSIONS: Nonpharmacologic approaches to the treatment of insomnia should be considered for hospitalized patients. When sedative-hypnotic medications must be administered, the pharmacokinetic profile of intermediate-acting benzodiazepines (e.g., lorazepam, temazepam) makes them good first-line agents. Zaleplon and zolpidem are also attractive hypnotic agents; however, they are typically reserved for second-line therapy due to cost. Trazodone may be an alternative for patients unable to take benzodiazepines.

Respiratory protection as a function of respirator fitting characteristics and fit-test accuracy.

The fitting characteristics of particulate respirators are no longer assessed in the National Institute for Occupational Safety and Health respirator certification program. It is important for respirator program administrators to understand the implications of that change and the additional burden it may impose. To address that issue, a typical respirator fit-testing program is analyzed using a mathematical model that describes the effectiveness of a fit-testing program as a function of the fitting characteristics of the respirator and the accuracy of the fittesting method. The model is used to estimate (1) the respirator assignment error, the percentage of respirator wearers mistakenly assigned an ill-fitting respirator; (2) the number of fit-test trials necessary to qualify a group of workers for respirator use; and (3) the number of workers who will fail the fit-test with any candidate respirator model and thereby fail to qualify for respirator use. Using data from previous studies, the model predicts respirator assignment errors ranging from 0 to 20%, depending on the fitting characteristics of the respirator models selected and the fit-testing method used. This analysis indicates that when respirators do not necessarily have good fitting characteristics, respirator program administrators should exercise increased care in the selection of respirator models and increased care in fit-testing. Also presented are ways to assess the fitting characteristics of candidate respirator models by monitoring the first-time fit-testing results. The model demonstrates that significant public health and economic benefits can result when only respirators having good fitting characteristics are purchased and respirators are assigned to workers using highly accurate fit-testing methods.

Manganese dioxide exposures and respirator performance at an alkaline battery plant.

Two industrial hygiene studies were conducted at an alkaline battery plant to evaluate worker exposures to manganese dioxide particulate and the effectiveness of filtering facepiece respirators. The work areas studied included the plant's powder-processing tower and press rooms where manganese was blended, compacted with graphite, and inserted into battery cans. Full-shift personal breathing zone monitoring was conducted to estimate manganese dust exposures of press operators, mechanics, and material handlers. In-facepiece and personal breathing zone air sampling pairs were also collected using a program protection factor protocol to estimate the protection provided by the respirators. Particle size evaluations were made using nylon cyclones and Marple personal multi-stage impactors. All samples were analyzed for manganese by inductively coupled argon plasma, atomic emission spectroscopy via NIOSH analytical method 7300 utilizing a modified acid digestion procedure. Fifty-four, full-shift, time-weighted average (TWA) exposures to total manganese ranged from 0.1 to 5.4 milligrams per cubic meter (mg/m3); worker exposures were substantially lower during a follow-up study due to engineering control improvements. Concurrent area sample comparisons of total and respirable manganese revealed that the respirable particulate mass fractions ranged from 6 to 32 percent, and mass median aerodynamic diameters determined from personal breathing zone air samples were mostly greater than 10 micrometers. Fifteen respirator performance evaluations were conducted using Moldex 2200 respirators fitted with 25 millimeter cassettes and light weight sampling probes. Protection factors ranged from 5 to 220, with a geometric mean and standard deviation of 31 and 2.97, respectively. The 5th percentile protection factor estimate was 5, as calculated from the protection factor distribution for this sample set. In 1995, the American Conference of Governmental Industrial Hygienists (ACGIH) lowered the elemental and inorganic manganese dust Threshold Limit Value (TLV) from 5 mg/m3 to 0.2 mg/m3 to address adverse pulmonary and central nervous system effects and male infertility. Although most personal breathing zone concentrations were above 0.2 mg/m3, none of the in-facepiece concentrations exceeded this concentration. Parkinson's-like symptoms have been reported in the literature for high manganese dust and fume exposures, but the importance of low dust exposures for producing neurological effects is uncertain.

Vitamins for the management of cardiovascular disease: a simple solution to a complex problem?

Attention is focusing on the relationship between homocysteine and cardiovascular disease and the role of vitamins in the management of this prevalent ailment. Epidemiologic studies have shown that a relationship between elevated homocysteine concentrations and cardiovascular disease may exist; however, a cause-and-effect relationship has not been proven. The B vitamins are key components of homocysteine metabolism, and the trend is toward their being increasingly prescribed for cardiovascular disease. Prescribing of antioxidant vitamins, vitamin E in particular, has increased as well. Vitamin E may decrease the risk of nonfatal myocardial infarction in patients with coronary artery disease, but its benefit in preventing fatal myocardial infarction has not been shown. Vitamin supplements are not warranted in all patients with cardiovascular disease but may have a place in therapy for selected patients.

Levels of carbon dioxide in helmet systems used during orthopaedic operations.

The use of isolation helmets has gained popularity as a method of possible protection of the operating-room personnel from diseases that can be transmitted during operative procedures. However, the use of these systems has been associated with a variety of symptoms, including fatigue, diaphoresis, nausea, headache, and irritability. These symptoms have often been attributed to the mental stress of the operative procedure or the physical discomfort of the helmet. As far as we know, no manufacturers include the measured levels of carbon dioxide or the rate of air exchange of their helmet system. A possible common cause of discomfort with helmet systems is the level of carbon dioxide to which the person wearing the device is exposed. We measured the levels of carbon dioxide in four helmet systems from three different manufacturers during light exercise designed to approximate the exertion during an orthopaedic operation. All but one unit failed to meet the exposure limits recommended by the National Institute for Occupational Safety and Health and the Occupational Safety and Health Administration regarding exposure to carbon dioxide. One unit, the Stackhouse Freedom Aire self-contained system, did meet these standards, but the levels of carbon dioxide in this helmet were more than 1000 per cent greater than the ambient levels in air (440 parts per million compared with 4939 parts per million). Isolation systems must be evaluated carefully not only for comfort but also for the physiological effects caused by exposure to elevated levels of carbon dioxide. Operating-room personnel who use such systems should be aware that many of the physical symptoms that they experience may be associated with elevated levels of carbon dioxide.

Optimal control of the chemotherapy of HIV.

Using an existing ordinary differential equation model which describes the interaction of the immune system with the human immunodeficiency virus (HIV), we introduce chemotherapy in an early treatment setting through a dynamic treatment and then solve for an optimal chemotherapy strategy. The control represents the percentage of effect the chemotherapy has on the viral production. Using an objective function based on a combination of maximizing benefits based on T cell counts and minimizing the systemic cost of chemotherapy (based on high drug dose/strength), we solve for the optimal control in the optimality system composed of four ordinary differential equations and four adjoint ordinary differential equations.

Gender bias against and sexual harassment of AMWA members in Massachusetts.

Despite the increasing participation of women in medicine over the past few decades, hindrances to professional advancement for women physicians and medical students persist. The present study sought to assess the prevalence of gender bias and sexual harassment in a sample of women physicians and medical students. Within a one-year period, 54% of respondents encountered some form of sex discrimination. In addition, approximately one-fourth experienced sexual harassment (27%) and/or discrimination related to parenthood (24%). Unwanted sexual attention not viewed as sexual harassment was experienced by more than twice as many respondents (55%). Other forms of discrimination were reported as well: age (22%), sexual preference (20%), and race (7%). Perceptions of the extent of sex discrimination and sexual harassment, of their impact on professional commitment, and of the adequacy of solutions at institutions varied directly with whether or not respondents had experienced some form of employment discrimination within the past 12 months. This study points to the need for clarification of what constitutes sexual harassment and for the creation of safe, effective mechanisms to remedy and prevent all forms of gender bias.