PURPOSE:High-dose-rate (HDR) brachytherapy (BT) is a well-tolerated and effective treatment for prostate cancer. There is limited research, however, investigating toxicity outcomes with HDRBT treatment among veterans. The objective of this study is to assess the impact on health-related quality of life (hrQOL) and physician-graded toxicities associated with HDRBT as monotherapy among veterans treated at Edward Hines, Jr. Veterans Affairs Hospital in Hines, Illinois.METHODS:Between 2016 and 2019, 74 veterans with low- or intermediate-risk prostate cancer were treated with HDRBT as monotherapy with 27 Gy in 2 fractions, delivered over 2 implants. Veteran-reported hrQOL in the genitourinary (GU), gastrointestinal (GI), and sexual domains was assessed using the International Prostate Symptoms Score (IPSS) and Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. Mixed linear effect models were used to assess differences in the hrQOL scores at follow-up compared with baseline scores. Statistically significant differences in hrQOL scores from baseline were further assessed for clinical significance, using minimal clinically important difference (MCID) evaluations.RESULTS:Median follow-up was 18 months. Veterans reported declines in GU, GI, and sexual hrQOL scores immediately after treatment, with the IPSS and EPIC-26 hrQOL scores all displaying significant decrease from baseline over time. The majority of the declines in hrQOL scores met criteria for MCID. These hrQOL scores trended toward a return to baseline, with the EPIC-26 urinary obstruction score returning to baseline at the 18-month follow-up assessment and the EPIC-26 bowel score returning to baseline at the 12-month follow-up. The IPSS, urinary incontinence, and sexual scores did not return to baseline at 18 months. The grade 2 maximum physician-graded GU, GI, and sexual toxicity rates were 65%, 5%, and 53%, respectively. There was 1 incidence of grade 3 GU toxicity but no grade 3 GI or sexual toxicity.CONCLUSIONS:HDRBT as monotherapy is a well-tolerated treatment option for veterans with low- or intermediate-risk prostate cancer, with favorable veteran-reported and physician-graded toxicities. Veterans should be educated about HDRBT as an option when counseled regarding treatment for localized prostate cancer.

In this paper we propose an algorithm to estimate the parameters, including time delay, of continuous time systems based on instrumental variable identification methods. To overcome the multiple local minima of the cost function associated with the estimation of a time delay system, we utilize the useful redundancy technique. Specifically, the cost function is filtered through a set of low-pass filters to improve convexity with the useful redundancy technique exploited to achieve convergence to the global minimum of the optimization problem. Numerical examples are presented to demonstrate the effectiveness of the proposed algorithm.

This chapter investigates the problem of heart rate regulation during cycle-ergometer exercise using both a non-model-based and a model-based control strategy along with a real-time damped parameter estimation scheme. A recursive damped parameter estimation method is also developed, by incorporation of a weighting upon the one-step parameter variation, which in contrast to the conventional parameter estimation schemes can avoid the occurrence of the so-called blowup phenomena. Delivering a feedback signal when the pedals are not in a suitable position to efficiently exert force may be ineffective and this may, in turn, lead to the cognitive disengagement of the user from the feedback controller. The chapter examines a novel form of control system which is called an 'actuator-based event-driven control system'. The proposed control and estimation scheme were experimentally verified using several …

Background: Improving upper limb function is a core element of stroke rehabilitation, needed to maximise recovery and reduce disability. There is an increasing number of medical devices available to improve motor control of the upper limb following stroke, but yet there is no systematic review combining information about these devices and to evaluate the effectiveness in improving upper limb motor control. Objective: (1) identify all existing sensor-based assistive technology targeted at improving motor control of the upper limb following stroke, and (2) investigate the effectiveness of current sensor-based assistive technology for improving the motor control of the upper limb following stroke. Search Methods: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE; EMBASE; CINAHL; AMED; IEEE Explorer; ProQuest Dissertations and Theses (International), ISI Proceedings (Conference) databases, and occupational therapy (OT Seeker) and physiotherapy (PEDRO) databases. Data collection and analysis: Following exclusion of irrelevant titles by one review author, two review authors independently screened abstracts according to inclusion and exclusion criteria. The quality of evidence was determined independently by two authors using the Pedro levels of evidence scale. We systematically tabulated data and performed meta-analysis where studies used the same outcome measures. Results: 2364 records were screened, and 221 full-text articles were evaluated for eligibility. Finally, 65 studies for objective 1, and 29 randomized controlled trials for objective 2 were included. Studies were divided into 7 groups for objective 2. Results were statistically significant for EMG and Electrical Simulation (standardised mean difference (SMD) 0.46, 95% confidence intervals (CI) -0.03 to 0.96, based on 2 studies with 65 participants). However, results were not statistically significant for the other device groups. Authors’ Conclusions: EMG and Electrical Stimulation showed a significant effect in improving upper limb function, but it is unknown whether effects are sustained in the longer term. Further studies are needed to investigate the effectiveness of sensor-based devices to improve upper limb motor control.

In this paper, a new dynamic model describing the epileptic seizure initiation through transition from interictal to ictal state in a brain predisposed to epilepsy is suggested. The model follows Freeman’s approach where the brain is viewed as a network of interconnected oscillators. The proposed nonlinear model is experimentally motivated and relies on changes in synaptic strength in response to excitatory spikes. This model exhibits a threshold beyond which a bifurcation toward a short-term plasticity state occurs leading to seizure onset. A resulting explanatory assumption is that when considering epilepsy, brain regions are characterized by abnormally low thresholds toward short-term synaptic plasticity. It is shown by simulation that the proposed model enables some experimentally observed qualitative features to be reproduced. Moreover, a preliminary discussion on the impact of the underlying assumptions on the fundamental issue of seizure control is proposed through an EEG based feedback control scheme.

PURPOSE:Pulsed reduced-dose-rate radiotherapy (PRDR) is a reirradiation technique that reduces the effective dose rate and increases the treatment time, allowing sublethal damage repair during irradiation. PATIENTS AND METHODS:A total of 103 patients with recurrent glioma underwent reirradiation using PRDR (86 considered to have Grade 4 at PRDR). PRDR was delivered using a series of 0.2-Gy pulses at 3-min intervals, creating an apparent dose rate of 0.0667 Gy/min to a median dose of 50 Gy (range, 20-60) delivered in 1.8-2.0-Gy fractions. The mean treatment volume was 403.5±189.4 cm3 according to T2-weighted magnetic resonance imaging and a 2-cm margin. RESULTS:For the initial or upgraded Grade 4 cohort (n=86), the median interval from the first irradiation to PRDR was 14 months. Patients undergoing PRDR within 14 months of the first irradiation (n=43) had a median survival of 21 weeks. Those treated ≥14 months after radiotherapy had a median survival of 28 weeks (n=43; p=0.004 and HR=1.82 with a 95% CI ranging from 1.25 to 3.10). These data compared favorably to historical data sets, because only 16% of the patients were treated at first relapse (with 46% treated at the second relapse, 32% at the third or fourth relapse, and 4% at the fourth or fifth relapse). The median survival since diagnosis and retreatment was 6.3 years and 11.4 months for low-grade, 4.1 years and 5.6 months for Grade 3, and 1.6 years and 5.1 months for Grade 4 tumors, respectively, according to the initial histologic findings. Multivariate analysis revealed age at the initial diagnosis, initial low-grade disease, and Karnofsky performance score of ≥80 to be significant predictors of survival after initiation of PRDR. CONCLUSION:PRDR allowed for safe retreatment of larger volumes to high doses with palliative benefit.

Identification of continuous-time systems typically present problems due to the facts that one cannot, in general, measure the time derivatives of the signals and, also, the sampled nature of the data. We utilise indirect inference as the underlying principle for continuous time system identification. Indirect inference has been widely used in the econometrics area for time series modeling. Here we adapt the indirect inference technique to include systems with an exogenous input and apply it to the problem of system identification. We use an example problem posed by Rao and Garnier to show the effectiveness of the indirect inference technique when contrasted to other continuous-time methods of identification.

This paper develops the idea of min–max robust experiment design for dynamic system identification. The idea of min–max experiment design has been explored in the statistics literature. However, the technique is virtually unknown by the engineering community and, accordingly, there has been little prior work on examining its properties when applied to dynamic system identification. This paper initiates an exploration of these ideas. The paper considers linear systems with energy (or power) bounded inputs. We assume that the parameters lie in a given compact set and optimise the worst case over this set. We also provide a detailed analysis of the solution for an illustrative one parameter example and propose a convex optimisation algorithm that can be applied more generally to a discretised approximation to the design problem. We also examine the role played by different design criteria and present a simulation example illustrating the merits of the proposed approach.

PID controllers are the most widely used control scheme in industry. Traditionally these controllers have been implemented in analog or digital form on specifically dedicated communication links. However, there has been significant recent interest into deploying control over general purpose communication channels, which allow one to transmit data, voice and control signals. Naturally the successful design of such a Networked Control System necessitates a blend of techniques which reflect both Control and Communication aspects. The present work examines the effect of channel noise (or, equivalently, of channel capacity) on closed loop system behaviour. It is shown, and experimentally verified, how performance can be optimized via signal coding.

In this paper we propose a new approach to robust optimal experiment design. The key departure from earlier work is that we specifically account for the fact that, prior to the experiment, we possess only partial knowledge of the system. We also give a detailed analysis of the solution for a simple case and propose a concave optimization algorithm that can be applied more generally.

Image-guided IMRT is a revolutionary concept whose clinical implementation is rapidly evolving. Methods of executing beam intensity modulation have included individually designed compensators, static multi-leaf collimators (MLC), dynamic MLC, and sequential (serial) tomotherapy. We have developed helical tomotherapy as an innovative solution to overcome some of the limitations of other IMRT systems. The unique physical design of helical tomotherapy allows the realization of the concepts of adaptive radiotherapy and conformal avoidance. In principle, these advances should improve normal tissue sparing and permit dose reconstruction and verification, thereby allowing significant biologically effective dose escalation. Recent radiobiological findings can be translated into altered fractionation schemes that aim to improve the local control and long-term survival. This strategy is being tested at the University of Wisconsin using helical tomotherapy with its highly precise delivery and verification system along with meticulous and practical forms of immobilization. Innovative techniques such optical guidance, respiratory gating, and ultrasound assessments are being designed and tailored for helical tomotherapy use. The intrinsic capability of helical tomotherapy for megavoltage CT (MVCT) imaging for IMRT image-guidance is being optimized. The unique features of helical tomotherapy might allow implementation of image-guided IMRT that was previously impossible or impractical. Here we review the technological, physical, and radiobiological rationale for the ongoing and upcoming clinical trials that will use image-guided IMRT in the form of helical tomotherapy; and we describe our plans for testing our hypotheses in a rigorous prospective fashion.

BACKGROUND:Dissecting cellulitis of the scalp can be an extremely painful and disfiguring dermatological condition. The associated pain can be severe enough in some cases to require opioid analgesics, and this pain in conjunction with the disfigurement can induce significant emotional distress. Conservative treatments often fail to provide relief. Radiation therapy has been successfully used in the past but with outdated equipment and techniques.OBJECTIVES:To evaluate the efficacy and toxicity of modern external beam radiation therapy techniques for the treatment of dissecting cellulitis of the scalp.METHODS:Four patients with intractable dissecting cellulitis of the scalp were treated with electrons or a combination of electrons and photons to the entire scalp. Daily fraction sizes were 2.5 or 3 Gy and initially prescribed to 15-21 Gy. Patients were re-evaluated 3-4 weeks after completion of therapy. Any residual hair growth was treated with additional radiation treatments to ensure full epilation, up to a maximum dose of 35 Gy.RESULTS:Rapid resolution of pain was seen in all patients with pain. Regression of nodules and decreased discharge was seen in all patients following treatment and cosmesis was subjectively improved. No long-term toxicity has been observed.CONCLUSIONS:Using modern techniques and equipment, radiation therapy appears to be a reasonable option for patients with severe/refractory dissecting cellulitis of the scalp. Acute effects are mild and well tolerated. Aside from alopecia, which was present to some extent in all patients before treatment, no long-term complications have been observed.

Intensity-modulated radiation therapy (IMRT) represents a significant technological advancement in the ability to deliver highly conformal radiation therapy. Thanks to increased availability, general clinical implementation has become progressively more common. However, there are several precautions worthy of comment regarding the clinical applications of IMRT. In theory, the increased irradiated volume and leakage radiation that occasionally accompanies IMRT could contribute to unanticipated complications and safety concerns. The protracted delivery time of IMRT with the associated increased linac monitor units can result in photoactivation of elements within the linac collimator, thereby inadvertently increasing radiation exposure to patients and staff when high-energy photons are used. The increased volumes of normal tissue exposed to lower doses of radiation through IMRT theoretically could promote carcinogenesis and complications due to the bystander effect, low-dose hyper-radiosensitivity, and diminished repair of double strand DNA breaks at very low doses. Tumor control may be adversely affected by the lower radiation dose-rates of delivery sometimes associated with IMRT as well the occasionally seen low dose “cold shoulder” on the dose-volume histograms. Unusual clinical reactions can appear as a result of the complex, unfamiliar dose-distributions occasionally generated by IMRT treatment planning. Here we discuss some of the precautions worthy of consideration when using IMRT and how these might be addressed in routine practice.

Description This chapter presents a case study of constrained control and estimation in the area of networked control. Networked control is a term used to describe control actions that take place over a networked communication system. A key issue that arises in this context is the need to quantise data so that it can be communicated over the network. Quantisation occurs in both time and space and is needed on bot the" up-link"(between the plant and the control computer) and the" down-link"(between the control computer and the plant). In this chapter we show how this problem can be formulated in the framework of constrained control and estimation.

We read with interest, “Treating the

Purpose: The decrease of biologic effect if delivery of dose fractions takes more than a few minutes has been occasionally recognized in the literature but has been insufficiently studied. It has been recognized as a problem in the long exposures necessary for stereotactic radiotherapy and is also a potential problem in some applications of IMRT. Modeling repair rates is a complex function of dose per fraction, dose rate, half-times of repair, and nature of the tissue of interest (the alpha/beta ratio of intrinsic radiosensitivity to repair capacity). In this article, we model repair rates for a range of doses per fraction and draw conclusions.Methods and Materials: We review the data on half-times of repair in tissues in situ in animals and human patients and conclude that a single first-order (exponential) repair rate is no longer an appropriate assumption for most tissues. At least 2 half-times of repair, and perhaps a distribution of half-times, are required. The faster components have a median half-time of 0.3 h (range, 0.08-1.2 h), and the longer components have a median of 4 h (range, 2.4->6 h). Modeling repair rates by a two-component model is the simplest approach. We have used two models of repair to represent these ranges, one with equal proportions of 0.2 h + 4.0 h half-times, the other with 0.4 h + 4.0 h half-times of repair. Data are also reviewed on the few experiments that have been reported with cell culture that investigate this problem.Results: Computations indicate that any fraction delivery that lasts more than half an hour might experience a clinically significant loss of cell-sterilizing effect. We suggest that a loss of more than 10% in biologically effective dose should be compensated for and show modeled doses and fraction durations for which this situation seems to be likely. It will be dose, tissue, and system dependent and will require more investigation at the clinical level.Conclusion: It is suggested that any radiotherapy schedule that requires more than half an hour for the delivery of 1 fraction should have careful records made and reported, to look for a possible decrease of biologic effect with fraction duration. (C) 2004 Elsevier Inc.