Validation of MTF measurement for digital mammography quality control

The modulation transfer function (MTF) describes the spatial resolution properties of imaging systems. In this work, the accuracy of our implementation of the edge method for calculating the presampled MTF was examined. Synthetic edge images with known MTF were used as gold standards for determining the robustness of the edge method. These images simulated realistic data from clinical digital mammography systems, and contained intrinsic system factors that could affect the MTF accuracy, such as noise, scatter, and flat-field nonuniformities. Our algorithm is not influenced by detector dose variations for MTF accuracy up to 1/2 the sampling frequency. We investigated several methods for noise reduction, including truncating the supersampled line spread function (LSF), windowing the LSF, applying a local exponential fit to the LSF, and applying a monotonic constraint to the supersampled edge spread function. Only the monotonic constraint did not introduce a systematic error; the other methods could result in MTF underestimation. Overall, our edge method consistently computed MTFs which were in good agreement with the true MTF. The edge method was then applied to images from a commercial storage-phosphor based digital mammography system. The calculated MTF was affected by the size (sides of 2.5, 5, or 10 cm) and the composition (lead or tungsten) of the edge device. However, the effects on the MTF were observed only with regard to the low frequency drop (LFD). Scatter nonuniformity was dependent on edge size, and could lead to slight underestimation of LFD. Nevertheless, this negative effect could be minimized by using an edge of 5 cm or larger. An edge composed of lead is susceptible to L-fluorescence, which causes overestimation of the LFD. The results of this work are intended to underline the need for clear guidelines if the MTF is to be given a more crucial role in acceptance tests and routine assessment of digital mammography systems: the MTF algorithm and edge object test tool need to be publicly validated.     

Cost-Effectiveness Assessment of Monitoring Abiraterone Levels in Metastatic Castration-Resistant Prostate Cancer Patients

ObjectivesAbiraterone acetate is registered for the treatment of metastatic castration-sensitive and resistant prostate cancer (mCRPC). Treatment outcome is associated with plasma trough concentrations (C_min) of abiraterone. Patients with a plasma C_min below the target of 8.4 ng/mL may benefit from treatment optimization by dose increase or concomitant intake with food. This study aims to investigate the cost-effectiveness of monitoring abiraterone C_min in patients with mCRPC.MethodsA Markov model was built with health states progression-free survival, progressed disease, and death. The benefits of monitoring abiraterone C_min followed by a dose increase or food intervention were modeled via a difference in the percentage of patients achieving adequate C_min taking a healthcare payer perspective. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainties and their impac to the incremental cost-effectiveness ratio (ICER).ResultsMonitoring abiraterone followed by a dose increase resulted in 0.149 incremental quality-adjusted life-years (QALYs) with €22 145 incremental costs and an ICER of €177 821/QALY. The food intervention assumed equal effects and estimated incremental costs of €7599, resulting in an ICER of €61 019/QALY. The likelihoods of therapeutic drug monitoring (TDM) with a dose increase or food intervention being cost-effective were 8.04%and 81.9%, respectively.ConclusionsMonitoring abiraterone followed by a dose increase is not cost-effective in patients with mCRPC from a healthcare payer perspective. Monitoring in combination with a food intervention is likely to be cost-effective. This cost-effectiveness assessment may assist decision making in future integration of abiraterone TDM followed by a food intervention into standard abiraterone acetate treatment practices of mCRPC patients.     

Long-term care bioethics committees: A cooperative model

Special Articles

Long-term care bioethics committees: A cooperative model     

Microcomputer-based automatic regulation of extracorporeal circulation: a trial for the application of fuzzy inference

Since its establishment many researchers have been trying to automate the process of extracorporeal circulation (ECC). We developed a preliminary experimental model of an automatic regulatory system for ECC. The purpose of the system was to regulate basic hemodynamic parameters such as pump flow and withdrawal blood volume. It was divided into three main components: data sampling unit, central processing unit, and controlling unit. Based on this model we were able to achieve autoregulation of ECC using minimum configuration; however, the system lacked smoothness. This was partly because it was based on a "static" regulation system which used conditional statements having multiple parameters. In this study, we applied fuzzy logic to the former model to achieve more accurate and reliable regulation. We report experimental results for the new system and compare the data between clinical circulation in 13 infants (mean body weight, 13.32 +/- 5.99 kg) and experimental regulation in 7 mongrel dogs (mean body weight, 11.9 +/- 2.53 kg). The comparative study revealed no statistical difference between the two groups. This result suggests that the automatic regulation of ECC may be an alternative to manual operation by a professional perfusionist in the near future.     

TP53 gene mutations predict the response to neoadjuvant treatment with 5-fluorouracil and mitomycin in locally advanced breast cancer.

PURPOSE: Recent studies have found an association between certain TP53 mutations and resistance to anthracycline-based primary medical therapy in breast cancer. The purpose of this study was to investigate whether TP53 mutational status also might influence the response to a non-anthracycline-containing regimen in primary breast cancer. EXPERIMENTAL DESIGN: Thirty-five patients with locally advanced breast cancer were investigated for TP53 mutations before receiving combination chemotherapy with 5-fluorouracil (1000 mg/m(2) on days 1 and 2) and mitomycin (6 mg/m(2) on day 2), administered every 3 weeks for 2-10 cycles in the neoadjuvant setting. RESULTS: Mutations in the TP53 gene, in particular those affecting loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy (i.e., increase in the diameter product of tumor lesion by >/=25%; P = 0.177 for all mutations and P = 0.006 for those affecting L2/L3 domains, respectively). No statistically significant correlation between TP53 LOH and response to therapy was seen. CONCLUSION: This study revealed a significant association between lack of response to 5-fluorouracil and mitomycin and mutations affecting the L2/L3 domains of the p53 protein. Together with our previous finding that such mutations predict resistance to weekly doxorubicin, our data suggest that mutations affecting this particular domain of the p53 protein may cause resistance to several different cytotoxic compounds applied in breast cancer treatment.     

Motivation in pediatric motor rehabilitation: A systematic search of the literature using the self-determination theory as a conceptual framework

Objective: Motivation is suggested as an important factor in pediatric motor rehabilitation. Therefore, we reviewed the existing evidence of (motivational) motor rehabilitation paradigms, and how motivation influences rehabilitation outcome using self-determination theory as conceptual framework. Methods: PubMed and Web-of-Science databases were systematically searched until June 2015. Data were independently extracted and critiqued for quality by three authors. Studies reporting motivational aspects were included. Most studies examined new technology (e.g., virtual reality [VR]). Results: Out of 479 records, three RCT, six case-control, and six non-comparative studies were included with mixed quality. Motivation was rarely reported. Training individualization to the child’s capabilities with more variety seemed promising to increase motivation. Motivation increased when the exercises seemed helpful for daily activities. Conclusions: Motivation in pediatric rehabilitation should be comprehensively assessed within a theoretical framework as there are indications that motivated children have better rehabilitation outcomes, depending on the aspect of motivation.     

The genetics of congenital aniridia—a guide for the ophthalmologist

Congenital aniridia is a rare panocular disease caused by fundamental disturbances in the development of the eye, characterized primarily by hypoplasia of the iris and macula. Severe secondary complications such as keratopathy, cataract, and glaucoma are common and often lead to considerable visual impairment or blindness. Many complications in aniridia patients are difficult to treat and present a challenge for the ophthalmologist. Increasingly, associated nonocular features of the disease are also being recognized. Over the past decades, major steps have been made in the understanding of the genetic basis of aniridia. Moreover, recent studies have prepared the ground for future treatment options based on specific mutations. Therefore, specific knowledge about genetics in aniridia has become more important than ever. We provide an overview of the field of aniridia genetics and its clinical implications.