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We describe a 70 year old patient with a history of epilepsy, who developed a derealisation disorder after discontinuing the use of valproic acid. An experimental treatment with rTMS led to a remarkable decrease of his symptoms. We determined our target, the right ventrolateral prefrontal cortex (VLPFC), with the use of neuronavigation. During treatment no complications occurred, specifically no epileptic seizures.

Introduction: Previous studies have shown interference between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy in the cell cycle, thus reducing efficacy. In this randomised controlled trial we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR-mutated nonsmall cell lung cancer (NSCLC)., Materials and Methods: Treatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0-3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2-16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival, objective response rate (ORR) and toxicity., Results: Between April 2014 and September 2016, 22 patients were randomised equally into both arms; the study was stopped due to slow accrual. Median follow-up was 64 months. Median PFS was 13.7 months (95% CI 5.2-18.8) for CPE and 10.3 months (95% CI 7.1-15.5; hazard ratio (HR) 0.62, 95% CI 0.25-1.57) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.24, 95% CI 0.07-0.83; p=0.02). ORR was 64% for CPE versus 55% for erlotinib monotherapy. Median overall survival was 31.7 months (95% CI 21.8-61.9 months) for CPE compared to 17.2 months (95% CI 11.5-45.5 months) for erlotinib monotherapy (HR 0.58, 95% CI 0.22-1.41 months). Patients treated with CPE had higher rates of treatment-related fatigue, anorexia, weight loss and renal toxicity., Conclusion: Intercalating erlotinib with cisplatin-pemetrexed provides a longer PFS compared to erlotinib alone in EGFR -mutated NSCLC at the expense of more toxicity., Competing Interests: Conflict of interest: R.G.P. Gijtenbeek has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: V. van der Noort has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: J.G.J.V. Aerts has received support for the present manuscript from Roche, Lilly and Amgen; consulting fees from MSD, BMS, Boehringer Ingelheim, Amphera, Eli-Lilly, Takeda, Bayer, Roche, Astra Zeneca and BIOCAD, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from MSD, BMS, Boehringer Ingelheim, Amphera, Eli-Lilly, Takeda, Bayer, Roche, Astra Zeneca and BIOCAD, outside the submitted work; and patents planned, issued or pending for an allogenic tumour cell lysate, Amphera, combination immunotherapy in cancer, and a biomarker for immunotherapy, unrelated to this submission. Conflict of interest: J.A. Staal-van den Brekel has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: E.F. Smit has received support for the present manuscript from Roche, Lilly and Amgen; grants or contracts from Boehringer Ingelheim, Bayer, Roche/Genentech, AstraZeneca and Bristol-Myers Squibb, outside the submitted work; and consulting fees from Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol-Myers Squibb, Merck KGaA, MSD Oncology, Takeda, Bayer, Novartis, Daiichi Sankyo and Seattle Genetics, outside the submitted work. Conflict of interest: F.H. Krouwels has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: F.A. Wilschut has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: T.J.N. Hiltermann has received support for the present manuscript from Roche, Lilly and Amgen; grants or contracts received from Roche, BMS and AstraZeneca, outside the submitted work; consulting fees received from Roche, BMS, AstraZeneca and MSD, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events received from BMS, outside the submitted work. Conflict of interest: W. Timens has received support for the present manuscript from Roche, Lilly and Amgen; and consulting fees received from Merck Sharp Dohme and Bristol-Myers-Squibb, outside the submitted work; and is a board member of the Dutch Society of Pathology and a member of the Council for Research and Innovation of the Federation of Medical Specialists. Conflict of interest: E. Schuuring has received support for the present manuscript from Roche, Lilly and Amgen; grants or contracts from Abbott, Biocartis, Astrazeneca, Invitae/Archer, Bayer, Bio-Rad, Roche, Agena Bioscience, CC Diagnostics and Boehringer Ingelheim, outside the submitted work; consulting fees from MSD/Merck, AstraZeneca, Roche, Novartis, Bayer, BMS, Lilly, Amgen, Illumina, Agena Bioscience, CC Diagnostics, Janssen Cilag (Johnson&Johnson) and Astellas Pharma, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Bio-Rad, Seracare, Roche, Biocartis, Lilly, Agena Bioscience and Illumina, outside the submitted work; and support for attending meetings and/or travel from BioRad and Biocartis, outside the submitted work; and is an unpaid board member of the Dutch Society of Pathology, the European Society of Pathology and the European Liquid Biopsy Society. Conflict of interest: J.D.J. Janssen has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: M. Goosens has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: P.M. van den Berg has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: A.J. de Langen reports grants from BMS, MSD, Boehringer and AstraZeneca, and nonfinancial support from Merck Serono and Roche, outside the submitted work. Conflict of interest: J.A. Stigt has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: B.E.E.M. van den Borne has received support for the present manuscript from Roche, Lilly and Amgen. Conflict of interest: H.J.M. Groen has received support for the present manuscript from Roche, Lilly and Amgen; grants or contracts from Roche and Boehringer Ingelheim, outside the submitted work; and consulting fees from Lilly, Novartis, Roche/Genentech and AstraZeneca, outside the submitted work. Conflict of interest: W.H. van Geffen has received support for the present manuscript from Roche, Lilly and Amgen; has unpaid roles for ERS and NVALT, outside the submitted work; and there have been trials run by his department funded by Roche and Amgen. Conflict of interest: A.J. van der Wekken has received support for the present manuscript from Roche, Lilly and Amgen; grants or contracts from AstraZeneca, Pfizer, Boehringer Ingelheim, Takeda and Roche, outside the submitted work; consulting fees from AstraZeneca, Novartis, Boehringer Ingelheim, Roche, Janssen, Pfizer, Lilly, Takeda and Merck, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Pfizer, outside the submitted work; and support for attending meetings and/or travel received from Lilly, outside the submitted work; and has a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, for CPCT, outside the submitted work., (Copyright ©The authors 2022.)

Purpose of Review: The current review focuses on serious pulmonary toxicity after inhalation of over the counter available pyrethroid-based insecticides. Pyrethroid is a synthetic product of pyrethrin, which in turn is the active ingredient of pyrethrum, a flower extract., Recent Findings: On the contrary, a large gap of knowledge exists in the association of interstitial lung disease (ILD) with pyrethroids. So far, two cases of ILD, one associated with pyrethrin and one associated with pyrethrum, were described. Existing literature on both other (pulmo)toxic effects of pyrethroids in human and animals is summarized., Summary: We present three cases of severe pulmonary toxicity after inhalation of pyrethroid-based insecticides demanding hospitalization and oxygen therapy. One of these cases died. Although a causal relationship was hard to establish, these cases all demonstrated an obvious history of (repeated) pyrethroid exposure associated with ILD. Moreover, other causes of ILD as well as infections were excluded. Furthermore, studies in mammals as well as aquatic animals confirm (pulmonary) toxicity of pyrethroids. The occurrence of toxicity is dose-dependent but also associated with individual susceptibility. Therefore, we would like to acknowledge that awareness of potential hazards of commercially available insecticides containing pyrethroids to both medical physicians and the public is mandatory., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Synthetic-aperture (SA) imaging is a popular method to visualize the reflectivity of an object from ultrasonic reflections. The method yields an image of the (volume) contrast in acoustic impedance with respect to the embedding. Typically, constant mass density is assumed in the underlying derivation. Due to the band-limited nature of the recorded data, the image is blurred in space, which is quantified by the associated point spread function. SA volume imaging is valid under the Born approximation, where it is assumed that the contrast is weak. When objects are large with respect to the wavelength, it is questionable whether SA volume imaging should be the method-of-choice. Herein, we propose an alternative solution that we refer to as SA interface imaging. This approach yields a vector image of the discontinuities of acoustic impedance at the tissue interfaces. Constant wave speed is assumed in the underlying derivation. The image is blurred in space by a tensor, which we refer to as the interface spread function. SA interface imaging is valid under the Kirchhoff approximation, where it is assumed that the wavelength is small compared to the spatial dimensions of the interfaces. We compare the performance of volume and interface imaging on synthetic data and on experimental data of a gelatin cylinder with a radius of 75 wavelengths, submerged in water. As expected, the interface image peaks at the gelatin-water interface, while the volume image exposes a peak and trough on opposing sides of the interface.

Introduction: Docetaxel and erlotinib are registered second-line treatments for wild-type EGFR NSCLC. Previous studies suggested a predictive value of the VeriStrat test in second-line therapy of NSCLC, classifying patients as either VeriStrat good or VeriStrat poor. EMPHASIS-lung aimed at exploring this predictive effect in patients with squamous cell NSCLC. The trial closed prematurely because of low accrual and results from other trials. Our analysis includes an exploratory combined analysis with results from the PROSE trial., Methods: EMPHASIS-lung was a randomized phase III multicenter trial exploring the differential effect of second-line erlotinib versus docetaxel on progression-free survival (PFS) in VeriStrat good versus VeriStrat poor patients with squamous cell NSCLC., Results: A total of 80 patients were randomized, with 72.5% categorized as VeriStrat good. Patient characteristics were balanced between VeriStrat status and treatment groups. The median PFS times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 4.1 and 1.6 months, respectively, versus 1.9 and 2.1 months, respectively, in the VeriStrat poor cohort. The median overall survival (OS) times with docetaxel and erlotinib treatment in the VeriStrat good cohort were 7.8 and 8.4 months, respectively, and 4.4 and 5.2 months, respectively, in the VeriStrat poor cohort. An additional exploratory analysis was performed; in it, 47 patients from the squamous cell subgroup of PROSE were included in a combined analysis, contributing with 45 PFS and 41 OS events., Conclusions: The final analysis of EMPHASIS-lung did not show a differential effect on PFS for erlotinib versus docetaxel stratified by VeriStrat status. Similarly, in the combined analysis, no significant treatment by VeriStrat status interaction was observed (interaction p = 0.24 for PFS and 0.45 for OS, stratified by study)., (Copyright © 2017 International Association for the Study of Lung Cancer. All rights reserved.)

Psychopathology, psychosocial problems and substance use (PPS) commonly occur in pregnant women, and can have a negative impact on the course of pregnancy and the healthy development of the child. As PPS often remains undetected and untreated during pregnancy, we developed and implemented a four-step screen-and-treat protocol in routine obstetric care, with: (i) screening including triage and subsequent confirmation, (ii) indication assessment, (iii) transfer towards care and (iv) utilization of care. Adherence to the protocol and risk factors associated with dropout were examined for 236 Dutch pregnant women in a deprived urban area. Seventy-nine percent of women accepted the screening, 21% dropped out during triage, 15% during confirmation, 3% during transfer and 8% thereafter. Provided reasons for dropout were lack of time and lack of perceived benefit. In particular, smokers, multiparous women, and women of non-Western ethnicity dropout on the way towards mental and psychosocial care. For a successful implementation of the protocol in the future, with improved adherence of pregnant women to the protocol, education of women on PPS risks, motivational skills and compulsory treatment are worth investigation.

We investigate the possibility of light beams that are both narrow and long range with respect to the wavelength. On the basis of spectral electromagnetic field representations, we have studied the decay of the evanescent waves, and we have obtained some bounds for the width and range of a light beam in the near-field region. The range determines the spatial bound of the near field in the direction of propagation. For a number of representative examples we found that narrow beams have a short range. Our analysis is based on the uncertainty relations between spatial position and spatial frequency.

We present a study on the far-field patterns of light transmitted through sub-wavelength metallic hole-arrays. Spectral imaging measurements are used here on hole arrays for the first time. It provides both spatial and spectral information of the transmission in far-field. The visibility of the images, measured in two illumination modes: Köhler and collimated, is calculated for different planes in and out of focus. The transmission under collimated illumination reveals that 75% of the beam if non-divergent. The results are in agreement with the low divergence measured by Lezec [Science 297, 820 (2002)].

Background: Bronchioloalveolar carcinoma (BAC) is suggested to be less aggressive than other types of lung cancer. To assess the option of treatment modification, actual outcome data were studied and compared with results for other types of lung cancer., Method: Retrospective analysis of all consecutive patients who underwent resection for stage I lung cancer in our hospital. For 18 BAC cases, histological specimens were re-evaluated and in three cases diagnosis was revised., Results: In the period 1989 through 2000, 15 patients with BAC and 260 patients with other tumour types underwent surgery in our hospital. Five-year survival rates were 24 and 53%, respectively, (p = 0.01)., Conclusions: Given the poor results after standard surgery, parenchyma-sparing operations do not seem justified in patients with invasive BAC.

In this work, an iterative inversion algorithm for deblurring and deconvolution is considered. The algorithm is based on the conjugate gradient scheme and uses the so-called weighted L2-norm regularizer to obtain a reliable solution. The regularizer is included as a multiplicative constraint. In this way, the appropriate regularization parameter will be controlled by the optimization process itself. In fact, the misfit in the error in the space of the blurring operator is the regularization parameter. Then, no a priori knowledge on the blurred data or image is needed. If noise is present, the misfit in the error consisting of the blurring operator will remain at a large value during the optimization process; therefore, the weight of the regularization factor will be more significant. Hence, the noise will, at all times, be suppressed in the reconstruction process. Although one may argue that, by including the regularization factor as a multiplicative constraint, the linearity of the problem has been lost, careful analysis shows that, under certain restrictions, no new local minima are introduced. Numerical testing shows that the proposed algorithm works effectively and efficiently in various practical applications.

Associations between markers and complex quantitative traits were investigated in a collection of 146 modern two-row spring barley cultivars, representing the current commercial germ plasm in Europe. Using 236 AFLP markers, associations between markers were found for markers as far apart as 10 cM. Subsequently, for the 146 cultivars the complex traits mean yield, adaptability (Finlay-Wilkinson slope), and stability (deviations from regression) were estimated from the analysis of variety trial data. Regression of those traits on individual marker data disclosed marker-trait associations for mean yield and yield stability. Support for identified associations was obtained from association profiles, i.e., from plots of P-values against chromosome positions. In addition, many of the associated markers were located in regions where earlier QTL were found for yield and yield components. To study the oligogenic genetic base of the traits in more detail, multiple linear regression of the traits on markers was carried out, using stepwise selection. By this procedure, 18-20 markers that accounted for 40-58% of the variation were selected. Our results indicate that association mapping approaches can be a viable alternative to classical QTL approaches based on crosses between inbred lines, especially for complex traits with costly measurements.

With the development of clinical diagnostic techniques to investigate the coronary circulation in conscious humans, the in vitro validation of such newly developed techniques is of major importance. The aim of this study was to develop an in vitro model that is able to mimic the coronary circulation in such a way that coronary pressure and flow signals under baseline as well as hyperaemic conditions are approximated as realistically as possible and are in accordance with recently gained insights into such signals in conscious man. In the present in vitro model the heart, the systemic and coronary circulation are modelled on the basis of the elements of a lumped parameter mathematical model only consisting of elements that can be represented by segments in an experimental set-up. A collapsible tube, collapsed by the ventricular pressure, represents the variable resistance and volume behaviour of the endocardial part of the myocardium. The pressure and flow signals obtained are similar to physiological human coronary pressure and flow, both for baseline and hyperaemic conditions. The model allows for in vitro evaluation of clinical diagnostic techniques.

A 56-year-old woman visited our hospital for mild exertional dyspnea. Radiological investigations revealed a giant bulla of the left lung that was treated with video-assisted thoracoscopic bullectomy. The result of treatment was a better stamina, and, more strikingly, a major change of voice.

In this paper a nonlinear inversion method is presented for determining the mass density of an elastic inclusion from the knowledge of how the inclusion scatters known incident elastic waves. The algorithm employed is an extension of the multiplicative regularized contrast source inversion method (MR-CSI) to elasticity. This method involves alternate determination of the mass density contrast and the contrast sources (the product of the contrast and the fields) in each iterative step. The simple updating schemes of the method allow the introduction of an extra regularization term to the cost functional as a multiplicative constraint. This so-called MR-CSI method (MR-CSI) has been proven to be very effective for the acoustic and electromagnetic inverse scattering problems. Numerical examples demonstrate that the MR-CSI method shows excellent edge preserving properties by robustly handling noisy data very well, even for more complicated elastodynamic problems.

The total variation minimization method for deblurring noise is shown to be effective in increasing the resolution in a contrast source inversion approach to index reconstruction from measured scattered field data. The main drawback is the presence of an artificial weighting parameter in the cost functional, which can only be determined through considerable experimentation Therefore, we introduce the total variation as a multiplicative constraint. Numerical examples demonstrate that the algorithm based on this multiplicative regularization seems to be robust and handling noisy data very well without the necessity of the weighting parameter.

SAR distributions were measured in the CDRH phantom, a 1 cm fat-equivalent shell filled with an abdomen-equivalent liquid (sigma = 0.4-1.0 S m-1; dimensions 22 x 32 x 57 cm) to demonstrate the feasibility of the ring applicator to obtain deep heating. The ring electrodes were fixed in a PVC tube; diameter 48 cm, ring width 20 cm and gap width between both rings 31.6 cm. Radio-frequency energy was fed to the electrodes at eight points. The medium between the electrodes and the phantom was deionised water. The SAR distribution in the liquid tissue volume was obtained by a scanning E-field probe measuring the E-field in all three directions. With equal amplitude and phase applied to all feeding points, a uniform SAR distribution was measured in the central cross-section at 30 MHz. With RF energy supplied to only four adjacent feeding points (others were connected to a 50 omega load), the feasibility to perform amplitude steering was demonstrated; SAR values above 50% of the maximum SAR were measured in one quadrant only. SAR distributions obtained at 70 MHz showed an improved focusing ability; a maximum at the centre exists for an electric conductivity of the abdomen-equivalent tissue of 0.6 and 0.4 S m-1.

Previously, we described a defective Autographa californica nuclear polyhedrosis virus (AcMNPV) which must contain cis-acting elements required for DNA synthesis, such as the origin(s) of replication (ori). Defective genomes of AcMNPV generated after serial undiluted passage were analyzed further. Three small separated regions were retained in DNA of defective AcMNPV and accumulated in extracellular defective interfering viruses as well as in intracellular DNA after 40 passages. Two of these regions have now been identified as containing putative ori. They are located on the HindIII-B fragment between map units (m.u.) 50.1 and 53.2 and on the HindIII-Q fragment between m.u. 87.2 and 88.9 of the physical map of AcMNPV DNA, respectively. Transfection of Spodoptera frugiperda cells with plasmids containing these sequences followed by superinfection with intact helper AcMNPV resulted in amplification of these plasmids, as demonstrated by the Dpnl sensitivity assay. The replicating activity of HindIII-Q is putatively located within the 1000-bp region containing a highly repetitive DNA (hr5), which is also ascribed to enhance delayed-early gene expression. In order to demonstrate replicating activity of test plasmids, it appeared essential to transfect the cells well before superinfection with helper virus.

An efficient iterative method for solving quasi-static electromagnetic field problems is presented. The electromagnetic field is generated by an inductive applicator and is represented as a superposition of two constituents, viz. a primary field in absence of the tissue configuration and a secondary field generated by the presence of the tissue. Then, for the secondary field a quasi-static approximation is employed. In the quasi-static field equations a relaxation function is introduced, such that the resulting equations can be solved iteratively. For a realistic three-dimensional model of a human hand numerical results are presented.

An efficient iterative method for solving quasi-static electromagnetic field problems is presented. A relaxation function is introduced in the quasi-static field equations. Then, the resulting equations can be solved by iteration. The method is similar to the one of solving a Laplace equation by computing the stationary state of a diffusion equation. Next, for a radially layered configuration the numerical results are compared with the results from an existing integral equation method. Subsequently, for a realistic three-dimensional model of a human knee numerical results are arrived at.

An extensive comparison between measured and computed heat absorption distributions in several phantoms inside the 'coaxial TEM' applicator is presented. The influence of the width of the aperture and of the presence of a PVC tube is especially considered.

The energy deposition pattern within a radially layered fat-muscle phantom, diameter 135 mm, heated by a novel ring capacitor applicator has been determined experimentally as well as theoretically. Good to excellent agreement is found between measured and predicted energy distributions. For the specific absorption rate in the muscle tissue the differences are in general smaller than 6%. When the ring electrodes are placed directly on the phantom surface both measured and predicted energy distributions show the presence of superficial hot spots located within the fat layer at the site of the ring electrodes. The theoretical distributions showed that the radial component of the E-field contributes for more than 90% to the energy absorption at the hot spot in the fatty tissue in front of the ring electrodes. Introducing a small air gap (10 mm) between the phantom surface and the ring electrode results in a decrease of the energy absorption within the fatty tissue at the hot spot location by 30%. Further theoretical analysis of the energy distribution within the inhomogeneous model showed that the intensity of the hot spots at the ring electrodes can be controlled by adjustment of the applicator configuration. Independent of the size of the electrode to phantom gap the specific absorption rate values predicted in the fat-muscle model show a more favorable distribution at a frequency of 27.12 MHz than at 13.56 MHz. For a similar electrode to phantom gap the specific absorption rate within the fatty tissue is approximately two times lower at 27.12 than at 13.56 MHz. For the model calculations performed the best ratio of fat to muscle SAR (0.2) is obtained with distilled water as bolus medium in the gap.

The electromagnetic heat dissipation in a radially layered biological tissue inside a ring capacitor (RC) applicator has been investigated. A quasi-static model is introduced to compute the relevant electromagnetic field quantities. The method of computation employs the spatial Fourier transform of all field quantities with respect to the axial coordinate. After an iterative solution of a dual boundary value problem for the electric potential and the current density at the electrodes, an inverse Fourier transform is carried out to compute the quantities that are of interest to the deep-body system at hand. Comparison of numerical results with phantom measurements shows excellent agreement.

The electromagnetic heat dissipation in a radially layered biological tissue inside a circular cylinder has been investigated theoretically. The theory is based on a three-dimensional model and the electromagnetic field is assumed to be generated by a prescribed electric field along a ring-shaped aperture. The method of computation employs the spatial Fourier transform of all field quantities with respect to the axial coordinate, after which the field equations are solved in the spectral domain. Subsequently, an inverse Fourier transform is carried out to compute the quantities that are of interest to the clinical deep-body hyperthermia system at hand. For a number of representative configurations numerical results at 70 MHz are given.

A rigorous three-dimensional electromagnetic model predicting the complete field distribution in the space interior to the 'coaxial TEM' applicator is presented. The applicator consists of a radiating ring aperture, with a given electric-field distribution in the wall of a hollow circular cylinder. The method of calculation employs the spatial Fourier transform of all field quantities with respect to the axial co-ordinate, after which the field equations are solved in the spectral domain. Subsequently, an inverse Fourier transform is carried out to compute the quantities that are of interest to the optimum clinical deep-body hyperthermia system. Numerical results for a number of representative applicator configurations are given. The present results are compared with the ones that are obtained by a model based on the far-field approximation of a distribution of dipole sources located in the ring aperture.

Based upon a capacitive system a quasi-microwave cavity operating at a frequency of 13.56 or 27.12 MHz has been developed. The prototype consisted of two capacitive plates with a circular aperture at the centre of each plate in which a cylindrically shaped tissue volume can be placed. Phantom measurements showed that a second-generation applicator, consisting of two narrow rings with equal inner and outer diameter, gave identical results. Due to the positioning of the rings along the enclosed tissue cylinder, the electrical field is mainly parallel to the body axis. SAR distributions were measured by infrared thermography in cylindrical, muscle equivalent phantoms enclosed in PVC-tubes using the 'split phantom' technique. For phantom diameters up to 13.5 cm a homogeneous heating, SAR 70-100 per cent of the maximum SAR, has been obtained over the tissue volume between the inner edges of the two rings. For these measurements the non-isolated ring electrodes are placed directly onto the PVC cover. When the phantom diameter, excluding PVC cover, is increased to 22.5 cm the SAR values at the centre vary from 30 to 40 per cent of the maximum SAR value which is located near the inner edge of the rings. In this case a 1 cm gap between the rings and the PVC cover was used in order to reduce the intensity of the hot spots. In all experiments no cooling of the phantom surface or ring electrodes has been used. The results from this initiating study indicate the feasibility of this type of applicator for regional deep heating, although more experimental work is needed when the applicator is used to heat tissue bodies with a diameter larger than 13.5 cm. Already, the applicator in its most simple design may be of clinical value for hyperthermic treatment of tumors in arms or legs.

The computational model developed by van den Berg has been used to perform two-dimensional simulations of tissue-equivalent phantoms heated by a 27 MHz ridged waveguide. The program is able to calculate temperature distributions for realistic inhomogenous tissue configurations (as derived from CT scans) in about 20 min on a PDP 11-44. Results for tissue-equivalent phantoms are evaluated with respect to their accuracy in predicting actual temperature distributions by comparing them with measured temperature distributions. In general the computer simulation tends to overestimate the depth of penetration; this can be ascribed to the two dimensional approach followed which does not take into account the divergence of the electric field in the third dimension. This effect can to a certain degree be compensated by assigning a higher value for the electrical conductivity of the medium. For homogenous phantoms this results in a satisfactory agreement between measured and calculated temperature distributions. Furthermore, a correct approximation for the electric field distribution over the aperture appears to be of importance, since it significantly influences the calculation results, especially for waveguide loads whose size exceeds the width of the ridge area. For inhomogeneous media the simulation results, using realistic (literature) values for the electrical conductivity, can be used with these limitations in mind, as a best-case estimate of the absorbed power distribution at depth. For more accurate simulations a three-dimensional computer model is ultimately needed.