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Large reductions in anthropogenic emissions of particulate matter and its precursor emissions have occurred since the enactment of the Clean Air Act Amendments of 1990. The Interagency Monitoring of Protected Visual Environments network has measured PM2.5gravimetric mass (mass of particles with aerodynamic diameters less than 2.5 μm, also referred to here as fine mass, “FM”) and speciated PM2.5aerosol composition at remote sites since 1988. Measured species include inorganic anions such as sulfate, nitrate, and chloride, carbonaceous aerosols such as organic (OC) and elemental carbon (EC), and elemental concentrations used to estimate fine dust (FD). Trends in seasonal and annual mean mass concentrations were calculated from 2000 through 2021, a period that includes the largest reductions in emissions. On average, annual mean FM at remote sites in the continental United States has decreased at a rate of −1.8% yr−1. This reduction is largely due to annual mean trends in sulfate (−6.1% yr−1), nitrate (−2.7% yr−1), EC (−2.2% yr−1), FD (−1.3% yr−1), and OC (−0.9% yr−1), although the OC annual mean trend was insignificant. Seasonal and regional mean FM trends varied significantly, with strong reductions in the East in all seasons due to sulfate reductions, and flat and insignificant trends in summer and fall in the West due to the influence of biomass burning emissions on OC trends. Evaluating regional and seasonal mean trends in aerosol composition helps identify sources that continue to adversely impact air quality and hinder progress in FM reductions due to successful regulatory activity. Particulate matter in the atmosphere is made up of many species that have both anthropogenic and natural sources. Thanks to the Clean Air Act Amendments of 1990, anthropogenic emissions that lead to some particulate matter (PM) have decreased, which has resulted in measurable improvements in air quality in remote regions of the United States. Evaluating trends in aerosol measurements from a large‐scale monitoring network over the past two decades has shown that at remote sites in the United States, some aerosol species, like sulfates, nitrates, and some carbonaceous aerosols, have decreased significantly due to the emission reductions; but others, like mineral dust and carbonaceous aerosols from wildfire smoke, have not. In order to continue to make progress in improving air quality in the United States, targeting future sources for emission reductions will require accurate assessments of the contributions from these sources. Dust and wildfire smoke contributions to PM in remote locations across the United States are now larger fractions compared to two decades ago and will likely continue to grow with climate change. Fine mass seasonal mean concentrations have significantly decreased in remote regions of the U.S. in response to regulatory activitySulfate aerosols have decreased at the highest rate, followed by nitrate, elemental carbon, fine dust, and organic carbonFlat and insignificant trends in organic carbon and fine mass at western sites in summer/fall were influenced by biomass smoke emissions Fine mass seasonal mean concentrations have significantly decreased in remote regions of the U.S. in response to regulatory activity Sulfate aerosols have decreased at the highest rate, followed by nitrate, elemental carbon, fine dust, and organic carbon Flat and insignificant trends in organic carbon and fine mass at western sites in summer/fall were influenced by biomass smoke emissions

The Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) campaign conducted in the southeast United States (SEUS) during the summer of 2013 provided a singular opportunity to study local aerosol chemistry and investigate aerosol radiative properties and PM2.5relationships, focusing on the complexities involved in simplifying the relationship into a linear regression. We utilize three Southeastern Aerosol Research and Characterization network sites and one Environmental Protection Agency Chemical Speciation Network station that afforded simultaneous Aerosol Robotic Network (AERONET) aerosol optical depth (AOD) and aerosol mass, chemistry, and light scattering monitoring. Prediction of AERONET AOD using linear regression of daily‐mean PM2.5during the SEAC4RS campaign yielded r2of 0.36–0.53 and highly variable slopes across four sites. There were further reductions in PM2.5predictive skill using Moderate Resolution Imaging Spectroradiometer (MODIS) and Multi‐angle Imaging SpetroRadiometer (MISR) AOD data, which have shorter correlation lengths and times relative to surface PM2.5. Long‐term trends in aerosol chemistry and optical properties in the SEUS are also investigated and compared to SEAC4RS period data, establishing that the SEUS experienced significant reduction in aerosol mass, corresponding with changes in both aerosol chemistry and optical properties. These changes have substantial impact on the PM2.5‐AOD linear regression relationship and reinforce the need for long‐term aerosol observation stations in addition to concentrated field campaigns. Relationship between sub‐2.5 μm particulate matter and AOD in the SEUS is observed to vary significantly both temporally and spatiallyExtensive southeastern United States sub‐2.5 μm particulate matter chemical and optical characterization are provided for the time period of the SEAC4RS campaign and compared to that available two decades prior to the campaignStrong intersite correlations among the geographically similar sites in both the chemical constituents and total PM2.5mass result in spatial interpolation among ground stations a more reliable predictor of PM2.5than site‐specific AOD measurements

The length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression.

Understanding the spatial and temporal variability in fine mineral dust (FD, mineral aerosols with diameters less than 2.5 µm) and coarse aerosol mass (CM, mass of aerosols with diameters between 2.5 and 10 µm) is important for accurately characterizing and perhaps mitigating their environmental and climate impacts. The spatial and seasonal variability of ambient FD and CM was characterized at rural and remote sites across the United States for 2011–2014 using concentration and elemental chemistry data from the Interagency Monitoring of Protected Visual Environments (IMPROVE) aerosol monitoring network. FD concentrations were highest (and had ≥50% contributions to PM2.5mass) in the southwestern United States in spring and across the central and southeastern United States in summer (20–30% of PM2.5mass). CM was highest across the Southwest and southern Great Plains in spring and central United States in spring, summer, and fall (≥70% contributions to PM10mass). Similar FD and CM seasonal variability was observed near source regions in the Southwest, but a seasonal decoupling was observed in most other regions, suggesting the contribution of nonlocal sources of FD or perhaps non‐dust‐related CM. The seasonal and spatial variability in FD elemental ratios (calcium, iron, and aluminum) was fairly uniform across the West; however, in the eastern United States a shift in summer elemental composition indicated contributions from nonlocal source regions (e.g., North Africa). Finally, long‐term trend analyses (2000–2014) indicated increased FD concentrations during spring at sites across the Southwest and during summer and fall in the southeastern and central United States. Fine mineral dust and coarse aerosol mass varied significantly both seasonally and spatially at remote sites across the United StatesElemental composition of fine mineral dust suggests influence from long‐range transport from North Africa and Asia to the United StatesIncreases in fine mineral dust concentrations have occurred in the Southwest in spring and Midwest in summer and fall

Particulate matter (PM)2.5dust concentrations (mineral particles with aerodynamic diameters less than 2.5 µm) typically peak in spring and early summer at rural and remote sites across the southwestern United States. Trend analyses indicate that springtime regional mean PM2.5dust concentrations have increased from 1995 to 2014, especially in March (5.4% yr−1, p< 0.01). This increase reflects an earlier onset of the spring dust season across the Southwest by 1 to 2 weeks over the 20 year time period. March dust concentrations were strongly correlated with the Pacific Decadal Oscillation index (r= −0.65, p< 0.01), which was mostly in its negative phase from 2007 to 2014, during which the region was drier, windier, and less vegetated. The positive spring trend and its association with large‐scale climate variability have several important implications for visibility, particulate matter, health effects, and the hydrologic cycle in the region. Fine dust concentrations have increased across the southwestern United States in springThe onset of the spring dust season has shifted earlier by 1 to 2 weeksTrends in spring dust are influenced by large‐scale climate variability and drier, windier, and less vegetated conditions in the region

This report describes a successful outcome in a liver transplant recipient after deceased donor transmission of methicillin‐resistant Staphylococcus aureusconfirmed by whole genome sequencing. Also see case report by Wendt et al on page 2633.

Miniature coils for magnetic resonance imaging and spectroscopy are demonstrated. A rectangular Helmholtz arrangement based on a pair of substrates separated by spherical alignment spacers is investigated. An optimal geometry is developed using simple theory and verified by numerical analysis. Prototypes are fabricated using silicon substrates shaped by anisotropic etching to form a trough to hold an internal sample and pits for use as alignment features, and carrying Cu/Au conductors fabricated by electroplating. Q values of 11 are obtained, and devices containing an internal proton source are developed for use as fiducial markers in ¹H magnetic resonance imaging at 1.5 T. Magnetic resonance spectroscopy is also performed on the internal source, with a SNR of ≈85.

Preliminary experiences of the Sonotherm 6500 scanned focused ultrasound (SFUS) system in the hyperthermic treatment of bulky tumours in breast, superficial sites and within the pelvis in 22 patients are reported. Tumour volumes ranged from 235 to 603 cm3 (breast), 105 to 209 cm3 (superficial sites) and 24 to 905 cm3 (pelvis). Temperature distributions in 58 evaluable treatments were analysed in terms of temporal peak and time-averaged temperatures (highest and lowest temperatures, percentage of sensors exceeding index temperatures, etc.) achieved within scanned volumes. Mean number of sensors implanted into tumour was 14 in breast and superficial tumours and approximately 11 in pelvic tumours. Mean time-averaged maximum and minimum temperatures for the best treatments (i.e. for each patient, that with the highest percentage of sensors recording time averaged temperatures ≥42°C) administered to patients with tumours in the breast and superficial sites were 44·6 ± 1·7°C and 39·7 ± 1·1°C, respectively and the mean number of sensors exceeding 42°C was 58 ± 19%. In the case of pelvic tumours these figures were 41·6 ± 0·9°C, 40·0 ± 0·6°C and 8 ± 12%, respectively. Patient tolerance to treatments was, in general, good. Areas where technical improvement of the system is appropriate and further research and development are required are identified; these should lead to a better realization of the potential of the SFUS technique, particularly for pelvic tumours.

We investigate the feasibility of using in-fiber Bragg gratings for measuring acoustic fields in the megahertz range. We found that the acoustic coupling from the ultrasonic field to the grating leads to the formation of standing waves in the fiber. Because of these standing waves, the system response is complex and, as we show, the grating does not act as an effective probe. However, significant improvement in its performance can be gained by use of short gratings coupled with an appropriate desensitization of the fiber. A noise-limited pressure resolution of ≈4.5 × 10^-3 atm/√Hz was found.

The effect of a two-fraction heat treatment on mouse testis has been assessed by measuring testis weight loss at 1 week after treatment. The rate of repair of 'sublethal' heat damage following the first treatment was dependent on the severity of the treatment. Using a primary treatment of 41·5°C for 30 min, the weight loss following a test treatment of 41·5°C for 30 min returned to that of the test treatment alone within an interval of 16-24 h. Using a milder primary treatment of 40·0°C for 30 min, repair of sublethal heat damage appeared to be complete by 1-2 h. When a single test treatment was used, there was no evidence of heat-induced thermal resistance (thermotolerance) following primary treatments of 40·0 or 41·5°C for 30 min, for periods up to 24 h between treatments. A small degree of thermotolerance could, however, be demonstrated following the most severe primary treatment used if full dose: effect curves were obtained. Thermotolerance, manifest as a decrease in slope, was maximal at approximately 4 h after the primary treatment. The results are discussed with reference to other normal tissue data.

An analysis of 351 HT treatment sessions administered to 101 patients receiving radiotherapy and hyperthermia (RT + HT) who were entered into Phase III concurrent randomized trials for recurrent (BrR) and intact (BrI) breast tumours is presented. A complete response (CR) was recorded in 50 of 84 (595%) fields in the case of recurrent breast patients and in 10 of 17 (59%) fields in the case of the intact breast patients. In comparison, 15 of 60 (25%) patients entered into BrR who received RT alone and 8 of 12 (667%) patients receiving RT alone entered into BrI trial achieved CR. A set ot thermal parameters is defined and evaluated on a treatment by treatment basis. Patient and tumour characteristics influential on CR are identified and thermal parameters which have additional prognostic value are investigated. Multivariate logistic analysis of the non-thermal data showed that maximum depth of tumour, presence or history of disease outside the treated area and RT regimen were most influential on CR. Tumour volume (cm3) (OR = 0.996, 95% CI = 0.993-1 0004, p = 008) was not a strong prognostic covariate; tumour area and linear dimensions were even less significant (p = 0.41). The cumulative minimum thermal isoeffect dose (equivalent minutes at 43°C) accrued over the 1st, 1st and 2nd, and 1st, 2nd and 3rd treatment sessions was the only thermal parameter to exhibit an association with CR consistently. Other thermal parameters found to contribute to the predictive models were MINTIME > 42°C calculated for the 1st treatment session and %sensors > 43°C (peak) calculated for the 2nd treatment session.

The Gaussian beam model (GBM) has been shown to be a successful tool in the development of the current sheet applicator. As a result, the effectiveness of the GBM is investigated in single and dual array applications of the lucite cone applicator (LCA). The LCA is a modified water-filled waveguide applicator with an improved effective field size (EFS > 64 cm2, aperture 10 cm × 10 cm). The GB-source parameters were calculated from the emanating E-field of a single LCA. The SAR distribution from a single LCA was measured by E-field scanning and thermographic (TG) imaging, and compared with the GB-predicted SAR distribution. Deviations in theprincipal planes were found to be less than 5%. TG-measured and GB-predicted SAR distributions from three different dual LCA configurations were compared and evaluated. When water was used as intermedium between LCAs and phantom, a maximum SAR difference of27% xwas calculated. In the absence of water as intermedium, this difference increased to 44%. These large deviations were only found in areas where the measured SAR distribution was disturbed due to antenna interactions. The average SAR differences with and without water as intermedium were 7% respectively 11%, indicating hat the GBM can provide good qualitative information about the SAR distribution of dual LCA-arrays.

Scanned focused ultrasound (SFUS) is unique amongst noninvasive methods of inducing hyperthermia in that the absorbed power (SAR) distribution may be controlled at a scale of 0·5 cm or better. This high degree of spatial control of SAR implies that differences in local tissue cooling due to heterogeneity in perfusion, variations in the density of discrete thermally significant vessels and even local cooling around single large vessels may be compensated during SFUS treatments. In this paper we calculate thermal dose distributions arising from three different SFUS techniques: (1) the high-temperature short-duration (HTSD) ultrasound technique; (2) conventional systems employing a fixed scan and fixed SAR simulated by a uniform SAR; and (3) we optimize the SAR distribution using information from angiography and thermal models. These techniques are tested in the same anatomy having discrete vessels, a non-uniform vessel density and with little, if any, preheating of the incoming blood (i.e. the worst-case situation). The application of a uniform SAR to this volume resulted in a highly non-uniform thermal dose distribution. The situation is clearly improved in HTSD hyperthermia; however, the desired accuracy of positioning within the tumour is high, and to minimize background heating the focus must be stepped slowly and preferably in a semi-random pattern through the target volume. The third technique which employs spatial control over SAR resulted in the greatest uniformity in thermal dose. However, the use of this technique requires the input of the complete three-dimensional discrete vessel network and the availability of a tested three-dimensional discrete vessel thermal model.

A new technique is described for the treatment of menorrhagia by heating the whole of the endometrial cavity of the uterus. A capacitively coupled probe at 27-12 MHz is inserted into the uterine cavity, which causes the basilis layer to be raised to approximately 50-55°C whilst the rest of the pelvic contents remain at approximately normal (body) temperature. A major advantage of the method is that no special hysteroscopic skills are required, unlike the two other techniques currently used for endometrial ablation: the Nd-Yag laser or the hysteroresectoscopic loop. Also no toxic flushing/distension fluids are necessary, as are required for all hysteroscopic surgery. The method, however, does require the application of a large amount of RF power to the probe and so care must be taken to position the probe correctly in order to prevent any serious complications. Of 32 patients given a single treatment at a power level of 550 W for 20 min, the 'success rate' was 84% with 31 % becoming amenhorrhoiec and 53% showing significant reduction in menstrual bleeding. However, retreatment is possible and by this means, combined with improved treatment techniques, an even higher success rate could be achieved. In two of the earlier patients treated at 550 W a fistula was produced at the anterior vaginal wall which had to be surgically repaired. The probe was subsequently modified, since when this problem has not recurred. This new treatment approach offers an alternative to hysterectomy in the treatment of menorrhagia and may offer a number of significant advantages over methods currently used for endometrial ablation.

The effects of both hyperthermia alone and X-rays combined with hyperthermia on mouse testis have been investigated. Testis weight was measured 3 weeks after treatment. A linear dependence of testis weight on heating time was observed for temperatures in the range 39·5 to 43·75°C. The relationship between the reaction rate and the reciprocal of absolute temperature indicated that, over the temperature range considered, the activation energy associated with such thermal damage was (646 ± 45) × 103 J mol-1. No evidence was obtained to indicate a change in slope of the Arrhenius plot over this temperature range. Finally, despite the high sensitivity of the testis to heat and X-rays, no thermal enhancement of the weight loss after irradiation was observed when thermal treatments which, if given alone would produce some observable damage, were administered immediately after irradiation.

Determinants of the interaction of the 29-kDa NH2-terminal domain of fibronectin with heparin were explored by analysis of normal and mutant recombinant NH2-terminal fibronectin fragments produced in an insect cell Baculovirus host vector system. A genomic/cDNA clone was constructed that specified a secretable human fibronectin NH2 fragment. With the use of site-directed mutagenesis a set of 29 kDa fragments was obtained that contained glycine or glutamic acid residues in place of basic residues at various candidate sites for heparin binding in the five type I modules that make up the domain. The recombinant fragment containing the wild type sequence had a nearly normal circular dichroic spectra and a melting profile, as assayed by loss of ellipticity at 228 nm, that was indistinguishable from that of the native fragment obtained by trypsinization of plasma fibronectin. A substantial proportion of the wild type recombinant fragment bound to heparin-Sepharose, where it was eluted at the same NaCl concentration as the native fragment. The wild type fragment was capable of promoting matrix-driven translocation, a morphogenetic effect in artificial extracellular matrices that depends on the interaction of the fibronectin NH2 terminus with heparin-like molecules on the surfaces of particles. Mutant fragments in which arginines predicted to be most exposed in the folded fragment were converted to glycines retained the same affinity for heparin as the wild type fragment. In contrast, a mutant fragment in which the single basic residue (Arg99) in the minor loop ("Omega-loop") of the second type I module was converted to a glycine had an essentially normal melting profile but exhibited no binding to heparin and failed to promote matrix-driven translocation. A mutant fragment in which the single basic residue (Arg52) of the first type I module was converted to a glycine also completely lacked heparin binding activity, but one in which the single basic residue (Arg191) the fourth type I module was converted to a glycine retained the ability to bind heparin. A mutant fragment in which the single basic residue (Lys143) in the Omega-loop of the third type I module was converted to a glutamic acid lacked heparin binding activity but had a CD spectrum similar to the heparin-liganded native protein and was capable of promoting matrix-driven translocation. The results indicate that multiple residues in the Omega-loops of the fibronectin NH2-terminal domain participate in its interactions with heparin. In addition, the conformation of one of the nonbinding mutants may mimic the heparin-induced structural alteration in this fibronectin domain required for certain morphogenetic events.

A hot water interstitial hyperthermia unit was used to heat normal tissue in the thighs of rabbits and pigs. A 4°°4 array of metal needles or plastic tubes spaced at 10 or 14 mm was implanted. Temperature measurements were made using five-sensor thermocouple probes inserted parallel to the implanted needles or tubes. With a water temperature of 48°°C, tissue temperature within the implant exceeded 42.5°°C when tube spacing was 14 mm and reached 47°°C when the spacing was 10 mm. However, at the lower water temperature of 45.5°°C inter-tube spacing was more critical, since the tissue temperature was above 43.5°°C for a spacing of 10 mm but below 42.5°°C for a spacing of 14 mm. Temperatures observed in vivotended to be higher than those predicted by computer simulations, in which blood flow was assumed to be greater than that of resting muscle i.e. ≥≥0.45 kg m−−3s−−1. The results show that an interstitial system using hot water can be a simple and efficient method of inducing hyperthermia.

The current sheet applicator is an electromagnetic heating device whose size may be chosen virtually independent of frequency even though practical limitations may restrict it to VHF and UHF bands. In this paper we investigate absorbed power distributions in muscle tissue from current sheet applicators when used as elements of a planar array intended for superficial hyperthermic treatment of tumours. Advantages offered by current sheet applicators for tissue heating include compact size, a linear polarization of the induced electric field and relatively large heating area. It is shown that the effective field produced by a pair of these elements is continuous regardless of whether the common edges of the elements are perpendicular or parallel to the direction of impressed current. The feasibility of customizing the shape and size of the field is also illustrated. The absorbed power distribution patterns due to a coherently driven array operating around 434 MHz is relatively insensitive to phase variations of about 20°° but is sensitive to relative power level variations as low as 10%. Mutual coupling between array elements may be reduced to acceptable levels by incorporating suitable spacing between them. It is also demonstrated that there is good agreement between measurements of absorbed power distributions and predictions using the Gaussian beam model

The ability of a three-electrode capacitive heating device operating at 13·56 MHz to produce and effect spatial redistribution of hyperthermic temperatures is demonstrated through abdominal heating studies conducted with 80 kg female and 65 kg male pigs. Temperature-time profiles over the respective heating periods were obtained in anterior and posterior superficial tissue and in selected abdominal organs. At selected times during heating, spatial redistribution of elevated temperatures was effected through adjustment of power settings for one or more of the three electrodes, i.e. through manipulation of the specific absorption rate (SAR) in-vivo.

A total of 116 small superficiald tumours have been treated by radiation alone, hyperthermia alone, or radiation and hyperthermia combined in a Phase I/II study. Most tumours were metastases or local recurrences of adenocarcinoma of breast but other histologies were involved including melanoma. Hyperthermia was delivered predominantly by microwaves, but radiofrequency and ultrasound methods were also used. Rigorous thermal dosimetry, based on measurements from invasive multipoint thermocouple arrays, has shown that 58 per cent of hyperthermal treatments reached a minimum dose within tumour equivalent to 20 min at 43°C (minEq43); 24 per cent reached at least 60 minEq43. Minima of 20 minEq43 were achieved successfully on every intended occasion in a quarter of the 75 tumours heated, and on one/two occasions in 39; unfortunately, this minimum threshold was not reached at any point monitored at any hyperthermia session in 17(23 per cent) tumours. Tumours that received radiation and effective hyperthermia were more likely to disappear completely (CR rate 86 per cent) than those that were irradiated but inadequately heated (CR rate 35 per cent) (P< 0.001) or were treated by the same doses of radiation alone (CR rate 35 per cent) (P< 0.05). This improvement with hyperthermia became more apparent with suboptimal radiation doses. A small but measurable growth delay was imposed by heat alone with a poor complete response rate (11 per cent).The real-time use of a thermal dose unit in clinical practice facilitates hyperthermal treatment comparisons and provides an important parameter for checking the technical performance of a heat delivery system. The results of this study emphasizes the need for improvements in intratumour temperature distribution, in order to establish minimum threshold temperatures to enhance tumour response rates.

Selective inhibition of the low Km cyclic AMP-specific phosphodiesterase has been shown to inhibit inflammatory cell function and relax airway smooth muscle. These studies were conducted to characterize the bronchodilator and anti-inflammatory activity of rolipram, an archetypical cyclic AMP-specific phosphodiesterase inhibitor, in in vitro and in vivo guinea pig airway models. In isolated tracheal rings from ovalbumin (OA)-sensitive guinea pigs, both R- and S-enantiomers of rolipram (1 microM) significantly antagonized OA-induced contractions. In contrast, neither enantiomer at concentrations up to 1 microM significantly inhibited histamine- or LTD4-induced contractions. In superfusion and mediator release experiments, both enantiomers of rolipram significantly reduced antigen-induced prostaglandin D2 release, but had minimal effect on histamine release. In anesthetized, ventilated OA-sensitive guinea pigs, racemic rolipram or enantiomers reduced OA-induced bronchoconstriction with ID50 values of approximately 0.25 mg/kg i.v. Histamine- and leukotriene D4-induced bronchoconstriction were not affected by doses of rolipram which abolished the response to OA. Higher doses (3-10 mg/kg) reduced histamine-, but not the leukotriene D4-induced bronchoconstriction. In conscious OA-sensitive guinea pigs, intragastric pretreatment with rolipram dose-dependently reduced both the OA-induced decreases in specific conductance as well as the corresponding pulmonary eosinophil influx as assessed by both bronchoalveolar lavage and histological evaluation. Therefore, rolipram produces significant inhibition of antigen-induced bronchoconstrictor and inflammatory responses, thus providing strong evidence that this pharmacological approach may be of significant therapeutic value in allergic asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

During the last decade there has been great interest in the use of hyperthermia in cancer therapy. The reasons why elevated temperatures, either alone or together with radiotherapy or chemotherapy, may prove useful have been the subjects of several recent reviews (Connor et al., 1977; Field and Bleehen, 1979).*Clinical applications of hyperthermia fall into two broad categories—whole-body and localized hyperthermia. During whole-body hyperthermia, which has been used on patients with advanced and widespread malignancies, core temperature is maintained at 41.8–42°C for a few hours. This appears to be the range of maximum tolerated temperatures; the organs which limit such treatment are the liver, which may be relatively sensitive to thermal damage, and the heart. Methods of inducing whole-body hyperthermia include the use of wax baths (Pettigrew et al., 1974), hot air cabinets (Pomp, 1978), water blankets (Barlogie et al., 1979) and space suits (Bull et al., 1979). Common features of these methods are the reduction of heat losses from the patient and the introduction of thermal energy into the body to enable the desired level of hyperthermia to be reached rapidly. The heating techniques and associated monitoring of temperature are relatively simple and no further comment on them will be made here.Local hyperthermia offers a wider range of therapeutic possibilities, especially if the temperature in a tumour can be maintained above that of surrounding normal tissue.

Although recent research and experience have shown that hyperthermia administered alone, or in combination with ionizing radiations or drugs, may be useful in the treatment of cancer, there are many questions to be answered if such therapy is to be optimized. Many studies with experimental animals have been made using water-bath heating because of its simplicity. However, recent reports (Hume et al., 1979a; Robinson et al., 1978) indicate that temperature distributions in tissues heated in this way may be markedly affected by blood flow. Heating methods in which energy may be deposited at depth in tissues may produce more uniform temperature distributions than can be obtained by immersing tissues in hot water. Since the effects of hyperthermia are very strongly dependent on temperature, the development of methods to heat tissues uniformly is an important requirement both experimentally and clinically. Expertise acquired during the development of microwave heating techniques should prove particularly valuable since this means of inducing hyperthermia has been chosen in a number of clinical trials currently underway.In the present report a microwave heating system which allows four volumes of tissue to be treated simultaneously is described. It is particularly useful in experiments involving rodents. The temperature in each field may be monitored and individually controlled.

The non-uniform effects of hyperthermia observed in mouse intestine when heating is achieved by immersion of an exteriorized loop of jejunum in a hot bath were quantified. Intestinal damage was assayed by crypt destruction and correlated with local temperature and distance from major mesenteric blood vessels.The rate of rise of temperature during heating was much greater in regions far from blood vessels than in those close to vessels. Equilibrium temperatures in regions close to vessels were as much as 2°C below liquid bath temperature. Such temperature differentials agreed well with those predicted from the heterogeneity observed in crypt destruction. Both histological and thermometric data suggest that major blood vessels may influence tissue temperature over a distance of approximately 2 mm and, within this region, temperature gradients of 1°C per mm may exist.These findings raise questions concerning the interpretation of previously reported data from water-bath heating of both tumours and normal tissues. They also emphasize the need for consideration of the influence of blood flow on heating patterns during hyperthermal treatment of patients.