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Three experiments evaluated the effects of corn oil removal using centrifugation in ethanol plants, on animal performance and digestion characteristics by finishing cattle fed by-products. In Exp. 1, 225 crossbred steers (300 ± 9.1 kg) were utilized in a randomized block design with a 2 × 2 + 1 factorial arrangement of treatments. Factors consisted of oil concentration [de-oiled (DO) or full fat (FF)] and by-product type [condensed distillers solubles (CDS) or modified distillers grains plus solubles (MDGS)] compared to a corn-based control. Fat concentration was 6.0% for DO CDS, 21.1% for FF CDS, 9.2% for DO MDGS, and 11.8% for FF MDGS. No oil concentration by by-product type interactions (P ≥ 0.17) were observed. There were no differences in DMI, ADG, or G:F between DO and FF CDS (P ≥ 0.29) or DO and FF MDGS (P ≥ 0.58). No differences (P ≥ 0.25) due to oil concentration were observed for carcass characteristics. Experiment 2 was a 5 × 5 Latin Square digestion trial with treatments similar to Exp. 1. Fat concentration was 8.7% or 15.4% for DO or FF CDS and 9.2% or 12.3% for DO or FF MDGS. Intake and total tract digestibility of fat were greater (P ≤ 0.02) for FF CDS compared with DO CDS. Digestible energy (megacalorie per kilogram), adjusted for intake, was greater (P = 0.02) for steers fed FF CDS compared to DO CDS. Average ruminal pH for cattle fed FF MDGS was greater than DO MDGS (P = 0.06). In Exp. 3, 336 yearling, crossbred steers (352 ± 19 kg) were utilized in a randomized block design with a 2 × 3 + 1 factorial arrangement of treatments. Factors included oil concentration (DO or FF) and inclusion [35%, 50%, and 65% wet distillers grains plus solubles (WDGS)] along with a corn-based control. The fat concentrations of DO and FF WDGS were 7.9% and 12.4%, respectively. A linear interaction (P < 0.01) was observed for DMI, which produced different slopes for DO and FF WDGS. No linear or quadratic interactions were observed for BW, ADG, or G:F (P ≥ 0.31). For the main effect of oil concentration, there were no statistical differences (P > 0.19) for final BW, ADG, or G:F. No statistical differences were observed for all carcass traits (P ≥ 0.34). Corn oil removal via centrifugation had minimal impact on finishing performance suggesting that cattle fed DO by-products will have similar performance to cattle fed FF by-products in dry-rolled and high-moisture corn diets.

Four experiments evaluated the use of a complete starter feed (RAMP; Cargill Corn Milling, Blair, NE) for grain adaptation. In Exp. 1, 229 yearling steers (397 ± 28.4 kg BW) were used to compare a traditional adaptation program (CON) with adapting cattle with RAMP in either a 1- (RAMP-1RS) or 2- (RAMP-2RS) ration system. From d 23 to slaughter, cattle were fed a common finishing diet. In Exp. 2, 390 yearling steers (341 ± 14 kg BW) were used to compare accelerated grain adaptation programs with RAMP with 2 control treatments where RAMP was blended with a finishing diet containing either 25 (CON25) or 47.5% (CON47) Sweet Bran (Cargill Corn Milling) in 4 steps fed over 24 d to adapt cattle. Rapid adaptation treatments involved feeding RAMP for 10 d followed by a blend of RAMP and a 47% Sweet Bran finishing diet to transition cattle with 3 blends fed for 1 d each (3-1d), 2 blends fed for 2 d each (2-2d), or 1 blend fed for 4 d (1-4d). From d 29 to slaughter, all cattle were fed a common finishing diet. In Exp. 3, 300 steer calves (292 ± 21 kg BW) were used to compare the CON47 and 1-4d adaptation programs with directly transitioning cattle from RAMP, which involved feeding RAMP for 10 d and then switching directly to F1 on d 11 (1-STEP). From d 29 until slaughter, F2 was fed to all cattle. In Exp. 4, 7 ruminally fistulated steers (482 ± 49 kg BW) were used in a 35-d trial to compare the CON47 and 1-STEP adaptation programs. Ruminal pH and intake data from the first 6 d of F1and first 6 d of F2 were used to compare adaptation systems. Adaptation with RAMP-1RS and RAMP-2RS increased ( < 0.01) G:F compared with cattle adapted using CON in Exp. 1. Feeding RAMP-1RS increased ADG ( = 0.03) compared with CON. Intakes were similar ( = 0.39) among treatments. Daily gain, DMI, G:F, and carcass traits were similar ( > 0.11) among treatments in Exp. 2. Daily gain, DMI, and G:F were not different ( > 0.20) among treatments on d 39 or over the entire feeding period in Exp. 3. When F1 or F2 was being fed, DMI was similar ( ≥ 0.40) for CON47 and 1-STEP in Exp. 4. When F1 or F2 was being fed, 1-STEP cattle had lower average ruminal pH ( ≤ 0.03) and greater time below a pH of 5.3 ( ≤ 0.03). Using RAMP for grain adaptation improved performance compared with traditional adaptation. Rapid adaptation with RAMP decreased pH, but no performance differences were observed between long and rapid RAMP adaptation programs. Therefore, cattle started on RAMP do not require extensive adaptation before feeding a finishing diet with Sweet Bran.

Aims: Recent studies have demonstrated RAMP, a complete starter feed, to have beneficial effects for animal performance. However, how RAMP may elicit such responses is unknown. To understand if RAMP adaptation results in changes in the rumen bacterial community that can potentially affect animal performance, we investigated the dynamics of rumen bacterial community composition in corn-adapted and RAMP-adapted cattle., Methods and Results: During gradual acclimation of the rumen bacterial communities, we compared the bacterial community dynamics in corn and RAMP-adapted using 16S rRNA gene amplicon sequencing. Significant shifts in bacterial populations across diets were identified. The shift in corn-adapted animals occurred between adaptation step3 and step4, whereas in RAMP-adapted cattle, the shift occurred between step2 and step3. As the adaptation program progressed, the abundance of OTUs associated with family Prevotellaceae and S24-7 changed in corn-adapted animals. In RAMP-adapted animals, OTUs belonging to family Ruminococcaceae and Lachnospiraceae changed in abundance., Conclusions: Rumen bacteria can be acclimated faster to high concentrate diets, such as RAMP, than traditional adaptation programs and the speed of bacterial community acclimation depends on substrate composition., Significance and Impact of the Study: These findings may have implications for beef producers to reduce feedlot costs, as less time adapting animals would result in lower feed costs. However, animal feeding behavior patterns and other factors must be considered., (© 2016 The Authors published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.)

Two studies were conducted to optimize use of alkaline-treated corn stover and wheat straw and distillers grains as partial corn replacements. In Exp. 1, a finishing experiment used 30 pens (12 steers/pen) of calf-fed steers (initial BW = 374 ± 23.9 kg) with a 2 × 2 + 1 factorial arrangement of treatments with 6 replications per treatment. Factors were grind size, where corn stover was processed through a 2.54- or 7.62-cm screen, and chemical treatment (corn stover either fed in native, non-treated form [NT; 93.4% DM] or alkaline treated [AT; 5% CaO hydrated to 50% DM]). No interactions (P ≥ 0.38) were noted between grind size and chemical treatment. Feeding AT compared with NT improved (P ≤ 0.02) final BW, ADG, and G:F. Reducing grind size improved (P ≤ 0.01) ADG and G:F, and no interaction with chemical treatment was observed. Steers fed AT had similar DMI, ADG, G:F, and carcass characteristics compared with a 5% roughage control that contained 15 percentage units (DM basis) more corn. In Exp. 2, 60 individually fed steers (initial BW = 402 ± 61.4 kg) were randomly assigned to 10 diets. Six treatments evaluated 10, 25, or 40% dry-rolled corn (DRC), which was replaced with either a 2:1 or 3:1 ratio (DM basis) of modified distillers grains plus solubles (MDGS) and treated corn stover analyzed as a 2 × 3 factorial. An additional 3 treatments were added where a 3:1 ratio of MDGS:straw were compared with a 3:1 ratio of MDGS:stover. As DRC increased, G:F (P = 0.06) quadratically increased for 3:1 MDGS:stover diets. Increasing DRC increased (P = 0.07) G:F in treated stover diets, regardless of ratio. Increasing DRC increased (P = 0.10) ADG for 3:1 ratios for both straw and stover. Reducing grind size, feeding a maximum of 20% treated crop residue, and maintaining at least 25% corn in the diet are strategies for optimizing cattle performance when replacing dry-rolled and high-moisture corn with treated crop residues and distillers grains.

Crossbred yearling steers (n=80; 406 ± 2.7 kg of BW) were used to evaluate the effects of S concentration in dried distillers grains with solubles (DDGS) on growth performance, carcass characteristics, and ruminal concentrations of CH(4) and H(2)S in finishing steers fed diets based on steam-flaked corn (SFC) or dry-rolled corn (DRC) and containing 30% DDGS (DM basis) with moderate S (0.42% S, MS) or high S (0.65% S, HS). Treatments consisted of SFC diets containing MS (SFC-MS), SFC diets containing HS (SFC-HS), DRC diets containing MS (DRC-MS), or DRC diets containing HS (DRC-HS). High S was achieved by adding H(2)SO(4) to DDGS. Ruminal gas samples were analyzed for concentrations of H(2)S and CH(4). Steers were fed once daily in quantities that resulted in traces of residual feed in the bunk the following day for 140 d. No interactions (P ≥ 0.15) between dietary S concentration and grain processing were observed with respect to growth performance or carcass characteristics. Steers fed HS diets had 8.9% less DMI (P < 0.001) and 12.9% less ADG (P=0.006) than steers fed diets with MS, but S concentration had no effect on G:F (P=0.25). Cattle fed HS yielded 4.3% lighter HCW (P = 0.006) and had 16.2% less KPH (P=0.009) than steers fed MS. Steers fed HS had decreased (P=0.04) yield grades compared with steers fed MS. No differences were observed among treatments with respect to dressing percentage, liver abscesses, 12th-rib fat thickness, LM area, or USDA quality grades (P ≥ 0.18). Steers fed SFC had less DMI (P < 0.001) than steers fed DRC. Grain processing had no effect (P > 0.05) on G:F or carcass characteristics. Cattle fed HS had greater (P < 0.001) ruminal concentrations of H(2)S than cattle fed MS. Hydrogen sulfide concentration was inversely related (P ≤ 0.01) to ADG (r=-0.58) and DMI (r=-0.67) in cattle fed SFC, and to DMI (r=-0.40) in cattle fed DRC. Feeding DDGS that are high in dietary S may decrease the DMI of beef steers and compromise the growth performance and carcass characteristics of feedlot cattle., (© 2011 American Society of Animal Science. All rights reserved.)

We present evidence that a relatively widespread and common bat from South East Asia comprises two morphologically cryptic but acoustically divergent species. A population of the bicoloured leaf-nosed bat (Hipposideros bicolor) from Peninsular Malaysia exhibits a bimodal distribution of echolocation call frequencies, with peaks in the frequency of maximum energy at ca. 131 and 142 kHz. The two phonic types are genetically distinct, with a cytochrome b sequence divergence of just under 7%. We consider the mechanisms by which acoustic divergence in these species might arise. Differences in call frequency are not likely to effect resource partitioning by detectable prey size or functional range. However, ecological segregation may be achieved by differences in microhabitat use; the 131kHz H. bicolor is characterized by significantly longer forearms, lower wing loading, a lower aspect ratio and a more rounded wingtip, features that are associated with greater manoeuvrability in flight that may enable it to forage in more cluttered environments relative to the 142 kHz phonic type. We suggest that acoustic divergence in these species is a consequence of social selection for a clear communication channel, which is mediated by the close link between the acoustic signal and receptor systems imposed by the highly specialized nature of the hipposiderid and rhinolophid echolocation system.

Background and Purpose: Radiobiological studies suggest equivalent biological effects between continuous low dose rate brachytherapy (CLDR) and pulsed brachytherapy (PB) when pulses are applied without interruption every hour. However, radiation protection and institute-specific demands requested the design of a practical PB protocol substituting the CLDR boost in breast cancer patients. An office hours scheme was designed, considering the CLDR dose rate, the overall treatment time, pulse frequency and tissue repair characteristics. Radiobiological details are presented as well as the logistics and technical feasibility of the scheme after treatment of the first 100 patients., Materials and Methods: Biologically effective doses (BEDs) were calculated according to the linear quadratic model for incomplete repair. Radiobiological parameters included an alpha/beta value of 3 Gy for normal tissue late effects and 10 Gy for early normal tissue or tumour effects. Tissue repair half-time ranged from 0.1 to 6 h. The reference CLDR dose rate of 0.80 Gy/h was obtained retrospectively from analysis of patients' data. The treatment procedure was evaluated with regard to variations in implant characteristics after treatment of 100 patients., Results: A PB protocol was designed consisting of two treatment blocks separated by a night break. Dose delivery in PB was 20 Gy in two 10 Gy blocks and, for application of the 15 Gy boost, one 10 Gy block plus one 5 Gy block. The dose per pulse was 1.67 Gy, applied with a period time of approximately 1.5 h. An inter-patient variation of 30% (1 SD) was observed in the instantaneous source strength. Taking also the spread in implant size into account, the net variation in pulse duration amounted to 38%., Conclusion: An office hours PB boost regimen was designed for substitution of the CLDR boost in breast-conserving therapy on the basis of the BED. First treatment experience shows the office hour regimen to be convenient to the patients and no technical perturbations were encountered.

The objective of the present study was to investigate the radiosensitizing effect of carbogen breathing during pulsed x-ray irradiation in an experimental tumor model. Rat R1H rhabdomyosarcoma tumors were irradiated with 36 Gy total dose in 1 Gy high dose rate pulses, either hourly repeated, or in an 'office hours' protocol with irradiation-free overnight intervals. With the hourly, pulsed irradiation scheme, tumor growth delay (TGD) was significantly increased from 24.4+/-0.7 days in air-breathing animals to 29.0+/-0.9 days in animals breathing carbogen during irradiation. With irradiation during office hours, the TGD was shortened, and carbogen was less effective. The data show that carbogen acts as a radiosensitizer when applied during pulsed irradiation. Translation of the experimental data to clinical practice indicates that hyperoxygenation of the tumor during pulsed dose rate (PDR) or high dose rate (HDR) brachytherapy might enhance the tumor response of patients.

Hypotheses for divergence and speciation in rainforests generally fall into two categories: those emphasizing the role of geographic isolation and those emphasizing the role of divergent selection along gradients. While a majority of studies have attempted to infer mechanisms based on the pattern of species richness and congruence of geographic boundaries, relatively few have tried to simultaneously test alternative hypotheses for diversification. Here we discuss four examples, taken from our work on diversification of tropical rainforest vertebrates, in which we examine patterns of genetic and morphological variation within and between biogeographic regions to address two alternative hypotheses. By estimating morphological divergence between geographically contiguous and isolated populations under similar and different ecological conditions, we attempt to evaluate the relative roles of geographic isolation and natural selection in population divergence. Results suggest that natural selection, even in the presence of appreciable gene flow, can result in morphological divergence that is greater than that found between populations isolated for millions of years and, in some cases, even greater than that found between congeneric, but distinct, species. The relatively small phenotypic divergence that occurs among long-term geographic isolates in similar habitats suggests that morphological divergence via drift may be negligible and/or that selection is acting to produce similar phenotypes in populations occupying similar habitats. Our results demonstrate that significant phenotypic divergence: (1) is not necessarily coupled with divergence in neutral molecular markers; and (2) can occur without geographic isolation in the presence of gene flow.

Background: The feasibility and efficacy of high dose conformal radiotherapy were examined in the treatment of patients with locally advanced, unresectable pancreatic carcinoma., Methods: Forty-four patients with pathologically confirmed, unresectable pancreatic adenocarcinoma without distant metastases were treated in a Phase II study. The patients received three-dimensional, planned, high dose conformal radiotherapy (70-72 grays). Toxicity was scored according to the World Health Organization criteria. Follow-up time ranged from 7 months to 25 months (median, 9 months)., Results: The treatment was feasible. Forty-one patients received the intended total dose. Treatment was never stopped because of toxicity. Acute toxicity was mainly Grade 1 and Grade 2 (in 70% and 57% of patients, respectively), whereas Grade 3 toxicity was seen in 9% of patients. One fatal event occurred that was not treatment related. Late Grade 3 and Grade 4 gastrointestinal toxicity was seen in 3 patients and 2 patients, respectively. Late (Grade 5) gastrointestinal bleeding was observed in 3 patients, 2 of whom had local tumor progression. At 3 months, reduction in tumor size was seen in 27% of patients, stable disease was seen in 20% of patients, and local disease progression was seen in 40% of patients. Ultimately, local disease progression was observed in 44% of patients. No true partial or complete responses were documented. The median survival from the time of diagnosis was 11 months (10 months from the start of radiotherapy). Seventeen of 25 patients (68%) experienced pain relief., Conclusions: High dose conformal radiotherapy for the treatment of patients with locally advanced pancreatic carcinoma is feasible with acceptable toxicity. In case of pain, it can offer palliation. The efficacy of the treatment in terms of prolongation of life is not proven. Distant metastases remain the major problem.

Comparison of mitochondrial and morphological divergence in eight populations of a widespread leaf-litter skink is used to determine the relative importance of geographic isolation and natural selection in generating phenotypic diversity in the Wet Tropics Rainforest region of Australia. The populations occur in two geographically isolated regions, and within each region, in two different habitats (closed rainforest and tall open forest) that span a well characterized ecological gradient. Morphological differences among ancient geographic isolates (separated for several million years, judging by their mitochondrial DNA sequence divergence) were slight, but morphological and life history differences among habitats were large and occurred despite moderate to high levels of mitochondrial gene flow. A field experiment identified avian predation as one potential agent of natural selection. These results indicate that natural selection operating across ecological gradients can be more important than geographic isolation in similar habitats in generating phenotypic diversity. In addition, our results indicate that selection is sufficiently strong to overcome the homogenizing effects of gene flow, a necessary first step toward speciation in continuously distributed populations. Because ecological gradients may be a source of evolutionary novelty, and perhaps new species, their conservation warrants greater attention. This is particularly true in tropical regions, where most reserves do not include ecological gradients and transitional habitats.

The limited aperture size through which the em-field of the applicator is emanated and the constraining of this em-field near the bolus' edge is related to the appearance of superficial 'hot spot' phenomena in radiative hyperthermia. Regarding systems based on the concept of the annular phased array two questions arise: (1) what is the relative strength of the radial component present in the incident field of the radiators, and (2) in what way are fringing fields related to the bolus size? To address both of the above questions, the spatial distribution of the em-field emanated through the aperture of an applicator of the Amsterdam four waveguide-array system has been investigated for a long bolus and a short bolus. The em vector field emanated by the applicator has been characterized in two perpendicular planes, i.e. the aperture midplane and the sagittal midplane. It should be noted that this distribution depends on the propagation conditions throughout the coupling bolus, the phantom and other volumes attached, such as other applicators. Therefore two sets of propagation conditions have been measured: (1) the minimum number of parameters determining the propagation of the em-field namely one single waveguide, one bolus and a homogeneous phantom, and (2) the propagation conditions as for the clinical setting. It is stressed that the study concerns one specific radiative hyperthermia system, namely the AMC four-waveguide array, but that, based on the similarities discussed above, results may be extrapolated towards other radiative hyperthermia systems. According to the current study, bolus prolongation might lead to a clear clinical improvement, which is due to a decrease of the fringing field amplitude compared to the field amplitude in the centre of the aperture midplane. Bolus prolongation will lead to an extended heating area, the field lines being more aligned to the patient's main axis.

Hypoxic clonogenic cells are an important contributory factor in tumour radioresistance. The objective of the present study was to evaluate whether hyperbaric oxygen enhances tumour radiosensitivity, using a conventionally fractionated irradiation schedule, and whether the radiosensitizing potential is different from carbogen. Experiments were performed using the rhabdomyosarcoma R1H model transplanted subcutaneously in the flank of WAG/Rij rats. A total of 30 X-ray fractions of 2 Gy were given either in air, normobaric carbogen or high pressure oxygen (HPO) (240 kPa, 2.37 atm) without anaesthesia. The time taken to achieve complete remission was 38.7 +/- 3.6 days, 36.7 +/- 2.7 days and 32.4 +/- 4.1 days for air, normobaric carbogen and HBO, respectively. The differences between air and HBO (p = 0.002) and carbogen and HBO (p = 0.015) were significant. Use of carbogen and HBO produced the same local control probability at 150 days and this was significantly higher than local control under ambient conditions (p < 0.0001). It was concluded that the time to achieve complete remission of the rat rhabdomyosarcoma R1H can be shortened by HBO. Furthermore, both HBO and carbogen give higher local control probabilities than treatment under ambient conditions when used with a conventionally fractionated radiation schedule.

Purpose: Investigation of normal tissue sparing in pulsed brachytherapy (PB) relative to continuous low-dose rate irradiation (CLDR) by adjusting pulse frequency based on tissue repair characteristics., Method: Using the linear quadratic model, the relative effectiveness (RE) of a 20 Gy boost was calculated for tissue with an alpha/beta ratio ranging from 2 to 10 Gy and a half-time of sublethal damage repair between 0.1 and 3 h. The boost dose was considered to be delivered either in a number of pulses varying from 2 to 25, or continuously at a dose rate of 0.50, 0.80, or 1.20 Gy/h., Results: The RE of 20 Gy was found to be identical for PB in 25 pulses of 0.80 Gy each h and CLDR delivered at 0.80 Gy/h for any alpha/beta value and for a repair half-time > 0.75 h. When normal tissue repair half-times are assumed to be longer than tumor repair half-times, normal tissue sparing can be obtained, within the restriction of a fixed overall treatment time, with higher dose per pulse and longer period time (time elapsed between start of pulse n and start of pulse n + 1). An optimum relative normal tissue sparing larger than 10% was found with 4 pulses of 5 Gy every 8 h. Hence, a therapeutic gain might be obtained when changing from CLDR to PB by adjusting the physical dose in such a way that the biological dose on the tumor is maintained. The normal tissue-sparing phenomenon can be explained by an increase in RE with longer period time for tissue with high alpha/beta ratio and fast or intermediate repair half-time, and the RE for tissue with low alpha/beta ratio and long repair half-time remains almost constant., Conclusion: Within the benchmark of the LQ model, advantage in normal tissue-sparing is expected when matching the pulse frequency to the repair kinetics of the normal tissue exposed. A period time longer than 1 h may lead to a reduction of late normal tissue complications. This theoretical advantage emphasizes the need for better knowledge of human tissue-repair kinetics.

The Technical Committee and the Clinical Committee of the ESHO evaluated the experience of the institutes which are active in clinical regional hyperthermia using radiative equipment. Based on this evaluation, QA guidelines have been formulated. The focus of these guidelines lies on what must be done not on how it should be done. Subjects covered are: treatment planning, treatment, treatment documentation, requirements and characterization of equipment, safety aspects, hyperthermia staff requirements and instrumentation for quality assurance.

Distinguishing between primary and secondary intergradation among differentiated populations, and the relative importance of drift and selection, are persistent problems in evolutionary biology. An historical perspective on population interactions can provide insight into the nature of contacts, and thus help resolve these questions. Continuously distributed populations of Anolis marmoratus from the island of Basse Terre in the Guadeloupean archipelago of the Lesser Antilles show a striking degree of geographic variation in morphology. Initial surveys of mtDNA variation from throughout the Guadeloupean Archipelago revealed one case where levels of sequence difference and phylogenetic relationships of alleles from morphologically differentiated populations from the east coast of Basse Terre were consistent with primary intergradation. In this paper, I examine the genetic population structure of a series of populations spanning this north-south cline in morphological variation to test the hypothesis of primary intergradation. Sequences of the mitochondrial cytochrome-b gene from 50 individuals representing five populations spanning the cline were obtained and fourteen unique haplotypes (differing by 2% or less) were detected. Patterns of nucleotide substitution among haplotypes do not deviate from neutral expectation indicating no effect of selection at the level of mtDNA sequences. Estimates of population structure and gene flow were made using both summary statistics for nucleotide diversity (Nst) and cladistic methods. The results are sensitive to the choice of gene flow model, and this is discussed in detail. Mitochondrial variation in the northern populations may not be at equilibrium, and the phylogeny of alleles is consistent with a recent increase in effective population size. Estimates of nucleotide diversity, gene flow, and the phylogenetic relationships of haplotypes indicate that the southern-most population (representing the extreme of morphological variation along this cline) has been relatively isolated from populations to the north and has experienced a reduced effective population size. The apparent clinal variation between the southern population and the others may therefore reflect secondary contact and introgression rather than primary intergradation.

The Effective Field Sizes (EFS) and the Effective Heating Depths (EDH) of Contact Flexible Microstrip Applicators (CFMA), tuned at a frequency of 434 MHz, were determined on two fat/muscle phantoms. One phantom was box-shaped with a flat top layer of 1 cm thick artificial fat and the other one a tube of which the cross-section was elliptically shaped (25 x 36 cm) having a fat equivalent shell of 1 cm thick. For the muscle material a 6 g/l saline (NaCl) solution was used. On the flat rectangular phantom, the effective field size at 1 cm depth in saline was measured to be 4.7 x 13.5 cm, 17.5 x 17.7 cm and 12.5 x 14.0 cm for the 1H-applicator, the 3H-applicator and the 5H-applicator, respectively. For the 3H-and the 5H-applicator, the Specific absorption rate (SAR) distribution at 1 cm depth showed a single maximum of SAR for a thin bolus, which split into two separate "hot spots' for a thicker bolus. The Effective Heating Depths in the phantom with a flat surface were of the order of that of a plane wave (approximately 1.4 cm), whereas a larger EHD of 2.4 cm was achieved below the 3H-applicator bent to fit the elliptical phantom. Due to the large effective field size and the "flatness' of the SAR distribution, the applicators 3H and 5H are suitable to adequately treat large superficial tumours.

There are a number of potential advantages to be gained by using an array of applicators in hyperthermia treatments compared with single applicator systems. These advantages include the possibility of greater spatial control of power deposition and conformability to nonplanar sites. Arrays of applicators can be driven either coherently or incoherently. In the case of coherent operation, an added advantage is the ability to steer power deposition by varying the phases of the antennas. In this study, we investigated the relative merits of the two modes of operation when a 2 x 2 planar array of current sheet applicators is used. The effective field size (EFS) of the array was calculated using a Gaussian beam representation of the applicators on a layered model in which the fat layer had its thickness varied. Good agreement was obtained between the square of the electric field distribution (E2) and quantitative experimental results. It is shown that when the planar array is used with a fat layer greater than about 2 mm present, it should be driven incoherently as this results in a significantly larger EFS than that obtained when the array is driven coherently.

An approach to a solution of two major problems in operating Annular Phased Arrays in deep body hyperthermia is presented: an E-field sensor capable of measuring phase and amplitude at 70 MHz and the concept of a power transmission factor to determine the effective amplitude of each applicator. In the four-waveguide Phased Array operating at 70 MHz, which is in clinical use at the department of Radiotherapy of the Academic Medical Center (AMC), the incident fields of the waveguides were scanned in phase and amplitude over the complete aperture midplane, inside an elliptical and a square phantom filled with saline. As a check on the application of the superposition principle, superpositions of the incident fields were compared with the electric field in the measured interference set-ups. With all four applicators radiating at equal amplitude and in phase, the maximum difference over the complete midplane of the phantom between superimposed and measured interference scans was 20% and 10 degrees in the elliptical phantom, and 20% and 30 degrees in the square phantom. After having determined nominal amplitude and phase patterns by a vector probe, any interference set-up can be superimposed from measurement of the actual incident field of each applicator. Therefore, the availability of a vector sensor as described here will contribute to solve a problem of hyperthermia quality assurance: the performance evaluation of Phased Arrays.

The Amsterdam phantom with LED-matrix is applied as an instrument in testing the performance of four types of radiative deep-body hyperthermia systems, which are in clinical use in Germany and The Netherlands. The devices tested were Essen's BSD-1000, Berlin's BSD-2000, Utrecht's Coaxial TEM applicator and Amsterdam's Four-waveguide-array. Photographs were taken of the matrix of dipoles loaded with light-emitting diodes (LED) to visualize the distribution of the RF power deposition or specific absorption rate (SAR) in the aperture midplane. The utility of the phantom with LED matrix for various types of radiative hyperthermia systems is demonstrated. Within this preliminary study, the influence of important parameters on the SAR-pattern in the aperture midplane was demonstrated. After corrections on the phase relation of the applicators a central focus in the SAR distribution could be realized in all systems and could also be moved in any direction. The patterns of the central focus changed in its absolute values and its proportions depending on the relative relations of phase and amplitude of the lateral applicators with respect to the top and bottom applicator. Frequency dependency was recognized for the central focus of the BSD-1000 as well as for the irradiation pattern of a single applicator for the BSD-2000. In the Coaxial TEM applicator it was demonstrated that the dimension of the open water bolus influenced the absolute value of SAR in the aperture midplane.

We report the results of a case-control study designed to identify modifiable risk factors for childhood sledding injuries. Cases included all children injured while sledding (n = 17) during a five-day winter storm who presented for care to a Seattle pediatric emergency department. Two controls were chosen randomly for each case from children who presented to the same emergency department during the ensuing two months for any illness that did not require hospitalization. To qualify as controls, children had to have sledded during the same five-day period but not sustained an injury requiring medical attention. Data were collected on cases and controls using a telephone questionnaire. Analysis of risk factors revealed a significant increase in risk of injury for children who sledded in streets versus those who sledded in a park (OR = 5.1; 95% CI = 1.1-24.1), those who sledded without adult supervision (OR = 5.6; 95% CI = 1.1-26.9), and those whose parents had an annual income > or = $50,000 (OR = 5.7; 95% CI = 1.5-20.8). No difference in risk of injury was found regarding the type of sled used, the number of children, or their position on the sled or for those children with a history of prior sledding experience. We conclude that safe alternatives to sledding in the streets and an increase in adult supervision may reduce the number of childhood sledding injuries.

The utility of the light-emitting diode (LED) matrix, i.e. the qualitative localization of maxima and minima in the patterns of the specific absorption rate (SAR), can be extended to quantitative measurements by a method described. With the LED dipoles on the matrix representing light sources of similar characteristics, the minimal field strength necessary to produce light is a criterion which can be easily determined. From the power levels necessary to fulfil this criterion, relative SAR values have been calculated. The attenuation of field strength by the LED matrix has been measured by an additional dipole antenna with fibre-optic read-out, so that the calculated SAR profiles could be corrected for the relatively smaller attenuation near the edges. This technique has been tested for several set-ups in a 'Coaxial TEM applicator' and the resulting SAR profiles along the major axis of the aperture midplane were compared with SAR profiles determined using a single dipole E-field probe. Results show that, from a set of photographs at different power levels, SAR profiles can be constructed with limited accuracy along lines in any direction in the whole aperture midplane and by this the complete two-dimensional SAR pattern can be obtained.

Inhibition of calcium-evoked [3H]ACh release by different classes of calcium channel blockers was compared among calcium-naive synaptosomes from chick, frog and rat forebrain tissues. In all three species, [3H]ACh release was insensitive to nifedipine (0.03-3 microM) but was completely inhibited by cadmium (IC50 range = 0.7-1.7 microM) or cobalt (190-350 microM). In contrast, the peptide omega-conotoxin revealed marked species heterogeneity in that [3H]ACh release was potently blocked in chick and rat synaptosomes (IC50 congruent to 1 nM), whereas frog tissue was notably resistant (IC50 greater than 100 nM). Together, these data provide functional evidence for pharmacological heterogeneity among presynaptic calcium channels that subserve [3H]ACh release.

Calcium-naive synaptosomes were used to assess the effects of divalent cations on [3H]acetylcholine release from rat hippocampal homogenates. Following equilibration with calcium-free buffer (containing 10 microM EGTA), calcium reversibly increased [3H]acetylcholine efflux (up to five-fold) while causing no measurable efflux of lactate dehydrogenase. When substituted for calcium, strontium and barium behaved similarly although barium exhibited three-fold greater efficacy. In the presence of elevated potassium, 4-aminopyridine or tetraethylammonium, the secretagogue efficacy of calcium (but not barium) was markedly increased. The release-promoting effects of both cations were inhibited by lanthanum, magnesium, cadmium, and omega-conotoxin but were insensitive to nifedipine and cobalt (both 10 microM). In addition, stimulation of muscarinic cholinergic autoreceptors substantially inhibited both calcium and barium-evoked [3H]acetylcholine release. Taken together, these results indicate that cation-evoked transmitter release from calcium-naive synaptosomes is subject to normal neuroregulatory mechanisms and therefore should be useful for investigating presynaptic modulation of neuronal exocytosis.

An experimental study is described, leading to the design of a near-field electromagnetic radiation probe. A passive field probe with fibre-optic link has been constructed for use in hyperthermia phantoms, i.e. for measurements in lossy media--saline was used in this study as a simulation of biological tissue. The realization of a closed electric circuit on the probe proved to be a major influence on the sensitivity and dynamic range of the probe. The experiments also independently confirmed the dipole length, frequency variations between 5 and 110 MHz and the temperature of the probe as important parameters.

This paper reviews multicomponent behavioral medicine studies that contain cost-effectiveness and or cost-benefit data relevant to the field of biofeedback and relaxation training, primarily when assisted by biofeedback, with or without stress management, in the treatment of psychosomatic illness and pain. A model for evaluating biofeedback treatment is presented. Cost-effectiveness data concerning reduction in physician visits and/or medication use, decrease in medical care costs to patients, reduction in hospital stays and rehospitalization, reduction of mortality, and enhanced quality of life are reviewed. Evidence suggests that multicomponent behavioral medicine treatments are cost-effective on all dimensions reviewed. Cost/benefit ratios range between 1:2 and 1:5, with a median of 1:4. Evidence that could increase the cost effectiveness of biofeedback is reviewed.

Age-corrected mortalities from cancer at 17 major body sites were correlated with the apparent dietary selenium intakes estimated from food-consumption data in 27 countries. Significant inverse correlations were observed for cancers of large intestine, rectum, prostate, breast, ovary, lung and with leukemia; weak inverse associations were found for cancers of pancreas, skin and bladder. Similar inverse corelations were found between cancer mortalities at the above sites and the selenium concentrations in whole blood collected from healthy human donors in the U.S. and different countries. The results support the hypothesis that selenium has cancer-protecting effects in man. Other studies are cited which demonstrate that selenium prevents or retards tumor development in animals. A change of diet aimed at increasing the dietary selenium supply is suggested as a possible means of lowering the human cancer risk. It is postulated that the cancer mortalities in the U.S. and other Western industrialized nations would decline significantly if the dietary selenium intakes were increased to approximately twice the current average amount supplied by the U.S. diet.

Acidosis inhibits the hydroosmotic response to vasopressin. Since prostaglandins are known to modulate vasopressin-stimulated water flow we investigated the role of endogenous prostaglandin E2(PGE2) production in the pH-dependent response of the toad urinary bladder to vasopressin. Graded acidification of the serosal medial resulted in a progressive decline in vasopressin-stimulated water flow from 26.6 +/- 0.5 mg/min at pH 8.4 to 1.7 +/- 0.6 at pH 6.9. In these bladders basal PGE2 synthesis increased from 5.09 +/- 0.51 pmol/min per g hemibladder at pH 8.4 to 18.8 +/- 2.8 at pH 6.9. The addition of that concentration of PGE2 produced by the bladder at pH 7.4 (4 nM) to bladders at pH 8.4 resulted in 62-71% of the inhibition usually seen at pH 7.4; these data suggest that basal PGE2 production per se and not other products of prostaglandin synthesis or other pH-dependent events is responsible for the effect of acidosis. Preincubation with prostaglandin synthesis inhibitors reversed in major part the effect of serosal acidification on the response to submaximal concentrations of vasopressin and completely abolished the effect of pH on near maximal concentrations of the hormone. An increase in PGE2 synthesis after vasopressin was not seen at any pH. These studies establish that increased basal PGE2 synthesis plays a critical role in the pH dependence of the hydroosmotic response to vasopressin and demonstrate that factors that modulate the response to vasopressin may exert this effect by changing the basal rate of prostaglandin synthesis.

The joint administration of 2 ppm of arsenic as arsenite and of 2 ppm of selenium as selenite in the drinking water of inbred female C3H/St mice increases the incidence of spontaneous mammary adenocarcinoma significantly over the simultaneous controls and animals receiving 2 ppm As as arsenite or 2 ppm Se as selenite alone, indicating that arsenic abolishes the anticarcinogenic effect of selenium. Arsenite caused a significant increase of the tumor growth rates and raised the incidence of multiple tumors. The tumor growth rates in the As-Se group were also increased, but the incidence of multiple tumors was lower than in the 2 ppm As group.

The inhibitory effect of selenium on the genesis of spontaneous mammary tumors in C3H mice is statistically significant even at toxic levels of selenium (5 and 15 ppm of Se in form of selenite added to the supply water), no evidence for stimulation of tumor growth by selenium has been obtained. Arsenite lowers the tumor incidence at higher dosage (80 ppm of As in supply water) as well, but animals developing tumors under these conditions demonstrate significantly enhanced tumor growth rates. The addition of subtoxic concentrations of zinc (200 ppm in form of ZnCl2) to supply water containing 5 ppm of Se abolishes the cancer-protecting effect of selenium. The latter result is of possible importance with respect to the human breast cancer mortality experience: The calculated dietary zinc intakes of average adults in 28 countries correlate with the female age-corrected mortalities from breast cancer directly, with P less than 0.005. The zinc concentrations in whole blood from donors in different parts of the U.S.A. are also directly correlated with the female breast cancer mortalities.

The per-capita intakes of zinc, cadmium, copper and of chromium were estimated from food consumption data in 28 countries and were found to correlate directly with the age-corrected mortalities from cancers of intestine, prostate, breast, leukemia, skin and of other organs, suggesting that the anticarcinogenic effect of selenium is counteracted by other trace elements. Similarly calculated dietary intakes of manganese are inversely correlated, particularly with the mortalities from cancer of pancreas, an organ normally known to contain high concentrations of this element. Arsenic intakes correlate inversely with the male lung cancer mortalities. A number of other direct and inverse associations were observed which suggest that trace elements in the human diet may hav both benign and adverse effects on tumor development. The zinc concentrations in whole blood collected from healthy donors in the U.S. correlate directly with regional mortalities from cancers of intestine, breast and of other sites. The origin of these associations is discussed primarily in terms of the seleium-antagonistic effect of zinc and of some of the other elements considered. Results of animal experiments and of other studies are cited which support hypotheses that link human cancer development to possible deficiencies or excesses in the dietary trace element intakes.

Previous studies have identified several cellular requirements for mevalonic acid that appear unrelated to cholesterol, dolichol, or ubiquinone. To search for other products of mevalonic acid that might account for these requirements we cultured Swiss 3T3 cells in the presence of mevinolin, an inhibitor of mevalonic acid biosynthesis, then labeled the cells with exogenous radioactive mevalonic acid. Upon analyzing the radioactive material formed, we found that 40-50% of it was not extractable into lipid solvents, and that most of the lipid-insoluble material behaved like protein when treated with sodium dodecyl sulfate:chloroform:phenol, RNase, or proteinase K. Further analysis by electrophoresis revealed that radioactivity was associated with a few specific proteins that had apparent molecular weights of 13,000-58,000. Control experiments indicated that authentic radioactive (R)-mevalonic acid was the active precursor. Other lines of evidence suggested that mevalonate was first converted to an isoprenoid compound, then covalently incorporated into proteins by way of a cycloheximide-insensitive mechanism. These results suggest that Swiss 3T3 cells possess novel metabolic products of mevalonic acid metabolism that are formed by post-translational incorporation of isoprenoids into specific cell proteins.

Inbred female C3H/St mice exhibit the normal incidence of spontaneous mammary adenocarcinoma of 80--100% if they are maintained on a standard commercial laboratory diet containing 0.15 ppm of selenium with meat and dried skimmed milk as major sources of protein. The tumor incidence drops to 42% if animals of the same strain are kept on a diet containing 0.45 ppm of selenium, with fishmeal as the main source of protein. The tumor incidence declines further to 25, 19 and 10% if the animals in addition receive 0.1, 0.5, and 1.0 ppm of selenium in the drinking water. Selenium supplementation at these levels has no noticable adverse effects on weight-grains and survival of the mice. Selenium supplmented groups of animals also remained tumor-free for longer periods than the unsupplemented controls. The results of this study indicate that a diet rich in seafoods and cereals provides more selenium and may in turn lower the probability of cancer development. Reference is made to the average human diet in the U.S.A., which only contains 0.07--0.15 ppm of selenium due to the comparatively low consumption of cereals and seafoods. An equivalent mouse diet would not have any cancer-protecting effect in the C3H/St mice of our study. Australian workers have reported significantly lower tumor incidence in a different strain of C3H mice if it was kept in Australia rather than in the U.S.A. We have found that the Australian feed contained three times more selenium than that employed in the U.S.A. and propose that this difference in selenium content was primarily responsible for these previous observations.