Adriamycin/cyclophosphamide and adriamycin/melphalan in advanced L1210 leukaemia.

Adriamycin and cyclophosphamide are active agents in human and experimental tumours. Using the L1210 murine leukaemia, their effectiveness alone and in combination was studied. The combination is highly synergistic in this tumour, resulting in a greater than 50% survival rate when the agents used alone at optimal doses are not curative. DNA synthesis by tumour cells is substantially inhibited and the total ascitic population much reduced. In contrast, DNA synthesis in sensitive host tissues is less disturbed. There is no major difference in the pharmacology of the agents whether given alone or in combination. In very advanced disease the combination is no better than treatment with cyclophosphamide alone. The combination of adriamycin and melphalan in L1210 leukaemia also produces superior results to those obtained using either drug alone at its optimal dosage

The post-hemodialysis rebound: Predicting and quantifying its effect on Kt/V

The post-hemodialysis rebound: Predicting and quantifying its effect on Kt/V. Immediately after hemodialysis, the urea concentration rebounds upwards as urea continues to be transferred into the arterial circulation from peripheral body compartments. This rebound takes at least 30 minutes to complete. Hemodialysis is quantified as the Kt/V, calculated prom pre- and post-dialysis urea samples. Unless the post-dialysis sample is taken at least 30 minutes after dialysis, the Kt/V will be overestimated. This overestimation will be relatively greater in short high-efficiency dialyses, which have greater post-dialysis rebounds. We propose a method of correction that uses only the conventional pre- and immediate post-dialysis samples and is based on the physiologically-appropriate patient clearance time (tp). This is the time needed to clear all body compartments when the dialyzer clearance is infinite. The tp can be calculated from the pre-, immediate post- and 30-minute post-dialysis urea concentrations and was 35 minutes (SD 16) in 29 patients undergoing short (149 min) hemodiafiltration and standard (243 min) hemodialysis the following week. There was no significant difference between tp values calculated during the two treatments. Standard Kt/V can be corrected by multiplying by t/(t + tp) and dialysis time should be increased by tp × Kt/V minutes to compensate for the rebound. Despite individual variations in tp, a value of tp = 35 was sufficient to correct Kt/V in all patients. Kt/V corrected in this way agreed with Kt/V calculated using a 60-minute post-dialysis sample (r = 0.856, P < 0.001). The method predicted the 60-minute post-rebound concentration (SE 0.5mM, r = 0.983, P < 0.001) and the addition of 35 minutes to the treatment time corrected for the rebound in both conventional and short treatments. Similar simple equations corrected the error in V caused by rebound effects

Can a single image processing algorithm work equally well across all phases of DCE-MRI?

Image segmentation and registration are said to be challenging when applied to dynamic contrast enhanced MRI sequences (DCE-MRI). The contrast agent causes rapid changes in intensity in the region of interest and elsewhere, which can lead to false positive predictions for segmentation tasks and confound the image registration similarity metric. While it is widely assumed that contrast changes increase the difficulty of these tasks, to our knowledge no work has quantified these effects. In this paper we examine the effect of training with different ratios of contrast enhanced (CE) data on two popular tasks: segmentation with nnU-Net and Mask R-CNN and registration using VoxelMorph and VTN. We experimented further by strategically using the available datasets through pretraining and fine tuning with different splits of data. We found that to create a generalisable model, pretraining with CE data and fine tuning with non-CE data gave the best result. This interesting find could be expanded to other deep learning based image processing tasks with DCE-MRI and provide significant improvements to the models performance

Geographical variation in bill size across bird species provides evidence for Allen\u27s rule

Allen&rsquo;s rule proposes that the appendages of endotherms are smaller, relative to body size, in colder climates, in order to reduce heat loss. Empirical support for Allen&rsquo;s rule is mainly derived from occasional reports of geographical clines in extremity size of individual species. Interspecific evidence is restricted to two studies of leg proportions in seabirds and shorebirds. We used phylogenetic comparative analyses of 214 bird species to examine whether bird bills, significant sites of heat exchange, conform to Allen&rsquo;s rule. The species comprised eight diverse taxonomic groups&mdash;toucans, African barbets, Australian parrots, estrildid finches, Canadian galliforms, penguins, gulls, and terns. Across all species, there were strongly significant relationships between bill length and both latitude and environmental temperature, with species in colder climates having significantly shorter bills. Patterns supporting Allen&rsquo;s rule in relation to latitudinal or altitudinal distribution held within all groups except the finches. Evidence for a direct association with temperature was found within four groups (parrots, galliforms, penguins, and gulls). Support for Allen&rsquo;s rule in leg elements was weaker, suggesting that bird bills may be more susceptible to thermoregulatory constraints generally. Our results provide the strongest comparative support yet published for Allen&rsquo;s rule and demonstrate that thermoregulation has been an important factor in shaping the evolution of bird bills.<br /

Daily and annual cycles in thermoregulatory behaviour and cardio‑respiratory physiology of black and white tegu lizards

This study was designed to determine the manner in which metabolism is suppressed during dormancy in black and white tegu lizards (Tupinambis merianae). To this end, heart rate (f H), respiration rate (f R), and deep body temperature (T b) were continuously monitored in outdoor enclosures by radio-telemetry for nine months. There was a continuous decline in nighttime breathing and heart rate, at constant T b, throughout the late summer and fall suggestive of an active metabolic suppression that developed progressively at night preceding the entrance into dormancy. During the day, however, the tegus still emerged to bask. In May, when the tegus made a behavioural commitment to dormancy, T b (day and night) fell to match burrow temperature, accompanied by a further reduction in f H and f R. Tegus, under the conditions of this study, did arouse periodically during dormancy. There was a complex interplay between changes in f H and T b associated with the direct effects of temperature and the indirect effects of thermoregulation, activity, and changes in metabolism. This interplay gave rise to a daily hysteresis in the f H/T b relationship reflective of the physiological changes associated with warming and cooling as preferred T b alternated between daytime and nighttime levels. The shape of the hysteresis curve varied with season along with changes in metabolic state and daytime and nighttime body temperature preferences

Improving wrist imaging through a multicentre educational intervention: The challenge of orthogonal projections

YesIn relation to wrist imaging, the accepted requirement is two orthogonal projections obtained at 90°, each with the wrist in neutral position. However, the literature and anecdotal experience suggests that this principle is not universally applied. Method: This multiphase study was undertaken across eight different hospitals sites. Compliance with standard UK technique was confirmed if there was a change in ulna orientation between the dorsi-palmar (DP) and lateral wrist projections. A baseline evaluation for three days was randomly identified from the preceding three months. An educational intervention was implemented using a poster to demonstrate standard positioning. To measure the impact of the intervention, further evaluation took place at two weeks (early) and three months (late). Results: Across the study phases, only a minority of radiographs demonstrated compliance with the standard technique, with an identical anatomical appearance of the distal ulna across the projections. Initial compliance was 16.8% (n = 40/238), and this improved to 47.8% (n = 77/161) post-intervention, but declined to 32.8% (n = 41/125) within three months. The presence of pathology appeared to influence practice, with a greater proportion of those with an abnormal radiographic examination demonstrating a change in ulna appearances in the baseline cohort (