Ra-223, an α-particle emitting bone-seeking radionuclide, has recently been used in clinical trials for osseous metastases of prostate cancer. We investigated the relationship between absorbed fraction-based red marrow dosimetry and cell level-dosimetry using a model that accounts for the expected localization of this agent relative to marrow cavity architecture. We show that cell level-based dosimetry is essential to understanding potential marrow toxicity. The GEANT4 software package was used to create simple spheres representing marrow cavities. Ra-223 was positioned on the trabecular bone surface or in the endosteal layer and simulated for decay, along with the descendants. The interior of the sphere was divided into cell-size voxels and the energy was collected in each voxel and interpreted as dose cell histograms. The average absorbed dose values and absorbed fractions were also calculated in order to compare those results with previously published values. The absorbed dose was predominantly deposited near the trabecular surface. The dose cell histogram results were used to plot the percentage of cells that received a potentially toxic absorbed dose (2 or 4 Gy) as a function of the average absorbed dose over the marrow cavity. The results show (1) a heterogeneous distribution of cellular absorbed dose, strongly dependent on the position of the cell within the marrow cavity; and (2) that increasing the average marrow cavity absorbed dose, or equivalently, increasing the administered activity resulted in only a small increase in potential marrow toxicity (i.e. the number of cells receiving more than 4 or 2 Gy), for a range of average marrow cavity absorbed doses from 1 to 20 Gy. The results from the trabecular model differ markedly from a standard absorbed fraction method while presenting comparable average dose values. These suggest that increasing the amount of radioactivity may not substantially increase the risk of toxicity, a result unavailable to the absorbed fraction method of dose calculation.

This case report describes two patients with a very rare condition who presented with pathologic symptoms. Anomalous origin of the left coronary artery from the noncoronary cusp has been described as a "benign" lesion by some authors in the past, although rare cases of morbidity/mortality are described in the literature. Both reported patients underwent surgical repair for the lesion and at this writing are asymptomatic at follow-up evaluation. These two patients presenting with pathologic symptoms and undergoing surgery afford novel descriptions. The authors believe these descriptions add to our knowledge of this rare disorder.

ABSTRACT: BACKGROUND: The success and cost-effectiveness of bowel cancer screening depends on achieving and maintaining high screening uptake rates. The involvement of GPs in screening has been found to improve patient compliance. Therefore, the endorsement of screening by GPs may increase uptake rates amongst non-responders. METHODS: A two-armed randomised controlled trial will evaluate the effectiveness of a GP endorsed reminder in improving patient participation in the NHS Bowel Cancer Screening Programme (NHSBCSP). Up to 30 general practices in the West Midlands with a screening uptake rate of less than 50% will be recruited and patients identified from the patient lists of these practices. Eligible patients will be those aged 60 to 74, who have previously been invited to participate in bowel screening but who have been recorded by the Midlands and North West Bowel Cancer Screening Hub as non-responders. Approximately 4,380 people will be randomised in equal numbers to either the intervention (GP letter and duplicate FOBt kit) or control (no additional contact) arms of the trial. The primary outcome measure will be the difference in the uptake rate of FOBt screening for bowel cancer between the intervention and control groups at 13 weeks after the GP endorsed reminder and duplicate FOBt kit are sent. Secondary outcome measures will be subgroup analyses of uptake according to gender, age and deprivation quartile, and the validation of methods for collecting GP, NHSBCSP and patient costs associated with the intervention. Qualitative work (30 to 40 semi-structured interviews) will be undertaken with individuals in the intervention arm who return a FOBt kit, to investigate the relative importance of the duplicate FOBt kit, reminder to participate, and GP endorsement of that reminder in contributing to individuals' decisions to participate in screening. DISCUSSION: Implementing feasible, acceptable and cost-effective strategies to improve screening uptake amongst non-responders to invitations to participate is fundamentally important for the success of screening programmes. If this feasibility study demonstrates a significant increase in uptake of FOBt screening in individuals receiving the intervention, a definitive, appropriately powered future trial will be designed. Trial registration International Standard Randomised Controlled Trials No: ISRCTN86784060.

UNLABELLED (153)Sm-ethylenediamine tetramethylene phosphonic acid ((153)Sm-EDTMP) therapy for osteosarcoma is being investigated. In this study, we analyzed the influence of (153)Sm-EDTMP administered activity (AA), osteosarcoma tumor density, mass, and the shape of the tumor on absorbed dose (AD). We also studied the biologic implication of the nonuniform tumor AD distribution using radiobiologic modeling and examined the relationship between tumor AD and response. METHODS Nineteen tumors in 6 patients with recurrent, refractory osteosarcoma enrolled in a phase I or II clinical trial of (153)Sm-EDTMP were analyzed using the 3-dimensional radiobiologic dosimetry (3D-RD) software package. Patients received a low dose of (153)Sm-EDTMP (37.0-51.8 MBq/kg), followed on hematologic recovery by a second, high dose (222 MBq/kg). Treatment response was evaluated using either CT or MRI after each therapy. SPECT/CT of the tumor regions were obtained at 4 and 48 h or 72 h after (153)Sm-EDTMP therapy for 3D-RD analysis. Mean tumor AD was also calculated using the OLINDA/EXM unit-density sphere model and was compared with the 3D-RD estimates. RESULTS On average, a 5-fold increase in the AA led to a 4-fold increase in the mean tumor AD over the high- versus low-dose-treated patients. The range of mean tumor AD and equivalent uniform dose (EUD) for low-dose therapy were 1.48-14.6 and 0.98-3.90 Gy, respectively. Corresponding values for high-dose therapy were 2.93-59.3 and 1.89-12.3 Gy, respectively. Mean tumor AD estimates obtained from OLINDA/EXM were within 5% of the mean AD values obtained using 3D-RD. On an individual tumor basis, both mean AD and EUD were positively related to percentage tumor volume reduction (P = 0.031 and 0.023, respectively). CONCLUSION The variations in tumor density, mass, and shape seen in these tumors did not affect the mean tumor AD estimation significantly. The tumor EUD was approximately 2- and 3-fold lower than the mean AD for low- and high-dose therapy, respectively. A dose-response relationship was observed for transient tumor volume shrinkage.

We collected blood from 18 beluga whales (Delphinapterus leucas), live-captured in Bristol Bay, Alaska, USA, in May and September 2008, to establish baseline hematologic and serum chemistry values and to determine whether there were significant differences in hematologic values by sex, season, size/age, or time during the capture period. Whole blood was collected within an average of 19 min (range=11-30 min) after the net was set for capture, and for eight animals, blood collection was repeated in a later season after between 80-100 min; all blood was processed within 12 hr. Mean hematocrit, chloride, creatinine, total protein, albumin, and alkaline phosphatase were significantly lower in May than they were in September, whereas mean corpuscular hemoglobin concentration, monocytes, phosphorous, magnesium, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltranspeptidase, and creatinine kinase were significantly higher. Mean total protein, white blood cell count, neutrophils, and lymphocytes were significantly higher early in the capture period than they were later. No significant differences in blood analyte values were noted between males and females. Using overall body length as a proxy for age, larger (older) belugas had lower white blood cell, lymphocyte, and eosinophil counts as well as lower sodium, potassium, and calcium levels but higher creatinine levels than smaller belugas. These data provide values for hematology and serum chemistry for comparisons with other wild belugas.

As a consequence of the high potency and short range of alpha-particles, radiopharmaceutical therapy with alpha- particle emitting radionuclides is a promising treatment approach that is under active pre-clinical and clinical investigation. To understand and predict the biological effects of alpha-particle radiopharmaceuticals, dosimetry is required at the micro or multi-cellular scale level. At such a scale, highly non-uniform irradiation of the target volume may be expected and the utility of a single absorbed dose value to predict biological effects comes into question. It is not currently possible to measure the pharmacokinetic input required for micro scale dosimetry in humans. Accordingly, pre-clinical studies are required to provide the pharmacokinetic data for dosimetry calculations. The translation of animal data to the human requires a pharmacokinetic model that links macro- and micro-scale pharmacokinetics thereby enabling the extrapolation of micro-scale kinetics from macroscopic measurements. These considerations along with a discussion of the appropriate physical quantity and related units for alpha-particle radiopharmaceutical therapy are examined in this review.

The rapidly developing field of seismic oceanography (SO) uses frequencies far lower (10-200 Hz) than tradition acoustic oceanography, and is not a measure of particulate scattering strength, but rather a direct, quantitative measure of vertical temperature gradient. The temperature gradient is typically a very weak signal (reflection coefficients of 0.001 or less) in the presence of higher amplitude coherent noise, such as the direct wave, and the reverberation of the ship noise (in shallow water). Towing the system faster than 4-5 kts to cover greater distances quickly increases streamer noise. Our objective to develop SO into a useful oceanographic tool is, therefore, a signal-to-noise problem, with mostly coherent noise. Using data acquired in the first coastal application of SO (ADRIASEISMIC), we show the magnitude of the noise sources and how they have been mitigated to result in quantitative (albeit band-limited) measures of temperature gradient from a few tens of meters below the sea surface to just meters above the seafloor. The profiles allow the detailed tracking of very small ocean features, among them warm thermohaline intrusions and dense, cold, bottom water masses, both in places only 10 m thick.