Compartmental Model for ²²³Ra-Dichloride in Patients With Metastatic Bone Disease From Castration-Resistant Prostate Cancer.

Purpose223Ra-Dichloride is used for treatment of patients with metastatic bone disease from castration-resistant prostate cancer. The uptake and mechanism of action of 223Ra-Dichloride is not well understood. The aim of this work was to develop a compartmental model for 223Ra-Dichloride in patients to improve understanding of the underlying mechanisms.Methods and materialsA compartmental model was developed based on activity retention data from 6 patients (2 treatments of 110 kBq/kg 223Ra-Dichloride) for plasma, bone surfaces, small intestines, large intestines, and excretion data. Rate constants were extracted. Rate constant variability between patients and treatments was assessed. A population model was proposed and compared with the established International Commission on Radiological Protection-67 compartmental model.ResultsA single bone compartment cannot accurately describe activity retention in the skeleton. The addition of a second bone compartment improved the fit to skeleton retention data, and the Akaike information criterion decreased. Mean rate constants of 4.0 (range, 1.9-10.9) and 0.15 (0.07-0.39) h-1 were obtained for transport from plasma to first bone compartment and vice versa. Rate constants from first to second bone compartment and back of 0.03 (0.02-0.06) and 0.008 (0.003-0.011) h-1 were calculated. Rate constants for individual patients showed no significant difference between patients and treatments.ConclusionsThe developed compartmental model suggests that 223Ra-Dichloride initially locates at the bone surface and is then incorporated into the bone matrix relatively quickly. This observation could have implications for dosimetry and understanding of the effects of alpha radiation on normal bone tissue. Results suggest that a population model based on patient measurements is feasible

SpK: A fast atomic and microphysics code for the high-energy-density regime

SpK is part of the numerical codebase at Imperial College London used to model high energy density physics (HEDP) experiments. SpK is an efficient atomic and microphysics code used to perform detailed configuration accounting calculations of electronic and ionic stage populations, opacities and emissivities for use in post-processing and radiation hydrodynamics simulations. This is done using screened hydrogenic atomic data supplemented by the NIST energy level database. An extended Saha model solves for chemical equilibrium with extensions for non-ideal physics, such as ionisation potential depression, and non thermal equilibrium corrections. A tree-heap (treap) data structure is used to store spectral data, such as opacity, which is dynamic thus allowing easy insertion of points around spectral lines without a-priori knowledge of the ion stage populations. Results from SpK are compared to other codes and descriptions of radiation transport solutions which use SpK data are given. The treap data structure and SpK’s computational efficiency allows inline post-processing of 3D hydrodynamics simulations with a dynamically evolving spectrum stored in a treap

InfuShield: a shielded enclosure for administering therapeutic radioisotope treatments using standard syringe pumps.

The administration of radionuclide therapies presents significant radiation protection challenges. The aim of this work was to develop a delivery system for intravenous radioisotope therapies to substantially moderate radiation exposures to staff and operators. A novel device (InfuShield) was designed and tested before being used clinically. The device consists of a shielded enclosure which contains the therapeutic activity and, through the hydraulic action of back-to-back syringes, allows the activity to be administered using a syringe pump external to the enclosure. This enables full access to the pump controls while simultaneously reducing dose to the operator. The system is suitable for use with all commercially available syringe pumps and does not require specific consumables, maximising both the flexibility and economy of the system. Dose rate measurements showed that at key stages in an I mIBG treatment procedure, InfuShield can reduce dose to operators by several orders of magnitude. Tests using typical syringes and infusion speeds show no significant alteration in administered flow rates (maximum of 1.2%). The InfuShield system provides a simple, safe and low cost method of radioisotope administration

Individualized 131I-mIBG therapy in the management of refractory and relapsed neuroblastoma.

Objective Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) therapy is an established treatment modality for relapsed/refractory neuroblastoma, most frequently administered according to fixed or weight-based criteria. We evaluate response and toxicity following a dosimetry-based, individualized approach.Materials and methods A review of 44 treatments in 25 patients treated with I-mIBG therapy was performed. Patients received I-mIBG therapy following relapse (n=9), in refractory disease (n=12), or with surgically unresectable disease despite conventional treatment (n=4). Treatment schedule (including mIBG dose and number of administrations) was individualized according to the clinical status of the patient and dosimetry data from either a tracer study or previous administrations. Three-dimensional tumour dosimetry was also performed for eight patients.Results The mean administered activity was 11089±7222 MBq and the mean whole-body dose for a single administration was 1.79±0.57 Gy. Tumour-absorbed doses varied considerably (3.70±3.37 mGy/MBq). CTCAE grade 3/4 neutropenia was documented following 82% treatments and grade 3/4 thrombocytopenia following 71% treatments. Further acute toxicity was found in 49% of patients. All acute toxicities resolved with appropriate therapy. The overall response rate was 58% (complete or partial response), with a further 29% of patients having stable disease.Conclusion A highly personalized approach combining patient-specific dosimetry and clinical judgement enables delivery of high activities that can be tolerated by patients, particularly with stem cell support. We report excellent response rates and acceptable toxicity following individualized I-mIBG therapy

An Investigation into the Poor Survival of an Endangered Coho Salmon Population

To investigate reasons for the decline of an endangered population of coho salmon (O. kisutch), 190 smolts were acoustically tagged during three consecutive years and their movements and survival were estimated using the Pacific Ocean Shelf Tracking project (POST) array. Median travel times of the Thompson River coho salmon smolts to the lower Fraser River sub-array were 16, 12 and 10 days during 2004, 2005 and 2006, respectively. Few smolts were recorded on marine arrays. Freshwater survival rates of the tagged smolts during their downstream migration were 0.0–5.6% (0.0–9.0% s.e.) in 2004, 7.0% (6.2% s.e.) in 2005, and 50.9% (18.6% s.e.) in 2006. Overall smolt-to-adult return rates exhibited a similar pattern, which suggests that low freshwater survival rates of out-migrating smolts may be a primary reason for the poor conservation status of this endangered coho salmon population

A Synthesis of Tagging Studies Examining the Behaviour and Survival of Anadromous Salmonids in Marine Environments

This paper synthesizes tagging studies to highlight the current state of knowledge concerning the behaviour and survival of anadromous salmonids in the marine environment. Scientific literature was reviewed to quantify the number and type of studies that have investigated behaviour and survival of anadromous forms of Pacific salmon (Oncorhynchus spp.), Atlantic salmon (Salmo salar), brown trout (Salmo trutta), steelhead (Oncorhynchus mykiss), and cutthroat trout (Oncorhynchus clarkii). We examined three categories of tags including electronic (e.g. acoustic, radio, archival), passive (e.g. external marks, Carlin, coded wire, passive integrated transponder [PIT]), and biological (e.g. otolith, genetic, scale, parasites). Based on 207 papers, survival rates and behaviour in marine environments were found to be extremely variable spatially and temporally, with some of the most influential factors being temperature, population, physiological state, and fish size. Salmonids at all life stages were consistently found to swim at an average speed of approximately one body length per second, which likely corresponds with the speed at which transport costs are minimal. We found that there is relatively little research conducted on open-ocean migrating salmonids, and some species (e.g. masu [O. masou] and amago [O. rhodurus]) are underrepresented in the literature. The most common forms of tagging used across life stages were various forms of external tags, coded wire tags, and acoustic tags, however, the majority of studies did not measure tagging/handling effects on the fish, tag loss/failure, or tag detection probabilities when estimating survival. Through the interdisciplinary application of existing and novel technologies, future research examining the behaviour and survival of anadromous salmonids could incorporate important drivers such as oceanography, tagging/handling effects, predation, and physiology

Toward a Unified Genetic Map of Higher Plants, Transcending the Monocot-Dicot Divergence

Closely related (confamilial) genera often retain large chromosomal tracts in which gene order is colinear, punctuated by structural mutations such as inversions and translocations 1. To explore the possibility that conservation of gene order might extrapolate to more distantly related taxa, we first estimated an average structural mutation rate. Nine pairs of taxa, for which there exist both comparative genetic maps and plausible estimates of divergence time, showed an average of0.14 (±0.06) structural mutations per chromosome per million years of divergence (Myr; Table 1). This value is offered as a first approximation, acknowledging that refined comparative data and/or divergence estimates may impel revision

Radiative cooling effects on reverse shocks formed by magnetized supersonic plasma flows

We study the structure of reverse shocks formed by the collision of supersonic, magnetized plasma flows driven by an inverse (or exploding) wire array with a planar conducting obstacle. We observe that the structure of these reverse shocks varies dramatically with wire material, despite the similar upstream flow velocities and mass densities. For aluminum wire arrays, the shock is sharp and well-defined, consistent with magneto-hydrodynamic theory. In contrast, we do not observe a well-defined shock using tungsten wires, and instead we see a broad region dominated by density fluctuations on a wide range of spatial scales. We diagnose these two very different interactions using interferometry, Thomson scattering, shadowgraphy, and a newly developed imaging refractometer that is sensitive to small deflections of the probing laser corresponding to small-scale density perturbations. We conclude that the differences in shock structure are most likely due to radiative cooling instabilities, which create small-scale density perturbations elongated along magnetic field lines in the tungsten plasma. These instabilities grow more slowly and are smoothed by thermal conduction in the aluminum plasma

Early Marine Migration Patterns of Wild Coastal Cutthroat Trout (Oncorhynchus clarki clarki), Steelhead Trout (Oncorhynchus mykiss), and Their Hybrids

Hybridization between coastal cutthroat trout (Oncorhynchus clarki clarki) and steelhead or rainbow trout (Oncorhynchus mykiss) has been documented in several streams along the North American west coast. The two species occupy similar freshwater habitats but the anadromous forms differ greatly in the duration of marine residence and migration patterns at sea. Intermediate morphological, physiological, and performance traits have been reported for hybrids but little information has been published comparing the behavior of hybrids to the pure species.This study used acoustic telemetry to record the movements of 52 cutthroat, 42 steelhead x cutthroat hybrids, and 89 steelhead smolts, all wild, that migrated from Big Beef Creek into Hood Canal (Puget Sound, Washington). Various spatial and temporal metrics were used to compare the behavior of the pure species to their hybrids. Median hybrid residence time, estuary time, and tortuosity values were intermediate compared to the pure species. The median total track distance was greater for hybrids than for either cutthroat or steelhead. At the end of each track, most steelhead (80%) were located near or north of the Hood Canal, as expected for this seaward migrating species, whereas most cutthroat (89%) were within 8 kilometers of the estuary. Most hybrids (70%) were detected leaving Hood Canal, though a substantial percentage (20%) remained near the Big Beef Creek estuary. More hybrids (7.5%) than pure cutthroat (4.5%) or steelhead (0.0%) were last detected in the southern reaches of Hood Canal.Given the similarity in freshwater ecology between the species, differences in marine ecology may play an important role in maintaining species integrity in areas of sympatry