IntroductionPatients with intracranial hemorrhage due to traumatic brain injury are at high risk of developing venous thromboembolism including deep vein thrombosis (DVT) and pulmonary embolism (PE). Thus, there is a trade-off between the risks of progression of intracranial hemorrhage (ICH) versus reduction of DVT/PE with the use of prophylactic anticoagulation. Using decision analysis modeling techniques, we developed a model for examining this trade-off for trauma patients with documented ICH.MethodsThe decision node involved the choice to administer or to withhold low molecular weight heparin (LMWH) anticoagulation prophylaxis at 24 hours. Advantages of withholding therapy were decreased risk of ICH progression (death, disabling neurologic deficit, non-disabling neurologic deficit), and decreased risk of systemic bleeding complications (death, massive bleed). The associated disadvantage was greater risk of developing DVT/PE or death. Probabilities for each outcome were derived from natural history studies and randomized controlled trials when available. Utilities were obtained from accepted databases and previous studies.ResultsThe expected value associated with withholding anticoagulation prophylaxis was similar (0.90) to that associated with the LMWH strategy (0.89). Only two threshold values were encountered in one-way sensitivity analyses. If the effectiveness of LMWH at preventing DVT exceeded 80% (range from literature 33% to 82%) our model favoured this therapy. Similarly, our model favoured use of LMWH if this therapy increased the risk of ICH progression by no more than 5% above the baseline risk.ConclusionsOur model showed no clear advantage to providing or withholding anticoagulant prophylaxis for DVT/PE prevention at 24 hours after traumatic brain injury associated with ICH. Therefore randomized controlled trials are justifiable and needed to guide clinicians.

Embryonic stem cells are undifferentiated cells derived from early mouse embryos, which under appropriate culture conditions proliferate continuously in vitro. ES cells have been demonstrated to be pluripotent in vivo from their capacity to form teratocarcinomas and germ-line chimeric mice, dependent on the environment into which the stem cells are introduced. When ES cells are introduced under the kidney capsule, in vivo differentiation is chaotic with the teratocarcinoma composed of a wide variety of different cell types. If, however, the stem cells are returned into a preimplantation mouse embryo, in vivo differentiation proceeds in a normal and organized manner, and the ES cells colonize the three primary cell lineages of the developing embryo: the primitive ectoderm, endoderm, and mesoderm. This leads to the formation of chimeric offspring composed of cells of two different genetic constitutions: the host embryonic cells and those derived from the ES cells. The ES cells are capable of contributing to every tissue in the fetus, including the primordial germ cells. Furthermore, the trophectodermal and primitive endodermal derivatives in the extraembryonic tissues of the conceptus may also be colonized by ES cells. Recent studies have shown that murine ES cells are capable of supporting complete fetal development, following the aggregation of stem cells with tetraploid-cleavage-stage embryos.

The Environmental Impact Statement (EIS) for the proposed Australian National Repository for low and short-lived intermediate level radioactive waste was submitted to Environment Australia for approval in the summer of 2002 and has subsequently undergone a consultancy phase with comments sought from all relevant stakeholders. The consultancy period is now closed and responses to the comments have been prepared. This paper describes some of the issues relevant to determining the radiological risk associated with the repository to meet the requirements of the EIS. These include a brief description of the three proposed sites, a description of the proposed trench design, an analysis of the radioactive waste inventory, the proposed approach to developing waste acceptance criteria (WAC) and the approach taken to determine radiological risks during the post-institutional control phase. The three potential sites for the repository are located near the Australian Department of Defence site at Woomera, South Australia. One site is inside the Defense site and two are located nearby, but outside of the site perimeter. All have very similar, but not identical, topographical, geological and hydrogeological characteristics. A very simple trench design has been proposed 15 m deep and with 5 m of cover. One possible variant may be the construction of deeper borehole type vaults to dispose of the more active radioactive sources. A breakdown of the current and predicted future inventory will be presented. The current wastes are dominated in terms of volume by some contaminated soils, resulting from experiments to extract U and Th, and by the operational wastes from the HIFAR research reactor at ANSTO. A significant proportion of the radionuclide inventory is associated with small volumes of sources held by industry, medical, research and defence organisations. The proposed WAC will be described. These are based on the current Australian guidelines and best international practice. The preliminary radiological risk assessment considered the post-institutional control phase in detail with some 12 scenarios being assessed. These include the impact of potential climate change in the region. The results from the risk assessment will be presented and discussed. The assessment work is continuing and will support the license application for construction and operation of the site. Please note that this is not the final assessment for the licence application.

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