Critical Radionuclide/Critical Pathway Analysis for the U.S. Department of Energy's Savannah River Site

Many different radionuclides have been released to the environment from the Savannah River Site (SRS) during the facility's operational history. However, as shown by this analysis, only a small number of the released radionuclides have been significant contributors to potential doses and risks to off-site people. This article documents the radiological critical contaminant/critical pathway analysis performed for SRS. If site missions and operations remain constant over the next 30 years, only tritium oxide releases are projected to exceed a maximally exposed individual (MEI) risk of 1.0E-06 for either the airborne or liquid pathways. The critical exposure pathways associated with site airborne releases are inhalation and vegetation consumption, whereas the critical exposure pathways associated with liquid releases are drinking water and fish consumption. For the SRS-specific, nontypical exposure pathways (i.e., recreational fishing and deer and hog hunting), cesium-137 is the critical radionuclide.     

Performance of phase-I dose finding designs with and without a run-in intra-patient dose escalation stage

Dose-finding designs for phase-I trials aim to determine the recommended phase-II dose (RP2D) for further phase-II drug development. If the trial includes patients for whom several lines of standard therapy failed or if the toxicity of the investigated agent does not necessarily increase with dose, optimal dose-finding designs should limit the frequency of treatment with suboptimal doses. We propose a two-stage design strategy with a run-in intra-patient dose escalation part followed by a more traditional dose-finding design. We conduct simulation studies to compare the 3 + 3 design, the Bayesian Optimal Interval Design (BOIN) and the Continual Reassessment Method (CRM) with and without intra-patient dose escalation. The endpoints are accuracy, sample size, safety, and therapeutic efficiency. For scenarios where the correct RP2D is the highest dose, inclusion of an intra-patient dose escalation stage generally increases accuracy and therapeutic efficiency. However, for scenarios where the correct RP2D is below the highest dose, intra-patient dose escalation designs lead to increased risk of overdosing and an overestimation of RP2D. The magnitude of the change in operating characteristics after including an intra-patient stage is largest for the 3 + 3 design, decreases for the BOIN and is smallest for the CRM.     

Degree-constrained orientations of embedded graphs

We investigate the problem of orienting the edges of an embedded graph in such a way that the resulting digraph fulfills given in-degree specifications both for the vertices and for the faces of the embedding. This primal-dual orientation problem was first proposed by Frank for the case of planar graphs, in conjunction with the question for a good characterization of the existence of such orientations. We answer this question by showing that a feasible orientation of a planar embedding, if it exists, can be constructed by combining certain parts of a primally feasible orientation and a dually feasible orientation. For the general case of arbitrary embeddings, we show that the number of feasible orientations is bounded by \(2^{2g}\), where \(g\) is the genus of the embedding. Our proof also yields a fixed-parameter algorithm for determining all feasible orientations parameterized by the genus. In contrast to these positive results, however, we also show that the problem becomes \(N\!P\)-complete even for a fixed genus if only upper and lower bounds on the in-degrees are specified instead of exact values.