The Swan Point site in interior Alaska contains a significant multi-component archaeological record dating back to 14,200 cal BP. The site’s radiocarbon (14C) chronology has been presented in scattered publications that mostly focus on specific archaeological periods in Alaska, in particular its terminal Pleistocene components associated with the East Beringian tradition. This paper synthesizes the site’s 14C data and provides sequential Bayesian models for its cultural zones and subzones. The 14C and archaeological record at Swan Point attests that the location was persistently used over the last 14,000 years, even though major changes are evident within regional vegetation and local faunal communities, reflecting long-term trends culminating in Dene-Athabascan history.

Objectives: Multicomponent interventions (MCIs), consisting of at least two interventions, are common in rehabilitation and other healthcare fields. When the effectiveness of the MCI versus that of its single interventions is comparable or unknown, evidence of their expected incremental cost-effectiveness can be helpful in deciding which intervention to recommend. As such evidence often is unavailable this study proposes an approach to estimate what is more cost-effective; the MCI or the single intervention(s).

Methods: We reviewed the literature for potential methods. Of those identified, headroom analysis was selected as the most suitable basis for developing the approach, based on the criteria of being able to estimate the cost-effectiveness of the single interventions versus that of the MCI (a) within a limited time frame, (b) in the absence of full data, and (c) taking into account carry-over and interaction effects. We illustrated the approach with an MCI for cancer survivors.

Results: The approach starts with analyzing the costs of the MCI. Given a specific willingness-to-pay-value, it is analyzed how much effectiveness the MCI would need to generate to be considered cost-effective, and if this is likely to be attained. Finally, the cost-effectiveness of the single interventions relative to the potential of the MCI for being cost-effective can be compared.

Conclusions: A systematic approach using headroom analysis was developed for estimating whether an MCI is likely to be more cost effective than one (or more) of its single interventions.

The process of eukaryotic gene expression involves a diverse number of steps including transcription, RNA processing, transport, translation, and mRNA turnover. A critical step in understanding this process will be the development of mathematical models that quantitatively describe and predict the behavior of this complex system. We have simulated eukaryotic mRNA turnover in a linear multicomponent model based on the known mRNA decay pathways in yeast. Using rate constants based on experimental data for the yeast unstable MFA2 and stable PGK1 transcripts, the computational modeling reproduces experimental observations after minor adjustments. Subsequent analysis and a series of in silico experiments led to several conclusions. First, we demonstrate that mRNA half-life as commonly measured underestimates the average life span of an mRNA. Second, due to the properties of the pathways, the measurement of a half-life can predominantly measure different steps in the decay network. A corollary of this fact is that different mRNAs will be affected differentially by changes in specific rate constants. Third, the way to obtain the largest change of levels of mRNA for the smallest changes in rate is by changing the rate of deadenylation, where a large amount of regulation of mRNA decay occurs. Fourth, the 3′-to-5′ degradation of mRNA shows mRNA-specific rates of degradation that are dependent on the 5′ structure of the mRNA. These programs can be run over the Web, are adaptable to other eukaryotes, and provide outputs as graphs and virtual northern gels, which can be directly compared to experimental data. Therefore, this model constitutes a useful tool for the quantitative analysis of the process and control of mRNA degradation in eukaryotic cells.

The family of distributions which have the lack-of-memory property is extended by incorporating simple patterns of ageing in the model. Some relatively simple multivariate distributions, obtained in this manner, might prove to be more realistic than distributions like the multivariate exponential.