Determinants of patient recruitment in a multicenter clinical trials group: trends, seasonality and the effect of large studies

BACKGROUND: We examined whether quarterly patient enrollment in a large multicenter clinical trials group could be modeled in terms of predictors including time parameters (such as long-term trends and seasonality), the effect of large trials and the number of new studies launched each quarter. We used the database of all clinical studies launched by the AIDS Clinical Trials Group (ACTG) between October 1986 and November 1999. Analyses were performed in two datasets: one included all studies and substudies (n = 475, total enrollment 69,992 patients) and the other included only main studies (n = 352, total enrollment 57,563 patients). RESULTS: Enrollment differed across different months of the year with peaks in spring and late fall. Enrollment accelerated over time (+27 patients per quarter for all studies and +16 patients per quarter for the main studies, p < 0.001) and was affected by the performance of large studies with target sample size > 1,000 (p < 0.001). These relationships remained significant in multivariate autoregressive modeling. A time series based on enrollment during the first 32 quarters could forecast adequately the remaining 21 quarters. CONCLUSIONS: The fate and popularity of large trials may determine the overall recruitment of multicenter groups. Modeling of enrollment rates may be used to comprehend long-term patterns and to perform future strategic planning

Experimental determination of the flood wave transformation and the sediment resuspension in a small regulated stream in an agricultural catchment

This paper presents the methodology used for artificial flood experiments conducted in a small artificial, trained (regulated) channel on the Nučice experimental agricultural catchment (0.5 km2), central Czech Republic, and the results of the experiments. The aim was to monitor the transformation of the flood wave and the sediment transport within the channel. Two series of experiments were carried out in contrasting initial conditions: (a) in September, when the stream banks were dry, the baseflow was negligible, and the channel was fully overgrown with vegetation; and (b) in March, when the stream banks were almost water saturated, the baseflow was above the annual average, and there was no vegetation present. Within each campaign, three successive flood waves, each with an approximate volume of 17 m3 and peak flow of ca. 40 L s−1, were pumped into the upper part of the catchment drainage channel. The transformation of the flood wave and the sediment transport regime within an approximately 400 m long channel section were monitored by measuring the discharge, the turbidity, and the electrical conductivity in three profiles along the stream. On the basis of the results, it was concluded that there is a considerable amount of deposited sediment, even in the well-trained and straight channel that can be re-mobilized by small floods. Part of the recorded sediment therefore originates from the particles deposited during previous soil erosion events. The flood waves initiated in dissimilar instream conditions progressed differently – we show that the saturation of the channel banks, the stream vegetation and the actual baseflow had a strong influence on the flood transformation and the sediment regime in the channel. The sediment moves quickly in winter and early spring, but in the later part of the year the channel serves as a sediment trap and the resuspension is slower, if dense vegetation is present

Genetic variations in microRNA-binding sites of solute carrier transporter genes as predictors of clinical outcome in colorectal cancer

One of the principal mechanisms of chemotherapy resistance in highly frequent solid tumors, such as colorectal cancer (CRC), is the decreased activity of drug transport into tumor cells due to low expression of important membrane proteins, such as solute carrier (SLC) transporters. Sequence complementarity is a major determinant for target gene recognition by microRNAs (miRNAs). Single-nucleotide polymorphisms (SNPs) in target sequences transcribed into messenger RNA may therefore alter miRNA binding to these regions by either creating a new site or destroying an existing one. miRSNPs may explain the modulation of expression levels in association with increased/decreased susceptibility to common diseases as well as in chemoresistance and the consequent inter-individual variability in drug response. In the present study, we investigated whether miRSNPs in SLC transporter genes may modulate CRC susceptibility and patient's survival. Using an in silico approach for functional predictions, we analyzed 26 miRSNPs in 9 SLC genes in a cohort of 1368 CRC cases and 698 controls from the Czech Republic. After correcting for multiple tests, we found several miRSNPs significantly associated with patient's survival. SNPs in SLCO3A1, SLC22A2 and SLC22A3 genes were defined as prognostic factors in the classification and regression tree analysis. In contrast, we did not observe any significant association between miRSNPs and CRC risk. To the best of our knowledge, this is the first study investigating miRSNPs potentially affecting miRNA binding to SLC transporter genes and their impact on CRC susceptibility or patient's prognosis