SMARTer Discontinuation Trial Designs for Developing an Adaptive Treatment Strategy

Abstract Objective: Developing evidenced-based practices for the management of childhood psychiatric disorders requires research studies that address how to treat children during both the acute phase of the disorder and beyond. Given the selection of a medication for acute treatment, discontinuation trials are used to evaluate the effects of treatment duration (e.g., time on medication) and/or maintenance strategies following successful acute-phase treatment. Recently, sequential multiple assignment randomized trials (SMART) have been proposed for use in informing sequences of critical clinical decisions such as those mentioned. The objective of this article is to illustrate how a SMART study is related to the standard discontinuation trial design, while addressing additional clinically important questions with similar trial resources. Method: The recently completed Child/Adolescent Anxiety Multimodal Study (CAMS), a randomized trial that examined the relative efficacy of three acute-phase treatments for pediatric anxiety disorders, along with a next logical step, a standard discontinuation trial design, is used to clarify the ideas. This example is used to compare the discontinuation trial design relative to the SMART design. Results: We find that the standard discontinuation trial can be modified slightly using a SMART design to yield high-quality data that can be used to address a wider variety of questions in addition to the impact of treatment duration. We discuss how this innovative trial design is ultimately more efficient and less costly than the standard discontinuation trial, and may result in more representative comparisons between treatments. Conclusions: Mental health researchers who are interested in addressing questions concerning the effects of continued treatment (for different durations) following successful acute-phase treatment should consider SMART designs in place of discontinuation trial designs in their research. SMART designs can be used to address these and other questions concerning individualized sequences of treatment, such as the choice of a rescue treatment in case of postacute phase relapse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98496/1/cap%2E2011%2E0073.pd

Family History of Alcoholism and Childhood Adversity: Joint Effects on Alcohol Consumption and Dependence

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65494/1/j.1530-0277.1994.tb00085.x.pd

Integrated genetic map and genetic analysis of a region associated with root traits on the short arm of rye chromosome 1 in bread wheat

A rye–wheat centric chromosome translocation 1RS.1BL has been widely used in wheat breeding programs around the world. Increased yield of translocation lines was probably a consequence of increased root biomass. In an effort to map loci-controlling root characteristics, homoeologous recombinants of 1RS with 1BS were used to generate a consensus genetic map comprised of 20 phenotypic and molecular markers, with an average spacing of 2.5 cM. Physically, all recombination events were located in the distal 40% of the arms. A total of 68 recombinants was used and recombination breakpoints were aligned and ordered over map intervals with all the markers, integrated together in a genetic map. This approach enabled dissection of genetic components of quantitative traits, such as root traits, present on 1S. To validate our hypothesis, phenotyping of 45-day-old wheat roots was performed in five lines including three recombinants representative of the entire short arm along with bread wheat parents ‘Pavon 76’ and Pavon 1RS.1BL. Individual root characteristics were ranked and the genotypic rank sums were subjected to Quade analysis to compare the overall rooting ability of the genotypes. It appears that the terminal 15% of the rye 1RS arm carries gene(s) for greater rooting ability in wheat

Mining and validating grape (Vitis L.) ESTs to develop EST-SSR markers for genotyping and mapping

Grape expressed sequence tags (ESTs) are a new resource for developing simple sequence repeat (SSR) functional markers for genotyping and genetic mapping. An integrated pipeline including several computational tools for SSR identification and functional annotation was developed to identify 6,447 EST-SSR sequences from a total collection of 215,609 grape ESTs retrieved from NCBI. The 6,447 EST-SSRs were further reduced to 1,701 non-redundant sequences via clustering analysis, and 1,037 of them were successfully designed with primer pairs flanking the SSR motifs. From them, 150 pairs of primers were randomly selected for PCR amplification, polymorphism and heterozygosity analysis in V. vinifera cvs. Riesling and Cabernet Sauvignon, and V. rotundifolia (muscadine grape) cvs. Summit and Noble, and 145 pairs of these primers yielded PCR products. Pairwise comparisons of loci between the parents Riesling and Cabernet Sauvignon showed that 72 were homozygous in both cultivars, while 70 loci were heterozygous in at least one cultivar of the two. Muscadine parents Noble and Summit had 90 homozygous SSR loci in both parents and contained 50 heterozygous loci in at least one of the two. These EST-SSR functional markers are a useful addition for grape genotyping and genome mapping

Universal Primers Used for Species Identification of Foodstuff of Animal Origin: Effects of Oligonucleotide Tails on PCR Amplification and Sequencing Performance

M13 universal non-homologous oligonucleotide tails incorporated into universal primers have been shown to improve amplification and sequencing performance. However, a few protocols use these tails in the field of food inspection. In this study, two types of M13 tails (by Steffens and Messing) were selected to assess their benefits using universal cytochrome oxidase subunit I (COI) and 16S ribosomal RNA gene (16SrRNA) primers in standard procedures. The primer characteristics were tested in silico. Then, using 20 DNA samples of edible species (birds, fishes, and mammals), their performance during PCR amplification (band recovery and intensity) and sequencing (sequence recovery, length, and Phred score) was assessed and compared. While 16SrRNA tailed and non-tailed primers performed similarly, differences were found for COI primers. Messing’s tails negatively affected the reaction outputs, while Steffens’ tails significantly improved the band intensity and the length of the final contigs based on the individual bidirectional read sequence. This different performance could be related to a destabilization effect of certain tails on primers with unfavorable mismatches on the annealing region. Even though our results cannot be generalized because the tail performances are strictly dependent on laboratory conditions, they show that appropriate tails can improve the overall throughput of the analysis, supporting food traceabilit