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INDEPENDENT VARIABLE CONSIDERATIONS: BETWEEN-GROUP EXPERIMENTAL DESIGNS The primary goal of any experimental design is to hold constant all factors among experimental conditions except the single factor under investigation Such a design allows researchers to draw cause-and-effect conclusions about that factor, and the strength of those conclusions is a direct function of the extent to which variables other than the manipulated variable were equivalent across conditions In the strong inference approach to scienti c research (Platt, 1964), one constructs rival hypotheses about the cause-and-effect relationship observed between variables, accordingly conducts methodologically rigorous experiments designed to rule out one or more of those rival hypotheses, and subsequently conducts experiments aimed at ruling out further rival hypotheses about whatever remained unrejected by the previous experiment The process is recycled repeatedly, leading to increasingly speci c cause-and-effect conclusions.

A thorough analysis of mineralization and the progression of differentiation relies on biochemical assays and quanti cation of gene expression, respectively Routine assessments involve the quanti cation of total calcium content and the activity of alkaline phosphatase (ALP), a cell surface protein bound to the plasma membrane through phosphatidylinositol phospholipid complexes High ALP activities are associated with active formation of mineralized matrix, and highest levels are found in the mineralization front in bone healing [Bruder and Caplan, 1990] Particularly important in de ning the phenotype of the differentiating stem cells is an understanding of bone tissue development in relation to gene expression of the cells The mRNA expression of the genes encoding important proteins during osteogenic differentiation of hMSC in vitro has not yet been systematically investigated, and results from different studies are often contradictory.

The beauty of such an approach to scienti c investigation lies in its unique ability to discard rejected hypotheses in pursuit of highly speci c pieces of knowledge about a single causal relationship As is the case for any class of scienti c investigation, the primary goal of psychotherapy outcome research is to establish such cause-and-effect relationships, and thus the strong inference approach is the most powerful way to pursue this ultimate goal Through such an approach, investigators are well equipped to identify the mechanisms through which a psychotherapeutic procedure produces change With the identi cation of these mechanisms, we are able to acquire speci c knowledge about human behavior and simultaneously enable the application of this knowledge in developing increasingly effective psychotherapeutic interventions.

Identi cation of mRNA markers characterizing the progression of hMSC toward the osteogenic lineage is further complicated by the known variability of cells from different individuals or due to differences in the isolation protocols [Phinney et al, 1999] or limitations inherent to the techniques used (ie, semiquantitative techniques like Northern blots or conventional RT-PCR) [Frank et al, 2002] Recently established real-time quantitative RT-PCR technology has made mRNA analysis more reproducible, precise, and sensitive than conventional RT-PCR, because it allows (i) measurement of the amount of ampli ed product with a quantitative laser-based method and (ii) data collection in the early exponential phase of the PCR reaction, when none of the reagents is rate-limiting [Gibson et al, 1996] We developed real-time quantitative RT-PCR assays for genes encoding for (i) osteoblast-related membrane and extracellular matrix molecules (ie.

In the various psychotherapy outcome research designs that we describe in this chapter, participants are randomly assigned to different treatment conditions in which variables are held constant (ie, are equivalent) to varying degrees Each of these designs allows investigators to draw causal conclusions, but the speci city of those causal conclusions varies with the type of design employed Factors that are equivalent between conditions cannot explain ways in which the conditions differ in outcome Differences in outcome can only be causatively explained by the ways in which the conditions differed Thus, the fewer the dissimilarities and the greater the similarities between comparison conditions, the more speci c we can be in identifying the cause of observed differences in their outcome This section describes each of these research designs in the order of the scienti c rigor and speci city of causal conclusions associated with them Whereas the no-treatment.

For Mapping Layers, select one of the following:

, alkaline phosphatase (ALP), aggrecan (Agg), bone sialoprotein (BSP), osteopontin (OP), type 1 collagen (Col1)); (ii) bone morphogenetic protein 2 (BMP-2), an important growth factor determining cell mesenchymal precursors; and (iii) cbfa1 (a genetic.

= 0.1 0.0 r0 2 r0 4 r0 r4 r2 r2 0 r4 1 4 r6 r1 4 r5 Y = 0.4 r3 r6 r1 0 r3 r5 1 4 r7 0.1 r1 0 0.2 r2 0.3 r3 0.4 r4 0.5 r5 1 2 r7 0.6 r6 0.7 r7

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