Subtypes validation

Anderson CS, Taylor BV, Hankey GJ, Stewart-Wynne EG, Jamrozik KD. Validation of a clinical classification for subtypes of acute cerebral infarction. J Neurol Neurosurgery Psychiatry 1994 57 1175-1179. 

Identification and validation of biomarkers predictive of disease, particularly cancer, is a significant and expanding area in clinical research. Quality cancer biomarkers should facilitate early detection and diagnosis of the disease, with more specific markers used for classification (such as grade/stage) or subtype determination of the... 

Another crucial problem for any neurochemical model is cause and effect. Neuroleptics have a high affinity for dopamine receptors, particularly the D2-subtype. There is also a highly significant positive correlation (r > +0.9) between this receptor binding and their clinical potency (Seeman, 1980). But, this does not necessarily implicate elevated dopamine levels as the cause of schizophrenia. Moreover, blockade of dopamine receptors happens very rapidly, whereas clinical benefits are only seen after chronic treatment. Rose (1973) has criticised the reductionist statement that an abnormal biochemistry causes schizophrenia because it relates cause and effect at different organisational levels (namely, the molecular and behavioural). But, while it can be legitimate to discuss cause and effect at the same level that chlorpromazine blocks dopamine receptors (one molecule altering the response of another), it is not valid to infer that increased dopamine activity causes schizophrenia. Put another way ... 

Other taxometrics research has evaluated the validity of theoretical psychopathological subtypes. For example, Haslam and Beck (1994) used CCK procedures to test whether five proposed subtypes of major depression (e.g., endogenous, sociotropic, autonomous) reflect underlying categories. Again, because these theoretical subtypes of depression are not necessarily represented in the DSM, they do not speak directly to psychiatric nosology. 

De Lean, A., Hancock, A. A. and Lefkowitz, R. J. (1982). Validation and statistical analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes, Mol. Pharmacol., 21, 5-16. 

Another problem in validating targets for behavioral disorders related to neurotransmitter abnormalities is the interplay between several neurotransmitter systems in specific brain regions. For example, in the hippocampus, limbic, and nigral-striatal areas, functions connected by serotonin, norepinephrine, and dopamine are interconnected so that blocking selected receptor subtypes or changing synaptic levels of certain neurotransmitters may... 

Roy MA, Crowe RR Validity of the familial sporadic subtypes of schizophrenia. Am J Psychiatry 151 805-814, 1994... 

The Liebowitz Social Anxiety Scale (LSAS) measures fear, anxiety and avoidant behavior in 24 commonly feared social situations and performances. There are 13 performance-related items and 11 items that rate the social situations (Heimberg et al, 1999). The LSAS is the standard established outcome measure in most of the pivotal trials for social anxiety. Cut-offs of 30 for social anxiety disorder and 60 for its generalized subtype on the LSAS total scores represent a balance of specificity and sensitivity. There are two valid versions of the LSAS a clinician-administered version and a self-rating version (Fresco et al.. 2001). 

There are three subtypes of MDD melancholia, or classic depression atypical, or nonclassic depression and psychotic depression. These three subtypes have construct validity based on differences in the following ... 

Thase ME, Kupfer DJ, Ulrich RF (1986) Electroencephalographic sleep in psychotic depression a valid subtype. Arch Gen Psychiatry 43 886-893... 

In the third and last section, we will report the construction of a new pharmacophore model for metabotropic glutamate receptor subtype 4 (mGlu4R) agonists. In spite of the fact that the available dataset is particularly difficult for pharmacophore modeling, we will show that the validation methods used allowed us to have great confidence in the hypotheses generated. 

Validation The use of TMAs enables analysis of large data sets, however this does not by any means suggest that the data set is not skewed. This skewing may be the result of the institution s location (population distributions with regards to race, ethnicity, access to health care), type of practice (community hospital versus referral center). These collectively might influence the tumor size, grade and subtype composition of the cases in the dataset. Such abnormalities of the dataset need to be compensated the involvement of a biostatistician from the start (i.e from case selection) helps to prevent the creation of biased TMAs. It is useful to perform common biomarker analysis on sections from the created TMA to confirm the normal distribution of known parameters. Comparison of this data with prior clinical data (e.g. ER analysis) obtained from whole section analysis is particularly useful to validate utility of the TMA. Alternatively the incidence of expression of a number of biomarkers in the TMA should be compared to that in published literature (using whole sections). 

The premise of this book is based on the presumption that introductory organic chemistry entails very little memorization. As presented in the chapters contained herein, this presumption is valid provided the student adheres to the philosophy that the study of organic chemistry can be reduced to the study of interactions between organic acids and bases. At this point, use of the principles presented in this book, in conjunction with more detailed coursework, allows students a broader understanding of organic chemistry reactions as described using combinations of fundamental organic mechanistic subtypes. 

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