Biomedical subjects

Timothy Clark

Publications and source records attributed to Timothy Clark.

41 records · Page 3Linked to original sources

PubMed2002

Can psychological distress be detected by response to a needle stick?

The purpose of this study was to determine whether an exaggerated response to a mildly painful stimulus would reflect abnormal levels of psychological distress in patients and, conversely, whether patients who show abnormal levels of psychological distress would have a low tolerance for a mildly painful stimulus. A total of 101 patients were given a mildly painful stimulus (30-gauge needle stick) and asked to record the amount of pain they felt on a scale of 0 to 10 (0 = no pain, 10 = severe pain). The mean response to the needle stick was a 1.9 on this scale. There was no gender difference, and the average did not change with increasing age. Psychological testing showed that 18% of the 101 patients had psychological distress prior to the needle stick. The pain ratings to needle stick of these 18 patients were not significantly different than those of patients without psychological distress (2.3 vs 1.9 on the scale). Seven percent of patients had a very low tolerance for pain (pain score of > or = 7). Evaluation of the psychological testing results on these patients showed no significant difference compared with known normal psychological values. Therefore, the assumption that patients who over-respond to a mildly painful stimulus have psychological distress is not valid. The results of this study suggest only that patients who over-respond to a needle stick have a low tolerance for pain. Furthermore, it is not valid to assume that patients who have psychological distress, poor coping abilities, or marked stress will respond in an exaggerated fashion to a mildly painful stimulus.

Journal Article↗

PubMedDate not supplied

New molecular descriptors based on local properties at the molecular surface and a boiling-point model derived from them.

New molecular descriptors based on statistical descriptions of the local ionization potential, local electron affinity, and the local polarizability at the surface of the molecule are proposed. The significance of these descriptors has been tested by calculating them for the Maybridge database in addition to our set of 26 descriptors reported previously. The new descriptors show little correlation with those already in use. Furthermore, the principal components of the extended set of descriptors for the Maybridge data show that especially the descriptors based on the local electron affinity extend the variance in our set of descriptors, which we have previously shown to be relevant to physical properties. The first nine principal components are shown to be most significant. As an example of the usefulness of the new descriptors, we have set up a QSPR model for boiling points using both the old and new descriptors.

Journal Article↗

PubMedDate not supplied

Surface-integral QSPR models: local energy properties.

Surface-integral models based on AM1 semiempirical molecular orbital calculations are presented for the free energies of solvation in water, n-octanol, and chloroform and for the enthalpy of solvation in water. A parametrized function of four local properties calculated at the isodensity surface (the molecular electrostatic potential, local ionization energy, electron affinity, and polarizability) is integrated over the triangulated surface area to obtain the target quantity. The resulting models give results only slightly less accurate than those reported for parametrized generalized Born/polar surface area models despite relying only on gas-phase calculations. The water and octanol free-energy models were validated by calculating the water-octanol partition coefficient for a test set of organic compounds with moderate success. The models lead to a local solvation energy, which can be projected onto the molecular isodensity surface and provides insight into "hot" areas for solvation in water or the other solvents.

Algorithms↗

PubMedDate not supplied

An analytical, variable resolution, complete description of static molecules and their intermolecular binding properties.

A fully analytical description of molecular shape, as defined by the shrink-wrap isodensity or solvent-excluded surfaces and local properties related to Coulomb, donor/acceptor, and polarizability (dispersion) interactions is described. The molecular surface and four local properties adequate for describing intermolecular interactions (the molecular electrostatic potential and the local ionization energy, electron affinity, and polarizability) are fitted to spherical-harmonic expansions, which provide a compact and information-rich description of the properties of the static molecule. The resolution of the description can be varied from isotropic to near atomistic detail by adjusting the order of the individual spherical-harmonic expansions. Examples are given to illustrate the effect of truncating the different spherical-harmonic approximations.

Journal Article↗

PubMedDate not supplied

In silico prediction of buffer solubility based on quantum-mechanical and HQSAR- and topology-based descriptors.

We present an artificial neural network (ANN) model for the prediction of solubility of organic compounds in buffer at pH 6.5, thus mimicking the medium in the human gastrointestinal tract. The model was derived from consistently performed solubility measurements of about 5000 compounds. Semiempirical VAMP/AM1 quantum-chemical wave function derived, HQSAR-derived logP, and topology-based descriptors were employed after preselection of significant contributors by statistical and data mining approaches. Ten ANNs were trained each with 90% as a training set and 10% as a test set, and deterministic analysis of prediction quality was used in an iterative manner to optimize ANN architecture and descriptor space, based on Corina 3D molecular structure and AM1/COSMO single point wave function. In production mode, a mean prediction value of the 10 ANNs is created, as is a standard deviation based quality parameter. The productive ANN based on Corina geometries and AM1/COSMO wave function gives an r2cv of 0.50 and a root-mean-square error of 0.71 log units, with 87 and 96% of the compounds having an error of less than 1 and 1.5 log units, respectively. The model is able to predict permanently charged species, e.g. zwitterions or quaternary amines, and problematic structures such as tautomers and unresolved diastereomers almost as well as neutral compounds.

Buffers↗