Addressing species specific metabolism and solubility issues in a quinoline series of oral PDE4 inhibitors.

Species specific conversion of the lead PDE4 inhibitor 1 to the quinolone 3 was identified as the major route of metabolism in the cynomolgus monkey. Modification of the template to give the cinnoline 9 retained potency and selectivity, and greatly improved the pharmacokinetic profile in the cynomolgus monkey compared with 1. Additional SAR studies aimed at improving the solubility of 9 are also described.

Equatorial pacific seismic reflectors as indicators of global oceanographic events.

The origin of a series of regionally correlatable seismic horizons in the Neogene sediments of the central equatorial Pacific is examined through seismic modeling and the detailed analyses of stratigraphic and physical property relationships in Deep Sea Drilling Project cores. These regionally traceable reflectors are synchronous; the younger reflectors are the direct result of carbonate dissolution events, the older ones of stratigraphically selective diagenetic processes. The changes in ocean chemistry associated with these events appear to be linked to global reorganizations of surface and bottom-water circulation patterns, the most dramatic of which are associated with reorganizations of North Atlantic bottom waters. These deepwater seismic horizons appear to correlate with the major events on the "relative sea-level" curve of Vail et al. for the Neogene.

Spatiotemporal boundary formation: boundary, form, and motion perception from transformations of surface elements.

Continuous surface boundaries, object shape, and global motion can be perceived from information that is fragmentary in both space and time. The authors report investigations indicating that accretion and deletion of texture is only 1 member of a broader class of element transformations that produce boundaries, shape, and motion, through spatiotemporal boundary formation (SBF). The authors report 4 experiments exploring SBF. The first 3 examine the class of transformations producing SBF, indicating that local element changes in color, orientation, or location are all effective. A 4th experiment examines temporal constraints on SBF. Integration of local element changes to produce boundaries, form, and global motion appears to be confined to a 165-ms window. Two classes of spatiotemporal integration models are considered; the relation between SBF and other cases of boundary interpolation are discussed.

Color perimetry.

Seven subjects were studied to determine the reproducibility of color isopters utilizing a Tubingen perimeter with targets equated for radiant energy and separate for heterochromatic flicker luminance. Achromatic threshold recognition of targets for equal luminance gave smaller isopters with longer wavelengths (red). Color recognition thresholds, on the other hand, showed large blue, midzone red and green, and small yellow isopters. The target recognition and color recognition thresholds for equal energy targets gave smaller red isopters. The data support Traquair's contention that all color isopters would be equivalent if hue, saturation, and intensity were equated. Clinically, the detection of subtle peripheral and central field defects might reside in the use of appropriately selected equally bright-colored targets.

A common mechanism for illusory and occluded object completion.

New phenomena and results are reported that implicate a common contour interpolation mechanism in illusory and occluded (modal and amodal) object completion. In 3 experiments, a speeded classification task was used to study novel quasimodal displays in which occluded and illusory contours join. Results showed the same advantages in speed and accuracy over control displays for quasimodal, illusory, and occluded displays. The implications of quasimodal displays, along with another new display type in which contour linkages must precede determination of modal or amodal appearance, are considered. These logical considerations and empirical results suggest that amodal and modal completion depend on a common underlying mechanism that connects edges across gaps.

Spatio-temporal boundary formation: the role of local motion signals in boundary perception.

Spatio-temporal boundary formation (SBF) refers to a perceptual process responsible for perception of moving, bounded surfaces from sequential changes in spatially separated local elements. Previous research has indicated that this process produces perception of global form, continuous boundaries and global motion from spatially and temporally sparse element changes. In the present paper, we sought to distinguish between two classes of models for SBF: form-precedes-motion and motion-precedes-form models. Experiment 1 tested the effects of the addition of spurious motion signals, a manipulation that should affect a motion-precedes-form computation but not a form-precedes-motion computation. Shape identification in a 10-alternative forced-choice procedure was disrupted by this manipulation, supporting the former class of models. A particular computational scheme, edge orientation from motion (EOFM) instantiating a motion-precedes-form model is described and tested in Experiment 2. The EOFM model should be disrupted when initiating element changes occur in a certain type of sequential order, relative to randomly arranged changes. Sequential changes markedly disrupted performance, supporting this EOFM approach. The results favor motion-precedes-form models of SBF and are consistent with the particular computational scheme proposed.

Surface integration influences depth discrimination.

Image fragments arising from partial occlusion may be perceptually unified by a surface integration process on the basis of similar color or texture. In a new objective measure pitting surface feature similarity against binocular disparity, observers discriminated whether a colored circle had either crossed or uncrossed disparity relative to a surrounding gray rectangle. Sensitivity to disparity was impaired only when (1) the configuration of the other surface fragments in the display supported the integration of a surface behind the rectangle and circle, and (2) matched the color of the central circle. Results were consistent with the hypothesis that a surface integration process integrated similarly-colored surface fragments into a smooth surface, even when those fragments were at different depths. Surface integration caused small and reliable effects on depth perception despite unambiguous disparity information. Perceived depth does not depend solely upon disparity, and may be determined after three-dimensional figural unity is established.

Discordance between physician and patient perceptions in the treatment of diabetes mellitus: a pilot study of the relationship to adherence and glycemic control.

Glycolsylated hemoglobin (G Hb) levels and data on adherence and patient-provider discordance in beliefs about diabetes were collected from 42 insulin-requiring patients with diabetes. Discordance was calculated for both degree of discordance (absolute amount of disagreement) and direction of discordance (degree to which physician > patient or patient < physician). Patients generally agreed with physicians in perceptions of severity, costs of adherence, and immediate and long-term benefits of adherence. Significant differences were found between these dimensions. Only discordance on long-term benefits of adherence correlated with adherence, with greater discordance related to greater adherence. Discordance on the cost dimension correlated negatively with G Hb, suggesting better glycemic control with greater disagreement. Those who underestimate the cost of adherence show greater adherence. Adherence did not correlate significantly with glycemic control.

Evaluating alternative treatments for homeless substance-abusing men: outcomes and predictors of success.

The present study was designed to explore the relative efficacy of three types of service delivery intervention models for homeless men with alcohol and/or drug problems: integrated comprehensive residential services provided at one site (Group 1); on-site shelter-based intensive case management with referrals to a community network of services (Group 2); and usual care shelter services with case management (Group 3). In addition to assessing the relative efficacy of these approaches in terms of drug and alcohol use, residential stability, economic and employment status, the project also sought to examine what personal factors best predicted successful outcomes for clients. Clients were assessed at baseline and approximately six months following discharge. All three treatment groups improved significantly over time in terms of reduced alcohol and cocaine use, increased employment, and increased stable housing, but no differential improvement was found among groups. Successful outcomes were predicted by lower recent and lifetime substance use, fewer prior treatment episodes, more stable housing at baseline, fewer incarcerations, and less social isolation.