Preventing anchoring errors in clinical judgment.

When anchoring occurs, estimates of client pathology and prognosis are differentially related to the time judges are exposed to salient, pathognomonic case material. In the present study with 73 undergraduates, a debiasing condition was contrasted with a no-debiasing condition. In the debiasing condition, Ss were warned of possible anchoring errors and how to avoid them. M. L. Friedlander and S. J. Stockman (see record 1983-31114-001) found a robust anchoring bias among experienced clinicians. Results indicate that debiasing was irrelevant because neither the replication sample nor the debiased sample demonstrated significant anchoring errors in their judgments. Post hoc tests showed that (a) Ss' mean judgments did not differ significantly from those of the clinicians in Friedlander and Stockman but that (b) Ss reported significantly less confidence in their performance than the professionals. The implication that relatively more experienced, confident judges may be more susceptible to anchoring errors is discussed with respect to consistency and information-processing explanations for anchoring bias. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bioreductive activation of a series of analogues of 5-aziridinyl-3-hydroxymethyl-1-methyl-2-[1H-indole-4, 7-dione] prop-beta-en-alpha-ol (EO9) by human DT-diaphorase

The enzyme DT-diaphorase (NAD(P)H:quinone acceptor oxidoreductase, EC 1.6.99.2.; DTD) is believed to be a good target for enzyme-directed bioreductive drug development because elevated levels of enzyme activity have been described in several human tumour types and it plays a key role in the bioreductive activation of several quinone-based anticancer drugs. As part of an ongoing program to develop new bioreductive drugs, the ability of a series of indoloquinone compounds to serve as substrates for and to be bioreductively activated by purified recombinant human DTD was investigated. Of the seven compounds evaluated, EO9, EO68 and EO4 were substrates for human DTD, but only EO4 was reduced to a DNA cross-linking species, and this DNA damage was both concentration dependent and inhibited by dicoumarol. A broad spectrum of chemosensitivity was observed in the H460 non-small cell lung cancer cell line, with the most potent compounds being EO4 (IC50 = 23.9 nM), EO9 (IC50 = 34.5 nM) and EO68 (IC50 = 37.8 nM). Relatively minor structural changes resulted in major changes in both substrate specificity and cytotoxic potency. Comparative chemosensitivity studies demonstrated that EO4, EO9 and EO68 are preferentially toxic towards DTD-rich H460 cells compared with DTD-deficient H596 cells (ratio of IC50 values for H596 cells to H460 cells were 113.8, 92.2 and 103.9 respectively). In conclusion, this study has identified two new compounds that are substrates for human DTD, one of which (EO4) is reduced to a DNA cross-linking species. Further studies in a broad panel of cell lines and human tumour xenografts are warranted for EO4 and EO68 based upon the result of this study.     

Optical Characteristics of ZnTeO Thin Films Synthesized by Pulsed Laser Deposition and Molecular Beam Epitaxy

Oxygen incorporation into ZnTe was studied using pulsed laser deposition and molecular beam epitaxy. Oxygen incorporation at the high partial pressures studied for pulsed laser deposition was found to result in increasing visible transparency with oxygen incorporation, and is attributed to the formation of TeO _x based on bonding information obtained by x-ray photoelectron spectroscopy measurements. Oxygen incorporation by a plasma source during the growth of ZnTe by molecular beam epitaxy was found to result in an electronic band at 0.5 eV below the ZnTe band edge, possessing strong radiative properties and a resonant-like optical absorption coefficient with a peak α > 5000 cm⁻¹. The ZnTeO thin films grown by MBE have an epitaxial structure similar to ZnTe, where it is unclear whether the properties are due to the formation of a high-density defect level or the formation of a dilute alloy.     

Processing of spodumene-modified mullite ceramics

The use of β-spodumene (Li₂O·Al₂O₃·4SiO₂) has been investigated as a liquid-phase sintering aid for the densification of mullite processed from fumed silica and ESP (alumina) dust. XRD, DTA, SEM and Vickers indentation were used to characterize the effect of spodumene on the phase relations, sintering behaviour, microstructure and mechanical properties of mullite. The results show that the presence of spodumene significantly reduces the porosity, improves the sintering behaviour and enhances the formation of mullite at 1550 °C. Spodumene-modified mullite ceramics also have better physical and mechanical properties. This revised version was published online in November 2006 with corrections to the Cover Date.     

Physical properties of aliphatic polycarbonates made from CO2 and epoxides

A homologous series of aliphatic polycarbonates with different side‐chain lengths was synthesized by ring‐opening polymerization of terminal epoxides with CO₂ using zinc adipionate as catalyst [patented process of Empower Materials (formerly PAC Polymers Inc.)]. Additionally, a polycarbonate was made having a cyclohexane unit in its backbone, together with a terpolymer having both cyclohexane and propylene units. After characterization of thermal properties the aliphatic polycarbonates were found to be completely amorphous. Polycarbonates derived from long‐chain epoxides showed a glass‐transition temperature (T_g) below room temperature, whereas polycarbonates derived from cyclohexene oxide showed a T_g of 105°C, the highest yet reported for this class of polymers. The initial decomposition temperature of the polymers in air and nitrogen atmospheres was found to be less than 300°C. The mechanical properties and the dynamic mechanical relaxation behavior of the polymers were also reported. The effect of the chemical structure on the physical properties of aliphatic polycarbonates was discussed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1163–1176, 2003     

Biopsy-negative malignant esophageal stricture: diagnosis by endoscopic ultrasound

Endoscopic ultrasound (EUS) of the esophagus has been used primarily in staging biopsy-proven cancers. Its use as a primary diagnostic modality for esophageal malignancy has not been previously described. We report our recent experience in four patients with dysphagia and endoscopic biopsies negative for malignancy, including one patient with clinical and manometric features suggestive of achalasia. In all cases, EUS revealed a large infiltrating tumor invading through the esophageal wall into the surrounding tissues, and in one case into the aorta. Computed tomography suggested the possibility of a tumor in only one of the cases. Two patients underwent esophagectomy and were found to have adenocarcinoma. Two patients underwent repeat biopsy with alternative aggressive biopsy techniques and were found to have squamous cell carcinoma. We conclude that EUS is useful in the diagnosis of esophageal cancer and should be performed in selected patients with esophageal strictures whose biopsies are negative for malignancy; i.e., those with suspicious endoscopic or radiographic appearance, atypical presentation (e.g., profound weight loss, short duration of symptoms, or advanced age), and failure to respond to treatment.     

Antitumor response to recombinant murine interferon gamma correlates with enhanced immune function of organ-associated, but not recirculating cytolytic T lymphocytes and macrophages

The mechanism of therapeutic activity for recombinant murine interferon-gamma (rMu IFN gamma) in the treatment of metastatic disease was investigated by comparing effector cell augmentation with therapeutic activity in mice bearing experimental lung metastases (B16-BL6 melanoma). Effector cell functions in spleen, peripheral blood, and lung (the tumor-bearing organ) were tested after 1 week and 3 weeks of rMu IFN gamma administration (i.v. three times per week). Natural killer (NK), lymphokine-activated killer (LAK), cytolytic T lymphocyte (CTL) activities against specific and nonspecific targets, and macrophage tumoristatic activity were measured. rMu IFN gamma demonstrated immunomodulatory activity in most assays of immune function. The optimal therapeutic protocol of rMu IFN gamma (2.5 x 10(6) U/kg, three times per week) prolonged survival and decreased the number of pulmonary metastatic foci. This therapeutic activity was correlated with specific CTL activity from pulmonary parenchymal mononuclear cells (PPMC), but not from spleen or blood. Macrophage tumoristatic activity in PPMC also correlated with therapeutic activity, but activity in alveolar macrophages did not. However, therapeutic activity did not correlate with NK or LAK activity at any site. These results demonstrate that the optimal therapeutic protocol is the same as the optimal immunomodulatory dose for pulmonary CTL and macrophage activities. Furthermore, while immunological monitoring may help to optimize treatment protocols, current monitoring procedures that use readily accessible sites, particularly peripheral blood, may not accurately predict the therapeutic efficacy of biological response modifiers in clinical trials.     

Basolateral amygdala stimulation evokes glutamate receptor-dependent dopamine efflux in the nucleus accumbens of the anaesthetized rat

Afferents from the basolateral amygdala and dopamine projections from the ventral tegmental area to the nucleus accumbens have both been implicated in reward-related processes. The present study used in vivo chronoamperometry with stearate-graphite paste electrodes in urethane-anaesthetized rats to determine how basolateral amygdala efferents to the nucleus accumbens synaptically regulate dopamine efflux. Repetitive-pulse (20 Hz for 10 s) electrical stimulation of the basolateral amygdala evoked a complex pattern of changes in monitored dopamine oxidation currents in the nucleus accumbens related to dopamine efflux. These changes were characterized by an initial increase that was time-locked to stimulation, a secondary decrease below baseline, followed by a prolonged increase in the dopamine signal above baseline. The effects of burst-patterned stimulation (100 Hz, 5 pulses/burst, 1-s interburst interval, 40 s) of the basolateral amygdala on the basal accumbens dopamine signal were similar to those evoked by 20 Hz stimulation, with the lack of a secondary suppressive component. Infusions of the ionotropic glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid (APV) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the nucleus accumbens dose-dependently blocked or attenuated the initial and prolonged increases in the dopamine signal following 20 Hz or burst-patterned basolateral amygdala stimulation. Infusions of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine selectively blocked the intermediate suppressive effect of 20 Hz basolateral amygdala stimulation on dopamine oxidation currents. Blockade of glutamate receptors or inhibition of dopamine neuronal activity via infusions of either APV + DNQX, lidocaine or gamma-hydroxybutyric acid, respectively, into the ventral tegmental area did not effect the pattern of changes in the accumbens dopamine signal evoked by basolateral amygdala stimulation. These data suggest that the glutamatergic basolateral amygdala inputs to nucleus accumbens dopamine terminals synaptically facilitate or depress dopamine efflux, and these effects are independent of dopamine neuronal firing activity. Moreover, these results imply that changes in nucleus accumbens dopamine levels following presentation of reward-related stimuli may be mediated, in part, by the basolateral amygdala.     

A winning strategy for managing simulation projects

In this paper a winning strategy for conducting successful simulation studies is proposed. The proposed approach emphasizes risk reduction through incremental model development and encourages user commitment through team work. A case study, based on a medium-sized manufacturing facility in Missouri, is used to illustrate its application. This successful strategy can be easily adopted on other similar simulation studies.