Partnership to engage St. Louis high school students in investigative genetics.

The authors describe the Modern Genetics Project, based on a successful hands-on science implementation model that was developed and field-tested in St. Louis area high schools between 1992 and 1998. The project, begun in 1991, features a curriculum enhancement unit, "Modern Genetics for All Students," that combines strong scientific content, hands-on investigations, and human health applications, with reference to developing national and state science-teaching standards for this topic. The unit provides a significantly higher level of hands-on involvement throughout the school year for students than is found in traditional biology classrooms. This project aims to enhance scientific literacy among St. Louis high school students (all grades) of all learning levels and all socioeconomic, racial, and ethnic backgrounds; many of the students using the curriculum are from underrepresented minorities. This long-term project is carried out by a strong partnership among scientists at Washington University, implementation specialists from the Mathematics and Science Education Center of the Cooperating School Districts of St. Louis, project evaluators from Southern Illinois University at Edwardsville, and biology teachers at local high schools. Funding was originally from the National Institutes of Health and is now from the Howard Hughes Medical Institute. In 1998, there were 31 teachers and approximately 3,200 students participating in the project. Both quantitative and qualitative evaluations of the project during the 1995-96 and 1996-97 school years indicate that there were significant gains in knowledge and attitudes among the students of all racial, ethnic, and socioeconomic groups represented, and among both boys and girls.     

Surgical subspecialty block utilization and capacity planning: a minimal cost analysis model

BACKGROUND: Operational inefficiencies in the use of operating rooms (ORs) are hidden by traditional measures of OR utilization. To better detect these inefficiencies, the authors defined two new terms, underutilization and overutilization, and illustrated how these measures might be used to evaluate the use of surgical subspecialty ORs. The authors also described capacity planning (optimizing surgical subspecialty block time allotments) using a minimal cost analysis (MCA) model. METHODS: The authors evaluated post hoc all surgeries performed over 6 yr at a large teaching hospital. To prepare utilization estimates, surgical records were categorized relative to budgeted OR block time for each subspecialty. Surgical cases beginning and ending during budgeted OR block time were categorized as budgeted utilization, budgeted time not used for surgery was underutilization, and cases beginning before/after budgeted block time were classified as overutilization. Cases that overlapped budgeted and nonbudgeted OR block time were parsed and the portions were assigned appropriately. Probability distributions were fitted to the historical patterns of surgical demand, and MCA block time budgets were estimated that minimized the costs of underutilization and overutilization for each subspecialty. To illustrate the potential savings if these MCA budgets were implemented, the authors compared actual operational costs to the estimated MCA budget costs and expressed the savings as a percentage of actual costs. RESULTS: The authors analyzed data from 58,251 surgical cases and 10 surgical subspecialty blocks. Classic utilization for each block-day by surgical subspecialty ranged from 44-113%. Average daily block-specific underutilization ranged from 16 to 60%, whereas overutilization ranged from 4 to 49%. CONCLUSIONS: Underutilization and overutilization are important measures because they may be used to evaluate the quality of OR schedules and the efficiency of OR utilization. Overutilization and underutilization also allow capacity planning using an MCA model This study indicated that the potential savings, if the MCA budgets were to be implemented, would be significant.     

Afterimages, grating induction and illusory phantoms

Under some conditions (dark or light inspection areas) illusory gratings often appear to be in-phase with the inducing gratings and under others (gray inspection area) illusory gratings often appear to be out-of-phase with the inducing gratings. McCourt reported that point-by-point brightness matches reveal only out-of-phase illusory gratings, no matter what the luminance of the inspection area (McCourt, M. E. (1994). Vision Research, 34, 1609-1617). Since the technique used might have led to afterimages which mimic out-of-phase illusory gratings, the present series of experiments was undertaken to determine how such afterimages might bias illusory grating judgments. Afterimages were induced during fixation with brief flashes of inducing gratings within the inspection area (Experiment 1), or by vertical shifts in the entire stimulus which exposed the retina to real gratings prior to judgments within the inspection area (Experiment 2). Experiment 2 was replicated with drifting inducing gratings (Experiment 3). The subjects were asked to indicate whether illusory gratings appeared in- or out-of-phase. The results of all three experiments reveal that out-of-phase illusory gratings predominate, and that afterimages can only bias judgments with stationary displays. It is suggested that grating induction is perceived when subjects attend to local contrast differences, while phantom visibility is facilitated when attention is captured by the more global aspects of the stimulus.     

Discovery of novel non-peptide CCR1 receptor antagonists

Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these disorders. A novel series of 4-hydroxypiperidines has been discovered by high throughput screening (HTS) which potently inhibits the binding of MIP-1alpha and RANTES to the recombinant human CCR1 chemokine receptor. The structure-activity relationships of various segments of this template are described as the initial HTS lead 1 was optimized synthetically to the highly potent receptor antagonist 6s. This compound has been shown to have at least 200-fold selectivity for inhibition of CCR1 over other human 7-TM receptors, including other chemokine receptors. In addition, data obtained from in vitro functional assays demonstrate the functional antagonism of compound 6s and structurally related analogues against the CCR1 receptor in a concentration dependent manner. The discovery and optimization of potent and selective CCR1 receptor antagonists represented by compound 6s potentially represent a novel approach to the treatment of chronic inflammatory diseases.     

Actigraphically recorded motor activity and immobility across sleep cycles and stages in healthy male subjects

The aim of this study was to compare the extent to which activity and immobility measures are related to sleep stages and sleep cycles in order to improve the informative value of actigraphic assessment of sleep. We therefore performed simultaneous ambulatory polysomnography and wrist-activity monitoring (AM) in 14 healthy male subjects without sleep complaints. In this context, a simple method for transforming raw motor activity data into a time-series reflecting onset and duration of activity and immobility clusters is introduced. Our results demonstrate that nocturnal AM measures were significantly affected by sleep stage. Low activity levels and particularly prolonged episodes of uninterrupted immobility were associated with increasing sleep depth. On the other hand, high activity levels and prolonged episodes of activity were related to intermittent wakefulness during sleep. Our results suggest that measures reflecting the occurrence and duration of activity and immobility clusters provide a better approach in studying the relationship between activity/immobility and sleep stages. Except for the duration of uninterrupted immobility episodes, which showed a significant decrease in the fourth cycle, none of the AM measures showed a significant cycle-to-cycle variation. Consequently, mean nocturnal motor activity measures provide an accurate reflection of the total sleep period. However, none of the AM-derived measures seems useful in evaluating the cycle structure during sleep.     

"Akinetic depression" in schizophrenia.

It is possible that some "postpsychotic depressions" may be a toxic effect of antipsychotic drugs. Out of a total of 94 schizophrenic patients, 28 developed a mild akinesia and 32 never developed extrapyramidal symptoms. Those who developed akinesia became less psychotic, but they also experienced a significant, although modest, increase in depression ratings. Successful treatment of the akinesia resulted in significant improvements in depression, somatic concern, anxiety, emotional withdrawal, blunted affect, and motor retardation on both physicians' and nurses' ratings. A high association between akinesia and both objectively rated and subjectively experienced sedative effect indicates that an 'akinetic depression' is not likely if the patient does not look or feel drowsy. The 32 nonakinetic patients also became less psychotic, but not more depressed.     

Next move for Hungary

After 40 years of communism, Hungary is a tired nation. But now an enormous task faces its government; bringing its antiquated healthcare system into line with those of western Europe. Annabelle May reports from a conference in Budapest.