Early acquisition and conversion of Pseudomonas aeruginosa in Hispanic youth with cystic fibrosis in the United States

BackgroundFor unknown reasons, Hispanic patients with cystic fibrosis (CF) have more severe pulmonary disease than non-Hispanic white patients. In CF, the pulmonary pathogen Pseudomonas aeruginosa is associated with worse outcomes. We sought to determine if Hispanic patients with CF are at an increased risk of acquiring P. aeruginosa or acquire it earlier than non-Hispanic white patients.MethodsThis is a longitudinal study comparing the timing and risk of acquisition of different forms of P. aeruginosa between Hispanic and non-Hispanic white patients aged 0-21 years old with CF in the CF Foundation Patient Registry (CFFPR) in 2008-2013. The age at the initial acquisition of P. aeruginosa (initial acquisition, mucoid, chronic, multidrug-resistant) was summarized using Kaplan-Meier survival curves and analyzed using Cox proportional hazards regression models.ResultsOf 10,464 patients, 788 (7.5%) were Hispanic and 9,676 (92.5%) were non-Hispanic white. Hispanic patients acquired all forms of P. aeruginosa at a younger age than non-Hispanic white patients. Hispanic patients had a higher risk of acquiring P. aeruginosa than non-Hispanic white patients: the hazard ratio (HR) was 1.26 (95% CI 1.16-1.38, p<0.001) for initial P. aeruginosa, 1.59 (95% CI 1.43-1.77, p<0.001) for mucoid P. aeruginosa, 1.91 (95% CI 1.64-2.23, p<0.001) for multidrug-resistant P. aeruginosa, and 1.39 (95% CI 1.25-1.55, p<0.001) for chronic P. aeruginosa.ConclusionsHispanic patients have an increased risk of acquiring P. aeruginosa and acquire it at an earlier age than non-Hispanic white patients in the United States. This may contribute to increased morbidity and mortality in Hispanic patients with CF.     

Parameters influencing piezoelectric shock wave lithotripsy of biliary calculi

A total of 225 human gallbladder stones were divided into sets of two, three, or four identical calculi (with maximum diameters of 6-26 mm) and submitted to piezoelectric shock wave lithotripsy in vitro in order to investigate the influence of the following parameters on stone disintegration: shock wave intensity, pulse frequency, and various physicochemical parameters such as the volume and viscosity of the fluid surrounding the stone, the hardness of the calculus, and its chemical composition. The fragmentation efficacy increased with enhanced shock wave energy (P less than 0.01). If the volume of the fluid (30 mL) surrounding the calculus was small, the disintegration end-point (defined by maximum fragment diameters less than or equal to 4 mm) was achieved after a lower number of pulses (median: 250 pulses) than in the case of a large fluid volume (80 mL) (500 pulses; P less than 0.01). On the other hand, however, factors such as the shock wave pulse rate (0.9 Hz vs 1.6 Hz), variations in viscosity of a water-jelly mixture surrounding the stone, the chemical composition of the stones as determined by X-ray diffractometry, and stone hardness were found to have no significant influence on the fragmentation efficacy.     

Spatial games and the maintenance of cooperation.

The Prisoner's Dilemma (PD) is a widely employed metaphor for problems associated with the evolution of cooperative behavior. We have recently proposed an alternative approach to the PD, by exploring "spatial games" in which players--who are either pure cooperators, C, or pure defectors, D--interact with neighbors in some spatial array; in each generation, players add up the scores from all encounters, and in the next generation a given cell is retained by its previous owner or taken over by a neighbor, depending on who has the largest score. Over a wide range of the relevant parameters, we find that C and D persist together indefinitely (without any of the complex strategies that remember past encounters, and anticipate future ones, which characterize essentially all previous work on the iterated PD). Our earlier work, however, dealt with symmetric spatial lattices in two dimensions, deterministic winning and discrete time. We show here that the essential results remain valid in more realistic situations where the spatial distributions of cells are random in two or three dimensions, and where winning is partly probabilistic (rather than being determined by the largest local total). The essential results also remain valid (pace Huberman and Glance [Huberman, B. A. & Glance, N. S. (1993) Proc. Natl. Acad. Sci. USA 90, 7716-7718]) when interactions occur in continuous rather than discrete time.     

Fly me, I'm tropical

Leprosy, malaria and jigger fleas are all in a week's work for London's Hospital for Tropical Diseases. But some fear that the internal market could bring its 170-year history to a close, reports Annabelle May.     

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.