Universal energy scaling law for optimally excited nonlinear oscillators.

We compute the optimal temporal profile for an external driving force F(t) that can maximize the energy absorption of any driven nonlinear oscillator. The technique is based on constraining the maximum amplitude of the force field such that optimal control theory can provide quasianalytical solutions. We illustrate this computational technique for the undamped Duffing oscillator as well as for a driven quantum mechanical two-level system. We find that under optimal force conditions the asymptotic time-dependence of the maximum amplitude growth is given by a power law X(t)∼t^{2/α}, where the (possibly noninteger) exponent is determined by the highest degree of the oscillator's nonlinearity α. As a universal result, this predicts that the maximal energy absorption of any nonlinear oscillator grows (under an optimized force field) quadratically in time. We also find for the two-level system that-even under optimized excitation conditions-the maximally achievable inversion does not monotonically increase with the force amplitude. It is characterized by an interesting sequence of n-cycle thresholds as well as a self-termination of the growth.

Minimizing DILI risk in drug discovery - A screening tool for drug candidates.

Drug-induced liver injury (DILI) is a leading cause of acute hepatic failure and a major reason for market withdrawal of drugs. Idiosyncratic DILI is multifactorial, with unclear dose-dependency and poor predictability since the underlying patient-related susceptibilities are not sufficiently understood. Because of these limitations, a pharmaceutical research option would be to reduce the compound-related risk factors in the drug-discovery process. Here we describe the development and validation of a methodology for the assessment of DILI risk of drug candidates. As a training set, 81 marketed or withdrawn compounds with differing DILI rates - according to the FDA categorization - were tested in a combination of assays covering different mechanisms and endpoints contributing to human DILI. These include the generation of reactive metabolites (CYP3A4 time-dependent inhibition and glutathione adduct formation), inhibition of the human bile salt export pump (BSEP), mitochondrial toxicity and cytotoxicity (fibroblasts and human hepatocytes). Different approaches for dose- and exposure-based calibrations were assessed and the same parameters applied to a test set of 39 different compounds. We achieved a similar performance to the training set with an overall accuracy of 79% correctly predicted, a sensitivity of 76% and a specificity of 82%. This test system may be applied in a prospective manner to reduce the risk of idiosyncratic DILI of drug candidates.

A consultant's perspective. Renal care of Louisiana.

Much has been said regarding the evolution of managed care and what the ultimate impact of managed care will have on the renal industry. The members of NIPA, under the guidance of its Board of Directors, formed RenalCare of Louisiana in order that the nephrologists could take the lead in defining and monitoring the quality of care delivered to ESRD and pre-ESRD patients under an at-risk payment methodology. NIPA places its members in the "drivers seat" in the development and implementation of a renal disease management organization, and therefore, the re-engineering of the renal delivery system in Louisiana will be headed by Louisiana nephrologists rather than for-profit dialysis chains.

What are the options for nephrologists under capitation?

Nephrologists will play a pivotal role in changing tomorrow's renal delivery system. Nephrologists still control patients and drive the health care delivered to patients suffering from ESRD. As a result, practice management companies, independent consulting firms, renal societies, hospitals, dialysis providers, insurance companies, managed care plans, government agencies, and, yes, even independent practice groups are exploring business strategies that will unite nephrologists under a common goal--that of an integrated renal delivery network. Nephrologists face what is probably their professional career's most important business decision: Partner with such organizations as hospitals, dialysis providers, or practice management companies, or form an independent nephrologist owned IPA and contract with an MSO. As nephrologists evaluate the options, they should seek partners that will at a minimum provide the following: a business plan that spells out the relationships of all the players; practice evaluations that can improved efficiencies; skilled day-to-day practice management; model legal documents; human resource management; expert, pro-physician reimbursement negotiation, coupled with a system to track contract profitability; case management, critical paths, practice guidelines; and renal industry expertise. Above all, nephrologists should seek partners in the formation of an integrated delivery system that offer an attitude dedicated to physician empowerment in the interest of good patient care.

A computer-generated shift report.

To maintain quality patient care while reducing overtime costs, a change in the traditional verbal shift report was needed. A pilot study examined alternate methods, format changes, benefits and nursing recommendations. Using a computer-generated nursing care plan cover sheet, a change was made to an automated written shift report.

Consumer acceptance of display packs of beef stored under N(2) or CO(2) in master packs.

Display-packaged samples of beef steak and of ground beef were delivered to the homes of 120 panelists. Each panelist received a set of samples of each meat. Each set consisted of one sample freshly prepared for retail display from vacuum-packaged product, one retail-packaged and then stored in a master pack under N(2) and one retail-packaged and the stored under CO(2). The samples in each set were prepared from the same strip loin or batch of coarsely ground beef and had been stored for between 21 and 23 days at 2°C. The panelists completed questionnaires on the attributes of the meats while they were packaged, when they were unpackaged for cooking, and when they were eaten. The responses to each question were tabulated, and the probability of the χ(2) statistics was calculated for each table. There were no significant differences in the general acceptability of the steaks from the three storage treatments. Significant numbers of panelists judged that ground beef prepared from vacuum-packaged product was of better colour and had less exudate, but was of poorer eating quality than the product from master packs. However, the majority of panelists did not distinguish between ground beef from the three storage treatments. The consumer responses indicate that controlled-atmosphere master packaging of display packs may offer a means of preserving display-ready beef for times that would allow wide distribution of the product through current commercial systems.

Changes in the microflora on commercial beef trimmings during their collection, distribution and preparation for retail sale as ground beef.

A commercial process for ground meat production, from the collection of meat plant trimmings to the retailing of consumer packs of ground beef, was examined. The selected process compiled with current concepts of Good Manufacturing Practice. During storage for up to 18 days before grinding, most trimming developed a flora of lactobacilli, of up to 10(7) CFU/g. Numbers of coliforms and of Escherichia coli on stored trimmings increased little and not at all, respectively. Increased total counts, and numbers of both coliforms and E. coli in displayed product indicated loss of control of the temperature of the displayed packaged product. It appears that the need to store a product, taking into account the unpredictable fluctuations in supply and demand, will inevitably result in much ground beef carrying large numbers of spoilage bacteria. Furthermore, currently accepted Good Practice in the retail handling of ground beef does not adequately control either spoilage or the growth of pathogenic bacteria.

Fluorescence detection of tumors. Early diagnosis of microscopic lesions in preclinical studies.

BACKGROUND: The growth of microscopic tumor lesions at or beyond treatment field margins poses a major problem in the diagnosis and treatment of cancer. Early detection techniques that clearly define the location or field spread of disease may improve the planning of disease treatment. METHODS: In vivo fluorescence photometry is a non-imaging technique that digitally displays relative fluorescence values in volts proportional to the luminescence intensity detected by a silicon photodiode. The sensitivity of the instrument has allowed the detection of micrometastases in preclinical studies. RESULTS: Statistical analysis demonstrates that the photosensitizer Photofrin (dihematoporphyrin ether and/or ester) (Quadra Logic Technologies, QLT, Vancouver, B.C., Canada), currently used for photodynamic therapy, administered in doses lower than those used in clinical studies, is useful for the detection of occult disease. With the drug doses used, cutaneous photosensitivity was avoided in the animal models tested. The results in Lobund-Wistar rats with transplantable prostatic adenocarcinoma (PA-III) demonstrated the utility of this technique in detecting clinically occult disease, with a prediction rate of approximately 94% with drug doses as low as 0.25-0.5 mg/kg. CONCLUSIONS: With the use of the hamster buccal cavity model involving the initiation and promotion of premalignant and malignant conditions by 9,10 dimethyl-1,2-benzanthracene, the technique could discern these two stages of disease with significance levels that were less than 0.05 and 0.01, respectively.

Accuracy of chest film screening by technologists in the New York early lung cancer detection program.

A study of the feasibility of using specially trained radiologic technologists to screen chest radiographs was undertaken as part of an early lung cancer detection program. In their initial examination, 8,000 men had posteroanterior and lateral chest films which were prepared and evaluated by two specially trained technologists prior to interpretation by a radiologist. The technologists' accuracy in screening was subsequently assessed by comparison with the radiologist's interpretation and with clinical follow-up information. There were differences in the level of suspicion of the two technologists, but both were effective in selecting a subset of the screened population that contained the men with radiologically identifiable lung cancer.

Preliminary report of the lung cancer detection program in New York.

The early lung cancer detection program in New York is described, and preliminary prevalence rate data are reported. Cigarette-smoking men over the age of 45, who are considered at high risk, are encouraged to enroll in the program and, to date, 6,612 have done so. These men receive PA and lateral chest x-rays annually, while a randomly selected sub-population of about half also have sputum cytology every four months. A controlled study of sputum cytology as an adjunct to the chest x-ray is now in progress. There were 15 cases of late lung cancer (pathologic stages II and III) detected at the initial examination, and 11 early cases (pathologic stages O and I). In the population of 3,387 men who had x-rays alone there were three early lung cancers detected; in the population of 3,225 men who had both examinations four early cancers were detected by x-ray and four by cytology. In addition, three cases of larynx cancer were detected by cytology. The early lung cancers detected by x-ray were peripheral and most were bronchiolar or adenocarcinoma; the early cancers detected by cytology were central epidermoid carcinoma of major bronchi. No early carcinomas were detected by both techniques. These findings suggest that a combination of chest x-rays and sputum cytology can be more effective than either one alone in detecting early lung cancer.