Evaluation of a nonlinear Hertzian-based model reveals prostate cancer cells respond differently to force than normal prostate cells.

Understanding how the mechanical properties of cells alter with disease may help with the development of novel diagnostics and treatment regimes. The emergence of tools such as the atomic force microscope (AFM) has enabled us to physically measure the mechanical properties of cells. However, suitable models for the analysis of real experimental data are either absent, or fail to provide a simple analysis tool in which experimental data can be analyzed quickly and reliably. The Hertz model has been widely used to study AFM data on living cells, however it makes assumptions that are untrue for cells, namely that cells behave as linear elastic bodies. This article presents and evaluates an alternative nonlinear Hertz model, which allows the Young's modulus to vary according to a second order polynomial function of indentation depth. Evaluation of the model revealed that prostate cancer cells (PC3) responded more uniformly to force compared to the normal PNT2 cells. Also, more energy (J) was needed to deform the normal prostate cells compared to the prostate cancer cells. Finally, the model described here suggests that overall the normal prostate cells behave in a more linear fashion to applied force compared to the prostate cancer cells.

Laryngomalacia in a 12-year-old child after laryngeal mask use.

OBJECTIVE: We present an unusual case of a 12-year-old child with state-dependent laryngomalacia presenting after anaesthesia with a laryngeal mask airway. METHOD: Current literature on state-dependent laryngomalacia and injury following laryngeal mask use is reviewed. RESULTS: A child who had previously suffered with laryngomalacia as an infant presented with disturbed breathing at night and during exercise. After anaesthesia using a laryngeal mask airway, these symptoms became more pronounced. Microlaryngoscopy revealed laryngomalacic type movement of the larynx. CONCLUSION: Our case seems to support a more complex, multifactorial aetiology for laryngomalacia, including both the neurological control of the larynx as well as its structure.

Drug-intake regulation and the interplay between economic costs and benefits: comment on Lynch and Carroll (2001).

W. J. Lynch and M. E. Carroll's (2001) review argues against aversive effects and for satiation and direct effects as the mechanisms responsible for the descending limb of the dose-response function. Analysis is provided that suggests they may prematurely dispose of the aversive-effects account. Further analysis of the evidence for satiation and direct effects supports the authors' contention that neither can be exclusively supported. A brief behavioral-economic analysis of drug-intake regulation and the descending limb of the dose-response function is presented.

Needle sharing in opioid-dependent outpatients: psychological processes underlying risk.

Needle sharing contributes to the spread of the human immunodeficiency virus and other health concerns and remains a persistent problem among injection drug users. We determined whether needle sharing may be related to the discounting of the value of delayed outcomes. Outpatients in treatment for heroin dependence indicated preference for immediate versus delayed hypothetical monetary and heroin outcomes in a titration procedure that determined indifference points at various delays. The degree to which the delayed outcomes lost value was estimated with a nonlinear decay model. Participants who agreed to share a needle in a scenario (N=15) discounted delayed money more steeply than did the nonsharing group (N=17). Both groups discounted delayed heroin more steeply than delayed money. Persistent needle sharing may be related to the relative inability of delayed outcomes to impact current behavior. Training to mitigate the effect of delay on outcome value may offer reductions in needle sharing and drug abuse.

Three predictions of the economic concept of unit price in a choice context.

Economic theory makes three predictions about consumption and response output in a choice situation: (a) When plotted on logarithmic coordinates, total consumption (i.e., summed across concurrent sources of reinforcement) should be a positively decelerating function, and total response output should be a bitonic function of unit price increases; (b) total consumption and response output should be determined by the value of the unit price ratio, independent of its cost and benefit components; and (c) when a reinforcer is available at the same unit price across all sources of reinforcement, consumption should be equal between these sources. These predictions were assessed in human cigarette smokers who earned cigarette puffs in a two-choice situation at a range of unit prices. In some sessions, smokers chose between different amounts of puffs, both available at identical unit prices. Individual subjects' data supported the first two predictions but failed to support the third. Instead, at low unit prices, the relatively larger reinforcer (and larger response requirement) was preferred, whereas at high unit prices, the smaller reinforcer (and smaller response requirement) was preferred. An expansion of unit price is proposed in which handling costs and the discounted value of reinforcers available according to ratio schedules are incorporated.

Similar consumption and responding across single and multiple sources of drug.

Two experiments were conducted to assess whether total response output and total consumption would be similar when drugs are available from single and multiple sources of reinforcement, as predicted by behavioral economics. In Experiment 1, cigarette-deprived smokers were exposed to a concurrent-chains schedule in which equal fixed-ratio schedules served as the initial links, and different reinforcer magnitudes (i.e., number of cigarette puffs) were arranged across alternatives. After the session, obtained unit price was calculated and imposed in the next session when a different number of puffs was available according to a single fixed-ratio schedule. Thus, the unit price at which cigarette puffs could be earned was yoked within subjects across the single and concurrent-chains schedules. When plotted as a function of unit price, similar consumption and response rates were usually obtained across these schedules. Experiment 2 addressed a weakness of Experiment 1, namely, that responding was allocated exclusively to the larger reinforcer magnitude in concurrent-chains conditions, and therefore this schedule may have functioned as a single schedule. In Experiment 2, subjects were instructed to alternate responding between the two alternative schedules. Instructions produced approximately equal response allocation between the two alternatives. Again, similar consumption and response rates were observed across the single and instructed concurrent-chains schedules. These findings are discussed in the context of direct effects and behavioral economics perspectives of drug self-administration.

Abstinence and price effects on demand for cigarettes: a behavioral-economic analysis.

AIMS: To examine the separate and combined effects of cigarette pricing and cigarette abstinence on smoking. DESIGN: Within-subject design in which participants experienced all levels of price and abstinence conditions. SETTING: Laboratory conditions. PARTICIPANTS: Nine human cigarette smokers. INTERVENTION: Cigarette prices were manipulated across a 60-fold range (US$0.02-$1.20) in separate abstinent (5 + hours of non-smoking) and non-abstinent conditions. Participants earned money by pulling a response plunger (US$0.10 per 100 pulls) and could either keep the money or spend it on cigarette puffs. MEASUREMENTS: Total response output, cigarette consumption, price elasticity of demand and spending patterns. FINDINGS: Participants spent their earnings on cigarette puffs more quickly when abstinent than when they had smoked ad libitum before the session, and latency to spend money on puffs was a linear increasing function of price. Effects of abstinence on rates of smoking were a function of the price at which cigarette puffs could be purchased. At low prices participants smoked more puffs per session when abstinent, but this difference was negligible at high puff prices. Abstinence and non-abstinence effects were temporary, and tended to wane in the second 90 minutes of the sessions. During the first half of the sessions, demand for cigarettes was more inelastic during the abstinent condition than the non-abstinent condition, indicating relative insensitivity to price increases when abstinent. CONCLUSIONS: Behavioral-economic procedures and measures are sensitive to cigarette-abstinence manipulations and the laboratory methods employed here may prove beneficial in evaluating the probable effects of public-policy initiatives designed to reduce cigarette use.

Comparing the reinforcing efficacy of nicotine containing and de-nicotinized cigarettes: a behavioral economic analysis.

RATIONALE: Smoking-related respiratory stimuli produced by de-nicotinized cigarettes may function as conditioned reinforcers, but behavioral data on such reinforcing effects are limited. OBJECTIVES: The present experiment compared the reinforcing efficacy of cigarettes that provided only smoking-related stimuli (de-nicotinized cigarettes) and cigarettes that provided both smoking-related stimuli and nicotine. METHODS: Eight human subjects responded on a progressive-ratio schedule in which the number of plunger pulls required for standardized cigarette puffs increased across sessions. In one phase, the breakpoints, number of puffs earned per session, peak response rates, ratio producing peak response rates, and the elasticity of demand for cigarette puffs were compared for nicotine-containing and de-nicotinized cigarettes when each cigarette type was the only one available. In another phase, subjects chose between the two cigarette types at some of the prices examined in the previous phase. RESULTS: Nicotine-containing and de-nicotinized cigarettes produced similar measures of reinforcing efficacy when each was presented alone, but there was a strong preference for nicotine-containing cigarettes when subjects were given a choice. CONCLUSIONS: These data support suggestions that smoking-produced sensory stimuli may function as conditioned reinforcers and that the relative reinforcing efficacy of cigarettes is determined by the combined effects of the nicotine/conditioned reinforcing complex provided by smoking.

Impulsivity and cigarette smoking: delay discounting in current, never, and ex-smokers.

RATIONALE: Impulsivity is implicated in drug dependence. Recent studies show problems with alcohol and opioid dependence are associated with rapid discounting of the value of delayed outcomes. Furthermore, discounting may be particularly steep for the drug of dependence. OBJECTIVES: We determined if these findings could be extended to the behavior of cigarette smokers. In particular, we compared the discounting of hypothetical monetary outcomes by current, never, and ex-smokers of cigarettes. We also examined discounting of delayed hypothetical cigarettes by current smokers. METHODS: Current cigarette smokers (n=23), never-smokers (n=22) and ex-smokers (n=21) indicated preference for immediate versus delayed money in a titration procedure that determined indifference points at various delays. The titration procedure was repeated with cigarettes for smokers. The degree to which the delayed outcomes were discounted was estimated with two non-linear decay models: an exponential model and a hyperbolic model. RESULTS: Current smokers discounted the value of delayed money more than did the comparison groups. Never- and ex-smokers did not differ in their discounting of money. For current smokers, delayed cigarettes lost subjective value more rapidly than delayed money. The hyperbolic equation provided better fits to the data than did the exponential equation for 74 out of 89 comparisons. CONCLUSIONS: Cigarette smoking, like other forms of drug dependence, is characterized by rapid loss of subjective value for delayed outcomes, particularly for the drug of dependence. Never- and ex-smokers could discount similarly because cigarette smoking is associated with a reversible increase in discounting or due to selection bias.

Discounting of delayed rewards in opioid-dependent outpatients: exponential or hyperbolic discounting functions?

Recent theories of substance abuse have used value discounting of delayed rewards to partly explain the decision to take drugs. Normative-economic theory holds that an exponential function describes the effects of delay on discounting, whereas the matching law posits a hyperbolic discounting function. The ability of these functions to describe 18 human heroin-dependent individuals' monetary- and heroin-reward delay-discounting functions was assessed. In the 1st condition, participants chose between immediate and delayed hypothetical monetary rewards. Delayed rewards were $1,000, and the immediate reward amount was adjusted until choices reflected indifference. In the 2nd condition, participants chose between immediate and delayed heroin (the delayed amount was that which each participant reported he or she could purchase with $1,000). The hyperbolic function produced significantly higher R2 values and significantly lower sums of squared error values. Consistent with previous findings, delayed heroin rewards were discounted at a significantly higher rate than were delayed monetary rewards.

A comparison of measures of relative reinforcing efficacy and behavioral economics: cigarettes and money in smokers.

In this experiment, we compared behavioral economic measures and measures of the relative reinforcing efficacy of cigarettes and money between-participants. The experiment proceeded in two phases. In the first phase, money and cigarettes were available on separate progressive ratio (PR) schedules when they were solely available. The response requirement for the PR schedule increased across sessions, rather than within a session. In the second phase, money and cigarettes were made concurrently available at some of the response requirements employed during the PR schedule. Measures of (1) PR breakpoint, (2) peak response rate, (3) preference, (4) elasticity and (5) Pmax (the price at which the greatest amount of responding occurs) were compared within participant. Across the PR- and concurrent-schedule conditions, the three measures of reinforcing efficacy (breakpoint, response rate and preference) yielded an inconsistent assessment of the relative reinforcing efficacy of money and cigarettes. The reinforcer that resulted in greater peak response rates varied across subjects, while PR breakpoint was higher for cigarettes in all participants. Further, in concurrent schedules, preferences for cigarettes or money reversed across the response requirements. Behavioral economic analyses suggest that Pmax and elasticity are related to PR breakpoint, and that preference can be predicted from a comparison of the demand curves under single-schedule conditions. Implications for the concept of reinforcing efficacy are discussed.

Challenges and issues related to implementation of nursing vocabularies in computer-based systems.

As key stakeholders from the clinical setting and vendor communities, the authors share a summary of their collective experience related to the challenges and issues associated with implementing the vocabularies recognized by the American Nurses Association in several installations of commercially available clinical information systems. Although the focus of the article is on summarizing the challenges and issues, it is of note that the authors' experiences across care settings suggest that the experience and effort of using one of the ANA-recognized vocabularies in a computer-based system are essentially worthwhile and positive. The issues and challenges fall into two categories: 1) those related to the developmental status of nursing vocabularies, and 2) those related to the adoption or implementation of new technology.

Making sense of sensitivity in the human operant literature.

Human operant behavior is often said to be controlled by different variables or governed by different processes than nonhuman operant behavior. Support for this claim within the operant literature comes from data suggesting that human behavior is often insensitive to schedules of reinforcement to which nonhuman behavior has been sensitive. The data that evoke the use of the terms sensitivity and insensitivity, however, result from both between-species and within-subject comparisons. We argue that because sensitivity is synonymous with experimental control, conclusions about sensitivity are best demonstrated through within-subject comparisons. Further, we argue that even when sensitivity is assessed using within-subject comparisons of performance on different schedules of reinforcement, procedural differences between studies of different species may affect schedule performance in important ways. We extend this argument to age differences as well. We conclude that differences across populations are an occasion for more precise experimental analyses and that it is premature to conclude that human behavior is controlled by different processes than nonhuman behavior.

Modeling the effects of combined behavioral and pharmacological treatment on cigarette smoking: behavioral-economic analyses.

Effects of different response requirements, response-independent cigarette puffs, and an alternative nondrug reinforcer on cigarette smoking were assessed in 2 experiments. The response requirement to obtain 2 puffs on a cigarette was manipulated while various numbers of response-independent puffs were provided (0, 6, or 12 in Experiment 1; 0 or 12 in Experiment 2). In Experiment 2, effects of response-dependent money ($0.25) on smoking were assessed within subjects. Response-dependent puff consumption decreased as price increased and as the number of response-independent puffs increased. Concurrently available money also decreased response-dependent smoking. The largest decrease in smoking occurred when puffs were at the highest price and when response-independent puffs and response-dependent money were both concurrently available. Findings suggest that combined pharmacological and behavioral interventions produce the greatest reductions in smoking.

Factor analyses of handedness items in left and right-handed intellectually gifted and nongifted children.

Handedness questionnaire items from the General Scale of the Lateral Preference Schedule (Dean, 1988) were administered to 423 intellectually gifted and 226 nongifted children to investigate the underlying processes that contribute to laterality. Handedness items were factor analyzed using principal components (PC) analysis with varimax rotation. PC analyses computed separately for gifted and nongifted left and right-handed writers yielded very different factor structures. Left-handers (regardless of gifted status) tended to have factor structures marked by items that loaded saliently on more than one factor. Whereas a four factor solution best fit the data for the nongifted left-handers, a three factor solution was the best fit for the gifted left-handed children. The factor structure for the left-handed gifted children was marked by two factors where the item "draw" was the only item to load both positively and saliently, a pattern not evident among the nongifted left-handers. These results suggested different underlying patterns contributing to laterality among these groups of children.

Impulsive and self-control choices in opioid-dependent patients and non-drug-using control participants: drug and monetary rewards.

Delay discounting was investigated in opioid-dependent and non-drug-using control participants. The latter participants were matched to the former on age, gender, education, and IQ. Participants in both groups chose between hypothetical monetary rewards available either immediately or after a delay. Delayed rewards were $1,000, and the immediate-reward amount was adjusted until choices reflected indifference. This procedure was repeated at each of 7 delays (1 week to 25 years). Opioid-dependent participants were given a second series of choices between immediate and delayed heroin, using the same procedures (i.e., the amount of delayed heroin was that which could be purchased with $1,000). Opioid-dependent participants discounted delayed monetary rewards significantly more than did non-drug-using participants. Furthermore opioid-dependent participants discounted delayed heroin significantly more than delayed money.