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1.  Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial 
Critical Care  2014;18(2):R48.
Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF.
We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction <40%, (2) acute pulmonary oedema or respiratory failure of predominantly cardiac origin requiring mechanical ventilation and (3) currently receiving vasopressor and/or inotropic support. Patients in the intervention group received a 3 ml/kg bolus of half-molar sodium lactate over the course of 15 minutes followed by 1 ml/kg/h continuous infusion for 24 hours. The control group received only a 3 ml/kg bolus of Hartmann’s solution without continuous infusion. The primary outcome was CO assessed by transthoracic echocardiography 24 hours after randomisation. Secondary outcomes included a measure of right ventricular systolic function (tricuspid annular plane systolic excursion (TAPSE)), acid-base balance, electrolyte and organ function parameters, along with length of stay and mortality.
The infusion of half-molar sodium lactate increased (mean ± SD) CO from 4.05 ± 1.37 L/min to 5.49 ± 1.9 L/min (P < 0.01) and TAPSE from 14.7 ± 5.5 mm to 18.3 ± 7 mm (P = 0.02). Plasma sodium and pH increased (136 ± 4 to 146 ± 6 and 7.40 ± 0.06 to 7.53 ± 0.03, respectively; both P < 0.01), but potassium, chloride and phosphate levels decreased. There were no significant differences in the need for vasoactive therapy, respiratory support, renal or liver function tests, duration of ICU and hospital stay or 28- and 90-day mortality.
Infusion of half-molar sodium lactate improved cardiac performance and led to metabolic alkalosis in AHF patients without any detrimental effects on organ function.
Trial registration NCT01981655. Registered 13 August 2013.
PMCID: PMC4057379  PMID: 24666826
2.  Down but not out: myocardial depression in sepsis 
Critical Care  2012;16(3):132.
Myocardial depression in septic patients is well recognized yet still poorly understood. The prognostic significance in terms of overall mortality when it is identified, remains in dispute. Parameters of left ventricular function measured by tissue Doppler imaging may assist in resolving whether dysfunction identified early in the course of sepsis is a good prognostic sign.
PMCID: PMC3580648  PMID: 22748042
3.  Is early ventricular dysfunction or dilatation associated with lower mortality rate in adult severe sepsis and septic shock? A meta-analysis 
Critical Care  2013;17(3):R96.
Reversible myocardial depression occurs early in severe sepsis and septic shock. The question of whether or not early ventricular depression or dilatation is associated with lower mortality in these patients remains controversial. Most studies on this topic were small in size and hence lacked statistical power to answer the question. This meta-analysis attempted to answer the question by increasing the sample size via pooling relevant studies together.
PubMed, Embase (and Medline) databases and conference abstracts were searched to July 2012 for primary studies using well-defined criteria. Two authors independently screened and selected studies. Eligible studies were appraised using defined criteria. Additional information was sought the corresponding authors if necessary. Study results were pooled using random effects models. Standardized mean differences (SMD) between survivor and non-survivor groups were used as the main effect measures.
A total of 62 citations were found. Fourteen studies were included in the analysis. The most apparent differences between the studies were sample sizes and exclusion criteria. All studies, except four pre-1992 studies, adopted the Consensus definition of sepsis. Altogether, there were >700 patients available for analysis of the left ventricle and >400 for the right ventricle. There were no significant differences in left ventricular ejection fractions, right ventricular ejection fractions, and right ventricular dimensions between the survivor and non-survivor groups. When indexed against body surface area or body height, the survivors and non-survivors had similar left ventricular dimensions. However, the survivors had larger non-indexed left ventricular dimensions.
This meta-analysis failed to find any evidence to support the view that the survivors from severe sepsis or septic shock had lower ejection fractions. However, non-indexed left ventricular dimensions were mildly increased in the survivor group but the indexed dimensions were similar between the groups. Both survivors and non-survivors had similar right ventricular dimensions.
PMCID: PMC4056117  PMID: 23706109
4.  Identification of sepsis subtypes in critically ill adults using gene expression profiling 
Critical Care  2012;16(5):R183.
Sepsis is a syndromic illness that has traditionally been defined by a set of broad, highly sensitive clinical parameters. As a result, numerous distinct pathophysiologic states may meet diagnostic criteria for sepsis, leading to syndrome heterogeneity. The existence of biologically distinct sepsis subtypes may in part explain the lack of actionable evidence from clinical trials of sepsis therapies. We used microarray-based gene expression data from adult patients with sepsis in order to identify molecularly distinct sepsis subtypes.
We used partitioning around medoids (PAM) and hierarchical clustering of gene expression profiles from neutrophils taken from a cohort of septic patients in order to identify distinct subtypes. Using the medoids learned from this cohort, we then clustered a second independent cohort of septic patients, and used the resulting class labels to evaluate differences in clinical parameters, as well as the expression of relevant pharmacogenes.
We identified two sepsis subtypes based on gene expression patterns. Subtype 1 was characterized by increased expression of genes involved in inflammatory and Toll receptor mediated signaling pathways, as well as a higher prevalence of severe sepsis. There were differences between subtypes in the expression of pharmacogenes related to hydrocortisone, vasopressin, norepinephrine, and drotrecogin alpha.
Sepsis subtypes can be identified based on different gene expression patterns. These patterns may generate hypotheses about the underlying pathophysiology of sepsis and suggest new ways of classifying septic patients both in clinical practice, and in the design of clinical trials.
PMCID: PMC3682285  PMID: 23036193
Sepsis; severe sepsis; septic shock; gene expression profiling; microarray analysis; biomedical informatics; critical care; intensive care
5.  Hemodynamic Monitoring 
PMCID: PMC3432346  PMID: 22957295
6.  A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia 
Critical Care  2012;16(4):R157.
Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. We conducted gene-expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure, such as bacterial pneumonia, and noninfective systemic inflammatory response syndrome.
Whole-blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene-expression beadarrays. Differentially expressed genes were determined by linear mixed-model analysis and overrepresented biological pathways determined by using GeneGo MetaCore.
The gene-expression profile of H1N1 influenza A pneumonia was distinctly different from those of bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene-expression profile is characterized by upregulation of genes from cell-cycle regulation, apoptosis, and DNA-damage-response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene-expression profile of influenza infection persisted through 5 days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection in whom bacterial co-infection subsequently developed, the influenza gene-expression signature remained unaltered, despite the presence of a superimposed bacterial infection.
The whole-blood expression-profiling data indicate that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed the identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly.
PMCID: PMC3580747  PMID: 22898401
7.  Response Strength in Extreme Multiple Schedules 
Four pigeons were trained in a series of two-component multiple schedules. Reinforcers were scheduled with random-interval schedules. The ratio of arranged reinforcer rates in the two components was varied over 4 log units, a much wider range than previously studied. When performance appeared stable, prefeeding tests were conducted to assess resistance to change. Contrary to the generalized matching law, logarithms of response ratios in the two components were not a linear function of log reinforcer ratios, implying a failure of parameter invariance. Over a 2 log unit range, the function appeared linear and indicated undermatching, but in conditions with more extreme reinforcer ratios, approximate matching was observed. A model suggested by McLean (1991), originally for local contrast, predicts these changes in sensitivity to reinforcer ratios somewhat better than models by Herrnstein (1970) and by Williams and Wixted (1986). Prefeeding tests of resistance to change were conducted at each reinforcer ratio, and relative resistance to change was also a nonlinear function of log reinforcer ratios, again contrary to conclusions from previous work. Instead, the function suggests that resistance to change in a component may be determined partly by the rate of reinforcement and partly by the ratio of reinforcers to responses.
PMCID: PMC3266739  PMID: 22287804
response rate; reinforcer rate; matching law; multiple schedules; keypeck; pigeons
8.  Cardiac biomarkers in the intensive care unit 
Cardiac biomarkers (CB) were first developed for assisting the diagnosis of cardiac events, especially acute myocardial infarction. The discoveries of other CB, the better understanding of cardiac disease process and the advancement in detection technology has pushed the applications of CB beyond the 'diagnosis' boundary. Not only the measurements of CB are more sensitive, the applications have now covered staging of cardiac disease, timing of cardiac events and prognostication. Further, CB have made their way to the intensive care setting where their uses are not just confined to cardiac related areas. With the better understanding of the CB properties, CB can now help detecting various acute processes such as pulmonary embolism, sepsis-related myocardial depression, acute heart failure, renal failure and acute lung injury. This article discusses the properties and the uses of common CB, with special reference to the intensive care setting. The potential utility of "multimarkers" approach and microRNA as the future CB are also briefly discussed.
PMCID: PMC3313856  PMID: 22397488
9.  Appreciating the Strengths and Weaknesses of Transthoracic Echocardiography in Hemodynamic Assessments 
Transthoracic echocardiography (TTE) is becoming the choice of hemodynamic assessment tool in many intensive care units. With an ever increasing number of training programs available worldwide, learning the skills to perform TTE is no longer a limiting factor. Instead, the future emphasis will be shifted to teach the users how to recognize measurement errors and artefacts (internal validity), to realize the limitations of TTE in various applications, and finally how to apply the information to the patient in question (external validity). This paper aims to achieve these objectives in a common area of TTE application—hemodynamic assessments. We explore the strengths and weaknesses of TTE in such assessments in this paper. Various methods of hemodynamic assessments, such as cardiac output measurements, estimation of preload, and assessment of fluid responsiveness, will be discussed.
PMCID: PMC3290825  PMID: 22454777
10.  Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis 
Critical Care  2011;15(3):R149.
Sepsis is a complex immunological response to infection characterized by early hyper-inflammation followed by severe and protracted immunosuppression, suggesting that a multi-marker approach has the greatest clinical utility for early detection, within a clinical environment focused on Systemic Inflammatory Response Syndrome (SIRS) differentiation. Pre-clinical research using an equine sepsis model identified a panel of gene expression biomarkers that define the early aberrant immune activation. Thus, the primary objective was to apply these gene expression biomarkers to distinguish patients with sepsis from those who had undergone major open surgery and had clinical outcomes consistent with systemic inflammation due to physical trauma and wound healing.
This was a multi-centre, prospective clinical trial conducted across four tertiary critical care settings in Australia. Sepsis patients were recruited if they met the 1992 Consensus Statement criteria and had clinical evidence of systemic infection based on microbiology diagnoses (n = 27). Participants in the post-surgical (PS) group were recruited pre-operatively and blood samples collected within 24 hours following surgery (n = 38). Healthy controls (HC) included hospital staff with no known concurrent illnesses (n = 20). Each participant had minimally 5 ml of PAXgene blood collected for leucocyte RNA isolation and gene expression analyses. Affymetrix array and multiplex tandem (MT)-PCR studies were conducted to evaluate transcriptional profiles in circulating white blood cells applying a set of 42 molecular markers that had been identified a priori. A LogitBoost algorithm was used to create a machine learning diagnostic rule to predict sepsis outcomes.
Based on preliminary microarray analyses comparing HC and sepsis groups, a panel of 42-gene expression markers were identified that represented key innate and adaptive immune function, cell cycling, WBC differentiation, extracellular remodelling and immune modulation pathways. Comparisons against GEO data confirmed the definitive separation of the sepsis cohort. Quantitative PCR results suggest the capacity for this test to differentiate severe systemic inflammation from HC is 92%. The area under the curve (AUC) receiver operator characteristics (ROC) curve findings demonstrated sepsis prediction within a mixed inflammatory population, was between 86 and 92%.
This novel molecular biomarker test has a clinically relevant sensitivity and specificity profile, and has the capacity for early detection of sepsis via the monitoring of critical care patients.
PMCID: PMC3219023  PMID: 21682927
11.  Do we need a critical care ultrasound certification program? Implications from an Australian medical-legal perspective 
Critical Care  2010;14(3):313.
Medical practitioners have a duty to maintain a certain standard of care in providing their services. With critical care ultrasound gaining popularity in the ICU, it is envisaged that more intensivists will use the tool in managing their patients. Ultrasound, especially echocardiography, can be an 'easy to learn, difficult to manage' skill, and the competency in performing the procedure varies greatly. In view of this, several recommendations for competency statements have been published in recent years to advocate the need for a unified approach to training and certification. In this paper, we take a slightly different perspective, from an Australian medical-legal viewpoint, to argue for the need to implement a critical care ultrasound certification program. We examine various issues that can potentially lead to a breach of the standard of care, hence exposing the practitioners and/or the healthcare institutions to lawsuits in professional negligence or breach of contract. These issues, among others, include the failure to use ultrasound in appropriate situations, the failure of hospitals to ensure practitioners are properly trained in the skills, the failure of practitioners to perform an ultrasound study that is of a reasonable standard, and the failure of practitioners to keep themselves abreast of the latest developments in treatment and management. The implications of these issues and the importance of having a certification process are discussed.
PMCID: PMC2911686  PMID: 20550724
12.  Signaled and Unsignaled Terminal Links in Concurrent Chains I: Effects of Reinforcer Probability and Immediacy 
Eight pigeons responded in a three-component concurrent-chains procedure, with either independent or dependent initial links. Relative probability and immediacy of reinforcement in the terminal links were both varied, and outcomes on individual trials (reinforcement or nonreinforcement) were either signaled or unsignaled. Terminal-link fixed-time schedules were varied across components within conditions to yield immediacy ratios of 1∶2, 1∶1 and 2∶1. The probabilities of reinforcement were varied across conditions to yield reinforcer ratios of 1∶5, 1∶2, 2∶1 and 5∶1. Results showed that a model based on the generalized matching law provided a good description of response allocation, accounting for 92% of the variance overall. As expected, sensitivity to probability was greater in the unsignaled conditions. However, sensitivity to immediacy was also greater in the unsignaled conditions, suggesting that the effect of signaling terminal-link outcomes may not be limited to probability but apply to reinforcer variables in general. The effects of signaling can be explained in terms of conditioned reinforcement added to each alternative's outcomes in the matching law. There was some evidence for an interaction between reinforcer probability and immediacy, particularly for the dependent-schedules group, such that sensitivity to immediacy was greater at moderate rather than extreme reinforcer ratios. However, further analysis suggested that this could have been due to a ceiling effect on response allocation imposed by dependent scheduling. Overall, the present results show that the generalized matching law can provide a useful account of choice between outcomes that vary in both probability and immediacy of reinforcement.
PMCID: PMC2972784  PMID: 21541175
concurrent chains; reinforcer probability; reinforcer immediacy; signaled reinforcement; key peck; pigeons
13.  Aberrant Cell Cycle and Apoptotic Changes Characterise Severe Influenza A Infection – A Meta-Analysis of Genomic Signatures in Circulating Leukocytes 
PLoS ONE  2011;6(3):e17186.
Influenza A infection is a global disease that has been responsible for four pandemics over the last one hundred years. However, it remains poorly understood as to why some infected individuals succumb to life threatening complications whilst others recover and are relatively unaffected. Using gene-expression analysis of circulating leukocytes, here we show that the progression towards severe influenza A infection is characterised by an abnormal transcriptional reprogramming of cell cycle and apoptosis pathways. In severely infected humans, leukocyte gene-expression profiles display opposing cell cycle activities; an increased aberrant DNA replication in the G1/S phase yet delayed progression in the G2/M phase. In mild infection, cell cycle perturbations are fewer and are integrated with an efficient apoptotic program. Importantly, the loss of integration between cell cycle perturbations and apoptosis marks the transition from a mild viral illness to a severe, life threatening infection. Our findings suggest that circulating immune cells may play a significant role in the evolution of the host response. Further study may reveal alternative host response factors previously unrecognized in the current disease model of influenza.
PMCID: PMC3050844  PMID: 21408152
14.  Genome-wide transcription profiling of human sepsis: a systematic review 
Critical Care  2010;14(6):R237.
Sepsis is thought to be an abnormal inflammatory response to infection. However, most clinical trials of drugs that modulate the inflammatory response of sepsis have been unsuccessful. Emerging genomic evidence shows that the host response in sepsis does not conform to a simple hyper-inflammatory/hypo-inflammatory model. We, therefore, synthesized current genomic studies that examined the host response of circulating leukocytes to human sepsis.
Electronic searches were performed in Medline and Embase (1987 to October 2010), supplemented by additional searches in multiple microarray data repositories. We included studies that (1) used microarray, (2) were performed in humans and (3) investigated the host response mediated by circulating leukocytes.
We identified 12 cohorts consisting of 784 individuals providing genome-wide expression data in early and late sepsis. Sepsis elicited an immediate activation of pathogen recognition receptors, accompanied by an increase in the activities of signal transduction cascades. These changes were consistent across most cohorts. However, changes in inflammation related genes were highly variable. Established inflammatory markers, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-1 or interleukin-10, did not show any consistent pattern in their gene-expression across cohorts. The finding remains the same even after the cohorts were stratified by timing (early vs. late sepsis), patient groups (paediatric vs. adult patients) or settings (clinical sepsis vs. endotoxemia model). Neither a distinctive pro/anti-inflammatory phase nor a clear transition from a pro-inflammatory to anti-inflammatory phase could be observed during sepsis.
Sepsis related inflammatory changes are highly variable on a transcriptional level. We did not find strong genomic evidence that supports the classic two phase model of sepsis.
PMCID: PMC3219990  PMID: 21190579
15.  Use of a novel parenchymal clamp for laparoscopic and open partial nephrectomy 
Increasing data advocates the wider use of partial nephrectomy for renal tumours amenable to this approach. We describe the initial North American use of a novel parenchymal clamp in an open and a laparoscopic partial nephrectomy. Initial results in 3 patients (2 open, 1 laparoscopic) demonstrate excellent preservation of renal function and good oncologic outcomes. Hilar dissection was avoided in all cases and the estimated blood loss was low. In our small series, we found this device to be a safe and useful adjunct to partial nephrectomy.
PMCID: PMC2950775  PMID: 20944792
16.  Procalcitonin: seeking a niche 
Critical Care  2009;13(3):149.
For over a decade there has been intense interest given to the role of procalcitonin in the diagnosis and management of sepsis in critically ill patients. Early opinions strongly supported the diagnostic role but data accumulating from numerous subsequent studies are less supportive, even when used in very selective settings. Although there remains sufficient reason to support the use of procalcitonin in guiding antibiotic therapy or perhaps providing prognostic information, it may be time to focus our efforts on the early diagnosis of sepsis in the critically care setting on alternative, more promising methods.
PMCID: PMC2717415  PMID: 19519928
17.  Rapid Acquisition of Preference in Concurrent Chains: Effects of D-amphetamine on Sensitivity to Reinforcement Delay 
The purpose of this study was to examine effects of d-amphetamine on choice controlled by reinforcement delay. Eight pigeons responded under a concurrent-chains procedure in which one terminal-link schedule was always fixed-interval 8 s, and the other terminal-link schedule changed from session to session between fixed-interval 4 s and fixed-interval 16 s according to a 31-step pseudorandom binary sequence. After sufficient exposure to these contingencies (at least once through the pseudorandom binary sequence), the pigeons acquired a preference for the shorter reinforcement delay within each session. Estimates of the sensitivity to reinforcement immediacy were similar to those obtained in previous studies. For all pigeons, at least one dose of d-amphetamine attenuated preference and, hence, decreased estimates of sensitivity to reinforcement immediacy; in most cases, this effect occurred without a change in overall response rates. In many cases, the reduced sensitivity to reinforcement delay produced by d-amphetamine resulted primarily from a decrease in the asymptotic level of preference achieved within the session; in some cases, d-amphetamine produced complete indifference. These findings suggest that a reduction in the sensitivity to reinforcement delay may be an important behavioral mechanism of the effects of psychomotor stimulants.
PMCID: PMC2211442  PMID: 18338676
preference; reinforcement delay; acquisition; behavioral mechanisms; d-amphetamine; key peck; pigeons
18.  Bench-to-bedside review: The value of cardiac biomarkers in the intensive care patient 
Critical Care  2008;12(3):215.
The use of cardiac biomarkers in the intensive care setting is gaining increasing popularity. There are several reasons for this increase: there is now the facility for point-of-care biomarker measurement providing a rapid diagnosis; biomarkers can be used as prognostic tools; biomarkers can be used to guide therapy; and, compared with other methods such as echocardiography, the assays are easier and much more affordable. Two important characteristics of the ideal biomarker are disease specificity and a linear relationship between the serum concentration and disease severity. These characteristics are not present, however, in the majority of biomarkers for cardiac dysfunction currently available. Those clinically useful cardiac biomarkers, which naturally received the most attention, such as troponins and B-type natriuretic peptide, are not as specific as was originally thought. In the intensive care setting, it is important for the user to understand the degree of specificity of these biomarkers and that the interpretation of the results should always be guided by other clinical information. The present review summarizes the available biomarkers for different cardiac conditions. Potential biomarkers under evaluation are also briefly discussed.
PMCID: PMC2481437  PMID: 18557993
19.  Rapid Acquisition in Concurrent Chains: Evidence for a Decision Model 
Pigeons' choice in concurrent chains can adapt to rapidly changing contingencies. Grace, Bragason, and McLean (2003) found that relative initial-link response rate was sensitive to the immediacy ratio in the current session when one of the terminal-link fixed-interval schedules was changed daily according to a pseudorandom binary sequence (e.g., Schofield & Davison, 1997). The present experiment tested whether the degree of variation in delays across sessions had any effect on acquisition rate in Grace et al.'s (2003) rapid-acquisition procedure. In one condition (“minimal variation”), the left terminal link was always fixed-interval 8 s and the right terminal link was either fixed-interval 4 s or fixed-interval 16 s. In the other condition (“maximal variation”), a unique pair of fixed-interval values was used in each session. Responding was sensitive to the current-session immediacy ratio in both conditions, but across subjects there was no systematic difference in sensitivity. These results challenge the view that initial-link responding in the rapid-acquisition procedure is determined by changes in the learned value of the terminal-link stimuli, and suggests instead that a process resembling categorical discrimination may control performance. A decision model based on the assumption that delays are categorized as short or long relative to the history of delays provided a good account of the data and shows promise in being able to explain other choice phenomena.
PMCID: PMC1472631  PMID: 16673825
choice; concurrent chains; rapid-acquisition procedure; conditioned reinforcement value; generalized matching; categorical discrimination; key peck; pigeons
20.  Rapid acquisition of preference in concurrent chains. 
We report two experiments using a concurrent-chains procedure in which one terminal-link schedule was fixed-interval 8 s and the alternative schedule changed randomly from day to day. In Experiment 1, the alternative schedule varied between 4 s and 16 s according to a pseudorandom binary sequence similar to the one used by Hunter and Davison (1985). Similar to results with concurrent schedules, pigeons' response allocation in the initial link was most sensitive to the schedules arranged in the current session, although some effect of prior history was evident. Overall sensitivity was lower than for comparable data from steady-state research. In Experiment 2, a unique value between 2 s and 32 s was used for the alternative-schedule delay in each session. Sensitivity levels were similar to Experiment 1 and remained unchanged across 61 sessions of training. For all subjects, sensitivity was greater when the alternative-schedule delay was greater than 8 s compared with when it was less than 8 s. Generalized-matching plots revealed evidence of clustering of data points into two groups for some pigeons, suggesting that a process similar to a categorical discrimination may have at least partly determined response allocation. Overall, this research shows that pigeons' initial-link response allocation can adjust rapidly to frequent changes in the terminal links.
PMCID: PMC1284956  PMID: 14674731
21.  Contrast and reallocation of extraneous reinforcers as a function of component duration and baseline rate of reinforcement 
Four pigeons responded on multiple schedules arranged on a “main” key in a two-key experimental chamber. A constant schedule component was alternated with another component that was varied over conditions. On an extra response key, conjoint schedules of reinforcement that operated in both components were arranged concurrently with the multiple schedule on the main key. On the main key, changes in reinforcement rate in the varied component were inversely related to changes in response rates in the constant component (behavioral contrast). On the extra key, some reinforcers were reallocated between components, depending on the schedules in effect on the main key in the varied component. In the varied component, the obtained rates of reinforcement on the extra key were inversely related to main-key reinforcement rate. In the constant component, extra-key reinforcer rates were positively related to main-key reinforcer rates obtained in the varied component, and were not a function of response rates on the extra key. In two comparisons, the rate at which components alternated and the value of the main-key schedule in the constant component were varied. Consistent with earlier work, long components reduced the extent of contrast. Reductions in contrast as a function of component duration were accompanied by similar reductions in the extent of reinforcer reallocation on the extra key. In the second comparison, lowering the rate of reinforcement in the constant component increased the rate at which extra-key reinforcers were obtained, reduced the extent of reinforcer reallocation, and reduced contrast. Overall, the results are consistent with the suggestion that some contrast effects are due to the changes in extraneous reinforcement during the constant component, and that manipulations of component duration, and manipulations of the rate of reinforcement in the constant component, affect contrast because they influence the extent of extraneous reinforcer real-location.
PMCID: PMC1334397  PMID: 16812757
behavioral contrast; reallocation hypothesis; extraneous reinforcers; component duration; component value; multiple schedules; concurrent schedules; key peck; pigeons
22.  Resistance to reinforcement change in multiple and concurrent schedules assessed in transition and at steady state 
Behavioral momentum theory relates resistance to change of responding in a multiple-schedule component to the total reinforcement obtained in that component, regardless of how the reinforcers are produced. Four pigeons responded in a series of multiple-schedule conditions in which a variable-interval 40-s schedule arranged reinforcers for pecking in one component and a variable-interval 360-s schedule arranged them in the other. In addition, responses on a second key were reinforced according to variable-interval schedules that were equal in the two components. In different parts of the experiment, responding was disrupted by changing the rate of reinforcement on the second key or by delivering response-independent food during a blackout separating the two components. Consistent with momentum theory, responding on the first key in Part 1 changed more in the component with the lower reinforcement total when it was disrupted by changes in the rate of reinforcement on the second key. However, responding on the second key changed more in the component with the higher reinforcement total. In Parts 2 and 3, responding was disrupted with free food presented during intercomponent blackouts, with extinction (Part 2) or variable-interval 80-s reinforcement (Part 3) arranged on the second key. Here, resistance to change was greater for the component with greater overall reinforcement. Failures of momentum theory to predict short-term differences in resistance to change occurred with disruptors that caused greater change between steady states for the richer component. Consistency of effects across disruptors may yet be found if short-term effects of disruptors are assessed relative to the extent of change observed after prolonged exposure.
PMCID: PMC1334377  PMID: 16812750
behavioral momentum theory; resistance to change; multiple schedules; concurrent schedules; alternative reinforcement; key peck; pigeons
23.  Contrast and undermatching with regular or irregular alternation of components 
Behavioral contrast and response-ratio sensitivity to reinforcement were compared in multiple schedules in which components alternated strictly or according to a pseudorandom sequence. Average component durations in the two regimes were always 60 s, and order of presentation of component alternation regimes was counterbalanced across subjects. In Part 1, the reinforcer rate in one component was reduced from 60 per hour to zero, while that in the other component was unchanged. Positive behavioral contrast occurred in the constant component in that response rates increased, but neither the reliability nor the magnitude of contrast was affected by the manner in which components alternated. Part 2 was similar, except that a number of different reinforcer rates were used in the varied component. Neither contrast nor sensitivity of response ratios to changes in reinforcer ratios depended on the regime of component alternation. Thus, the predictability in time of future reinforcement conditions, which is a feature of regular multiple scheduling, does not appear to be a determinant of multiple-schedule performance.
PMCID: PMC1334428  PMID: 16812729
behavioral contrast; undermatching; component alternation; multiple schedules; key peck; pigeons
24.  Contrast and reallocation of extraneous reinforcers between multiple-schedule components 
Four pigeons responded in components of multiple schedules in which two responses were available and reinforced with food. Pecks on the left key (“main” key) were reinforced at a constant rate in one component and at a rate that varied over conditions in the other component. When reinforcer rate was varied, behavioral contrast occurred in the constant component. On the right key (“extra” key), five variable-interval schedules and one variable-ratio schedule, presented conjointly, arranged reinforcers for responses in all conditions. These conjoint schedules were common to both multiple-schedule components—rather than unique to particular components—and reinforcers from these schedules could therefore be arranged in one component and obtained during the other component. In this way, the additional reinforcers were analogous to the “extraneous” reinforcers thought to maintain behavior other than pecking in conventional multiple schedules. Response rate on the extra key did not change systematically over conditions in the constant component, and in the varied component extra responding was inversely related to main-key reinforcement. All subjects obtained more extra-key reinforcers in whichever component arranged fewer main-key reinforcers. Consistent with the theory that reallocation of extraneous reinforcers may cause behavioral contrast, absolute reinforcer rate for the extra key in the constant component was low in conditions that produced positive contrast on the main key and high in those that produced negative contrast. Also consistent with this theory, behavioral contrast was reduced in two conditions that canceled extra-key reinforcers that had been arranged but not obtained at the end of components. Thus, a constraint on reallocation markedly reduced the extent of contrast.
PMCID: PMC1322097  PMID: 16812677
extraneous reinforcers; reallocation; behavioral contrast; multiple schedules; key peck; pigeons
25.  Resistance to change and the law of effect 
Three experiments using multiple schedules of reinforcement explored the implications of resistance-to-change findings for the response-reinforcer relation described by the law of effect, using both steady-state responding and responding recorded in the first few sessions of conditions. In Experiment 1, when response-independent reinforcement was increased during a third component, response rate in Components 1 and 2 decreased. This response-rate reduction was proportionately greater in a component in which reinforcer magnitude was small (2-s access to wheat) than in the component in which it was large (6-s access to wheat). However, when reinforcer rates in the two components were varied together in Experiments 2 and 3, response-rate change was the same regardless of the magnitude of reinforcers used in the two components, so that sensitivity of response rates to reinforcer rates (Experiment 2) and of response-rate ratios to reinforcer-rate ratios (Experiment 3) was unaffected by the magnitude of the reinforcers. Therefore, the principles determining resistance to change, described by behavioral momentum theory, seem not to apply when the source of behavior change is the variation of reinforcement contingencies that maintain the behavior. The use of extinction as a manipulation to study resistance to change is questioned.
PMCID: PMC1323233  PMID: 16812656
resistance to change; quantitative law of effect; generalized matching law; sensitivity to reinforcement; behavioral momentum; multiple schedules; key peck; pigeons

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