Complex cognitive algorithms preserved by selective social learning in experimental populations.

Many human abilities rely on cognitive algorithms discovered by previous generations. Cultural accumulation of innovative algorithms is hard to explain because complex concepts are difficult to pass on. We found that selective social learning preserved rare discoveries of exceptional algorithms in a large experimental simulation of cultural evolution. Participants (N = 3450) faced a difficult sequential decision problem (sorting an unknown sequence of numbers) and transmitted solutions across 12 generations in 20 populations. Several known sorting algorithms were discovered. Complex algorithms persisted when participants could choose who to learn from but frequently became extinct in populations lacking this selection process, converging on highly transmissible lower-performance algorithms. These results provide experimental evidence for hypothesized links between sociality and cognitive function in humans.

Rational randomness: the role of sampling in an algorithmic account of preschooler's causal learning.

Probabilistic models of cognitive development indicate the ideal solutions to computational problems that children face as they try to make sense of their environment. Under this approach, children's beliefs change as the result of a single process: observing new data and drawing the appropriate conclusions from those data via Bayesian inference. However, such models typically leave open the question of what cognitive mechanisms might allow the finite minds of human children to perform the complex computations required by Bayesian inference. In this chapter, we highlight one potential mechanism: sampling from probability distributions. We introduce the idea of approximating Bayesian inference via Monte Carlo methods, outline the key ideas behind such methods, and review the evidence that human children have the cognitive prerequisites for using these methods. As a result, we identify a second factor that should be taken into account in explaining human cognitive development--the nature of the mechanisms that are used in belief revision.

Inflammatory response and body composition in chronic obstructive pulmonary disease.

Weight loss in chronic obstructive airways disease (COPD) is associated with an increased energy cost of breathing. To determine an association between body composition and the inflammatory response we studied 80 clinically stable patients. Body composition was determined anthropometrically and skeletal muscle mass was determined as the creatinine-height index (CHI). Forty patients had their nitrogen balance determined. Circulating concentrations of interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and their soluble receptors were determined for 68 patients. Body mass index (BMI) was normal (> 20 kg/m(2)) in 55 patients, of whom 17 (31%) had a low CHI (< 80% predicted). A reduced CHI was associated with increased circulating levels of IL-6 (p = 0.001), TNF-alpha (p = 0.032) and their soluble receptors IL-6sr (p = 0.002), TNF-alpha sr1 (p = 0.03), and TNF-alpha sr2 (p = 0.001). Patients with a normal BMI and low CHI had inflammatory mediator levels similar to patients with a low BMI and CHI; both were significantly greater than in those with a normal BMI and CHI. Nitrogen balance was similar between normal and low CHI groups, although nitrogen excretion was significantly increased in the low CHI group. Skeletal muscle loss in COPD is probably multifactorial in origin, but our data suggest a link with systemic inflammation, even when weight loss is inapparent.

Cost effectiveness of an outpatient multidisciplinary pulmonary rehabilitation programme.

BACKGROUND: Pulmonary rehabilitation programmes improve the health of patients disabled by lung disease but their cost effectiveness is unproved. We undertook a cost/utility analysis in conjunction with a randomised controlled clinical trial of pulmonary rehabilitation versus standard care. METHODS: Two hundred patients, mainly with chronic obstructive pulmonary disease, were randomly assigned to either an 18 visit, 6 week rehabilitation programme or standard medical management. The difference between the mean cost of 12 months of care for patients in the rehabilitation and control groups (incremental cost) and the difference between the two groups in quality adjusted life years (QALYs) gained (incremental utility) were determined. The ratio between incremental cost and utility (incremental cost/utility ratio) was calculated. RESULTS: Each rehabilitation programme for up to 20 patients cost pound 12,120. The mean incremental cost of adding rehabilitation to standard care was pound -152 (95% CI -881 to 577) per patient, p=NS. The incremental utility of adding rehabilitation was 0.030 (95% CI 0.002 to 0.058) QALYs per patient, p=0.03. The point estimate of the incremental cost/utility ratio was therefore negative. The bootstrapping technique was used to model the distribution of cost/utility estimates possible from the data. A high likelihood of generating QALYs at negative or relatively low cost was indicated. The probability of the cost per QALY generated being below pound 0 was 0.64. CONCLUSIONS: This outpatient pulmonary rehabilitation programme produces cost per QALY ratios within bounds considered to be cost effective and is likely to result in financial benefits to the health service.

Generalization, similarity, and Bayesian inference.

Shepard has argued that a universal law should govern generalization across different domains of perception and cognition, as well as across organisms from different species or even different planets. Starting with some basic assumptions about natural kinds, he derived an exponential decay function as the form of the universal generalization gradient, which accords strikingly well with a wide range of empirical data. However, his original formulation applied only to the ideal case of generalization from a single encountered stimulus to a single novel stimulus, and for stimuli that can be represented as points in a continuous metric psychological space. Here we recast Shepard's theory in a more general Bayesian framework and show how this naturally extends his approach to the more realistic situation of generalizing from multiple consequential stimuli with arbitrary representational structure. Our framework also subsumes a version of Tversky's set-theoretic model of similarity, which is conventionally thought of as the primary alternative to Shepard's continuous metric space model of similarity and generalization. This unification allows us not only to draw deep parallels between the set-theoretic and spatial approaches, but also to significantly advance the explanatory power of set-theoretic models.

Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial.

BACKGROUND: Pulmonary rehabilitation seems to be an effective intervention in patients with chronic obstructive pulmonary disease. We undertook a randomised controlled trial to assess the effect of outpatient pulmonary rehabilitation on use of health care and patients' wellbeing over 1 year. METHODS: 200 patients with disabling chronic lung disease (the majority with chronic obstructive pulmonary disease) were randomly assigned a 6-week multidisciplinary rehabilitation programme (18 visits) or standard medical management. Use of health services was assessed from hospital and general-practice records. Analysis was by intention to treat. FINDINGS: There was no difference between the rehabilitation (n=99) and control (n=101) groups in the number of patients admitted to hospital (40 vs 41) but the number of days these patients spent in hospital differed significantly (mean 10.4 [SD 9.7] vs 21.0 [20.7], p=0.022). The rehabilitation group had more primary-care consultations at the general-practitioner's premises than did the control group (8.6 [6.8] vs 7.3 [8.3], p=0.033) but fewer primary-care home visits (1.5 [2.8] vs 2.8 [4.6], p=0.037). Compared with control, the rehabilitation group also showed greater improvements in walking ability and in general and disease-specific health status. INTERPRETATION: For patients chronically disabled by obstructive pulmonary disease, an intensive, multidisciplinary, outpatient programme of rehabilitation is an effective intervention, in the short term and the long term, that decreases use of health services.

Competing strategies in categorization: expediency and resistance to knowledge restructuring.

The authors investigated people's ability to restructure their knowledge when additional information about a categorization task is revealed. In 2 experiments, people first learned to rely on a fairly accurate (but imperfect) predictor. At various points in training, a complex relationship between 2 other predictors was revealed in a schematic diagram that could support perfect performance. In Experiment 1, people adopted the complex strategy when it was revealed at the outset but were unable to restructure their knowledge after the expedient predictor had been learned. In Experiment 2, expedient knowledge persisted even with an adaptive display. The persistence of expedient knowledge is explained by associative blocking of potential alternative cues. A 3rd experiment analyzed the strategies people use with and without the diagram. The study confirmed that the diagram, when presented at the outset, significantly alters people's approach to the task.

The effect of dipyridamole and theophylline on hypercapnic ventilatory responses: the role of adenosine.

The purine nucleoside, adenosine, has been implicated as a neuromodulator in central respiratory depression during prolonged exposure to hypoxia. It may also be a mediator of hypoxic hyperpnoea, acting on the carotid bodies. As there may be adenosine-sensitive mechanisms of hypoxic respiratory control, we sought to determine whether adenosine might be involved as a respiratory modulator in another central but non-oxygen-related control mechanism, the ventilatory response to hyperoxic hypercapnia. Twelve normal subjects were studied following 3 days of oral treatment with placebo, dipyridamole (which potentiates adenosine effects by inhibiting cellular uptake), and theophylline (a specific adenosine antagonist of cell surface receptors). The drugs were given in a random order, double-blind fashion. Resting end-tidal carbon dioxide tension (PET,CO2) and the maximum rate of isometric inspiratory pressure change at the mouth ((dP/dt) max), an index of respiratory drive, were determined in all subjects on each treatment. Hyperoxic, hypercapnic ventilatory responses were determined in seven of these subjects using a rebreathing technique. For each hypercapnic response, minute ventilation (V1E) and (dP/dt) max were plotted against PET,CO2 breath-by-breath. Resting PET,CO2 breathing room air was lower with theophylline (5.47 (SD 0.21) kPa) than with placebo (5.74 (0.26) kPa) or dipyridamole (5.86 (0.34) kPa), with no significant drug differences in resting (dP/dt)max. However, neither the slope nor the PET, CO2 intercept of the relationship between ventilation or respiratory drive and PET, CO2 were altered by the study drugs under hyperoxic conditions. We conclude that endogenous adenosine-related mechanisms are unlikely to be involved in determining either the sensitivity or the threshold of the ventilatory response to carbon dioxide under hyperoxic conditions. However, in normoxia, a centrally-acting, tonic, adenosine-mediated, respiratory modulation is not ruled out.

Effect of adenosine infusion on oxygen induced carbon dioxide retention in severe chronic obstructive pulmonary disease.

BACKGROUND: In normal subjects intravenous adenosine infusion has been shown to stimulate ventilation with a consequent fall in arterial partial pressure of carbon dioxide (Paco2), probably by an action on the carotid bodies. The objective of this study was to determine whether the increase in Paco2 seen when patients with ventilatory failure secondary to chronic obstructive pulmonary disease (COPD) are given a high concentration of oxygen to breathe might be ameliorated by an intravenous infusion of adenosine. METHODS: Eight subjects with chronic stable ventilatory failure secondary to COPD were studied. Their mean (SE) forced expiratory volume in one second (FEV1) was 0.63 (0.12) 1 with forced vital capacity (FVC) of 1.63 (0.21) 1. They received continuous intravenous infusions of saline and adenosine in random order, double blind. The infusions were administered for two minutes at 20 micrograms/kg/min, increasing in increments of 20 micrograms/kg/min every two minutes to a maximum infusion rate of 80 micrograms/kg/min adenosine (or an equivalent saline infusion rate), or until side effects supervened. The infusions were continued at that rate for five minutes, after which the fractional inspired oxygen (FIO2) was raised to 0.50 during a further 20 minutes of the infusion at that rate. Haemoglobin oxygen saturation (SaO2) and transcutaneous PCO2 (PtcCO2) were monitored throughout the procedure. Spirometric tests were performed before and after each infusion. RESULTS: Adenosine infusion was accompanied by a fall in PtcCO2 from a mean (SE) of 7.29 (0.42) kPa to 6.95 (0.48) kPa: mean difference -0.34 (95% confidence interval, -0.56 to -0.11) kPa. During saline infusion oxygen administration resulted in an increase in transcutaneous PtcCO2 from 7.35 (0.34) kPa to 7.88 (0.28) kPa: mean difference 0.53 (95% CI 0.20 to 0.85) kPa. PtcCO2 did not rise above baseline levels when oxygen was administered during the adenosine infusion. A small fall in FVC was seen following adenosine infusion. CONCLUSIONS: The increase in PtcCO2 seen when patients with stable ventilatory failure secondary to severe COPD are given a high concentration of oxygen to breathe is counteracted by a continuous intravenous infusion of adenosine.

Effect of theophylline and dipyridamole on the respiratory response to isocapnic hypoxia in normal human subjects.

1. Twelve healthy young men took part in this investigation of the effect of oral theophylline and dipyridamole (two drugs known to affect the pharmacological effects of the purine nucleoside adenosine) on the respiratory response to isocapnic hypoxia. 2. The subjects underwent hypoxic rebreathing manoeuvres after 3-day pretreatments with each of the drugs for 12 h and were at least 2 h postprandial. For each in-Minute ventilation, the maximum rate of isometric inspiratory pressure development at the mouth and the ratio of inspiratory duration to total breath duration were analysed breath-by-breath and regressions of these variables upon the haemoglobin oxygen saturation were performed. 3. The slopes and intercepts of the lines describing the relationships of minute ventilation and the maximum rate of isometric inspiratory pressure development at the mouth with haemoglobin oxygen saturation were unaffected by the study drugs, and no differences in the pattern of breathing were observed. 4. We conclude that oral administration of these drugs does not result in alteration of the response of the respiratory system to progressive isocapnic hypoxia. 5. This suggests that either adenosine has no physiological role in hypoxic respiratory control as measured, or that it has opposing peripheral chemoreceptor and central respiratory centre effects which could not be distinguished by the techniques used.

Rib cage mechanics after median sternotomy.

A substantial reduction in lung volumes occurs after sternotomy, but the mechanism or mechanisms are unclear. Measurements were made of lung volumes and of chest wall motion with four pairs of magnetometers (two pairs for anteroposterior rib cage, one for lateral rib cage, and one for anteroposterior abdominal dimensions) in 16 men before and one week and three months after coronary artery grafting. Reductions in all lung volumes occurred after sternotomy and were greater in the supine than in the sitting position. Supine vital capacity was reduced one week after surgery, with almost complete recovery at three months. One week after sternotomy there was a significant reduction in tidal volume from a mean (95% confidence limits) value of 0.88 (0.76-1.00) litre to 0.61 (0.52-0.70) l, and in supine rib cage displacement from 3.87 (1.96-5.78) mm to 0.44 (-0.61-1.49) mm in the lateral plane. Respiratory frequency increased from 16 (13-19) to 21 (19-24)/min. Coordination of the rib cage was assessed by measuring the difference in timing of onset of chest wall motion and airflow in four planes. At one week nine of 14 patients showed uncoordination between airflow and rib cage motion in one or more dimensions, and this was still present in three patients at three months. No loss of the temporal relation between airflow and abdominal wall motion was detected. The results suggest that reduced and uncoordinated rib cage expansion contributes to the restrictive ventilatory defect that follows median sternotomy.

Ventilatory effects of hypoxia and adenosine infusion in patients after bilateral carotid endarterectomy.

1. We have studied the carotid body contribution to hypoxic respiratory drive, using a hypoxic/hyperoxic switching technique, and the ventilatory response to intravenous infusion of adenosine, a recently described respiratory stimulant, in five patients with bilateral carotid endarterectomy. 2. The contribution made by the carotid bodies to total ventilatory drive during hypoxia varied from 2.5% to 45.9%. 3. The ventilatory response to adenosine infusion varied from a 7% decrease to a 25% increase in ventilation. 4. Those patients with intact hypoxic ventilatory drive showed respiratory stimulation, whereas of the two patients with attenuated chemoreflexes, one showed no stimulation and the other depression of ventilation in response to adenosine infusion. 5. We conclude that adenosine exerts its respiratory stimulant effect via an action on the peripheral chemoreceptors. This may coexist with a centrally mediated respiratory depression that is masked when the carotid bodies are intact.

Influence of inspired oxygen concentration on the dynamics of the exercise hyperpnoea in man.

In order to determine the role of the carotid bodies on the ventilatory control characteristics during the non-steady-state phase of exercise in man, six normal males performed cycle ergometry with four repetitions of a 6 min, constant-load work bout at inspired O2 fractions (FI,O2) of 0.12, 0.15, 0.21, 0.30 and 1.00. Each test began with unloaded pedalling; this was followed by a constant load which was 90% of the subject's anaerobic threshold at FI,O2 = 0.12. Ventilation (VE), CO2 output (VCO2) and O2 uptake (VO2) were determined breath-by-breath during the test and the time constants of response (tau VE, tau VCO2 and tau VO2) were established by least-squares techniques, following interpolation (1 s), temporal alignment and averaging of the four responses. In each subject, tau VE and tau VCO2 increased as functions of increasing FI,O2, and were inverse functions of the proportional contribution to VE of peripheral chemoreceptor drive (as estimated from hyperoxic-transition or 'Dejours' tests). tau VE averaged 40 s at FI,O2 = 0.12 and 112 s at FI,O2 = 1.00, each response being well fitted by a single exponential. However, tau VO2 was not significantly affected by the alterations in FI,O2. Although there was no discernible peripheral chemosensitivity at FI,O2 = 0.30 or 1.00, the tau VE increased appreciably between these inspirates. We therefore conclude that the peripheral chemoreceptors are important, but not exclusive determinants of the exponential response characteristics during the non-steady-state phase of the exercise hyperpnoea in man. This supports the contention of a component of the control being humorally mediated even during moderate exercise.