Both humans and non-humans discount the value of rewards that are delayed or uncertain, and individuals that discount delayed rewards at a relatively high rate are considered impulsive. To ...investigate the neural mechanisms that mediate delay discounting, the present study examined the effects of excitotoxic lesions of the nucleus accumbens (NAC) on discounting of reward value by delay and probability. Rats were trained on delay (
n
=
24) or probability discounting (
n
=
24) tasks. Following training, excitotoxic lesions of the NAC were made by intracranial injections of 0.5
μl 0.15
M quinolinic acid (
n
=
12) or vehicle (
n
=
12) aimed at the NAC (AP +1.6, ML ±1.5, DV −7.1). NAC lesions did not alter performance in animals tested with a constant delay (4
s) or probability (0.4) of reinforcement. However, when tested with between session changes in the delay (0, 1, 2, 4, and 8
s) of reinforcement, the lesioned rats had flatter discount curves than the sham group, indicating that they were less sensitive to frequent changes in the delay to reward. In contrast, the NAC lesions did not affect discounting of probabilistic rewards. NAC lesions impaired the ability to adapt to frequent between session changes in the delay to reward but did not increase or decrease discounting when the delay was held constant across sessions. NAC lesions may disrupt the ability of the animals to predict the timing of delayed rewards when the delay to reward is changed frequently.
This paper examines firms’ investment-timing decisions in an oligopolistic set-up. Facing demand uncertainty, firms decide whether to invest early or wait until uncertainty has been resolved. We show ...that the precise form that investment commitment takes matters for the investment-timing outcomes that emerge. When firms can commit immediately to the final investment level, investment leadership may occur and early investment is referred to as being primarily “aggressive”. By contrast, the presence of a time lag between
when and
how much firms invest yields symmetric investment-timing outcomes only; we argue that early investment is mainly “defensive” in that case.
The critical issue for Japan - as elsewhere - is what to do with the public sector. Perhaps more than any other advanced societies, Japan needs to rediscover the creative role of the state. Yet at ...present, Japan's fiscal politics and policy debate are dominated by an ideological rejection of the state. The great irony here, of course, is that not so long ago Japan was the master in fashioning an efficient and effective public sector to foster a manufacturing economy. The size of Japan's structural deficit poses hard choices. It cannot be cut drastically in the short run without risking serious damage to the economy. In short, the burden of debt payments from the budget is expanding and that rate of expansion threatens to accelerate. Fiscal rigidity undermines the public sector's capacity to respond effectively to the opportunities and pitfalls that the rise of the new economy entails.
Noxious stimuli in the esophagus cause pain that is referred to the anterior chest wall because of convergence of visceral and somatic afferents within the spinal cord. We sought to characterize the ...neurophysiological responses of these convergent spinal pain pathways in humans by studying 12 healthy subjects over three visits (V1, V2, and V3). Esophageal pain thresholds (Eso-PT) were assessed by electrical stimulation and anterior chest wall pain thresholds (ACW-PT) by use of a contact heat thermode. Esophageal evoked potentials (EEP) were recorded from the vertex following 200 electrical stimuli, and anterior chest wall evoked potentials (ACWEP) were recorded following 40 heat pulses. The fear of pain questionnaire (FPQ) was administered on V1. Statistical data are shown as point estimates of difference +/- 95% confidence interval. Pain thresholds increased between V1 and V3 Eso-PT: V1-V3 = -17.9 mA (-27.9, -7.9) P < 0.001; ACW-PT: V1-V3 = -3.38 degrees C (-5.33, -1.42) P = 0.001. The morphology of cortical responses from both sites was consistent and equivalent P1, N1, P2, N2 complex, where P1 and P2 are is the first and second positive (downward) components of the CEP waveform, respectively, and N1 and N2 are the first and second negative (upward) components, respectively, indicating activation of similar cortical networks. For EEP, N1 and P2 latencies decreased between V1 and V3 N1: V1-V3 = 13.7 (1.8, 25.4) P = 0.02; P2: V1-V3 = 32.5 (11.7, 53.2) P = 0.003, whereas amplitudes did not differ. For ACWEP, P2 latency increased between V1 and V3 -35.9 (-60, -11.8) P = 0.005 and amplitudes decreased P1-N1: V1-V3 = 5.4 (2.4, 8.4) P = 0.01; P2-N2: 6.8 (3.4, 10.3) P < 0.001. The mean P1 latency of EEP over three visits was 126.6 ms and that of ACWEP was 101.6 ms, reflecting afferent transmission via Adelta fibers. There was a significant negative correlation between FPQ scores and Eso-PT on V1 (r = -0.57, P = 0.05). These data provide the first neurophysiological evidence of convergent esophageal and somatic pain pathways in humans.
The objective of this article is to examine the pathways by which children's physical health status, environmental, family, and child factors affect children's academic performance and prosocial ...behaviour, using a theoretically-based and empirically-based model of competence development. The model proposes that 3 types of relational processes, dealing with opportunity, support, and skill development through participation, lead to competence. Structural equation modelling was performed on cross-sectional, parent-report data for approximately 10,000 Canadian children aged 6-11 years from the 1994-95 National Longitudinal Survey of Children and Youth. The analyses controlled for family socioeconomic status and child's age and sex, and included 3 groups of children (those with activity-limiting conditions, non-activity-limiting conditions, or no health problems). There was little evidence that children with chronic conditions were at direct risk for poorer outcomes. Children with activity-limiting conditions were at increased indirect risk for academic difficulties through the role played by cognitive functioning. Cognitive functioning and hyperactivity/inattention difficulties were the major predictors of academic performance. Recreational participation and behavioural functioning were the main predictors of prosocial behaviour. The pathways in the model also indicated the importance of family functioning, social support to parents, and neighbourhood cohesion. In conclusion, the findings indicate the utility of the model of competence development in understanding the pathways and processes by which various factors affect children's academic and social outcomes.
Resilient families are able to adapt to adversities, but the nature of family resilience is not well understood. This study examines patterns of family functioning that may protect families from the ...negative impact of alcohol abuse. Naturally occurring patterns of family functioning are identified and associations between these patterns and parenting, current parental alcohol use, recent family stressful events, supportive relationships outside the family, and demographic characteristics are assessed. Cross-sectional data are analyzed from racially diverse American and Canadian families (N = 674) who have at least one parent with an alcohol abuse problem and a child between ages 9 and 12 years. Cluster analyses derived from family functioning indicators are used to identify naturally occurring family patterns. Multivariate assessments evaluated relationships between family functioning clusters and potentially influencing factors. The study results reveal a continuum of family functioning associated with parenting, child’s perception of teacher caring, and race.
Metastatic renal cell cancer is one of the immuno-sensitive tumors. Apart from the immuno-modulating agents IFNalpha and IL-2, thalidomide has been reported to be effective in this type of cancer. ...However, bone metastases and bulky metastases, show limited response to immunotherapy, are often site of recurrent disease and are therefore often treated later with radiotherapy. In this phase II study, we evaluated toxicity and efficacy of the combination of continuous low dose (1 mIU/m2) s.c. IL-2 and thalidomide (200 mg once daily) in 22 patients with progressive metastatic renal cell cancer. In addition, 13 soft tissue lesions and two bone metastases in 13 patients were concurrently treated with fractionated radiotherapy. T cell number and activation in blood was measured by immunoflowcytometry. Nearly all patients developed grade 1-2 toxicity consisting of fatigue, sensory neuropathy, constipation and dizziness. Five patients had a grade 3-4 toxic event: four patients with deep venous thrombosis requiring anticoagulant therapy, and one patient who developed radiation myelopathy. On systemic response evaluation ten patients showed ongoing SD with a mean progression free survival of 9 months. One patient showed a PR (at an irradiated site). Regarding local response to irradiation, seven lesions showed a PR for a mean time period of 8.7 months, whereas seven were stable for 6 months. The radiation response of one lesion was not evaluable. Immunoflowcytometry showed an increase in number and activation of lymphocytes (mainly Natural Killer--NK-cells), which was absent or even decreased in irradiated patients. The combination of sc. low dose IL-2, thalidomide and radiotherapy is feasible, but relatively toxic and does not lead to higher responses at non-irradiated sites. The combination of immunotherapy and concurrent radiotherapy is effective at 60% of the relatively large evaluable sites. Progressive myelopathy developed in one patient, possibly due to radiotherapy in combination with thalidomide.
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