Quantifying the Effects of Trust in Supply Chains During Promotional Periods

Analytical modelling of supply chains has tended to focus on the material flows whilst neglecting the study of information dissemination through the supply chain. An important factor influencing these flows is the level of trust between supply chain partners. The dimensions of such trust are examined here and a brief review of research aimed at evaluating its importance in this area is undertaken. An optimal control model is then constructed to calculate the cost implications of the prevailing level of trust in a multi-echelon supply chain faced with satisfying a promotion for the end product. The mechanism by which both low and high levels of trust distort demand information as it is transmitted along the supply chain is investigated. A sensitivity analysis reveals that these results are essentially unaffected by the cost structures assumed. Lastly, two methods designed to compensate for low levels of trust are appraised

SENSITIZATION TO KAPPA OPIOID MECHANISMS ASSOCIATED WITH TOLERANCE TO THE ANORECTIC EFFECTS OF CATHINONE

To evaluate the possibility that tolerance to the anorectic effects of cathinone (CATH), an amphetamine-like compound, involves the sensitization of endogenous kappa opioid mechanisms, the influence of chronic treatment with CATH on the effects of the selective kappa opioid agonist U50488H (U50) on food and water intake was evaluated in rats. Since kappa agonists specifically increase urine output, the interaction between CATH and U50 on this physiological function was also evaluated. Acutely, CATH produced anorexia and diuresis, whereas water intake was not affected. U50 resulted in an increase in both food and water intake as well as urine output. After 9 days of daily CATH, tolerance to its anorectic effects had developed. In addition, water intake, which was not affected acutely by CATH, was significantly enhanced with respect to controls treated daily with water. In a group treated chronically with U50, its diuretic effect was unchanged, but water intake was no longer increased after 9 days of treatment. Food intake in this group remained higher than control intake for at least 19 days, but this hyperphagic effect was not detectable on day 34. On days 10 and 20 of the chronic regimen, the administration of U50 to the chronic CATH group resulted in a doubling of the hyperphagic response to U50, and this effect was naloxone-reversible. Water intake was also increased but to a lesser extent. The diuretic effect of U50 did not appear to be influenced by chronic CATH administration. Despite sensitization to the hyperphagic effects of U50 in the chronic CATH group, 3H-bremazocine binding to crude synaptosomal membranes of whole brain did not differ between chronically water-, CATH-, or U50-treated animals. These results suggest that tolerance to the anorectic effects of an amphetamine-like agent is associated with a sensitization to kappa-opiate mediated activation of feeding

Vulnerability of fourth ventricle choroid plexus in suddenunexplained fetal and infant death syndromes related tosmoking mothers

The human choroid plexuses in the ventricular system represent the main source of cerebrospinal fluid secretion and constitute a major barrier interface that controls the brain\u2019s environment. The present study focused on the choroid plexus of the fourth ventricle, the main cavity of the brainstem containing important nuclei and/or structures mediating autonomic vital functions. In serial sections of 84 brainstems of subjects aged from 17 gestational weeks to 8 postnatal months of life, the deaths due to both known and unknown causes, we examined the cytoarchitecture and the developmental steps of the fourth ventricle choroid plexus to determine whether this structure shows morphological and/or functional alterations in unexplained perinatal deaths (Sudden Infant Death Syndrome and Sudden Intrauterine Unexplained Death Syndrome). High incidence of histological and immunohistochemical alterations (prevalence of epithelial dark cells, the presence of cystic cells in the stroma, decreased number of blood capillaries, hyperexpression of substance P and apoptosis) were prevalently observed in unexplained death victims (p<0.05 vs. controls). A significant correlation was found between maternal smoking in pregnancy and choroidal neuropathological parameters (p<0.01). This work underscores the negative effects of prenatal exposure to nicotine on the development of the autonomic nervous system, and in particular of the fourth ventricle choroid plexus that is a very vulnerable structure in the developing CSF-brain system

Acute effects of cocaine on the neurobiology of cognitive control

Compromised ability to exert control over drug urges and drug-seeking behaviour is a characteristic of addiction. One specific cognitive control function, impulse control, has been shown to be a risk factor for the development of substance problems and has been linked in animal models to increased drug administration and relapse. We present evidence of a direct effect of cocaine on the neurobiology underlying impulse control. In a laboratory test of motor response inhibition, an intravenous cocaine administration improved task performance in 13 cocaine users. This improvement was accompanied by increased activation in right dorsolateral and inferior frontal cortex, regions considered critical for this cognitive function. Similarly, for both inhibitory control and action monitoring processes, cocaine normalized activation levels in lateral and medial prefrontal regions previously reported to be hypoactive in users relative to drug-naive controls. The acute amelioration of neurocognitive dysfunction may reflect a chronic dysregulation of those brain regions and the cognitive processes they subserve. Furthermore, the effects of cocaine on midline function suggest a dopaminergically mediated intersection between cocaine's acute reinforcing effects and its effects on cognitive control

Parallel studies of cocaine-related neural and cognitive impairment in humans and monkeys

Cocaine users display profound impairments in executive function. Of all the components of executive function, inhibition, or the ability to withhold responding, has been studied the most extensively and may be most impaired. Consistent with these deficits, evidence from imaging studies points to dysregulation in medial and ventromedial prefrontal cortices, areas activated during performance of inhibition tasks. Other aspects of executive function including updating, shifting and decision making are also deficient in cocaine users, and these deficits are paralleled by abnormalities in patterns of prefrontal cortical activation. The extent to which cocaine plays a role in these effects, however, is not certain, and cannot be determined solely on the basis of human studies. Investigations using a non-human primate model of increasing durations of cocaine exposure revealed that initially the effects of cocaine were restricted to ventromedial and orbital prefrontal cortices, but as exposure was extended the intensity and spatial extent of the effects on functional activity also expanded rostrally and laterally. Given the spatial overlap in prefrontal pathology between human and monkey studies, these longitudinal mapping studies in non-human primates provide a unique window of understanding into the dynamic neural changes that are occurring early in human cocaine abuse

Positron emission tomography imaging studies of dopamine receptors in primate models of addiction

Animal models have provided valuable information related to trait and state variables associated with vulnerability to drug addiction. Our brain imaging studies in monkeys have implicated D2 receptors in cocaine addiction. For example, an inverse relationship between D2 receptor availability and rates of cocaine self-administration has been documented. Moreover, environmental variables, such as those associated with formation of the social hierarchy, can impact receptor availability and sensitivity to the abuse-related effects of cocaine. Similarly, both D2 receptor availability and cocaine self-administration can be altered by chronic drug administration and fluctuations in hormone levels. In addition, cocaine self-administration can be altered in an orderly fashion by presentation of an acute stressor, such as acting as an intruder into an unfamiliar social group, which can shift the cocaine dose–response curve to the left in subordinate monkeys and to the right in dominant animals, suggesting an interaction between social variables and acute stressors. Conversely, irrespective of social rank, acute environmental enrichment, such as increasing the size of the living space, shifts the cocaine dose–response curve to the right. These findings highlight a pervasive influence of the environment in modifying the reinforcing effects of cocaine and strongly implicate brain D2 receptors