Clashes and Compromises: Investment Policies in Tourism Destinations

The authors solve a linear problem where a potential conflict between two agents (Destination manager and Firm) arises in a tourism destination. The Destination manager has to choose how to allocate limited resources (capital and land) between either second homes or hotels. This conflict stems from the assumption of agents who have different linear preferences with respect to the allocation of limited resources. As a solution to this policy problem the authors consider three different policies: no intervention (laissez faire), taxation and temporary de-taxation policy. Comparing these different policies, they show that a compromise solution (internal solution), which results from the de-taxation policy, may be preferred by both agents over the clash of interests outcomes (corner solutions). Thus, the authors show that in a framework of \u201cconflict\u201d between agents a compromise solution may be preferable to both the absence of public intervention and the imposition of a tax by a public policy maker who has the discretionary \u201cpower to regulate\u201d conflicts

How important is tourism for growth?

We revisit the tourism-led growth hypothesis by utilising a panel set of 108 countries over the period 1996-2017. We quantify the effects of tourism on the entire conditional distribution of economic growth for both relatively poor and relatively rich countries within a panel quantile regression framework. We address the unobserved heterogeneity and potential endogeneity concerns. We reveal that the lower the conditional growth rate a country experiences the more important is tourism development for the conditional growth distribution for both developing and developed countries. The size of the effect in developed countries is twice as high as in developing ones. On the other hand, tourism specialisation is beneficial only at higher quantiles of the conditional growth distribution and only for developed countries. On the contrary, it brings about an undesirable effect in developing countries. Finally, we examine the impact of a reduction in tourism activity on economic growth due to an exogenous shock (i.e., COVID-19). Simulation analysis based on the quantile regression estimates shows that countries facing relatively low growth rates conditionally to the growth distribution are affected the most. Policymakers may consider the importance of tourism activity in the growth process and formulate strategies that align with the growth experience of each country

Protein-Kinase-C inhibitors and gemfibrozil prevent the enhancing effect of very low density lipoproteins on the biosynthesis of plasminogen activator inhibitor type 1 by HepG2 cells

Triglyceride-rich lipoproteins (VLDL) have been previously shown to enhance the biosynthesis of plasminogen activator inhibitor type 1 (PAl-1) by HepG2 cells. This study was undertaken to assess whether the effect of VLDL on PAI-1 antigen and mRNA induction could be by protein kinase C (PKC) signaling pathway. To this end confluent HepG2 cells were first incubated for 16 h with VLDL isolated from normal donors, at the 100 \ub5g/ml concentration with or without inhibitors of PKC. At the end of incubation PAI-1 antigen released in the conditioned medium was determined by ELISA and PAI-1 mRNA expression was assessed by Northern analysis. Exposure of HepG2 cells to 100 \ub5g/ml VLDL resulted in a twofold increase in PAI-1 antigen release and total PAI-1 mRNA expression. H7 (50 11M) and sphingosine (3-5 \ub5M) almost completely prevented (> 80%) the effect of VLDL on PAI-1 antigen release and total PAI-1 mRNA accumulation. In addition down regulation of PKC, obtained by preincubation of HepG2 cells with PMA (100 nM) for 24h, prevented the effect of VLDL on PAI-1 biosynthesis. Established that the effect of VLDL on PAI-1 biosynthesis was mediated by activation of PKC signaling pathway we evaluated whether fibric acid derivatives influenced PAI-1 biosynthesis in unstimulated HepG2 cells and in cells exposed to VLDL. In unstimulated HepG2 cells, Gemfibrozil (0.1-0.75 mM) significantly reduced PAI-1 antigen release (-85% at the 0.75 mM concentration) and mRNA expression, whereas Bezafibrate at the highest concentration used (1 mM) reduced PAI-1 antigen release by 20%, with no effect on PAI-1 mRNA expression. In VLDL treated cells, only Gemfibrozil, at the 0 .75 mM concentration, attenuated (-50%) the biosynthesis of PAI-1 as induced by VLDL (100 \ub5g/ml) . It is concluded that VLDL enhance PAI-1 biosynthesis through activation of PKC and that Gemfibrozil, but not Bezafibrate, attenuates PAI-1 induction in these cells

Plasminogen activator inhibitor type-1 synthesis and mRNA expression in HepG2 cells are regulated by VLDL

The effect of VLDL on plasminogen activator inhibitor type 1 biosynthesis in HepG2 cells was investigated. Exposure of HepG2 cells to VLDL (range, 10 to 100 micrograms protein per milliliter) for 16 hours resulted in an enhanced release of PAI-1 antigen and PAI activity into conditioned medium, accompanied by the accumulation of intracellular triglycerides. By using a monoclonal antibody (IgG C7) specific to the LDL receptor, we showed that the effect of VLDL is mediated by its interaction with the LDL receptor. Enhanced PAI-1 release was due to increased biosynthesis: PAI-1 mRNA was doubled, mainly because of the effect on the 2.2-kb PAI-1 mRNA rather than the 3.2-kb transcript. Addition of insulin with the VLDL further enhanced PAI-1 antigen release and PAI-1 mRNA accumulation. The effect of VLDL on steady state levels of PAI-1 mRNA was apparently not due to an increase of gene transcription but to stabilization of both PAI-1 mRNA transcripts. The enhancing effect of VLDL on PAI-1 biosynthesis in HepG2 cells may raise PAI-1 antigen levels not only in hypertriglyceridemic states but also in those conditions in which both insulin and VLDL are elevated

Increased prothrombotic state lasting as long as one month after on-pump and off-pump coronary surgery

OBJECTIVE: This study investigated whether the activation of coagulation, fibrinolysis, and endothelium occurring during the first postoperative month after on-pump coronary artery bypass surgery differs from that after off-pump coronary artery bypass grafting. METHODS: Thirty-five patients candidates to coronary surgery were randomized to undergo on-pump (n = 18) or off-pump (n = 17) coronary artery bypass grafting. Blood samples were collected before the intervention and to 1 month after surgery. RESULTS: Prothrombin fragment F1.2, thrombin-antithrombin complex, and D-dimer increased after surgery and were persistently higher than preoperative values as late as 30 postoperative days in both on- and off-pump groups; higher levels of these variables were detected after on-pump surgery relative to off-pump surgery only at the time point after termination of cardiopulmonary bypass (fragment F1.2 and thrombin-antithrombin complex) or from bypass end to 8 postoperative days (D-dimer). Fibrinogen levels decreased after surgery and then increased in parallel in both groups to 8 days after surgery. The von Willebrand factor level increased postoperatively in both groups and returned to baseline 30 days after surgery; it was higher after on-pump surgery from bypass end to 8 postoperative days. Soluble vascular cell adhesion molecule 1 was increased significantly from baseline in both groups 30 days after surgery, with no difference between groups. CONCLUSION: Patients undergoing off-pump surgery showed protection against activation of coagulation and fibrinolysis and against endothelial injury only during the intraoperative period; this was followed by the development of a prothrombotic pattern comparable to that of patients undergoing on-pump surgery lasting at least as late as 30 days after surgery

Effect of valsartan on angiotensin II-induced plasminogen activator inhibitor-1 biosynthesis in arterial smooth muscle cells

Previous studies have shown that angiotensin II stimulates the synthesis of plasminogen activator inhibitor-1 in cultured vascular cells, which suggests that activation of the renin-angiotensin system may impair fibrinolysis. We have investigated the effects of angiotensin II and of valsartan, a recently developed angiotensin II antagonist that is highly specific and selective for the angiotensin II subtype 1 receptor, on plasminogen activator inhibitor-1 secretion by smooth muscle cells isolated from rat and human vessels. Angiotensin II induced a time- and concentration-dependent increase of plasminogen activator inhibitor activity in supernatants of rat aortic cells, which reached a plateau after 6 hours of incubation with 100 nmol/L angiotensin II (2.4+/-0.6-fold over control value; P:<0.001). The angiotensin II-induced plasminogen activator inhibitor activity was inhibited, in a concentration-dependent manner, by valsartan with an IC(50) value of 21 nmol/L. Valsartan fully prevented the angiotensin II-induced increase in plasminogen activator inhibitor-1 protein and mRNA. Furthermore, angiotensin II doubled the secretion of plasminogen activator inhibitor-1 by smooth muscle cells obtained from human umbilical and internal mammary arteries, and valsartan fully prevented it. Angiotensin II did not affect the secretion of tissue plasminogen activator antigen by any of the cell systems tested. Thus, valsartan effectively inhibits angiotensin II-induced plasminogen activator inhibitor-1 secretion without affecting that of tissue plasminogen activator in arterial rat and human smooth muscle cells

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives

Background The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores.Methods Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance.Results SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning.Conclusions In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors

Genetic background determines response to hemostasis and thrombosis

BACKGROUND: Thrombosis is the fatal and disabling consequence of cardiovascular diseases, the leading cause of mortality and morbidity in Western countries. Two inbred mouse strains, C57BL/6J and A/J, have marked differences in susceptibility to obesity, atherosclerosis, and vessel remodeling. However, it is unclear how these diverse genetic backgrounds influence pathways known to regulate thrombosis and hemostasis. The objective of this study was to evaluate thrombosis and hemostasis in these two inbred strains and determine the phenotypic response of A/J chromosomes in the C57BL/6J background. METHODS: A/J and C57Bl/6J mice were evaluated for differences in thrombosis and hemostasis. A thrombus was induced in the carotid artery by application of the exposed carotid to ferric chloride and blood flow measured until the vessel occluded. Bleeding and rebleeding times, as surrogate markers for thrombosis and hemostasis, were determined after clipping the tail and placing in warm saline. Twenty-one chromosome substitution strains, A/J chromosomes in a C57BL/6J background, were screened for response to the tail bleeding assay. RESULTS: Thrombus occlusion time was markedly decreased in the A/J mice compared to C57BL/6J mice. Tail bleeding time was similar in the two strains, but rebleeding time was markedly increased in the A/J mice compared to C57BL/6J mice. Coagulation times and tail morphology were similar, but tail collagen content was higher in A/J than C57BL/6J mice. Three chromosome substitution strains, B6-Chr5(A/J), B6-Chr11(A/J), and B6-Chr17(A/J), were identified with increased rebleeding time, a phenotype similar to A/J mice. Mice heterosomic for chromosomes 5 or 17 had rebleeding times similar to C57BL/6J mice, but when these two chromosome substitution strains, B6-Chr5(A/J )and B6-Chr17(A/J), were crossed, the A/J phenotype was restored in these doubly heterosomic progeny. CONCLUSION: These results indicate that susceptibility to arterial thrombosis and haemostasis is remarkably different in C57BL/and A/J mice. Three A/J chromosome substitution strains were identified that expressed a phenotype similar to A/J for rebleeding, the C57Bl/6J background could modify the A/J phenotype, and the combination of two A/J QTL could restore the phenotype. The diverse genetic backgrounds and differences in response to vascular injury induced thrombosis and the tail bleeding assay, suggest the potential for identifying novel genetic determinants of thrombotic risk