On the relationship between tariff levels and the nature of mergers

This paper employs an endogenous merger formation approach in a two-country oligopoly model of trade to examine the international linkages between the nature of mergers and tariff levels. Firms sell differentiated products and compete in a Bertrand fashion in product markets. We find two effects playing key roles in determining equilibrium market structure: the tariff saving effect and the protection gain effect. The balance between these two effects implies that, when foreign country practices free trade, unilateral tariff reduction by a domestic country yields international mergers irrespective of the substitutability levels. By contrast, when foreign tariffs are sufficiently high and products are close substitutes, national mergers obtain in the equilibrium. Therefore, the implications of unilateral trade liberalization on the equilibrium market structure depends on the trade regime in foreign country especially when products are close substitutes. Unlike this asymmetric result of unilateral trade liberalization, we find that when bilateral tariffs are sufficiently low, international mergers arise. These results fit well with the fact that global trade liberalization has been accompanied by an increase in international merger activities. Finally, from a welfare perspective, we show that international mergers are preferable to national mergers and thus social and private merger incentives become aligned together as trade gets bilaterally liberalized.international mergers, national mergers, tariff saving, protection gain

Post-Translational Regulation of the Activity of ERK/MAPK and PI3K/AKT Signaling Pathways in Neuroblastoma Cancer

Pathogenesis of cancer is a multi-step process containing a number of cellular alterations such as post-translational dysregulation of intracellular signaling proteins. These alterations control several functions in carcinogenesis such as angiogenesis, metastasis, evading growth suppressors, and sustaining proliferative signaling. Data of various studies has demonstrated that Phosphatidylinositol 3-kinase (PI3K/AKT) and Mitogen-activated protein kinase (ERK/MAPK) pathways are both abnormally activated in many cancer types, including neuroblastoma. ERK/MAPK and PI3K/AKT signaling pathways that are regulated by sequential phosphorylation upon extracellular stimulation have many important functions in cell cycle, migration, proliferation and apoptosis. Besides their aberrant phosphorylation/activation, there is a crosstalk between these two pathways resulting in an anti-apoptotic effect. In this chapter, carcinogenetic abnormalities in post-translational regulation of the activity of ERK/MAPK and PI3K/AKT pathways in neuroblastoma and other cancers will be summarized. In addition, several crosstalk nodes between two pathways will be briefly explained. All these concepts are not only crucial for thoroughly understanding the molecular basis of carcinogenesis but also choosing the appropriate molecular targets for effective diagnosis and treatment

On the relationship between tariff levels and the nature of mergers

This paper employs an endogenous merger formation approach in a two-country oligopoly model of trade to examine the international linkages between the nature of mergers and tariff levels. Firms sell differentiated products and compete in a Bertrand fashion in product markets. We find two effects playing key roles in determining equilibrium market structure: the tariff saving effect and the protection gain effect. The balance between these two effects implies that, when foreign country practices free trade, unilateral tariff reduction by a domestic country yields international mergers irrespective of the substitutability levels. By contrast, when foreign tariffs are sufficiently high and products are close substitutes, national mergers obtain in the equilibrium. Therefore, the implications of unilateral trade liberalization on the equilibrium market structure depends on the trade regime in foreign country especially when products are close substitutes. Unlike this asymmetric result of unilateral trade liberalization, we find that when bilateral tariffs are sufficiently low, international mergers arise. These results fit well with the fact that global trade liberalization has been accompanied by an increase in international merger activities. Finally, from a welfare perspective, we show that international mergers are preferable to national mergers and thus social and private merger incentives become aligned together as trade gets bilaterally liberalized

On the relationship between tariff levels and the nature of mergers

This paper employs an endogenous merger formation approach in a two-country oligopoly model of trade to examine the international linkages between the nature of mergers and tariff levels. Firms sell differentiated products and compete in a Bertrand fashion in product markets. We find two effects playing key roles in determining equilibrium market structure: the tariff saving effect and the protection gain effect. The balance between these two effects implies that, when foreign country practices free trade, unilateral tariff reduction by a domestic country yields international mergers irrespective of the substitutability levels. By contrast, when foreign tariffs are sufficiently high and products are close substitutes, national mergers obtain in the equilibrium. Therefore, the implications of unilateral trade liberalization on the equilibrium market structure depends on the trade regime in foreign country especially when products are close substitutes. Unlike this asymmetric result of unilateral trade liberalization, we find that when bilateral tariffs are sufficiently low, international mergers arise. These results fit well with the fact that global trade liberalization has been accompanied by an increase in international merger activities. Finally, from a welfare perspective, we show that international mergers are preferable to national mergers and thus social and private merger incentives become aligned together as trade gets bilaterally liberalized

Multisite international collaborative clinical trials in mania.

Multi-regional collaborative clinical trials include those conducted across heterogeneous areas of the world under common protocols. Such trials appear to be driven primarily to provide data required for regulatory approval or licensing of new drug products in a relatively rapid and presumably efficient and cost-effective manner. Commonly, they include underserved populations and areas where costs of trials are lower than in most developed countries. In addition, such studies can potentially make innovative treatments widely and rapidly available in vast, international markets. Other potential benefits to collaborating sites may include diffusion of knowledge and improvement of research skills, as well as improvement of treatment and a broader salutary impact on health services and perhaps on employment opportunities and economic growth (Demol +6; Weihrauch, 1997; Glickman et al. 2009; Gopal et al. 2005; Greco +6; Diniz, 2008; ICH Guideline, 2002; Smulevich et al. 2005; U.S. FDA, 1998). Successful conduct of international trials requires compliance with varying local and international laws, regulations and ethical requirements, and confronting a range of systems of review of ethical aspects of subject recruitment, compensation, consenting procedures, research protocols, and provision of aftercare – all which can add complexity. In addition, there is variance among regions, countries and cultures in levels of education, and in the nature of information, financial inducements, clinical care and aftercare provided to research subjects. Complexities arise also from culture-dependent conceptualizations of mental disorders, criteria for diagnosis, and efforts at validating, interpreting and scoring of symptom ratings designed to characterize changes during treatment, and methods for detecting adverse events. In the continuing quest to define core or universal features of psychiatric disorders, it is crucial to consider the anthropological and cultural context in which they develop and are modified (Karno +6; Jenkins, 1993; Lopez-Ibor, 2003;

Strength of selection pressure is an important parameter contributing to the complexity of antibiotic resistance evolution

Revealing the genetic changes responsible for antibiotic resistance can be critical for developing novel antibiotic therapies. However, systematic studies correlating genotype to phenotype in the context of antibiotic resistance have been missing. In order to fill in this gap, we evolved 88 isogenic Escherichia coli populations against 22 antibiotics for 3 weeks. For every drug, two populations were evolved under strong selection and two populations were evolved under mild selection. By quantifying evolved populations' resistances against all 22 drugs, we constructed two separate cross-resistance networks for strongly and mildly selected populations. Subsequently, we sequenced representative colonies isolated from evolved populations for revealing the genetic basis for novel phenotypes. Bacterial populations that evolved resistance against antibiotics under strong selection acquired high levels of cross-resistance against several antibiotics, whereas other bacterial populations evolved under milder selection acquired relatively weaker cross-resistance. In addition, we found that strongly selected strains against aminoglycosides became more susceptible to five other drug classes compared with their wild-type ancestor as a result of a point mutation on TrkH, an ion transporter protein. Our findings suggest that selection strength is an important parameter contributing to the complexity of antibiotic resistance problem and use of high doses of antibiotics to clear infections has the potential to promote increase of cross-resistance in clinics

Demographic, Clinical and Radiological Features of Healthcare Workers and Two Index Cases That Were Infected with COVID-19 (SARS-Cov-2)

To evaluate the index cases leading to the transmission of healthcare workers (HCWs) in Rize/Turkey Recep Tayyip Erdogan University Faculty of Medicine Education and Research Hospital with COVID-19 infection and the clinical features of infected HCWs. The first two COVID-19 test positive patients treated at Rize/Turkey between 10.03.2020 and 12.04.2020 and HCWs those who examined these two patients whose COVID-19 PCR test results were positive were included in this study. In Rize/Turkey, the first and second cases of positive COVID-19 which was recorded on 13.03.2020 on 25.03.2020, 27 HCWs (female, 63%, n = 17 and male, 37%, n = 10 and the mean age was 33.2 ± 6.9 years) who contacted during the treatment of these cases and became COVID-19 positive were examined. The median of symptom duration (days) of the HCWs was 5 days (range: 0–17 days). Fever, 55.6% (n = 15); malaise, 44.4% (n = 12); cough, 40.7% (n = 11); sore throat, 33.3% (n = 9); myalgia, 33.3% (n = 9); dyspnea, 14.8% (n = 4); diarrhea, 22.2% (n = 6); vomiting, 14.8% (n = 4); anosmia, 18.5% (n = 5); ageusia, 22.2% (n = 6) and headache, 37% (n = 10) of the cases. The rates of headache in female HCWs infected with COVID-19 were found to be significantly higher compared to men (52.9%). None of them had severe clinical situation requiring intensive care follow-up or acute respiratory distress syndrome (ARDS). Laboratory measurements of HCWs were carried out at the first when they had symptoms and when they recovered, and results were compared accordingly. The thorax computerized tomography (CT) findings of HCWs were normal in 74.1% (n = 20) of total. HCWs were initially affected by the COVID-19 pandemic. Early measures provided by the Health authorities, access to diagnosis and treatment, and the young age average in HCWs prevented severe outcomes such as severe clinical course and mortality at the beginning of the outbreak

Corrigendum to "Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action [European Neuropsychopharmacology (2020) 36, 121-136]"

The authors regret that there was an error in the author list, this should appear as above. The authors apologise for any inconvenience caused

Translating big data to better treatment in bipolar disorder - a manifesto for coordinated action

Bipolar disorder (BD) is a major healthcare and socio-economic challenge. Despite its substantial burden on society, the research activity in BD is much smaller than its economic impact appears to demand. There is a consensus that the accurate identification of the underlying pathophysiology for BD is fundamental to realize major health benefits through better treatment and preventive regimens. However, to achieve these goals requires coordinated action and innovative approaches to boost the discovery of the neurobiological underpinnings of BD, and rapid translation of research findings into development and testing of better and more specific treatments. To this end, we here propose that only a large-scale coordinated action can be successful in integrating international big-data approaches with real-world clinical interventions. This could be achieved through the creation of a Global Bipolar Disorder Foundation, which could bring government, industry and philanthropy together in common cause. A global initiative for BD research would come at a highly opportune time given the seminal advances promised for our understanding of the genetic and brain basis of the disease and the obvious areas of unmet clinical need. Such an endeavour would embrace the principles of open science and see the strong involvement of user groups and integration of dissemination and public involvement with the research programs. We believe the time is right for a step change in our approach to understanding, treating and even preventing BD effectively