Collapsing exchange rate regime: A theoretical and empirical investigation with special reference to Korea.

In addition to these results, this paper provides some policy implications for avoiding a future currency crisis. The implications are taken from both generation models: (1) the need of maintaining stable economic fundamentals (especially, current account balance and enough accumulation of usable foreign reserves) along with a more flexible exchange rate system; (2) the need of a stable financial system by controlling capital flows and thus by avoiding a moral hazard problem.In this regard, this paper attempts to examine the main causes of the Korean currency crisis by introducing the features stressed in both generation models. For this purpose, this paper develops a theoretical framework, which is based on the modified monetary model of exchange rate determination (or modified first generation models).The principal research findings show that the collapse probability of the Korean exchange rate regime might have been lowered by decreasing the external credit shocks, the magnitude of sterilization, and the variability of relative price shocks. The impact of the uncertainty surrounding domestic credit growth on the probabilities of regime collapse varies during the sample period.Two generations of currency crisis models coexist since the crises that occurred in some member countries of European Monetary System (EMS), and Mexico during the 1970s--1990s.The first group of models regard inconsistency between macroeconomic fundamentals and the existing fixed exchange rate regime as the root of the crisis. More recent theoretical researches, which are so-called second generation models of speculative attacks, put more weight on the speculation itself, than on the bad economic fundamentals, in examining the driving force of collapse of a fixed exchange rate regime. However, the Korean crisis seems to have both characteristics of first and second generation models; a mixture of weak fundamentals (stressed in the first view), and factors leading to a self-fulfilling attack such as financial panic and contagion effects (emphasized in the second view)

FAM167A is a key molecule to induce BCR-ABL-independent TKI resistance in CML via noncanonical NF-κB signaling activation

Abstract Background BCR-ABL-independent drug resistance is a barrier to curative treatment of chronic myeloid leukemia (CML). However, the molecular pathways underlying BCR-ABL-independent tyrosine kinase inhibitor (TKI) resistance remain unclear. Methods In silico bioinformatic analysis was performed to identify the most active transcription factor and its inducer that contribute to BCR-ABL-independent TKI resistance. Tandem mass spectrometry analysis was performed to identify the receptor for the noncanonical NF-κB activator FAM167A. In vitro and in vivo mouse experiments revealed detailed molecular insights into the functional role of the FAM167A-desmoglein-1 (DSG1) axis in BCL-ABL-independent TKI resistance. CML cells derived from CML patients were analyzed using quantitative reverse transcription PCR and flow cytometry. Results We found that NF-κB had the greatest effect on differential gene expression of BCR-ABL-independent TKI-resistant CML cells. Moreover, we found that the previously uncharacterized protein FAM167A activates the noncanonical NF-κB pathway and induces BCR-ABL-independent TKI resistance. Molecular analyses revealed that FAM167A activates the noncanonical NF-κB pathway by binding to the cell adhesion protein DSG1 to upregulate NF-κB-inducing kinase (NIK) by blocking its ubiquitination. Neutralization of FAM167A in a mouse tumor model reduced noncanonical NF-κB activity and restored sensitivity of cells to TKIs. Furthermore, FAM167A and surface DSG1 levels were highly upregulated in CD34+ CML cells from patients with BCR-ABL-independent TKI-resistant disease. Conclusions These results reveal that FAM167A acts as an essential factor for BCR-ABL-independent TKI resistance in CML by activating the noncanonical NF-κB pathway. In addition, FAM167A may serve as an important target and biomarker for BCR-ABL-independent TKI resistance

Clinical application of genomic profiling to find druggable targets for adolescent and young adult (AYA) cancer patients with metastasis

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Background: Although adolescent and young adult (AYA) cancers are characterized by biological features and clinical outcomes distinct from those of other age groups, the molecular profile of AYA cancers has not been well defined. In this study, we analyzed cancer genomes from rare types of metastatic AYA cancers to identify driving and/or druggable genetic alterations. Methods: Prospectively collected AYA tumor samples from seven different patients were analyzed using three different genomics platforms (whole-exome sequencing, whole-transcriptome sequencing or OncoScan (TM)). Using well-known bioinformatics tools (bwa, Picard, GATK, MuTect, and Somatic Indel Detector) and our annotation approach with open access databases (DAVID and DGIdb), we processed sequencing data and identified driving genetic alterations and their druggability. Results: The mutation frequencies of AYA cancers were lower than those of other adult cancers (median = 0.56), except for a germ cell tumor with hypermutation. We identified patient-specific genetic alterations in candidate driving genes: RASA2 and NF1 (prostate cancer), TP53 and CDKN2C (olfactory neuroblastoma), FAT1, NOTCH1, and SMAD4 (head and neck cancer), KRAS (urachal carcinoma), EML4-ALK (lung cancer), and MDM2 and PTEN (liposarcoma). We then suggested potential drugs for each patient according to his or her altered genes and related pathways. By comparing candidate driving genes between AYA cancers and those from all age groups for the same type of cancer, we identified different driving genes in prostate cancer and a germ cell tumor in AYAs compared with all age groups, whereas three common alterations (TP53, FAT1, and NOTCH1) in head and neck cancer were identified in both groups. Conclusion: We identified the patient-specific genetic alterations and druggability of seven rare types of AYA cancers using three genomics platforms. Additionally, genetic alterations in cancers from AYA and those from all age groups varied by cancer type.

A novel polymer-free everolimus-eluting stent with a nitrogen-doped titanium dioxide film inhibits restenosis and thrombosis in a swine coronary model

Background: Short-term outcomes regarding the safety and efficacy of a polymer-free everolimus-eluting stent (EES) with a nitrogen-doped titanium dioxide (N-TiO2) film in a swine coronary model have been reported. However, the long-term results of the use of this type of stent have not yet been evaluated or compared to those of other polymer-free coronary stents. Therefore, this study aimed to determine the mid- to long-term safety and efficacy of a polymer-free EES with an N-TiO2 film in a swine coronary model. Methods: Polymer-free EES with N-TiO2 films (n = 30) and polymer-free sirolimus-eluting stents (SES; n = 30) were implanted in 30 pigs. Quantitative coronary analysis and optical coherence tomography were conducted immediately and at 1 (quantitative coronary analysis only), 3, and 6 months after stenting. Histopathologic examinations were performed at 1, 3, and 6 months after stenting. Results: The polymer-free EES group had a lower percentage of neointimal growth than the polymer-free SES group at 3 months (22.5% ± 11.4% vs. 32.1% ± 12.3%; p < 0.001). The polymer-free EES group had a lower fibrin score than the polymer-free SES group at 1 month (1.9 ± 0.45 vs. 2.5 ± 0.54; p = 0.001). The re-endothelialization rates were similar between groups. The polymer-free EES group had a lower percentage of the area of stenosis than the polymer-free SES group throughout the follow-up period. Conclusions: The novel polymer-free EES with an N-TiO2 film has superior safety and efficacy than the polymer-free SES at the 6-month follow-up in a swine model

Genomic acquisition of a capsular polysaccharide virulence cluster by non-pathogenic Burkholderia isolates.

BACKGROUND: Burkholderia thailandensis is a non-pathogenic environmental saprophyte closely related to Burkholderia pseudomallei, the causative agent of the often fatal animal and human disease melioidosis. To study B. thailandensis genomic variation, we profiled 50 isolates using a pan-genome microarray comprising genomic elements from 28 Burkholderia strains and species. RESULTS: Of 39 genomic regions variably present across the B. thailandensis strains, 13 regions corresponded to known genomic islands, while 26 regions were novel. Variant B. thailandensis isolates exhibited isolated acquisition of a capsular polysaccharide biosynthesis gene cluster (B. pseudomallei-like capsular polysaccharide) closely resembling a similar cluster in B. pseudomallei that is essential for virulence in mammals; presence of this cluster was confirmed by whole genome sequencing of a representative variant strain (B. thailandensis E555). Both whole-genome microarray and multi-locus sequence typing analysis revealed that the variant strains formed part of a phylogenetic subgroup distinct from the ancestral B. thailandensis population and were associated with atypical isolation sources when compared to the majority of previously described B. thailandensis strains. In functional assays, B. thailandensis E555 exhibited several B. pseudomallei-like phenotypes, including colony wrinkling, resistance to human complement binding, and intracellular macrophage survival. However, in murine infection assays, B. thailandensis E555 did not exhibit enhanced virulence relative to other B. thailandensis strains, suggesting that additional factors are required to successfully colonize and infect mammals. CONCLUSIONS: The discovery of such novel variant strains demonstrates how unbiased genomic surveys of non-pathogenic isolates can reveal insights into the development and emergence of new pathogenic species.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Different outcomes between iso-osmolar and low-osmolar contrast media in acute myocardial infarction with renal impairment

Background: The selection of appropriate contrast media (CM) remains an important issue in terms of renal preservation in patients with acute myocardial infarction (AMI) and renal impairment scheduled for percutaneous coronary intervention (PCI). We compared the clinical outcomes of patients with AMI and renal impairment, depending on the CM type (iso-osmolar CM [IOCM] vs. low-osmolar CM [LOCM]) that was used during PCI. Methods: From the Convergent Registry of Catholic and Chonnam University for Acute Myocardial Infarction, 3174 post-PCI patients with AMI and renal impairment were subdivided into two groups (IOCM [n = 2101] and LOCM [n = 1073]). Results: Regarding in-hospital clinical outcomes, the IOCM group had a higher peak creatinine (Cr) level and lower “Cr differential” than the LOCM group. A higher proportion of dialysis was noted in the IOCM group. In 30-day clinical outcomes, the IOCM group showed higher incidence of new-onset heart failure (HF) but lower incidence of revascularization than the LOCM group. The differences in in-hospital and 30-day clinical outcomes were attenuated after inverse probability of treatment weighting, except for new-onset HF. All other variables in 30-day clinical outcomes, including all-cause death, non-fatal myocardial infarction, cerebrovascular accidents, stent thrombosis, and any dialysis events, were similar between the two groups. Conclusions: Iso-osmolar CM use did not prevent future incidence of dialysis compared to LOCM use in AMI patients with renal impairment

The role of PET/CT in detection of gastric cancer recurrence

<p>Abstract</p> <p>Background</p> <p>In the course of surveillance of gastric cancer recurrence after curative resection, contrast CT scan is used in general. However, new findings from CT scan are not always confirmatory for the recurrence. In this case, we usually use short-term follow up strategy or therapeutic intervention with clinical decision. Recently, the use of fusion Positron Emission Tomography/Computed Tomography (PET/CT) is increasing. The purpose of this study is to evaluate the efficacy and usefulness of PET/CT for detecting recurrence of gastric cancer after curative resection.</p> <p>Methods</p> <p>Fifty two patients who received curative resection of gastric cancer and had undergone PET/CT and contrast CT for surveillance of recurrence until Dec 2006 in Seoul National University Hospital were analyzed retrospectively. Recurrence of gastric cancer was validated by histologic confirmation (n = 17) or serial contrast CT follow up with at least 5 month interval (n = 35). McNemar's test and Fisher's exact test were used to evaluate sensitivity and specificity of PET/CT and contrast CT.</p> <p>Results</p> <p>Of 52 patients, 38 patients were confirmed as recurrence. The sensitivity was 68.4% (26/38) for PET/CT and 89.4% (34/38) for contrast CT (p = 0.057). The specificity was 71.4% (10/14) and 64.2% (9/14), respectively (p = 1.0). In terms of the recurred sites, the sensitivity and specificity of PET/CT were similar to those of contrast CT in all sites except peritoneum. Contrast CT was more sensitive than PET/CT (p = 0.039) for detecting peritoneal seeding. Additional PET/CT on contrast CT showed no further increase of positive predictive value regardless of sites. Among 13 patients whose image findings between two methods were discordant and tissue confirmation was difficult, the treatment decision was made in 7 patients based on PET/CT, showing the final diagnostic accuracy of 42.8% (3/7).</p> <p>Conclusion</p> <p>PET/CT was as sensitive and specific as contrast CT in detection of recurred gastric cancer except peritoneal seeding. However, additional PET/CT on contrast CT did not increase diagnostic accuracy in detection of recurred gastric cancer. Further studies are warranted to validate the role of PET/CT in detection of gastric cancer recurrence.</p