bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study on Japan's Outward FDI to Korea and China
Authors: Kim Hyun sung , Ku Ki bo
Published: January 2012

This paper addresses a comparative analysis of outward FDI to Korea and China by Japanese MNCs. The study aims to review the level of economic development of countries expanding overseas and the relativity of outward FDI patterns, and the change process of Japan's outward FDI from the standpoint of the Investment Development Path Theory. The result can be summarized as follows: First, as a result of examining the long-term changes of Japan's outward FDI, the development process can be mapped in the order of resource securing→entry into developed markets→production cost reduction→measurements to regional economic integration→establish international division of production→entry into developing countries for markets. In particular, the exchange rate factor called high Yen played a vital role in terms of production cost reduction. Second, as result of outward FDI compared with Korea and China, while the proportion of non-manufacturing industry is higher in the case of Korea, China still has a high proportion in the manufacturing industry. This implies that the investment towards Korea in Japan's outward FDI pattern is swaying toward developed countries. Third, since the 2000s, Japan's outward FDI to China began increasing tremendously, as a new phenomenon, by strategic asset seeking motivation, such as R&D base, rather than the traditional efficiency seeking or market seeking motivations. This explains that the strategic asset seeking motivation can be demonstrated both in South→North and North→South, which can exist in third or fourth phases of the IDP theory. It shows that, dynamics of different directions are also feasible within the strategic asset seeking motivation depending on technology levels.
China's Harmonious Asia Strategy
Authors: Hwang Jaeho , Dongxiao Chen
Published: January 2012

Although there is still no official policy paper or overall regional strategy towards Asia, the latest trend in Chinese diplomacy shows that China's strategy towards Asia is one of Harmonious Asia. The phrase connotes a sense of ‘togetherness’ that appeals strongly to the international society. To expatiate on the strategy, China proceeds along three tracks -economic cooperation, installing partnerships, and multilateral security. One could state that China's Asia strategy has been quite fruitful. However, there linger four future challenges to China's implementation of Harmonious Asia. That is, if the U.S. reinforces smart power; if Japan invents its own diplomacy; if China has difficulty harmonizing with regional states; and if China does not take sufficient responsibility. The possibility of voices calling for the need for a new system will rise once China becomes a responsible state and the regional states embrace China's subsequent leadership. Despite the potential and possibility, the reality of either a Sino-U.S. co-leadership structure or a Sino-U.S.-Japan tripartite concert will be unlikely to come to avail in the near future given the unremitting distrust between China and US/Japan on their strategic intentions vis-à-vis each other.
Supplier Relationship in Product Development: A Survey of the Chinese Automobile Industry during the Growth Period, 2005–2007
Authors: Kwak Jooyoung , Min Hyunjoo , Lee Peishan
Published: January 2012

This study compares supplier relationship by multinational assemblers in China vis-á-vis the Chinese assemblers in the stage of product development. We surveyed seven automobile firms (four international joint ventures and three Chinese firms) during 2005-2007, when the Chinese automobile industry began to rear up. Based on the survey, we examined the roles of suppliers, which is one of the critical dimensions in product development of the automobile industry.
Buddhist Nationalism and its Limitations in Colonial Myanmar: The Crossing of Tradition and Modernity
Authors: Jang Jun Young
Published: January 2012

The purpose of this article is to explore the characteristics of the Burmese Buddhist nationalism mainly led by Buddhist monks in colonial order. This study mainly focuses on the behaviors, ideas, and ideologies of whom took part in nationalist movement, permeating the westernized way of thinking. How did they cope with socio-economic change and weakening of the traditional Buddhist functions? Here, we choose three cases concerning on the nationalism in colonial era. First, the YMBA and the GCBA movement, as a religious one with Wunthanu movement, awakened to people unfairness of the British order in the aspects of traditional ascetical life. Second, the Saya San rebellion was a kind of mixed movement on tradition and modernity, which inclined to reestablish of the return of the millenarian kingdom with secular physical confrontation. Third, the main reason of the Oil Strike which had triggered in 1938 was basically economic and racial discrimination compared to Indian workers who had come to Myanmar in colonial period. However, there was a severe religious dissatisfaction behind the uprising that the British authorities despised the Buddhist cultures and practices. The nationalist movement in colonial Myanmar had evolved to their own form which contained the national unity and distinguished identity compared to other people focusing on Buddhism.
A Study in Terms of the Process of Democratization with Administrative Reform in Southern Europe
Authors: Yun Eun Gee
Published: January 2012

The political agents played a decisive role in the process of democratization to solve the economic crises and the internal disunity generated by the economic development. Economic development is not a sufficient but a necessary condition for the process of democratization. The role of political agent would be crucial for making transition to democracy. The transition to democracy in the case of Southern Europe can be explained by the interaction theory between structure and agent. The situation of economic crises and the change of economic structure, caused by the process of modernization, required the action of the political agents in Southern Europe. The article will explain the interaction theory between structure and political agents in the process of democratization.
Another Misadventure of Economists in the Tropics? Social Diversity, Cohesion, and Economic Development
Authors: de Soysa Indra
Published: January 2012

Several prominent economists have recently argued that ethnic and other forms of social diversity lead to economic failure. Apparently, serious social frictions caused by diverse preferences do not create conditions for the development of endogenous institutions that enhance good economic policies. Others, however, have shown that diversity reduces transaction costs within and between groups absent good public institutions, because of within-group social capital and ingroup policing in repeated dealings across groups. High diversity also reduces mass mobilization and forces consensus: ethnic diversity acts as a barrier against the concentration of absolute power. Using several measures of ethnic diversity, this study demonstrates that diversity and cultural difference reduce serious social frictions measured as the repression of political dissent. This study also finds that higher social diversity directly predicts higher levels of economic freedom, a proxy often used to gauge the market-friendliness of a country, the endogenous conditions often associated with economic success. The same results are true when a measure of the control of corruption is used. The results show that diversity enhances, not retards, the prospects for development and reduces social frictions. It may very well be that discourses of conflict, particularly the discourses of blame and recrimination based on ethnic ties where economic failure is apparent, is mistaken as the cause rather than the byproduct of crises, mistakenly attributed to historical conditions that have generated artificial borders. Empirically, diversity seems to foster, not displace, the preconditions for development.
The Clash of Civilizations and the Interaction between Fear and Hatred
Authors: Murshed Syed Mansoob
Published: January 2012

This paper models conflictive interaction between a West European state and a domestic dissident immigrant Muslim minority group in terms of fear and hatred. The genesis and production of both phenomena are modelled. Identity is crucial and provides the micro-foundations of dissident Muslim behaviour by solving the collective action problem; however, complex multiple identities are possible. Hatred of the West arises both because of the economic disadvantage experienced by Muslims in Europe, as well as historical grievances and contemporary foreign policy deemed to be against the Muslim world. The fear of visible Muslim minorities among the European host population may be partially a result of strident propaganda. The innovations of this paper lie in modelling the interaction between fear (treated like a public good) and hatred (a club good), as well as allowing multiple identities amongst dissidents. Policy implications include creating space allowing Muslim migrants to merge their cultural background with their adopted European identity, and redressing some of the economic disadvantage experienced by Muslims.
East Asian Economic Models for Chile
Authors: Paik Won K. , Johnson Sterling , Villavicencio Hernán
Published: January 2012

East Asia's economy grew rapidly from the 1970s through 2000s: Its population now constitutes about 50% of the world's population and its economic output, 45% of the GDP. In recent years, East Asia has become an important place for the Chilean economy, because it also constitutes the most dynamic market for Chilean exports, with reported annual growth rates of over 200%. This paper examines the Chilean economy and its enterprises with respect to those of the East Asian economic models of Keiretsu (Japan), Commonwealth (China), and Chaebol (South Korea), using a case study approach to understand the ways in which these East Asian economic models have affected economic performance and development. Our analysis shows that job specifications in East Asian structure are less detailed and not strictly tied to individual tasks, and that formal rules and procedures tend to be interpreted rather flexibly, which is similar to Chilean structures. This similarity could allow Chile to better understand Asia's success and to achieve a higher level of performance in its own operations. Economic groups and medium Chilean enterprises could learn from the ways in which Keiretsu, Commonwealth, and Chaebol expand into the global market, using different sources of competitive advantage, achieving higher efficiency and risk management, and developing more innovations.
A Matrix for Post-Soviet ‘Color Revolutions’: Exorcising the Devil from the Details
Authors: Baev Pavel K.
Published: January 2012

The spectacular and unexpected explosion of revolutionary energy in the Arab world since the start of 2011 makes it more relevant to re-examine the chain of attempts to depose the quasi-democratic regimes in the states that emerged from the break-up of the USSR. Often called “color revolutions”, these attempts brought some remarkable results in the mid-2000s, but—against common perceptions—continue. The analysis shows that the rate of success in the collection of 13 cases is close to 50%, but the track record of post-revolutionary development is rather disappointing. Nothing in the processed data suggests a decline in the dynamics of the revolutionary processes in the former Soviet space, but the diminishing attention from the West and the ageing of autocracies (particularly in Central Asia) could make the forthcoming revolutions uglier as they drive state failure stronger than democratic change. The most complex situation matures in Russia, which has assumed the leadership role in suppressing the wave of revolutions but is experiencing a crisis of its corrupt and un-modernizable authoritarian regime.
U.S. Advance Pricing Agreement: An Option to Resolve International Tax Dispute in Transfer Pricing Cases
Authors: Park Min
Published: January 2012

Obtaining a preliminary approval from its tax authority as to its mehodologies of transfer pricing would provide taxpayers with a safe harbor. This preliminary measure provides positive assurance against unexpected income allocation adjustments made by the tax authority. Such a procedure is commonly referred to as an “Advance Pricing Agreement(APA).”

In order to be an effective income allocation method, an APA must be an either binational or multinational. Only binational or multinational APA could supplement the judicial, administrative, and treaty mechanisms for resolving transfer pricing issues related to income allocation when the traditional methods fails or are difficult to apply.

The binational APA negates the need to obtain APAs from two tax authorities and reduces the possibility of lengthy competent authority audits and negotiation. Thus, the binational APA can decreases burdens on both the taxpayers and tax authorities, and also helps avoid the risk of double taxation.
Labor Hoarding and SRIRL Pardox: Some Evidences from United Kingdom and United States
Authors: Chung Yongkyun
Published: January 2012

The purpose of this study is to investigate the significance of the labor hoarding phenomenon in explaining the SRIRL paradox, or procyclical productivity. Accordingly previous work in these areas is particularly important. First, the direct measurement of labor hoarding shows how prominent the labor hoarding phenomenon is in various industries. Second, evidences of SRIRL at business cycle frequencies are mixed. Third, recent literature on labor hoarding tests indicates that labor hoarding is an indispensible ingredient to explain SRIRL or procyclical productivity among competing hypotheses.
Anthropological Studies of People, Place, and Culture and Their Implications for Area Studies
Authors: Bak Sangmee
Published: January 2012

Notions of people, place, and culture have been central to anthropological studies, and have reflected several critical changes the discipline has experienced. Two of the most salient changes are: the awareness of multivocality in cultures, and the recognition of the negotiated and contested nature of people, place, and culture. Using an ethnographic example from Insa-Dong in Seoul, Korea, a socio-historical construction of a place is examined. The relationship among people, place, and culture is not a neat juxtaposition with predetermined and clear-cut boundaries, but a constantly changing, and politically challenged one. It is, therefore, highly necessary to incorporate the dynamic aspects of this relationship in the use of anthropological studies in area studies.
South China Sea or “Asian Mediterranean Sea”: Re-Conceptualizing a Common Regional Maritime Zone
Authors: Casino Eric S. , Shin Myongsup
Published: January 2012

The division of Southeast Asia into “mainland” and “insular” components hides a focal, unifying geographic element-the central body of water that the two halves bracket and encircle as a common heritage. Because this body of water, like its Near Eastern counterpart, has been a common maritime highway for all traders of Asia since ancient times, it might just as well be called the “Asian Mediterranean Sea.” The main purpose of the paper is to argue that current and future policies related to the exploitation of marine resources in Southeast Asia, particularly in the Asian Mediterranean Sea, should be carried out on a region-wide and collaborative basis. Such a multilateral approach is supported by a fuller understanding of the past sociocultural, political and commercial relations that marked this region in pre-colonial and colonial periods.
Globalization and the Nation State: The Case of South Korea
Authors: Kim Yun Tae
Published: January 2012

Globalization is becoming a very important motive for the transformative role of the state in developed and developing societies. Whether prompted by the internal failure of the developmental state or by external pressures from international institutions, economic globalization has resulted in significant changes in the roles and capacities of the state. The state is adapting to the globalizing economy, rather than directly conflicting with the globalization process. Although the Korean state, to some extent, will continue to play a role in social transformation, the nature of the state has shifted away from the old-style of the developmental state that guides and directs domestic private business in the strategic industrial areas. Thus the economic consequence of the changing role of the state has resulted in a collaborationist alliance between the state and big business.
The Role of the Judge in the Common Law and Civil Law Systems: The Cases of the United States and European Countries
Authors: Yu Seon Bong
Published: January 2012

Traditionally, substantial differences between the common law and civil law systems in terms of judge's roles could be obviously identified. Today, however, it is becoming more difficult to identify the differences between the two systems. In the common law systems a good deal of codification has taken place and judges are playing a more active role in proceedings. On the other hand, judges in civil law systems are more inclined to follow precedents and a good deal of case law have been built up to assist in the interpretation of statutory codes. In this paper, I attempt to analyze some basic differences between the common law judge's roles and civil law judge's roles and contemporary trends.
The Role of Public Administration and Bureaucracy in Thailand
Authors: Lee Hwanbum
Published: January 2012

To restore the Thai economy within a reasonable period, the Thai government needs a continuous improvement or innovation of both public administration and bureaucracy. Since 1958 Thai public administration has been accepted a big role for the nation's modernization and has executed the goals of social and economic development. This study identifies the current status of not the only roles and functions of Thai public administration and bureaucracy, but also the Thai governmental administrative system both as part of its decisionmaking apparatus and in order to carry out those decisions. Additionally, this study examines the necessity of Thai governmental reform to improve productivity in public organizations.
Recombinant antibodies encoded by IGHV1-69 react with pUL32, a phosphoprotein of cytomegalovirus and B-cell superantigen
Authors: Steininger Christoph , Widhopf George F. , Ghia Emanuela M. , Morello Christopher S. , Vanura Katrina , Sanders Rebecca , Spector Deborah , Guiney Don , Jäger Ulrich , Kipps Thomas J.
Published: January 2012

Leukemia cells from patients with chronic lymphocytic leukemia (CLL) express a highly restricted immunoglobulin heavy variable chain (IGHV) repertoire, suggesting that a limited set of antigens reacts with leukemic cells. Here, we evaluated the reactivity of a panel of different CLL recombinant antibodies (rAbs) encoded by the most commonly expressed IGHV genes with a panel of selected viral and bacterial pathogens. Six different CLL rAbs encoded by IGHV1-69 or IGHV3-21, but not a CLL rAb encoded by IGHV4-39 genes, reacted with a single protein of human cytomegalovirus (CMV). The CMV protein was identified as the large structural phosphoprotein pUL32. In contrast, none of the CLL rAbs bound to any other structure of CMV, adenovirus serotype 2, Salmonella enterica serovar Typhimurium, or of cells used for propagation of these microorganisms. Monoclonal antibodies or humanized rAbs of irrelevant specificity to pUL32 did not react with any of the proteins present in the different lysates. Still, rAbs encoded by a germ line IGHV1-69 51p1 allele from CMV-seropositive and -negative adults also reacted with pUL32. The observed reactivity of multiple different CLL rAbs and natural antibodies from CMV-seronegative adults with pUL32 is consistent with the properties of a superantigen.
Platelet Ca2+ responses coupled to glycoprotein VI and Toll-like receptors persist in the presence of endothelial-derived inhibitors: roles for secondary activation of P2X1 receptors and release from intracellular Ca2+ stores
Authors: Fung C. Y. Eleanor , Jones Sarah , Ntrakwah Adwoa , Naseem Khalid M. , Farndale Richard W. , Mahaut-Smith Martyn P.
Published: January 2012

Inhibition of Ca2+ mobilization by cyclic nucleotides is central to the mechanism whereby endothelial-derived prostacyclin and nitric oxide limit platelet activation in the intact circulation. However, we show that ∼ 50% of the Ca2+ response after stimulation of glycoprotein VI (GPVI) by collagen, or of Toll-like 2/1 receptors by Pam3Cys-Ser-(Lys)4 (Pam3CSK4), is resistant to prostacyclin. At low agonist concentrations, the prostacyclin-resistant Ca2+ response was predominantly because of P2X1 receptors activated by ATP release via a phospholipase-C–coupled secretory pathway requiring both protein kinase C and cytosolic Ca2+ elevation. At higher agonist concentrations, an additional pathway was observed because of intracellular Ca2+ release that also depended on activation of phospholipase C and, for TLR 2/1, PI3-kinase. Secondary activation of P2X1-dependent Ca2+ influx also persisted in the presence of nitric oxide, delivered from spermine NONOate, or increased ectonucleotidase levels (apyrase). Surprisingly, apyrase was more effective than prostacyclin and NO at limiting secondary P2X1 activation. Dilution of platelets reduced the average extracellular ATP level without affecting the percentage contribution of P2X1 receptors to collagen-evoked Ca2+ responses, indicating a highly efficient activation mechanism by local ATP. In conclusion, platelets possess inhibitor-resistant Ca2+ mobilization pathways, including P2X1 receptors, that may be particularly important during early thrombotic or immune-dependent platelet activation.
Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics
Authors: Kumar Shaji , Fonseca Rafael , Ketterling Rhett P. , Dispenzieri Angela , Lacy Martha Q. , Gertz Morie A. , Hayman Suzanne R. , Buadi Francis K. , Dingli David , Knudson Ryan A. , Greenberg Alexandra , Russell Stephen J. , Zeldenrust Steven R. , Lust John A. , Kyle Robert A. , Bergsagel Leif , Rajkumar S. Vincent
Published: January 2012

Routine incorporation of FISH into multiple myeloma (MM) diagnostic testing has led to a better appreciation of the heterogeneity of genetic abnormalities associated with this disease. We studied a group of 484 patients with newly diagnosed symptomatic MM to better understand the prevalence of the various abnormalities and the prognostic significance of the overlapping abnormalities. A translocation involving the IgH locus and 1 of the 5 recurrent partner chromosomes was seen in 161 (33%) patients, and 275 (57%) had trisomy of at least 1 odd-numbered chromosome. High-risk FISH, defined as the presence of t(4;14), t(14;16), t(14;20), or loss of P53, was seen in 115 (24%) patients; the median overall survival for this group was 3.9 years, compared with “not reached” for standard-risk patients (P < .001). Among the patients with high-risk FISH, 49 patients who also had at least 1 trisomy had a median overall survival that was not reached, compared with 3 years for high-risk patients without a concurrent trisomy (P = .01). Based on the current findings, we conclude that the presence of trisomies in patients with t(4;14), t(14;16), t(14;20), or p53 deletion abnormalities in MM ameliorates the usual adverse impact associated with these prognostic markers.
Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children
Authors: Prentice Andrew M. , Doherty Conor P. , Abrams Steven A. , Cox Sharon E. , Atkinson Sarah H. , Verhoef Hans , Armitage Andrew E. , Drakesmith Hal
Published: January 2012

Iron supplementation strategies in the developing world remain controversial because of fears of exacerbating prevalent infectious diseases. Understanding the conditions in which iron will be absorbed and incorporated into erythrocytes is therefore important. We studied Gambian children with either postmalarial or nonmalarial anemia, who were given oral iron supplements daily for 30 days. Supplements administered on days 1 and 15 contained the stable iron isotopes 57Fe and 58Fe, respectively, and erythrocyte incorporation was measured in blood samples drawn 14 days later. We investigated how the iron-regulatory hormone hepcidin and other inflammatory/iron-related indices, all measured on the day of isotope administration, correlated with erythrocyte iron incorporation. In univariate analyses, hepcidin, ferritin, C-reactive protein, and soluble transferrin receptor (sTfR) strongly predicted incorporation of 57Fe given on day 1, while hepcidin, ferritin, and sTfR/log ferritin correlated with 58Fe incorporation. In a final multivariate model, the most consistent predictor of erythrocyte isotope incorporation was hepcidin. We conclude that under conditions of competing signals (anemia, iron deficiency, and infection), hepcidin powerfully controls use of dietary iron. We suggest that low-cost point-of-care hepcidin assays would aid iron supplementation programs in the developing world.
Desmosomal cadherins in zebrafish epiboly and gastrulation
Authors: Goonesinghe Alexander , Luan Xing-Ming , Hurlstone Adam , Garrod David
Published: January 2012

Background

The desmosomal cadherins (DCs), desmocollin (Dsc) and desmoglein (Dsg), are the adhesion molecules of desmosomes, intercellular adhesive junctions of epithelia and cardiac muscle. Both the DCs and desmosomes have demonstrably essential roles in mammalian development. In order to initiate their study in a more tractable developmental system we have characterised zebrafish DCs and examined their roles in early zebrafish development.

Results

We find that zebrafish possess one Dsc, the orthologue of mammalian Dsc1, which we designate zfDsc. Unlike mammalian Dscs, zfDsc exists only as the "a" form since it lacks the alternatively-spliced mini-exon that shortens the cytoplasmic domain to produce the "b" form. Zebrafish possess two Dsgs, designated zfDsgα and zfDsgβ, orthologues of mammalian Dsg2. They show 43.8% amino acid identity and the α form has a 43 amino acid glycine-rich sequence of unknown function in its extracellular domain. Both zfDsc and zfDsgα were present as maternal and zygotic transcripts whereas zfDsgβ was first expressed from 8 hours post-fertilisation (hpf). All three transcripts were present throughout subsequent stages of development. Morpholino knockdown of both zfDsc and zfDsgα expression produced similar defects in epiboly, axis elongation and somite formation, associated with abnormal desmosomes or reduced desmosome numbers.

Conclusions

These results demonstrate an important role for DCs and desmosomes in the early morphogenesis of the zebrafish embryo, provide a basis for more detailed analysis of their role and raise interesting questions relating to the evolution and functional significance of DC isoforms.
Community-based educational intervention to limit the dissemination of community-associated methicillin-resistant Staphylococcus aureusin Northern Saskatchewan, Canada
Authors: Golding George R , Quinn Brian , Bergstrom Kirsten , Stockdale Donna , Woods Shirley , Nsungu Mandiangu , Brooke Barb , Levett Paul N , Horsman Greg , McDonald Ryan , Szklarczuk Brian , Silcox Steve , Paton Shirley , Carson Mary , Mulvey Michael R , Irvine James ,   the Northern Antibiotic Resistance Partnership
Published: January 2012

Background

Surveillance examining the incidence of community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) was conducted over 8 years beginning in 2001 in three health regions covering the northern half of Saskatchewan. The annual rate of individuals reported with CA-MRSA infection in these regions dramatically increased from 8.2 per 10,000 population in 2001 (range to 4.4-10.1 per 10,000) to 168.1 per 10,000 in 2006 (range 43.4-230.9 per 10,000). To address this issue, a team of community members, healthcare professionals, educators and research scientists formed a team called "the Northern Antibiotic Resistance Partnership" (NARP) to develop physician, patient, community, and school based educational materials in an attempt to limit the spread of CA-MRSA.

Methods

Posters, radio broadcasts, community slide presentations, physician treatment algorithms, patient pamphlets, and school educational programs Do Bugs Need Drugshttp://www.dobugsneeddrugs.organd Germs Awayhttp://www.germsaway.cawere provided to targeted northern communities experiencing high rates of infections.

Results

Following implementation of this program, the rates of MRSA infections in the targeted communities have decreased nearly two-fold (242.8 to 129.3 infections/10,000 population) from 2006 to 2008. Through pre-and post-educational intervention surveys, this decrease in MRSA infections coincided with an increase in knowledge related to appropriate antimicrobial usage and hand washing in these communities.

Conclusion

These educational materials are all freely availablehttp://www.narp.caand will hopefully aid in increasing awareness of the importance of proper antimicrobial usage and hygiene in diminishing the spread ofS. aureusand other infectious diseases in other communities.
Mutant pfcrt "SVMNT" haplotype and wild type pfmdr1 "N86" are endemic in Plasmodium vivax dominated areas of India under high chloroquine exposure
Authors: Mallick Prashant K , Joshi Hema , Valecha Neena , Sharma Surya K , Eapen Alex , Bhatt Rajendra M , Srivastava Harish C , Sutton Patrick L , Dash Aditya P , Bhasin Virendra K
Published: January 2012

Background

Chloroquine resistance (CQR) phenotype in Plasmodium falciparum is associated with mutations in pfcrt and pfmdr-1 genes. Mutations at amino acid position 72-76 of pfcrt gene, here defined as pfcrt haplotype are associated with the geographic origin of chloroquine resistant parasite. Here, mutations at 72-76 and codon 220 of pfcrt gene and N86Y pfmdr-1 mutation were studied in blood samples collected across 11 field sites, inclusive of high and low P. falciparum prevalent areas in India. Any probable correlation between these mutations and clinical outcome of CQ treatment was also investigated.

Methods

Finger pricked blood spotted on Whatman No.3 papers were collected from falciparum malaria patients of high and low P. falciparum prevalent areas. For pfcrt haplotype investigation, the parasite DNA was extracted from blood samples and used for PCR amplification, followed by partial sequencing of the pfcrt gene. For pfmdr-1 N86Y mutation, the PCR product was subjected to restriction digestion with AflIII endonuclease enzyme.

Results

In 240 P. falciparum isolates with reported in vivo CQ therapeutic efficacy, the analysis of mutations in pfcrt gene shows that mutant SVMNT-S (67.50%) and CVIET-S (23.75%) occurred irrespective of clinical outcome and wild type CVMNK-A (7.91%) occurred only in adequate clinical and parasitological response samples. Of 287 P. falciparum isolates, SVMNTS 192 (66.89%) prevailed in all study sites and showed almost monomorphic existence (98.42% isolates) in low P. falciparum prevalent areas. However, CVIETS-S (19.51%) and CVMNK-A (11.84%) occurrence was limited to high P. falciparum prevalent areas. Investigation of pfmdr-1 N86Y mutation shows no correlation with clinical outcomes. The wild type N86 was prevalent in all the low P. falciparum prevalent areas (94.48%). However, mutant N86Y was comparably higher in numbers at the high P. falciparum prevalent areas (42.76%).

Conclusions

The wild type pfcrt gene is linked to chloroquine sensitivity; however, presence of mutation cannot explain the therapeutic efficacy of CQ in the current scenario of chloroquine resistance. The monomorphic existence of mutant SVMNT haplotype, infer inbreeding and faster spread of CQR parasite in areas with higher P. vivax prevalance and chloroquine exposure, whereas, diversity is maintained in pfcrt gene at high P. falciparum prevalent areas.
Automatic filtering of outliers in RR intervals before analysis of heart rate variability in Holter recordings: a comparison with carefully edited data
Authors: Karlsson Marcus , Hörnsten Rolf , Rydberg Annika , Wiklund Urban
Published: January 2012

Background

Undetected arrhythmic beats seriously affect the power spectrum of the heart rate variability (HRV). Therefore, the series of RR intervals are normally carefully edited before HRV is analysed, but this is a time consuming procedure when 24-hours recordings are analysed. Alternatively, different methods can be used for automatic removal of arrhythmic beats and artefacts. This study compared common frequency domain indices of HRV when determined from manually edited and automatically filtered RR intervals.

Methods and Results

Twenty-four hours Holter recordings were available from 140 healthy subjects of age 1-75 years. An experienced technician carefully edited all recordings. Automatic filtering was performed using a recursive procedure where RR intervals were removed if they differed from the mean of the surrounding RR intervals with more than a predetermined limit (ranging from 10% to 50%). The filtering algorithm was evaluated by replacing 1% of the beats with synthesised ectopic beats. Power spectral analysis was performed before and after filtering of both the original edited data and the noisy data set. The results from the analysis using the noisy data were used to define an age-based filtering threshold. The age-based filtration was evaluated with completely unedited data, generated by removing all annotations from the series of RR intervals, and then comparing the resulting HRV indices with those obtained using edited data. The results showed equivalent results after age-based filtration of both the edited and unedited data sets, where the differences in HRV indices obtained by different preprocessing methods were small compared to the mean values within each age group.

Conclusions

The study showed that it might not be necessary to perform the time-consuming careful editing of all detected heartbeats before HRV is analysed in Holter recordings.

In most subjects, it is sufficient to perform the regular editing needed for valid arrhythmia analyses, and then remove undetected ectopic beats and artefacts by age-based filtration of the series of RR intervals, particularly in subjects older than 30 years.
Analysis of EBNA-1 and LMP-1 variants in diseases associated with EBV infection in Chinese children
Authors: Ai Junhong , Xie Zhengde , Liu Chunyan , Huang Zhizuo , Xu Junmei
Published: January 2012

Background

In China, primary EBV infection occurs during childhood with seroprevalence reaching about 100% by 10 years of age. There are few studies on EBV variants in diseases associated with EBV infection in Chinese children. In this study, we investigated the diversity of the EBV genes (EBNA-1 and LMP-1) and the relationship between EBV variants and the clinical phenotypes in diseases associated with EBV infections in Chinese pediatric cases.

Results

The frequencies of EBV type I in the IM, HLH and HL samples were 98.4%, 100% and 95.8%, respectively. Three known EBNA-1 variants were identified, including V-val (all were V-val-v1 sub-variant), P-thr' and V-Leu (MT). The frequency of V-val-v1 was 98.6% in the IM samples, 100% in the HLH samples and 97.1% in the HL samples. There were no significant differences of the distribution of EBNA-1 variants between IM, HLH and HL samples (P > 0.05). Three known LMP-1 variants, including China 1, China 2 and Med, were identified and China 1 was predominant in all groups (IM 88.6%, HLH 100% and HL 100%). The frequency of del-LMP-1 was 88.6% in the IM samples, 100% in the HLH samples and 96.0% in the HL samples. There were no significant differences in the frequency of del-LMP-1 between the IM, HLH and HL samples (P > 0.05). The frequency of Xho I loss was 90.6% in the IM samples, 100% in the HLH samples and 100% in the HL samples, with no significant difference in frequency (P > 0.05). In the EBV type I strain, V-val-v1 variant (EBNA-1) was linked with China1 variant (LMP-1) in 88.9% of the IM samples, 100% of the HLH samples and 80.0% of the HL samples in this study.

Conclusions

Type I EBV was the most prevalent subtype EBV in Chinese pediatric cases and V-val-v1 (EBNA-1) and China1 (LMP-1) variants were the most dominant variants. There was a strong linkage between V-val-v1 (EBNA-1) variant and China1 (LMP-1) variant in type I EBV. The sequence variation in EBV genes may represent a geographic polymorphism since no preferential associations were found between specific EBV variants and specific diseases in this study.
Managing co-morbid depression and anxiety in primary care patients with asthma and/or chronic obstructive pulmonary disease: study protocol for a randomized controlled trial
Authors: Pommer Antoinette M , Pouwer François , Denollet Johan , Pop Victor J M
Published: January 2012

Background

Chronic Obstructive Pulmonary Disease (COPD) and asthma are common chronic diseases that are frequently accompanied by depression and/or anxiety. However, symptoms of depression and anxiety are often not recognized and therefore not treated. Currently, only a few studies have tested new clinical approaches that could improve the treatment of co-morbid depression and anxiety in these groups of patients.

Methods/design

The present randomized controlled study will be conducted within the framework of PoZoB (Praktijk Ondersteuning Zuid-Oost Brabant), a large primary care organization in the Netherlands. Patients with asthma/COPD and co-morbid anxiety/depression will be included in order to test the effectiveness of a disease management approach to treat these co-morbid disorders. Important elements of this approach are: 1) systematic screening to improve detection of anxiety and depression 2) treatment in case of positive screening 3) monitoring of anxiety and depression 4) intensified treatment in case of non-remission (stepped care).

Discussion

The present study is a large primary care study on the treatment of co-morbid depression and anxiety in patients with asthma and COPD. Strengths of this study are its randomized design, the focus on implementation in primary care and the fact that it applies the latest findings on the treatment of depression and anxiety. First results are expected in 2012/2013.

Trial registration

Netherlands Trial Register (NTR):NTR2626
Molecular detection of Setaria tundra (Nematoda: Filarioidea) and an unidentified filarial species in mosquitoes in Germany
Authors: Czajka Christina , Becker Norbert , Poppert Sven , Jöst Hanna , Schmidt-Chanasit Jonas , Krüger Andreas
Published: January 2012

Background

Knowledge of the potential vector role of Culicidae mosquitoes in Germany is very scanty, and until recently it was generally assumed that they are not involved in the transmission of anthroponotic or zoonotic pathogens in this country. However, anticipated changes in the course of global warming and globalization may alter their status.

Methods

We conducted a molecular mass screening of mosquitoes for filarial parasites using mitochondrial 12S rRNA-based real-time PCR.

Results

No parasites causing disease in humans such asDirofilariaspp. were detected in about 83,000 mosquitoes tested, which had been collected in 2009 and 2010 in 16 locations throughout Germany. However, minimum infection rates of up to 24 per 1000 mosquitoes were revealed, which could be attributed to mosquito infection withSetaria tundraand a yet unidentified second parasite.Setaria tundrawas found to be widespread in southern Germany in various mosquito species, exceptCulexspp. In contrast, the unidentified filarial species was exclusively found inCulexspp. in northern Baden-Württemberg, and is likely to be a bird parasite.

Conclusions

Although dirofilariasis appears to be emerging and spreading in Europe, the absence ofDirofilariaspp. or other zoonotic filariae in our sample allows the conclusion that the risk of autochthonous infection in Germany is still very low. Potential vectors ofS. tundrain Germany areOchlerotatus sticticus,Oc. cantans,Aedes vexansandAnopheles claviger. Technically, the synergism between entomologists, virologists and parasitologists, combined with state-of-the-art methods allows a very efficient near-real-time monitoring of a wide spectrum of both human and veterinary pathogens, including new distribution records of parasite species and the incrimination of their potential vectors.
Hyperinsulinemia enhances c-Myc-mediated mammary tumor development and advances metastatic progression to the lung in a mouse model of type 2 diabetes
Authors: Ferguson Rosalyn D , Novosyadlyy Ruslan , Fierz Yvonne , Alikhani Nyosha , Sun Hui , Yakar Shoshana , LeRoith Derek
Published: January 2012

Introduction

Hyperinsulinemia, which is common in early type 2 diabetes (T2D) as a result of the chronically insulin-resistant state, has now been identified as a specific factor which can worsen breast cancer prognosis. In breast cancer, a high rate of mortality persists due to the emergence of pulmonary metastases.

Methods

Using a hyperinsulinemic mouse model (MKR+/+) and the metastatic, c-Myc-transformed mammary carcinoma cell line Mvt1, we investigated how high systemic insulin levels would affect the progression of orthotopically inoculated primary mammary tumors to lung metastases.

Results

We found that orthotopically injected Mvt1 cells gave rise to larger mammary tumors and to a significantly higher mean number of pulmonary macrometastases in hyperinsulinemic mice over a period of six weeks (hyperinsulinemic, 19.4 ± 2.7 vs. control, 4.0 ± 1.3). When Mvt1-mediated mammary tumors were allowed to develop and metastasize for approximately two weeks and were then surgically removed, hyperinsulinemic mice demonstrated a significantly higher number of lung metastases after a four-week period (hyperinsulinemic, 25.1 ± 4.6 vs. control, 7.4 ± 0.42). Similarly, when Mvt1 cells were injected intravenously, hyperinsulinemic mice demonstrated a significantly higher metastatic burden in the lung than controls after a three-week period (hyperinsulinemic, 6.0 ± 1.63 vs. control, 1.5 ± 0.68). Analysis of Mvt1 cells both in vitro and in vivo revealed a significant up-regulation of the transcription factor c-Myc under hyperinsulinemic conditions, suggesting that hyperinsulinemia may promote c-Myc signaling in breast cancer. Furthermore, insulin-lowering therapy using the beta-adrenergic receptor agonist CL-316243 reduced metastatic burden in hyperinsulinemic mice to control levels.

Conclusions

Hyperinsulinemia in a mouse model promotes breast cancer metastasis to the lung. Therapies to reduce insulin levels in hyperinsulinemic patients suffering from breast cancer could lessen the likelihood of metastatic progression.
Early initiation of low-dose corticosteroid therapy in the management of septic shock: a retrospective observational study
Authors: Park Hye Yun , Suh Gee Young , Song Jae-Uk , Yoo Hongseok , Jo Ik Joon , Shin Tae Gun , Lim So Yeon , Woo Sookyoung , Jeon Kyeongman
Published: January 2012

Introduction

The use of low-dose steroid therapy in the management of septic shock has been extensively studied. However, the association between the timing of low-dose steroid therapy and the outcome has not been evaluated. Therefore, we evaluated whether early initiation of low-dose steroid therapy is associated with mortality in patients with septic shock.

Methods

We retrospectively analyzed the clinical data of 178 patients who received low-dose corticosteroid therapy for septic shock between January 2008 and December 2009. Time-dependent Cox regression models were used to adjust for potential confounding factors in the association between the time to initiation of low-dose corticosteroid therapy and in-hospital mortality.

Results

The study population consisted of 107 men and 71 women with a median age of 66 (interquartile range, 54 to 71) years. The 28-day mortality was 44% and low-dose corticosteroid therapy was initiated within a median of 8.5 (3.8 to 19.1) hours after onset of septic shock-related hypotension. Median time to initiation of low-dose corticosteroid therapy was significantly shorter in survivors than in non-survivors (6.5 hours versus 10.4 hours; P = 0.0135). The mortality rates increased significantly with increasing quintiles of time to initiation of low-dose corticosteroid therapy (P = 0.0107 for trend). Other factors associated with 28-day mortality were higher Simplified Acute Physiology Score (SAPS) 3 (P < 0.0001) and Sequential Organ Failure Assessment (SOFA) scores (P = 0.0007), dose of vasopressor at the time of initiation of low-dose corticosteroid therapy (P < 0.0001), need for mechanical ventilation (P = 0.0001) and renal replacement therapy (P < 0.0001), while the impaired adrenal reserve did not affect 28-day mortality (81% versus 82%; P = 0.8679). After adjusting for potential confounding factors, the time to initiation of low-dose corticosteroid therapy was still significantly associated with 28-day mortality (adjusted odds ratio (OR) 1.025, 95% confidence interval (CI) 1.007 to 1.044, P = 0.0075). The early therapy group (administered within 6 hours after the onset of septic shock, n = 66) had a 37% lower mortality rate than the late therapy group (administered more than 6 hours after the onset of septic shock, n = 112) (32% versus 51%, P = 0.0132).

Conclusions

Early initiation of low-dose corticosteroid therapy was significantly associated with decreased mortality.
Carboxyhemoglobin levels in medical intensive care patients: a retrospective, observational study
Authors: Fazekas Andreas S , Wewalka Marlene , Zauner Christian , Funk Georg-Christian
Published: January 2012

Introduction

Critical illness leads to increased endogenous production of carbon monoxide (CO) due to the induction of the stress-response enzyme, heme oxygenase-1 (HO-1). There is evidence for the cytoprotective and anti-inflammatory effects of CO based on animal studies. In critically ill patients after cardiothoracic surgery, low minimum and high maximum carboxyhemoglobin (COHb) levels were shown to be associated with increased mortality, which suggests that there is an 'optimal range' for HO-1 activity. Our study aimed to test whether this relationship between COHb and outcome exists in non-surgical ICU patients.

Methods

We conducted a retrospective, observational study in a medical ICU at a university hospital in Vienna, Austria involving 868 critically ill patients. No interventions were undertaken. Arterial COHb was measured on admission and during the course of treatment in the ICU. The association between arterial COHb levels and ICU mortality was evaluated using bivariate tests and a logistic regression model.

Results

Minimum COHb levels were slightly lower in non-survivors compared to survivors (0.9%, 0.7% to 1.2% versus 1.2%, 0.9% to 1.5%; P = 0.0001), and the average COHb levels were marginally lower in non-survivors compared to survivors (1.5%, 1.2% to 1.8% versus 1.6%, 1.4% to 1.9%, P = 0.003). The multivariate logistic regression analysis revealed that the association between a low minimum COHb level and increased mortality was independent of the severity of illness and the type of organ failure.

Conclusions

Critically ill patients surviving the admission to a medical ICU had slightly higher minimum and marginally higher average COHb levels when compared to non-survivors. Even though the observed differences are statistically significant, the minute margins would not qualify COHb as a predictive marker for ICU mortality.