Patan hospital experience in treating philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia patients with gleevec (imatinib mesylate); the first generation specific tyrosine kinase inhibitor

<p>Abstract</p> <p>Background</p> <p>Chronic Myeloid Leukemia (CML) is caused by the abnormal fusion protein BCR-ABL1, a constitutively active tyrosine kinase and product of the Philadelphia chromosome. Gleevec (Imatinib mesylate) is a selective inhibitor of this kinase. Treatment with this agent is known to result in hematologic, cytogenetic, and molecular responses. Patan hospital (Patan, Nepal) is one of the Gleevec International Patient Assistance Program (GIPAP) centers for patients with CML.</p> <p>Methods</p> <p>A total of 106 Philadelphia positive CML patients were enrolled in our center between Feb 2003 and Jun 2008, and 103 of them were eligible for cytogenetic and/or hematologic response analyses.</p> <p>Results</p> <p>Out of 103 patients, 27% patients underwent cytogenetic analysis. Imatinib induced major cytogenetic responses in 89% and complete hematologic responses in almost 100% of the patients with confirmed CML. After a mean follow up of 27 months, an estimated 90% of the patients on imatinib remained in hematologic remission and more than 90% of the patients are still alive. About 30% of patients developed some form of manageable myelosuppression. A few patients developed non-hematologic toxic side effects such as edema and hepatotoxicity.</p> <p>Conclusions</p> <p>Our study demonstrates that imatinib is safe to use in a developing country. Furthermore, we demonstrate that imatinib is very effective and induced long lasting responses in a high proportion of patients with Ph chromosome/BCR-ABL1 positive CML. Imatinib is well tolerated by our patients. The lack of cytogenetic analysis in the majority of our patients hindered our ability to detect inadequate responses to imatinib and adjust therapy appropriately.</p

Market structure, Regulation and the Speed of Mobile Network Penetration

The speed of market penetration (i.e. diffusion) is an important summary measure of how well the market works for potential consumers of a new product. This paper identifies the structural features associated with rapid diffusion of mobile telephony. We use a sample of thirty countries over the sixteen years in which average penetration rose from 2% to 97% of the population (earlier studies observed only the initial years of diffusion during which there was typically only one or two networks). We find a non-monotonic effect of market structure, with three firms maximising consumer uptake. Privatization and independent regulation are also important positive factors. Further results show that the market structure effect works only partially through the level of prices

Intellectual Property in Medical Imaging and Informatics: The Independent Inventor’s Perspective

While innovation and new product development is traditionally thought of as the exclusive domain of industry and academia, a large number of innovations in medicine and information technology have come from independent inventors, which account for almost 30% of new patents issued in the U.S. today. A large number of economic, political, and legal challenges exist within the current marketplace that serves as relative impediments to independent invention. This article explores the existing challenges facing the independent inventor and offers a number of recommendations and resources to facilitate independent inventors in their quest for innovation and entrepreneurship. The concept of “outsourcing innovation” is discussed as an alternative to the existing model of industry sponsored research and development (R&D), with the goal of combining the unique attributes and strengths of independent inventors and industry sponsors

Berry Anthocyanin, Acid, and Volatile Trait Analyses in a Grapevine-Interspecific F2 Population Using an Integrated GBS and rhAmpSeq Genetic Map

Increased map density and transferability of markers are essential for the genetic analysis of fruit quality and stress tolerance in interspecific grapevine populations. We used 1449 GBS and 2000 rhAmpSeq markers to develop a dense map for an interspecific F2 population (VRS-F2) that was derived by selfing a single F1 from a Vitis riparia x ‘Seyval blanc’ cross. The resultant map contained 2519 markers spanning 1131.3 cM and was highly collinear with the Vitis vinifera ‘PN40024’ genome. Quantitative trait loci (QTL) for berry skin color and flower type were used to validate the map. Four rhAmpSeq transferable markers were identified that can be used in pairs (one pistillate and one hermaphroditic) to predict pistillate and hermaphrodite flower type with ≥99.7% accuracy. Total and individual anthocyanin diglucoside QTL mapped to chromosome 9 near a 5-O-GLUCOSYLTRANSFERASE candidate gene. Malic acid QTL were observed on chromosome 1 and 6 with two MALATE DEHYRDROGENASE CYTOPLASMIC 1 and ALUMINUM-ACTIVATED MALATE TRANSPORTER 2-LIKE (ALMT) candidate genes, respectively. Modeling malic acid identified a potential QTL on chromosome 8 with peak position in proximity of another ALMT. A first-ever reported QTL for the grassy smelling volatile (E)-2-hexenal was found on chromosome 2 with a PHOSPHOLIPID HYDROPEROXIDE GLUTATHIONE PEROXIDASE candidate gene near peak markers

A Next-generation Marker Genotyping Platform (AmpSeq) in Heterozygous Crops: A Case Study for Marker-assisted Selection in Grapevine

Marker-assisted selection (MAS) is often employed in crop breeding programs to accelerate and enhance cultivar development, via selection during the juvenile phase and parental selection prior to crossing. Next-generation sequencing and its derivative technologies have been used for genome-wide molecular marker discovery. To bridge the gap between marker development and MAS implementation, this study developed a novel practical strategy with a semi-automated pipeline that incorporates traitassociated single nucleotide polymorphism marker discovery, low-cost genotyping through amplicon sequencing (AmpSeq) and decision making. The results document the development of a MAS package derived from genotyping-by-sequencing using three traits (flower sex, disease resistance and acylated anthocyanins) in grapevine breeding. The vast majority of sequence reads ( ⩾99%) were from the targeted regions. Across 380 individuals and up to 31 amplicons sequenced in each lane of MiSeq data, most amplicons (83 to 87%) had o10% missing data, and read depth had a median of 220–244 × . Several strengths of the AmpSeq platform that make this approach of broad interest in diverse crop species include accuracy, flexibility, speed, high-throughput, lowcost and easily automated analysis

Regime Type and Bilateral Treaty Formalization

How does domestic regime type affect bilateral cooperation, and one of its most visible manifestations, bilateral treaties? This article explains how domestic political regime affects bilateral cooperation and, contrary to the expectations of some scholars, why autocracies should be expected to be more likely than democracies to enter into bilateral treaties. If the preferences of a pair of states are not identical, the sets of agreements that each party would consent to (win-sets) need to overlap for a bilateral treaty to be acceptable. Because additional domestic constraints reduce the size of a country’s win-set, autocracies should have broader win-sets than democracies. Therefore, autocratic dyads should be more likely to formalize bilateral treaties than other pairs of states. Based on an original data set, I present empirical evidence showing that pairs of autocracies are more likely than other pairs of states to enter into agreements formalizing bilateral cooperation

External Design for Reputation, Perspective and Exposure

This paper analyses why and how design‐centred industrial firms with internal design teams contract external designers. This research is based on an exploratory multiple case study methodology, with a sample of five highly reputable design‐centred industrial firms, operating in hypercompetitive industries. While some results challenge the mainstream literature on design management, others expand the existing literature, highlighting that not all firms extract the same benefits from external designers; neither do all external designers bring the same benefits to firms. The paper shows that firms with internal design teams contract external design for (1) reputation (external designers sign products and bring their reputation to the product and to the firm), (2) perspective (external designers bring a different perspective, especially when they come from a different industry from the firm), and (3) exposure (external designers bring exposure that enriches internal design teams)

Macaque models of human infectious disease.

Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease

The coexistence of peace and conflict in South America: toward a new conceptualization of types of peace

South America's predominant democratic regimes and its increasing interdependence on regional trade have not precluded the emergence of militarized crises between Colombia and Venezuela or the revival of boundary claims between Chile and Peru. This way, how can we characterize a zone that, in spite of its flourishing democracy and dense economic ties, remain involved in territorial disputes for whose resolution the use of force has not yet been discarded? This article contends that existing classifications of zones of peace are not adequate to explain this unusual coexistence. Thus, its main purpose is to develop a new analytical category of regional peace for assessing this phenomenon: the hybrid peace. It aims to research the evolution of security systems in South America during the previous century and build a new, threefold classification of peace zones: negative peace zones, hybrid peace zones, and positive peace zones

State Control and the Effects of Foreign Relations on Bilateral Trade

Do states use trade to reward and punish partners? WTO rules and the pressures of globalization restrict states’ capacity to manipulate trade policies, but we argue that governments can link political goals with economic outcomes using less direct avenues of influence over firm behavior. Where governments intervene in markets, politicization of trade is likely to occur. In this paper, we examine one important form of government control: state ownership of firms. Taking China and India as examples, we use bilateral trade data by firm ownership type, as well as measures of bilateral political relations based on diplomatic events and UN voting to estimate the effect of political relations on import and export flows. Our results support the hypothesis that imports controlled by state-owned enterprises (SOEs) exhibit stronger responsiveness to political relations than imports controlled by private enterprises. A more nuanced picture emerges for exports; while India’s exports through SOEs are more responsive to political tensions than its flows through private entities, the opposite is true for China. This research holds broader implications for how we should think about the relationship between political and economic relations going forward, especially as a number of countries with partially state-controlled economies gain strength in the global economy