Somatic Mutations In Aging, Paroxysmal Nocturnal Hemoglobinuria, And Myeloid Neoplasms

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal blood disorder frequently associated with bone marrow failure that in rare instances can progress to leukemia. PNH clones of varying sizes occasionally present even in patients with hematologic malignancies and no known history of classical PNH, particularly in myelodysplastic neoplasms (MDS). Curiously, somatic driver mutations considered to be pathogenic and likely pathogenic in myeloid leukemias can be found in phenotypically normal, elderly individuals, as well as those with clonal disorders such as PNH, clonal hematopoiesis of indeterminate potential (CHIP), and age-related clonal hematopoiesis (ARCH). These mutations may be the critical link between PNH and the development of cancer. We suspect that PNH clones, derived from mutations in PIGA, may reflect a disordered bone marrow prone to additional genetic hits involved in tumorigenesis. It is uncertain, however, whether leukemic cells directly arise from PNH+ progenitors with additional genetic variants or if they are in fact distinct populations. Moreover, the specific driver mutations that underlie both PNH and myeloid neoplasms remains an area of active investigation. Our study aims to characterize the prevalence of myeloid neoplasm-associated somatic mutations in older adults and in patients who develop myeloid malignancies (MN+ patients), stratified by whether they also harbor PNH clones. We retrospectively examined the initial genetic evaluation by next-generation sequencing (NGS) of 197 individuals at Yale-New Haven Hospital and elicited the most common driver mutations and their association with age and PNH clonal presence. We demonstrated that pathogenic and likely pathogenic somatic mutations increased with age (average age of patients with one or more mutations was 69.8 years compared to 58.0 years in those with no mutations of interest, p\u3c 0.0001). Variants in SF3B1 (average age= 74.4 years, p= 0.0015), TP53 (average age= 72.8 years, p= 0.0057), SRSF2 (average age= 72.4 years, p= 0.0024), DNMT3A (average age= 71.9 years, p= 0.0059), TET2 (average age= 70.8 years, p= 0.0032), ASXL1 (average age= 70 years, p= 0.0052), and U2AF1 (average age= 69.7 years, p= 0.0082) were most commonly present in adults who were significantly older than those with no relevant mutations. Those with a diagnosis of a myeloid neoplasm were drastically more likely to harbor driver mutations (81.1% with at least one variant of interest vs. 23.5% among those without a myeloid neoplasm, p\u3c 0.0001), and had a greater number of mutations on average (1.95 vs. 0.38 mutations per patient, p\u3c 0.0001). Interestingly, MN+ patients who had a PNH clone ≥0.01% were significantly more likely to possess a neoplasm-associated mutation than those with no PNH clones (91.9% vs. 60.6%, p= 0.0005), indicating that the presence of PNH clones augments the odds of possessing cancer-related genetic lesions as early as the time of the initial evaluation. Specifically, patients who were both MN+ and PNH+ were more likely than their PNH- counterparts to have one or two pathogenic and likely pathogenic variants (58.1% vs. 27.3%), though they were equally likely to possess three or more mutations (33.9% vs. 33.3%). Furthermore, among all patients in the cohort ≥70 years, PNH presence significantly increased the overall likelihood of discovering relevant gene variants (78.9% vs. 48.7%, ?2 p= 0.0027). Among all patients, PNH clone presence was correlated with mutations in SF3B1 (85.7% of cases with SF3B1 variants had PNH clones compared 56.8% of cases with no mutations had PNH clones, Fisher’s exact test, p= 0.0402), and to a lesser degree, with RUNX1 (83.3% PNH+ cases, p= 0.0686) and DNMT3A (80.0% PNH+ cases, p= 0.0914). Finally, we qualitatively described that mutations in ASXL1, TET2, and SRSF2 tended to occur together; there were also concomitant mutations in TET2 with EZH2 and in SF3B1 with RUNX1. Therefore, we recommend early genetic screening of all elderly patients ≥70 years who present with PNH clones of any size in the peripheral blood as these patients have a higher likelihood of harboring pathogenic and likely pathogenic driver mutations. We demonstrated that certain neoplasm-associated mutations are common in elderly patients, while others correlated with PNH clone presence, and that some variants tend to co-occur. Future studies should address the molecular mechanisms of these lesions in leukemogenesis. The observation that PNH clone presence is significantly correlated with somatic mutations in MN+ disease suggests an important relationship between PNH clones and cancer, either as direct tumor precursor populations or as an incidental consequence of high genetic mutability in a vulnerable bone marrow

Technology transfer in the Asian Pacific region

노트 : Volume Title: Trade and protectionismChapter Tilte: Technology transfer in the Asian Pacific region: Implications of trends since the mid-1980

Understanding the Rise of Social Enterprises in Vietnam: Social Capital, Factors of Emergence and Policy Considerations

Social enterprises are important contributors to Vietnam's socio-economic development, namely by providing services in such areas as health and education. While the state-managed Central Institute of Economic Management (CIEM) has recently acknowledged their presence and put forth related public policy suggestions, there remains a lack of related government policies and sparse literature exploring the emergence of social enterprises. This thesis therefore aimed to enrich the literature and help inform potential government policy decisions by exploring possible explanations for social enterprise emergence in Vietnam, and examining the perceptions of social enterprises regarding related potential state policies. An analysis based on both qualitative and quantitative data, in conjunction with social capital theory and theoretical explanations for social enterprise emergence (Teasdale 2011), suggested that levels of social capital are not conducive to the rise of social enterprises in Vietnam, while the state's failure to adequately address its population's socio-economic needs was a primary explanation for social enterprise emergence. The CIEM's policy suggestions were also found to be strongly correlated with the expressed needs of Vietnamese social enterprises, indicating that these suggested policies are contextually relevant and their implementation could enable social enterprises to further address government shortcomings in meeting the country's development needs

Public Housing after Hurricane, Urban Renewal or Removal? The Case Studies of Beaumont and Galveston, Texas.

Decent housing is a goal for many people not only in the United States but elsewhere in the world. A house becomes the symbol of family spirit whether it is a single-family or multiple-family home. Public housing in the United States is housing of “last resort,” for families whose incomes do not allow them to find housing in the private market. Yet, many studies focusing on public housing find a host of social issues plaguing these units. The US Government has initiated various programs to improve the quality of public housing as well as the living condition of local resident through agenda of Department of Housing and Urban Development (HUD). HOPE VI is one of the major programs that focuses on distressed public housing. This program funds local government and housing authority in order to revitalized or rebuild public housing. This program has been very successful in providing high-quality housing for public housing residents. However, as any type of construction, housing usually received great damage when natural disaster happening. It can be partly damaged or completely destroyed due to the direct and indirect effects of disaster. Public housing, like most affordable housing, is often built in highly vulnerable areas, such as floodplains or other low-lying areas. When disasters such as hurricanes strike, housing located in these areas is likely to receive the greatest damage and recovery may be slower. This study looks at the case study of public housing in Galveston and Beaumont after Hurricane Ike (2008) and Rita (2005). After Hurricane Rita in 2005, Beaumont has rebuilt some public housing development with a HOPE VI grant awarded in 2007. These areas have successfully rebuilt through the cooperation of housing authority, local government, local residents, and developers. In contrast, Galveston could not reach agreement about the destiny of public housing after Hurricane Ike in 2008. This story becomes more serious when HUD announced that if Galveston cannot rebuild public housing in disaster area, they must refund the money to the federal Government. These two cities provide a comparative case study of the rebuilding of public housing after disaster, where on one successfully rebuilt while other did not. By looking at the secondary data sources, this research analyzes the situation of these places in different period: before the Hurricane, when the Hurricane happened, and after the Hurricane. The paper will address the similarities as well as differences between two case studies in term of historical profile, demography, public housing program characteristics, damage, and recovery. Besides, economic change after hurricane approached is addressed. The housing situation will be further analyzed in Galveston to clearly show the obstacles in which this city coped with. Finally, the study will conclude by suggesting some implications for theory, housing policy, management, and further research

PageRank algorithm for Directed Hypergraph

During the last two decades, we easilly see that the World Wide Web's link structure is modeled as the directed graph. In this paper, we will model the World Wide Web's link structure as the directed hypergraph. Moreover, we will develop the PageRank algorithm for this directed hypergraph. Due to the lack of the World Wide Web directed hypergraph datasets, we will apply the PageRank algorithm to the metabolic network which is the directed hypergraph itself. The experiments show that our novel PageRank algorithm is successfully applied to this metabolic network.Comment: 6 page

BIOLOGICAL NITRIFICATION-DENITRIFICATION TREATMENT OF AMMONIUM NITROGEN POLLUTED HANOI- GROUNDWATER USING A NOVEL ACRYL-RESIN FIBER FOR BIOMASS ATTACHMENT

Joint Research on Environmental Science and Technology for the Eart

Public Housing after Hurricane, Urban Renewal or Removal? The Case Studies of Beaumont and Galveston, Texas.

Decent housing is a goal for many people not only in the United States but elsewhere in the world. A house becomes the symbol of family spirit whether it is a single-family or multiple-family home. Public housing in the United States is housing of “last resort,” for families whose incomes do not allow them to find housing in the private market. Yet, many studies focusing on public housing find a host of social issues plaguing these units. The US Government has initiated various programs to improve the quality of public housing as well as the living condition of local resident through agenda of Department of Housing and Urban Development (HUD). HOPE VI is one of the major programs that focuses on distressed public housing. This program funds local government and housing authority in order to revitalized or rebuild public housing. This program has been very successful in providing high-quality housing for public housing residents. However, as any type of construction, housing usually received great damage when natural disaster happening. It can be partly damaged or completely destroyed due to the direct and indirect effects of disaster. Public housing, like most affordable housing, is often built in highly vulnerable areas, such as floodplains or other low-lying areas. When disasters such as hurricanes strike, housing located in these areas is likely to receive the greatest damage and recovery may be slower. This study looks at the case study of public housing in Galveston and Beaumont after Hurricane Ike (2008) and Rita (2005). After Hurricane Rita in 2005, Beaumont has rebuilt some public housing development with a HOPE VI grant awarded in 2007. These areas have successfully rebuilt through the cooperation of housing authority, local government, local residents, and developers. In contrast, Galveston could not reach agreement about the destiny of public housing after Hurricane Ike in 2008. This story becomes more serious when HUD announced that if Galveston cannot rebuild public housing in disaster area, they must refund the money to the federal Government. These two cities provide a comparative case study of the rebuilding of public housing after disaster, where on one successfully rebuilt while other did not. By looking at the secondary data sources, this research analyzes the situation of these places in different period: before the Hurricane, when the Hurricane happened, and after the Hurricane. The paper will address the similarities as well as differences between two case studies in term of historical profile, demography, public housing program characteristics, damage, and recovery. Besides, economic change after hurricane approached is addressed. The housing situation will be further analyzed in Galveston to clearly show the obstacles in which this city coped with. Finally, the study will conclude by suggesting some implications for theory, housing policy, management, and further research