145 research outputs found
ALTERNATIVE DISPUTE RESOLUTION AND PEACE MAKING FOR RESOLVING AGRIBUSINESS AND FOOD MANAGEMENT CONFLICT RESOLUTION IN THE FREE TRADE AREA OF THE AMERICAS GRASS ROOTS INITIATIVES WITH INTERNATIONAL APPLICATIONS
The FTAA (Free Trade Area of the Americas) will bring together 35 countries with five different languages and over 300 ethnic and cultural groups. As trade, cultural discourse, and other joint efforts develop between countries, private organizations, public entities and individuals, many disputes will arise. In a few countries, the rule of law can solve these disputes effectively. In most others, the rule of law cannot work because of political, social or even criminal events. As NAFTA showed, developing a successful and efficient dispute resolution mechanism is an important component of developing a successful working relationship of the agreement among all the parties and countries. Other Trade Agreements including NAFTA and WTO have found that the successful functioning of these agreements require all private and public parties to think carefully about resolving disputes ahead of time and setting up a number of alternative processes to be used by the parties. Only in Government-to-Government disputes is the system quite simple. Otherwise, there are several models which have been developed in the U.S. and other American countries which can assist in resolving agribusiness and food management conflict resolution in rural communities. Grass roots initiatives with international applications, disputes over land, grazing rights, homes, credit issues and financial resources can be a serious impediment to growth. In Arizona, U.S. and the Americas, this has caused large dollar value disputes, ill will, riots and even death. In both rural and agricultural based Arizona, U.S. and the Americas, this presentation highlights methodology and courses being developed to solve some of these conflicts.Agribusiness, International Relations/Trade,
The Important and Changing Role of Cooperatives and Producer Associations in the Southwest
Agribusiness,
Plasma Ang2 and ADAM17 levels are elevated during clinical malaria; Ang2 level correlates with severity and expression of EPCR-binding PfEMP1
The pathogenesis of Plasmodium falciparum malaria involves a complex interplay between parasite adhesion and inflammatory response that includes release of cytokines and activation of the endothelium with accompanying release of Angiopoitin 2 (Ang2) to the plasma. A-disintegrin and metalloproteinase 17 (ADAM17) is a protein responsible for releasing cytokines, including Tumor Necrosis Factor α (TNFα), and shedding of adhesion proteins. In this study, we show that plasma levels of ADAM17 are increased in Tanzanian children hospitalized with a malaria infection compared with asymptomatic children but similar to children hospitalized with other infectious diseases. The plasma levels of ADAM17 decreased during recovery after an acute malaria episode. Plasma levels of Ang2 were associated with markers of malaria severity and levels of var transcripts encoding P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) containing Cysteine Rich Inter Domain Region α1 (CIDRα1) domains predicted to bind Endothelial Protein C receptor (EPCR). ADAM17 levels were not associated with expression of var genes encoding different PfEMP1 types when controlling for age. These data are the first to report ADAM17 plasma levels in malaria-exposed individuals, and support the notion that parasite sequestration mediated by EPCR-binding PfEMP1 is associated with endothelial activation and pathology in severe paediatric malaria
Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque
Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events
Hundreds of variants clustered in genomic loci and biological pathways affect human height
Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy.
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This article is open access.The genetic contribution to longevity in humans has been estimated to range from 15% to 25%. Only two genes, APOE and FOXO3, have shown association with longevity in multiple independent studies.We conducted a meta-analysis of genome-wide association studies including 6,036 longevity cases, age ≥90 years, and 3,757 controls that died between ages 55 and 80 years. We additionally attempted to replicate earlier identified single nucleotide polymorphism (SNP) associations with longevity.In our meta-analysis, we found suggestive evidence for the association of SNPs near CADM2 (odds ratio [OR] = 0.81; p value = 9.66 × 10(-7)) and GRIK2 (odds ratio = 1.24; p value = 5.09 × 10(-8)) with longevity. When attempting to replicate findings earlier identified in genome-wide association studies, only the APOE locus consistently replicated. In an additional look-up of the candidate gene FOXO3, we found that an earlier identified variant shows a highly significant association with longevity when including published data with our meta-analysis (odds ratio = 1.17; p value = 1.85×10(-10)).We did not identify new genome-wide significant associations with longevity and did not replicate earlier findings except for APOE and FOXO3. Our inability to find new associations with survival to ages ≥90 years because longevity represents multiple complex traits with heterogeneous genetic underpinnings, or alternatively, that longevity may be regulated by rare variants that are not captured by standard genome-wide genotyping and imputation of common variants.Netherlands Organisation of Scientific Research NWO Investments
175.010.2005.011
911-03-012
Research Institute for Diseases in the Elderly
014-93-015
RIDE2
Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO)
050-060-810
Erasmus Medical Center
Erasmus University, Rotterdam
Netherlands Organization for the Health Research and Development (ZonMw)
Research Institute for Diseases in the Elderly (RIDE)
Ministry of Education, Culture and Science
Ministry for Health, Welfare and Sports
European Commission (DG XII)
Municipality of Rotterdam
National Institutes of Health
National Institute on Aging (NIA)
R01 AG005407
R01 AR35582
R01 AR35583
R01 AR35584
R01 AG005394
R01 AG027574
R01 AG027576
AG023629
R01AG29451
U01AG009740
RC2 AG036495
RC4 AG039029
P30AG10161
R01AG17917
R01AG15819
R01AG30146
U01-AG023755
U19-AG023122
NHLBI
HHSN 268201200036C
HHSN268200800007C
N01HC55222
N01HC85079
N01HC85080
N01HC85081
N01HC85082
N01HC85083
N01HC 85086
HL080295
HL087652
HL105756
National Institute of Neurological Disorders and Stroke (NINDS)
National Center for Advancing Translational Sciences, CTSI
UL1TR000124
National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC)
DK063491
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Center for Research Resources (NCRR)
NIH Roadmap for Medical Research
U01 AR45580
U01 AR45614
U01 AR45632
U01 AR45647
U01 AR45654
U01 AR45583
U01 AG18197
U01-AG027810
UL1 RR024140
NIAMS
R01-AR051124
RC2ARO58973
National Heart, Lung and Blood Institute's Framingham Heart Study
N01-HC-25195
Affymetrix, Inc
N02-HL-6-4278
Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine
Boston Medical Center
National Institute of Arthritis, Musculoskeletal and Skin Diseases
NIA
R01 AR/AG 41398
NIH
N01-AG-12100
NIA Intramural Research Program
Hjartavernd (the Icelandic Heart Association)
Althingi (the Icelandic Parliament)
Illinois Department of Public Health
Translational Genomics Research Institute
Italian Ministry of Health
ICS110.1/RF97.71
U.S. National Institute on Aging
263 MD 9164
263 MD 821336
Intramural Research Program of the NIH, National Institute on Aging
1R01AG028321
1R01HL09257
p53 Expression in Node-Positive Breast Cancer Patients: Results from the Cancer and Leukemia Group B 9344 Trial (159905)
p53 as a prognostic and predictive factor in early stage breast cancer, has had mixed results. We studied p53 protein expression, by immunohistochemistry, in a randomized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel (CALGB 9344, INT0148)
Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342
INTRODUCTION: The response to paclitaxel varies widely in metastatic breast cancer. We analyzed data from CALGB 9342, which tested three doses of paclitaxel in women with advanced disease, to determine whether response and outcomes differed according to HER2, hormone receptor, and p53 status. METHODS: Among 474 women randomly assigned to paclitaxel at a dose of 175, 210, or 250 mg/m(2), adequate primary tumor tissue was available from 175. Immunohistochemistry with two antibodies and fluorescence in situ hybridization were performed to evaluate HER2 status; p53 status was determined by immunohistochemistry and sequencing. Hormone receptor status was obtained from pathology reports. RESULTS: Objective response rate was not associated with HER2 or p53 status. There was a trend toward a shorter median time to treatment failure among women with HER2-positive tumors (2.3 versus 4.2 months; P = 0.067). HER2 status was not related to overall survival (OS). Hormone receptor expression was not associated with differences in response but was associated with longer OS (P = 0.003). In contrast, women with p53 over-expression had significantly shorter OS than those without p53 over-expression (11.5 versus 14.4 months; P = 0.002). In addition, triple negative tumors were more frequent in African-American than in Caucasian patients, and were associated with a significant reduction in OS (8.7 versus 12.9 months; P = 0.008). CONCLUSION: None of the biomarkers was predictive of treatment response in women with metastatic breast cancer; however, survival differed according to hormone receptor and p53 status. Triple negative tumors were more frequent in African-American patients and were associated with a shorter survival
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