61 research outputs found
North Carolina Cooperative Extension Professionals\u27 Climate Change Perceptions, Willingness, and Perceived Barriers to Programming: An Educational Needs Assessment
The educational needs assessment reported here measured North Carolina Cooperative Extension (NCCE) professionals\u27 perceptions of global warming and identified barriers to climate change programming. Survey results from 400 NCCE professionals show 70% are cautious, concerned, or alarmed about global warming. Liberal and female Extension professionals were more likely to be alarmed and concerned than their conservative and male counterparts. Respondents indicated willingness to engage in programming, but need in-service training to address conflicts, gather information, and emphasize relevancy. NCCE professionals perceive lack of audience interest, conflicts within available information, and lack of applied information as the greatest barriers to climate change programming
From Extractivism to Global Extractivism : The Evolution of an Organizing Concept
All the named authors were members of the Helsinki Research Working Group on Global Extractivisms and Alternatives, who jointly constructed this article. Equal authorship by all authors is recognised.Research on extractivism has rapidly proliferated, expanding into new empirical and conceptual spaces. We examine the origins, evolution, and conceptual expansion of the concept. Extractivism is useful to analyze resource extraction practices around the world. ‘Global Extractivism’ is a new conceptual tool for assessing global phenomena. We situate extractivism within an ensemble of concepts, and explore its relation to development, the state, and value. Extractivism as an organizing concept addresses many fields of research. Extractivism forms a complex of self-reinforcing practices, mentalities, and power differentials underwriting and rationalizing socio-ecologically destructive modes of organizing life-through subjugation, depletion, and non-reciprocity.Peer reviewe
Prime–boost vaccination with plasmid and adenovirus gene vaccines control HER2/neu(+ )metastatic breast cancer in mice
INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu(+ )cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models. METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad of mice as a model of solid tumor growth or was injected intravenously as a model of lung metastasis. SINCP-neu, a plasmid containing Sindbis virus genes and the gene for rat HER2/neu, and Adeno-neu, an E1,E2a-deleted adenovirus also containing the gene for rat HER2/neu, were tested as preventive and therapeutic vaccines. RESULTS: Vaccination with SINCP-neu or Adeno-neu before tumor challenge with A2L2 cells significantly inhibited the growth of the cells injected into the mammary fat or intravenously. Vaccination 2 days after tumor challenge with either vaccine was ineffective in both tumor models. However, therapeutic vaccination in a prime–boost protocol with SINCP-neu followed by Adeno-neu significantly prolonged the overall survival rate of mice injected intravenously with the tumor cells. Naive mice vaccinated using the same prime–boost protocol demonstrated a strong serum immunoglobulin G response and p185-specific cellular immunity, as shown by the results of ELISPOT (enzyme-linked immunospot) analysis for IFNγ. CONCLUSION: We report herein that vaccination of mice with a plasmid gene vaccine and an adenovirus gene vaccine, each containing the gene for HER2/neu, prevented growth of a HER2/neu-expressing breast cancer cell line injected into the mammary fat pad or intravenously. Sequential administration of the vaccines in a prime–boost protocol was therapeutically effective when tumor cells were injected intravenously before the vaccination. The vaccines induced high levels of both cellular and humoral immunity as determined by in vitro assessment. These findings indicate that clinical evaluation of these vaccines, particularly when used sequentially in a prime–boost protocol, is justified
Polyantigenic Interferon-γ Responses Are Associated with Protection from TB among HIV-Infected Adults with Childhood BCG Immunization
Surrogate immunologic markers for natural and vaccine-mediated protection against tuberculosis (TB) have not been identified. HIV-infected adults with childhood BCG immunization entering the placebo arm of the DarDar TB vaccine trial in Dar es Salaam, Tanzania, were assessed for interferon gamma (IFN-γ) responses to three mycobacterial antigen preparations--secreted Mycobacterium tuberculosis antigens 85 (Ag85), early secretory antigenic target 6 (ESAT-6) and polyantigenic whole cell lysate (WCL). We investigated the association between the number of detectable IFN-γ responses at baseline and the subsequent risk of HIV-associated TB. During a median follow-up of 3.3 years, 92 (9.4%) of 979 placebo recipients developed TB. The incidence of TB was 14% in subjects with no detectable baseline IFN-γ responses vs. 8% in subjects with response to polyantigenic WCL (P = 0.028). Concomitant responses to secreted antigens were associated with further reduction in the incidence of HIV-associated TB. Overall the percentage of subjects with 0, 1, 2 and 3 baseline IFN-γ responses to mycobacterial preparations who developed HIV-associated TB was 14%, 8%, 7% and 4%, respectively (P = 0.004). In a multivariate Cox regression model, the hazard of developing HIV-associated TB was 46% lower with each increment in the number of detectable baseline IFN-γ responses (P<0.001). Among HIV-infected adults who received BCG in childhood and live in a TB-endemic country, polyantigenic IFN-γ responses are associated with decreased risk of subsequent HIV-associated TB. ClinicalTrials.gov NCT0052195
Immune mechanisms in malaria: new insights in vaccine development.
Early data emerging from the first phase 3 trial of a malaria vaccine are raising hopes that a licensed vaccine will soon be available for use in endemic countries, but given the relatively low efficacy of the vaccine, this needs to be seen as a major step forward on the road to a malaria vaccine rather than as arrival at the final destination. The focus for vaccine developers now moves to the next generation of malaria vaccines, but it is not yet clear what characteristics these new vaccines should have or how they can be evaluated. Here we briefly review the epidemiological and immunological requirements for malaria vaccines and the recent history of malaria vaccine development and then put forward a manifesto for future research in this area. We argue that rational design of more effective malaria vaccines will be accelerated by a better understanding of the immune effector mechanisms involved in parasite regulation, control and elimination
Adenovirus-5-Vectored P. falciparum Vaccine Expressing CSP and AMA1. Part B: Safety, Immunogenicity and Protective Efficacy of the CSP Component
Background: A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.\ud
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Methodology/Principal Findings: NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at 1x1010 particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.\ud
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Significance: The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection
Matrix Metalloproteinases-8 and-9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study
Introduction Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients. Methods In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied. Results Plasma MMP-8 and -9 were higher in patients than in healthy controls (P20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P20% groups (PPeer reviewe
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
The Use of Blood Products in Adult Patients with Burns
Introduction: Burn anemia represents a common complication following a burn injury. Burn anemia etiology carries distinct features occurring at each stage of the post-injury and treatment periods resulting from different causes. We aimed to analyze the use of blood components in Finnish burn victims and to identify patient- and injury-related factors influencing their use. Methods: To study the use of blood products in burn patients, we used data collected from the Optimal Use of Blood registry, developed through co-operation between 10 major hospital districts and the Finnish Red Cross Blood Service. Burn patients 18years treated at the Helsinki University Hospital between 2005 and 2011 with an in-hospital stay 1day who received at least one transfusion during their hospital stay were included in this study. Results: Among all 558 burn patients, 192 (34%) received blood products during their hospital stay. The transfused cohort comprised 192 burn patients. The study cohort received a total of 6087units of blood components, 2422units of leukoreduced red blood cells, 1728units of leukoreduced platelets, and 420units of single-donor fresh frozen plasma or, after 2007, 1517units of Octaplas((R)) frozen plasma. All three types of blood components were administered to 29% of patients, whereas 45% received only red blood cells and 6% received only Octaplas. Transfused patients were significantly older (p Discussion: We show that Finnish adult burn patients received ample transfusions. The number of blood components transfused varied according to the anatomical location of the injury and patient survival. Whether the additional mortality is related directly to transfusions or is merely a manifestation of the more severe burn injury remains unknown.Peer reviewe
A framework of industrial knowledge spillovers in big-science centres
We employed the grounded theory method to construct a framework describing the distinctive mechanisms through which big-science centers generate industrial knowledge spillovers in the economy. Our focus is on large-scale big-science installations typically associated with experimental physics. We draw on social network, social capital, and inter-organizational learning theories to examine knowledge spillovers accruing to industrial partner companies in big-science?industry dyads. The context for the study is provided by CERN?s new particle accelerator project, the Large Hadron Collider (LHC). In addition to building a grounded theory framework for the study of industrial knowledge spillovers, our study demonstrates the distinctive potential that big-science centers offer as a source of knowledge spillovers in national innovation systems
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