Comparative Immunogenicity of Na-GST-1 Human Hookworm Vaccine with Synthetic Glucopyranosyl Lipid Adjuvant (GLA) in BALB/c Mice

More than 740 million people worldwide are infected with Hookworm. Hookworm infection is most prevalent in the poorest of the poor populations of the world, and has serious health effects. Hookworm infection causes blood loss leading to iron deficiency anemia and protein energy malnutrition, which results in a compromised immune response. Consequently, the target human population suffers from an increased susceptibility to infectious diseases including hookworm infection. We have developed recombinant adult hookworm vaccines against hookworm infection to break this vicious cycle. Toll-like receptor (TLR) 4 agonist are known to boost immune response in healthy and immunocompromised individuals. We believe that co-injecting Synthetic Glucopyranosyl Lipid Adjuvant (GLA) a novel TLR-4 agonist with adult hookworm Na-GST-1 + Alhydrogel® vaccine will produce a robust and sustainable immune response in this target human population. Here, we discuss the rationale of using GLA, study designs and the results of the pre-clinical immunogenicity studies of the Human Hookworm Na-GST-1 + Alhydrogel® Vaccine in BALB/c mice with and without GLA. We conclude that, GLA enhanced the immunogenicity of co-administered adult hookworm Na-GST-1 + Alhydrogel® vaccine, producing a strong anti-Na-GST-1 IgG response. These preclinical results lay the foundation of co-administrating GLA with adult hookworm Na-GST-1 + Alhydrogel® vaccine in Phase 1 clinical trial in Brazil

Potency Testing for NTD Vaccines: Determining Relative Potency for the Na-GST-1 Human Hookworm Vaccine

Over the next decade, a new generation of vaccines will target the neglected tropical diseases (NTDs) . The goal of most NTD vaccines will be to reduce the morbidity and decrease the chronic debilitating nature of these often-forgotten infections - outcomes that are hard to measure in the traditional potency-testing paradigm . The absence of measurable correlates of protection, a lack of permissive animal models for lethal infection, and a lack of clinical indications that do not include the induction of sterilizing immunity required us to reconsider the traditional bioassay methods for determining vaccine potency . Owing to these limitations, potency assay design for NTD vaccines will increasingly rely on a paradigm where potency testing is one among many tools to ensure that a manufacturing process yields a product of consistent quality . This potency test is a bioassay using BALB/c mice, which evaluates the immunogenicity of the vaccine at set time interval post manufacture . Herein, we discuss the results of 12 month potency testing of Necator americanus-glutathione-S- transferase-1 (Na-GST-1) vaccine . The Effective Dose 50 (ED50), with its 95% fiducial limits (FL) for each time point was determined along with the Relative Potency with its 95% FL for 3, 6, 9 and 12 months post manufacture . Potency testing has shown that storage at 4° C decreases the ED50 and increases the relative potency of Na-GST-1 vaccine . We proposed that the change in ED50 and relative potency coincide with higher affinity binding of the Na-GST-1 to the Alhydrogel® that occurred during storage at 4° C . These preclinical results lay the foundation for moving forward with Phase 1 clinical trial in Brazil

Developing an Institutional Arrangement for a Whole-of-Government and Whole-of-Community Approach to Regional Adaptation to Sea Level Rise: The Hampton Roads Pilot Project

Adaptation to sea level rise (SLR) requires coordination among local, state, and federal entities and collaboration across governments, nonprofits, businesses, and residents. This coordination and collaboration are reflected in institutional arrangements associated with a whole-of-government and whole-of-community approach to regional adaptation. This study analyzes the development of an interlocal agreement (ILA), the Hampton Roads Sea Level Rise Preparedness and Resilience Intergovernmental Planning Pilot Project (the Pilot Project), as an example of such an arrangement. This study assesses how factors throughout three phases of ILA development (initiation, implementation, and execution) influence outcomes and effectiveness. Drawing upon participant observation, document analysis, survey of participants, and interviews with key informants this study identifies factors that facilitate effective regional adaptation to SLR (impetus, agreement) and factors that hamper adaptation efforts (funding, ease of delivery), and offers insight into the complexities of institutional collective action to address contentious and challenging issues such as SLR

Temporally-Consistent Annual Land Cover from Landsat Time Series in the Southern Cone of South America

The impact of land cover change across the planet continues to necessitate accurate methods to detect and monitor evolving processes from satellite imagery. In this context, regional and global land cover mapping over time has largely treated time as independent and addressed temporal map consistency as a post-classification endeavor. However, we argue that time can be better modeled as codependent during the model classification stage to produce more consistent land cover estimates over long time periods and gradual change events. To produce temporally-dependent land cover estimates—meaning land cover is predicted over time in connected sequences as opposed to predictions made for a given time period without consideration of past land cover—we use structured learning with conditional random fields (CRFs), coupled with a land cover augmentation method to produce time series training data and bi-weekly Landsat imagery over 20 years (1999–2018) across the Southern Cone region of South America. A CRF accounts for the natural dependencies of land change processes. As a result, it is able to produce land cover estimates over time that better reflect real change and stability by reducing pixel-level annual noise. Using CRF, we produced a twenty-year dataset of land cover over the region, depicting key change processes such as cropland expansion and tree cover loss at the Landsat scale. The augmentation and CRF approach introduced here provides a more temporally consistent land cover product over traditional mapping methods.EEA SaltaFil: Graesser, Jordan. Boston University. Department of Earth and Environment; Estados UnidosFil: Stanimirova, Radost. Boston University. Department of Earth and Environment; Estados UnidosFil: Tarrio, Katelyn. Boston University. Department of Earth and Environment; Estados UnidosFil: Copati, Esteban J. Bolsa de Cereales (Buenos Aires); ArgentinaFil: Volante, J. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Verón, S. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Clima y Agua; ArgentinaFil: Verón, Sebastian. Universidad de Buenos Aires. Facultad de Agronomía; ArgentinaFil: Verón, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Banchero, S. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Clima y Agua; ArgentinaFil: Elena, Hernan Javier. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Abelleyra, D. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Clima y Agua; ArgentinaFil: Friedl, Mark A. Boston University. Department of Earth and Environment; Estados Unido

Disease-modifying drugs for knee osteoarthritis: can they be cost-effective?

OBJECTIVE: Disease-modifying osteoarthritis drugs (DMOADs) are under development. Our goal was to determine efficacy, toxicity, and cost thresholds under which DMOADs would be a cost-effective knee OA treatment. DESIGN: We used the Osteoarthritis Policy Model, a validated computer simulation of knee OA, to compare guideline-concordant care to strategies that insert DMOADs into the care sequence. The guideline-concordant care sequence included conservative pain management, corticosteroid injections, total knee replacement (TKR), and revision TKR. Base case DMOAD characteristics included: 50% chance of suspending progression in the first year (resumption rate of 10% thereafter) and 30% pain relief among those with suspended progression; 0.5%/year risk of major toxicity; and costs of $1,000/year. In sensitivity analyses, we varied suspended progression (20-100$1,000-$7,000). Outcomes included costs, quality-adjusted life expectancy, incremental cost-effectiveness ratios (ICERs), and TKR utilization. RESULTS: Base case DMOADs added 4.00 quality-adjusted life years (QALYs) and$230,000 per 100 persons, with an ICER of $57,500/QALY. DMOADs reduced need for TKR by 15$3,000/year achieved ICERs below $100,000/QALY if the likelihoods of suspended progression and pain relief were 20$5,000, these ICERs were attained if the likelihoods of suspended progression and pain relief were both 60%. CONCLUSIONS: Cost, suspended progression, and pain relief are key drivers of value for DMOADs. Plausible combinations of these factors could reduce need for TKR and satisfy commonly cited cost-effectiveness criteri

Lifetime risk and age of diagnosis of symptomatic knee osteoarthritis in the US

OBJECTIVE: To estimate the incidence and lifetime risk of diagnosed symptomatic knee osteoarthritis (OA) and the age at diagnosis of knee OA based on self-reports in the US population. METHODS: We estimated the incidence of diagnosed symptomatic knee OA in the US by combining data on age-, sex-, and obesity-specific prevalence from the 2007-2008 National Health Interview Survey, with disease duration estimates derived from the Osteoarthritis Policy (OAPol) Model, a validated computer simulation model of knee OA. We used the OAPol Model to estimate the mean and median ages at diagnosis and lifetime risk. RESULTS: The estimated incidence of diagnosed symptomatic knee OA was highest among adults ages 55-64 years, ranging from 0.37% per year for nonobese men to 1.02% per year for obese women. The estimated median age at knee OA diagnosis was 55 years. The estimated lifetime risk was 13.83%, ranging from 9.60% for nonobese men to 23.87% in obese women. Approximately 9.29% of the US population is diagnosed with symptomatic knee OA by age 60 years. CONCLUSION: The diagnosis of symptomatic knee OA occurs relatively early in life, suggesting that prevention programs should be offered relatively early in the life course. Further research is needed to understand the future burden of health care utilization resulting from earlier diagnosis of knee OA. Copyright 2013 by the American College of Rheumatology

TeV Particle Astrophysics II: Summary comments

A unifying theme of this conference was the use of different approaches to understand astrophysical sources of energetic particles in the TeV range and above. In this summary I review how gamma-ray astronomy, neutrino astronomy and (to some extent) gravitational wave astronomy provide complementary avenues to understanding the origin and role of high-energy particles in energetic astrophysical sources.Comment: 6 pages, 4 figures; Conference summary talk for "TeV Particle Astrophysics II" at University of Wisconsin, Madison, 28-31 August 200

Lifetime risk and age of diagnosis of symptomatic knee osteoarthritis in the US

The definitive version is available at www3.interscience.wiley.comOBJECTIVE: To estimate the incidence and lifetime risk of diagnosed symptomatic knee osteoarthritis (OA) and the age at diagnosis of knee OA based on self-reports in the US population. METHODS: We estimated the incidence of diagnosed symptomatic knee OA in the US by combining data on age-, sex-, and obesity-specific prevalence from the 2007-2008 National Health Interview Survey, with disease duration estimates derived from the Osteoarthritis Policy (OAPol) Model, a validated computer simulation model of knee OA. We used the OAPol Model to estimate the mean and median ages at diagnosis and lifetime risk. RESULTS: The estimated incidence of diagnosed symptomatic knee OA was highest among adults ages 55-64 years, ranging from 0.37% per year for nonobese men to 1.02% per year for obese women. The estimated median age at knee OA diagnosis was 55 years. The estimated lifetime risk was 13.83%, ranging from 9.60% for nonobese men to 23.87% in obese women. Approximately 9.29% of the US population is diagnosed with symptomatic knee OA by age 60 years. CONCLUSION: The diagnosis of symptomatic knee OA occurs relatively early in life, suggesting that prevention programs should be offered relatively early in the life course. Further research is needed to understand the future burden of health care utilization resulting from earlier diagnosis of knee OA. Copyright 2013 by the American College of Rheumatology

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version