Thirteen-Year Follow-up of Optic Disc Hemorrhages in the Ocular Hypertension Treatment Study

To determine the cumulative incidence of optic disc hemorrhage (ODH) before and after development of primary open angle glaucoma (POAG); determine the prognostic significance of ODH for the development of POAG; identify predictive factors for ODH

Analysis of Underground Storage Tanks System Materials to Increased Leak Potential Associated with E15 Fuel

The Energy Independence and Security Act (EISA) of 2007 was enacted by Congress to move the nation toward increased energy independence by increasing the production of renewable fuels to meet its transportation energy needs. The law establishes a new renewable fuel standard (RFS) that requires the nation to use 36 billion gallons annually (2.3 million barrels per day) of renewable fuel in its vehicles by 2022. Ethanol is the most widely used renewable fuel in the US, and its production has grown dramatically over the past decade. According to EISA and RFS, ethanol (produced from corn as well as cellulosic feedstocks) will make up the vast majority of the new renewable fuel requirements. However, ethanol use limited to E10 and E85 (in the case of flex fuel vehicles or FFVs) will not meet this target. Even if all of the E0 gasoline dispensers in the country were converted to E10, such sales would represent only about 15 billion gallons per year. If 15% ethanol, rather than 10% were used, the potential would be up to 22 billion gallons. The vast majority of ethanol used in the United States is blended with gasoline to create E10, that is, gasoline with up to 10% ethanol. The remaining ethanol is sold in the form of E85, a gasoline blend with as much as 85% ethanol that can only be used in FFVs. Although DOE remains committed to expanding the E85 infrastructure, that market will not be able to absorb projected volumes of ethanol in the near term. Given this reality, DOE and others have begun assessing the viability of using intermediate ethanol blends as one way to transition to higher volumes of ethanol. In October of 2010, the EPA granted a partial waiver to the Clean Air Act allowing the use of fuel that contains up to 15% ethanol for the model year 2007 and newer light-duty motor vehicles. This waiver represents the first of a number of actions that are needed to move toward the commercialization of E15 gasoline blends. On January 2011, this waiver was expanded to include model year 2001 light-duty vehicles, but specifically prohibited use in motorcycles and off-road vehicles and equipment. UST stakeholders generally consider fueling infrastructure materials designed for use with E0 to be adequate for use with E10, and there are no known instances of major leaks or failures directly attributable to ethanol use. It is conceivable that many compatibility issues, including accelerated corrosion, do arise and are corrected onsite and, therefore do not lead to a release. However, there is some concern that higher ethanol concentrations, such as E15 or E20, may be incompatible with current materials used in standard gasoline fueling hardware. In the summer of 2008, DOE recognized the need to assess the impact of intermediate blends of ethanol on the fueling infrastructure, specifically located at the fueling station. This includes the dispenser and hanging hardware, the underground storage tank, and associated piping. The DOE program has been co-led and funded by the Office of the Biomass Program and Vehicle Technologies Program with technical expertise from the Oak Ridge National Laboratory (ORNL) and the National Renewable Energy Laboratory (NREL). The infrastructure material compatibility work has been supported through strong collaborations and testing at Underwriters Laboratories (UL). ORNL performed a compatibility study investigating the compatibility of fuel infrastructure materials to gasoline containing intermediate levels of ethanol. These results can be found in the ORNL report entitled Intermediate Ethanol Blends Infrastructure Materials Compatibility Study: Elastomers, Metals and Sealants (hereafter referred to as the ORNL intermediate blends material compatibility study). These materials included elastomers, plastics, metals and sealants typically found in fuel dispenser infrastructure. The test fuels evaluated in the ORNL study were SAE standard test fuel formulations used to assess material-fuel compatibility within a relatively short timeframe. Initially, these material studies included test fuels of Fuel C, CE10a, CE17a, and CE25a. The CE17a test fuel was selected to represent E15 since surveys have shown that the actual ethanol upper limit can be as high as 17%. Later, CE50a and CE85a test fuels were added to the investigation and these results are being compiled for a follow-on report to be published in 2012. Fuel C was used as the baseline reference and is a 50:50 blend of isooctane and toluene. This particular composition was used to represent premium-grade gasoline and was also used as the base fuel for the ethanol blends, where it is denoted by 'C' in the fuel name. The level of ethanol is represented by the number following the letter E. Therefore a 10% blend of ethanol in Fuel C is written as CE10a, where 'a' represents an aggressive formulation of the ethanol that contains water, NaCl, acetic and sulfuric acids per the SAE J1681 protocol

Revealing components of the galaxy population through nonparametric techniques

The distributions of galaxy properties vary with environment, and are often multimodal, suggesting that the galaxy population may be a combination of multiple components. The behaviour of these components versus environment holds details about the processes of galaxy development. To release this information we apply a novel, nonparametric statistical technique, identifying four components present in the distribution of galaxy H$\alpha$ emission-line equivalent-widths. We interpret these components as passive, star-forming, and two varieties of active galactic nuclei. Independent of this interpretation, the properties of each component are remarkably constant as a function of environment. Only their relative proportions display substantial variation. The galaxy population thus appears to comprise distinct components which are individually independent of environment, with galaxies rapidly transitioning between components as they move into denser environments.Comment: 12 pages, 10 figures, accepted for publication in MNRA

Autoreactivity to Glucose Regulated Protein 78 Links Emphysema and Osteoporosis in Smokers

Rationale: Emphysema and osteoporosis are epidemiologically associated diseases of cigarette smokers. The causal mechanism(s) linking these illnesses is unknown. We hypothesized autoimmune responses may be involved in both disorders. Objectives: To discover an antigen-specific autoimmune response associated with both emphysema and osteoporosis among smokers. Methods: Replicate nonbiased discovery assays indicated that autoimmunity to glucose regulated protein 78 (GRP78), an endoplasmic reticulum chaperone and cell surface signaling receptor, is present in many smokers. Subject assessments included spirometry, chest CT scans, dual x-ray absorptiometry, and immunoblots for anti-GRP78 IgG. Anti-GRP78 autoantibodies were isolated from patient plasma by affinity chromatography, leukocyte functions assessed by flow cytometry, and soluble metabolites and mediators measured by immunoassays. Measurements and Main Results Circulating anti-GRP78 IgG autoantibodies were detected in plasma specimens from 86 (32%) of the 265 smoking subjects. Anti-GRP78 autoantibodies were singularly prevalent among subjects with radiographic emphysema (OR 3.1, 95%CI 1.7–5.7, p = 0.003). Anti-GRP78 autoantibodies were also associated with osteoporosis (OR 4.7, 95%CI 1.7–13.3, p = 0.002), and increased circulating bone metabolites (p = 0.006). Among emphysematous subjects, GRP78 protein was an autoantigen of CD4 T-cells, stimulating lymphocyte proliferation (p = 0.0002) and IFN-gamma production (p = 0.03). Patient-derived anti-GRP78 autoantibodies had avidities for osteoclasts and macrophages, and increased macrophage NFkB phosphorylation (p = 0.005) and productions of IL-8, CCL-2, and MMP9 (p = 0.005, 0.007, 0.03, respectively). Conclusions: Humoral and cellular GRP78 autoimmune responses in smokers have numerous biologically-relevant pro-inflammatory and other deleterious actions, and are associated with emphysema and osteoporosis. These findings may have relevance for the pathogenesis of smoking-associated diseases, and development of biomarker immunoassays and/or novel treatments for these disorders

Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

Background: The English National Health Service has made a major investment in nine partnerships between higher education institutions and local health services called Collaborations for Leadership in Applied Health Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and implement research through sustained interactions between academics and health services. CLAHRCs provide a natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery. This protocol describes an externally funded evaluation that focuses on implementation mechanisms and processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances. Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth comparative case studies of research implementation using multiple data collection methods including interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of data collection. We will test the wider applicability of emerging findings with a wider community using an interpretative forum. Discussion: The idea that collaboration between academics and services might lead to more applicable health research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g., Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts particularly with respect to integrated stakeholder involvement

Observational constraints on the distribution, seasonality, and environmental predictors of North American boreal methane emissions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106685/1/GBC_20128_REVISED_suppinfo.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106685/2/gbc20128.pd

UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans

Uncoordinated movement in Rab2 mutants is caused by impaired retention of cargo on dense core vesicles, not by defective synaptic vesicle release. (Also see the companion article by Edwards et al. in this issue.

Sarcolemma-localized nNOS is required to maintain activity after mild exercise

Many neuromuscular conditions are characterized by an exaggerated exercise- induced fatigue response that is disproportionate to activity level. This fatigue is not necessarily correlated with greater central or peripheral fatigue in patients(1), and some patients experience severe fatigue without any demonstrable somatic disease(2). Except in myopathies that are due to specific metabolic defects, the mechanism underlying this type of fatigue remains unknown(2). With no treatment available, this form of inactivity is a major determinant of disability(3). Here we show, using mouse models, that this exaggerated fatigue response is distinct from a loss in specific force production by muscle, and that sarcolemma-localized signalling by neuronal nitric oxide synthase ( nNOS) in skeletal muscle is required to maintain activity after mild exercise. We show that nNOS- null mice do not have muscle pathology and have no loss of muscle- specific force after exercise but do display this exaggerated fatigue response to mild exercise. In mouse models of nNOS mislocalization from the sarcolemma, prolonged inactivity was only relieved by pharmacologically enhancing the cGMP signal that results from muscle nNOS activation during the nitric oxide signalling response to mild exercise. Our findings suggest that the mechanism underlying the exaggerated fatigue response to mild exercise is a lack of contraction- induced signalling from sarcolemma- localized nNOS, which decreases cGMP- mediated vasomodulation in the vessels that supply active muscle after mild exercise. Sarcolemmal nNOS staining was decreased in patient biopsies from a large number of distinct myopathies, suggesting a common mechanism of fatigue. Our results suggest that patients with an exaggerated fatigue response to mild exercise would show clinical improvement in response to treatment strategies aimed at improving exercise- induced signalling.Paul D. Wellstone Muscular Dystrophy Cooperative Research Center Grant ; University of Iowa Cardiovascular Interdisciplinary Research ; National Research Service Award ; National Institute of Arthritis and Musculoskeletal and Skin Diseases ; National Institutes of Health ; Senator Paul D. Wellstone Fellowship ; Muscular Dystrophy Association Development Grant ; Howard Hughes Medical InstituteWe thank M. Anderson and M. Henry for comments, and M. M. Kilburg, K. Uppal, B. J. Steinmann and S. Watkins and members of the Campbell laboratory for scientific contributions. This work was supported in part by a Paul D. Wellstone Muscular Dystrophy Cooperative Research Center Grant. Y.M.K. was supported by grants from the University of Iowa Cardiovascular Interdisciplinary Research/ National Research Service Award (NRSA) Fellowship, from an individual NRSA Fellowship from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, from the National Institutes of Health (NIH), and from a Senator Paul D. Wellstone Fellowship. E.P.R. was supported by a Muscular Dystrophy Association Development Grant. R.M.W. was supported by the NIH. K.P.C. is an investigator of the Howard Hughes Medical Institute.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62850/1/nature07414.pd