Scientific Objectives, Measurement Needs, and Challenges Motivating the PARAGON Aerosol Initiative

Aerosols are involved in a complex set of processes that operate across many spatial and temporal scales. Understanding these processes, and ensuring their accurate representation in models of transport, radiation transfer, and climate, requires knowledge of aerosol physical, chemical, and optical properties and the distributions of these properties in space and time. To derive aerosol climate forcing, aerosol optical and microphysical properties and their spatial and temporal distributions, and aerosol interactions with clouds, need to be understood. Such data are also required in conjunction with size-resolved chemical composition in order to evaluate chemical transport models and to distinguish natural and anthropogenic forcing. Other basic parameters needed for modeling the radiative influences of aerosols are surface reflectivity and three-dimensional cloud fields. This large suite of parameters mandates an integrated observing and modeling system of commensurate scope. The Progressive Aerosol Retrieval and Assimilation Global Observing Network (PARAGON) concept, designed to meet this requirement, is motivated by the need to understand climate system sensitivity to changes in atmospheric constituents, to reduce climate model uncertainties, and to analyze diverse collections of data pertaining to aerosols. This paper highlights several challenges resulting from the complexity of the problem. Approaches for dealing with them are offered in the set of companion papers

Reply to ''Comments on 'Why Hasn't Earth Warmed as much as Expected?'''

In response to our article, Why Hasnt Earth Warmed as Much as Expected? (2010), Knutti and Plattner (2012) wrote a rebuttal. The term climate sensitivity is usually defined as the change in global mean surface temperature that is produced by a specified change in forcing, such as a change in solar heating or greenhouse gas concentrations. We had argued in the 2010 paper that although climate models can reproduce the global mean surface temperature history over the past century, the uncertainties in these models, due primarily to the uncertainty in climate forcing by airborne particles, mean that the models lack the confidence to actually constrain the climate sensitivity within useful limits for climate prediction. Knutti and Plattner are climate modelers, and they argued essentially that because the models could reproduce the surface temperature history, the issue we raised was moot. Our response amounts to straightening out this confusion; for the models to be constraining, they must be able to reproduce the surface temperature history with sufficient confidence, not just to match the measurements, but to exclude alternative histories. As before, we concluded that if we can actually make the aerosol measurements using currently available, state-of-the-art techniques, we can determine the aerosol climate forcing to the degree required to constrain that aspect of model climate sensitivity. A technical issue relating to the timescale over which a change in CO2 emissions would be equilibrated in the environmental energy balance was also discussed, again, a matter of differences in terminology

An Integrated Approach for Characterizing Aerosol Climate Impacts and Environmental Interactions

Aerosols exert myriad influences on the earth's environment and climate, and on human health. The complexity of aerosol-related processes requires that information gathered to improve our understanding of climate change must originate from multiple sources, and that effective strategies for data integration need to be established. While a vast array of observed and modeled data are becoming available, the aerosol research community currently lacks the necessary tools and infrastructure to reap maximum scientific benefit from these data. Spatial and temporal sampling differences among a diverse set of sensors, nonuniform data qualities, aerosol mesoscale variabilities, and difficulties in separating cloud effects are some of the challenges that need to be addressed. Maximizing the long-term benefit from these data also requires maintaining consistently well-understood accuracies as measurement approaches evolve and improve. Achieving a comprehensive understanding of how aerosol physical, chemical, and radiative processes impact the earth system can be achieved only through a multidisciplinary, inter-agency, and international initiative capable of dealing with these issues. A systematic approach, capitalizing on modern measurement and modeling techniques, geospatial statistics methodologies, and high-performance information technologies, can provide the necessary machinery to support this objective. We outline a framework for integrating and interpreting observations and models, and establishing an accurate, consistent, and cohesive long-term record, following a strategy whereby information and tools of progressively greater sophistication are incorporated as problems of increasing complexity are tackled. This concept is named the Progressive Aerosol Retrieval and Assimilation Global Observing Network (PARAGON). To encompass the breadth of the effort required, we present a set of recommendations dealing with data interoperability; measurement and model integration; multisensor synergy; data summarization and mining; model evaluation; calibration and validation; augmentation of surface and in situ measurements; advances in passive and active remote sensing; and design of satellite missions. Without an initiative of this nature, the scientific and policy communities will continue to struggle with understanding the quantitative impact of complex aerosol processes on regional and global climate change and air quality

Can Disease Management Target Patients Most Likely to Generate High Costs? The Impact of Comorbidity

CONTEXT: Disease management programs are increasingly used to manage costs of patients with chronic disease. OBJECTIVE: We sought to examine the clinical characteristics and measure the health care expenditures of patients most likely to be targeted by disease management programs. DESIGN: Retrospective analysis of prospectively obtained data. SETTING: A general medicine practice with both faculty and residents at an urban academic medical center. PARTICIPANTS: Five thousand eight hundred sixty-one patients enrolled in the practice for at least 1 year. MAIN OUTCOMES: Annual cost of diseases targeted by disease management. MEASUREMENTS: Patients’ clinical and demographic information were collected from a computer system used to manage patients. Data included diagnostic information, medications, and resource usage over 1 year. We looked at 10 common diseases targeted by disease management programs. RESULTS: Unadjusted annual median costs for chronic diseases ranged between $1,100 and$1,500. Congestive heart failure ($1,500), stroke ($1,500), diabetes ($1,500), and cancer ($1,400) were the most expensive. As comorbidity increased, annual adjusted costs increased exponentially. Those with comorbidity scores of 2 or more accounted for 26% of the population but 50% of the overall costs. CONCLUSIONS: Costs for individual chronic conditions vary within a relatively narrow range. However, the costs for patients with multiple coexisting medical conditions increase rapidly. Reducing health care costs will require focusing on patients with multiple comorbid diseases, not just single diseases. The overwhelming impact of comorbidity on costs raises significant concerns about the potential ability of disease management programs to limit the costs of care

High-throughput, quantitative analyses of genetic interactions in E. coli.

Large-scale genetic interaction studies provide the basis for defining gene function and pathway architecture. Recent advances in the ability to generate double mutants en masse in Saccharomyces cerevisiae have dramatically accelerated the acquisition of genetic interaction information and the biological inferences that follow. Here we describe a method based on F factor-driven conjugation, which allows for high-throughput generation of double mutants in Escherichia coli. This method, termed genetic interaction analysis technology for E. coli (GIANT-coli), permits us to systematically generate and array double-mutant cells on solid media in high-density arrays. We show that colony size provides a robust and quantitative output of cellular fitness and that GIANT-coli can recapitulate known synthetic interactions and identify previously unidentified negative (synthetic sickness or lethality) and positive (suppressive or epistatic) relationships. Finally, we describe a complementary strategy for genome-wide suppressor-mutant identification. Together, these methods permit rapid, large-scale genetic interaction studies in E. coli

The hemodynamic tolerability and feasibility of sustained low efficiency dialysis in the management of critically ill patients with acute kidney injury

<p>Abstract</p> <p>Background</p> <p>Minimization of hemodynamic instability during renal replacement therapy (RRT) in patients with acute kidney injury (AKI) is often challenging. We examined the relative hemodynamic tolerability of sustained low efficiency dialysis (SLED) and continuous renal replacement therapy (CRRT) in critically ill patients with AKI. We also compared the feasibility of SLED administration with that of CRRT and intermittent hemodialysis (IHD).</p> <p>Methods</p> <p>This cohort study encompassed four critical care units within a single university-affiliated medical centre. 77 consecutive critically ill patients with AKI who were treated with CRRT (n = 30), SLED (n = 13) or IHD (n = 34) and completed at least two RRT sessions were included in the study. Overall, 223 RRT sessions were analyzed. Hemodynamic instability during a given session was defined as the composite of a > 20% reduction in mean arterial pressure or any escalation in pressor requirements. Treatment feasibility was evaluated based on the fraction of the prescribed therapy time that was delivered. An interrupted session was designated if < 90% of the prescribed time was administered. Generalized estimating equations were used to compare the hemodynamic tolerability of SLED vs CRRT while accounting for within-patient clustering of repeated sessions and key confounders.</p> <p>Results</p> <p>Hemodynamic instability occurred during 22 (56.4%) SLED and 43 (50.0%) CRRT sessions (p = 0.51). In a multivariable analysis that accounted for clustering of multiple sessions within the same patient, the odds ratio for hemodynamic instability with SLED was 1.20 (95% CI 0.58-2.47), as compared to CRRT. Session interruption occurred in 16 (16.3), 30 (34.9) and 11 (28.2) of IHD, CRRT and SLED therapies, respectively.</p> <p>Conclusions</p> <p>In critically ill patients with AKI, the administration of SLED is feasible and provides comparable hemodynamic control to CRRT.</p

Racial differences in treatment and survival in older patients with diffuse large B-cell lymphoma (DLBCL)

<p>Abstract</p> <p>Background</p> <p>Diffuse large B-cell lymphoma (DLBCL) comprises 31% of lymphomas in the United States. Although it is an aggressive type of lymphoma, 40% to 50% of patients are cured with treatment. The study objectives were to identify patient factors associated with treatment and survival in DLBCL.</p> <p>Methods</p> <p>Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims, we identified 7,048 patients diagnosed with DLBCL between January 1, 2001 and December 31, 2005. Patients were followed from diagnosis until the end of their claims history (maximum December 31, 2007) or death. Medicare claims were used to characterize the first infused chemo-immunotherapy (C-I therapy) regimen and to identify radiation. Multivariate analyses were performed to identify patient demographic, socioeconomic, and clinical factors associated with treatment and with survival. Outcomes variables in the survival analysis were all-cause mortality, non-Hodgkin's lymphoma (NHL) mortality, and other/unknown cause mortality.</p> <p>Results</p> <p>Overall, 84% (n = 5,887) received C-I therapy or radiation treatment during the observation period: both, 26%; C-I therapy alone, 53%; and radiation alone, 5%. Median age at diagnosis was 77 years, 54% were female, 88% were white, and 43% had Stage III or IV disease at diagnosis. The median time to first treatment was 42 days, and 92% of these patients had received their first treatment by day 180 following diagnosis. In multivariate analysis, the treatment rate was significantly lower among patients ≥ 80 years old, blacks versus whites, those living in a census tract with ≥ 12% poverty, and extra-nodal disease. Blacks had a lower treatment rate overall (Hazard Ratio [HR] 0.77; P < 0.001), and were less likely to receive treatment within 180 days of diagnosis (Odds Ratio [OR] 0.63; P = 0.002) than whites. In multivariate survival analysis, black race was associated with higher all-cause mortality (HR 1.24; P = 0.01) and other/unknown cause mortality (HR 1.35; P = 0.01), but not mortality due to NHL (HR 1.16; P = 0.19).</p> <p>Conclusions</p> <p>In elderly patients diagnosed with DLBCL, there are large differences in treatment access and survival between blacks and whites.</p

Bacteria isolated from lung modulate asthma susceptibility in mice

Asthma is a chronic, non-curable, multifactorial disease with increasing incidence in industrial countries. This study evaluates the direct contribution of lung microbial components in allergic asthma in mice. Germ-Free and Specific-Pathogen-Free mice display similar susceptibilities to House Dust Mice-induced allergic asthma, indicating that the absence of bacteria confers no protection or increased risk to aeroallergens. In early life, allergic asthma changes the pattern of lung microbiota, and lung bacteria reciprocally modulate aeroallergen responsiveness. Primo-colonizing cultivable strains were screened for their immunoregulatory properties following their isolation from neonatal lungs. Intranasal inoculation of lung bacteria influenced the outcome of allergic asthma development: the strain CNCM I 4970 exacerbated some asthma features whereas the pro-Th1 strain CNCM I 4969 had protective effects. Thus, we confirm that appropriate bacterial lung stimuli during early life are critical for susceptibility to allergic asthma in young adults

Ocular disease in patients with ANCA-positive vasculitis

Anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis—the term recently applied to Wegener's granulomatosis—is a rare multi-system inflammation characterized by necrotizing granulomas and vasculitis. We investigated the ocular manifestations of this disease in a group of patients drawn from five inflammatory eye disease clinics across the United States. Of 8,562 persons with ocular inflammation, 59 individuals were diagnosed with ANCA-positive vasculitis; 35 males and 21 females, aged 16 to 96 years, were included in this study. Ocular diagnoses were scleritis (75.0%), uveitis (17.9%), and other ocular inflammatory conditions (33.9%) including peripheral ulcerative keratitis and orbital pseudotumor. Mean duration of ocular disease was 4.6 years. Oral corticosteroids and other systemic immunosuppressive agents were used by 85.7% and 78.5% of patients, respectively. Over time, patients with ANCA-positive vasculitis experienced 2.75-fold higher mortality than other patients with inflammatory eye disease