Big data challenges in overcoming China's water and air pollution: relevant data and indicators.

Big data are potentially useful for environmental management planning and actions that can be directed toward pollution control. China is using big data approaches to help reduce its current levels of pollution. However, also needed are better environmental indicators, measurement technologies, data management and reporting, and adaptive management and enforcement. Based on continental-extent monitoring and assessment programs in Europe and the USA, we recommend three major programmatic changes for China. (1) Establish long-term systemic environmental and human health objectives and indicators. (2) Adopt national standard methods for survey designs, sampling and analytical protocols, statistical analyses, and collaborative sampling programs. (3) Provide a transparent process for reporting and correcting data errors.

A Rare Case of Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma Transforming into Diffuse Large B-Cell Lymphoma.

Mucosa-associated lymphoid tissue lymphoma (MALToma) is a low grade B-cell lymphoma that develops from the lungs, intestinal tract, salivary gland, and other organs and is included under extranodal marginal zone lymphoma. When a primary pulmonary MALToma develops from bronchus-associated lymphoid tissue (BALT), it is called BALT lymphoma (BALToma). The etiology of MALToma is not clear; however, an association between chronic inflammatory conditions and BALToma has been observed. Transformation of MALToma to high grade lymphoma is very rare. We experienced a case of MALToma that had developed from the lungs in a patient who was undergoing treatment for latent tuberculosis and rapidly transformed into high grade B-cell lymphoma.

A novel function for the MAP kinase SMA-5 in intestinal tube stability.

Intermediate filaments are major cytoskeletal components whose assembly into complex networks and isotype-specific functions are still largely unknown. Caenorhabditis elegans provides an excellent model system to study intermediate filament organization and function in vivo. Its intestinal intermediate filaments localize exclusively to the endotube, a circumferential sheet just below the actin-based terminal web. A genetic screen for defects in the organization of intermediate filaments identified a mutation in the catalytic domain of the MAP kinase 7 orthologue sma-5(kc1) In sma-5(kc1) mutants, pockets of lumen penetrate the cytoplasm of the intestinal cells. These membrane hernias increase over time without affecting epithelial integrity and polarity. A more pronounced phenotype was observed in the deletion allele sma-5(n678) and in intestine-specific sma-5(RNAi) Besides reduced body length, an increased time of development, reduced brood size, and reduced life span were observed in the mutants, indicating compromised food uptake. Ultrastructural analyses revealed that the luminal pockets include the subapical cytoskeleton and coincide with local thinning and gaps in the endotube that are often enlarged in other regions. Increased intermediate filament phosphorylation was detected by two-dimensional immunoblotting, suggesting that loss of SMA-5 function leads to reduced intestinal tube stability due to altered intermediate filament network phosphorylation.

Incidence, Risk Factors and Outcomes of New Onset Supraventricular Arrhythmias in African American Patients with Severe Sepsis.

PURPOSE: New onset supraventricular arrhythmias (SVA) are commonly reported in mixed intensive care settings. We sought to determine the incidence, risk factors and outcomes of new onset SVA in African American (AA) patients with severe sepsis admitted to medical intensive care unit (MICU). METHODS: Patients admitted to MICU between January 2012 through December 2012 were studied. Patients with a previous history of arrhythmia or with new onset of ventricular arrhythmia were excluded. Data on risk factors, critical care interventions and outcomes were obtained. RESULTS: One hundred and thirty-one patients were identified. New onset SVA occurred in 34 (26%) patients. Of those 34, 20 (59%) had atrial fibrillation (AF), 6 (18%) had atrial flutter and 8 (24%) had other forms of SVA. Compared with patients without SVA, patients with new onset SVA were older (69 ± 12 yrs vs 59 ± 13 yrs, P=.003), had congestive heart failure (47% vs 24%, P=.015) and dyslipidemia (41% vs 15%, P=.002). Additionally, they had a higher mean mortality prediction model (MPM II) score (65 ± 25 vs 49 ± 26, P=.001) and an increased incidence of respiratory failure (85% vs 55%, P=.001). Hospital mortality in patients with new onset SVA was 18 (53%) vs 30 (31%); P=.024; however, in a multivariate analysis, new onset SVA was associated with non-significantly increased odds (OR 2.58, 95% CI 0.86-8.05) for in-hospital mortality. CONCLUSIONS: New onset SVA was prevalent in AA patients with severe sepsis and occurred more frequently with advanced age, increased severity of illness, congestive heart failure, and acute respiratory failure; it was associated with higher unadjusted in hospital mortality. However, after multiple adjustments, new onset SVA did not remain an independent predictor of mortality.

Obesity and Pulmonary Function in African Americans.

BACKGROUND: Obesity prevalence in United States (US) adults exceeds 30% with highest prevalence being among blacks. Obesity is known to have significant effects on respiratory function and obese patients commonly report respiratory complaints requiring pulmonary function tests (PFTs). However, there is no large study showing the relationship between body mass index (BMI) and PFTs in healthy African Americans (AA). OBJECTIVE: To determine the effect of BMI on PFTs in AA patients who did not have evidence of underlying diseases of the respiratory system. METHODS: We reviewed PFTs of 339 individuals sent for lung function testing who had normal spirometry and lung diffusion capacity for carbon monoxide (DLCO) with wide range of BMI. RESULTS: Functional residual capacity (FRC) and expiratory reserve volume (ERV) decreased exponentially with increasing BMI, such that morbid obesity resulted in patients breathing near their residual volume (RV). However, the effects on the extremes of lung volumes, at total lung capacity (TLC) and residual volume (RV) were modest. There was a significant linear inverse relationship between BMI and DLCO, but the group means values remained within the normal ranges even for morbidly obese patients. CONCLUSIONS: We showed that BMI has significant effects on lung function in AA adults and the greatest effects were on FRC and ERV, which occurred at BMI values < 30 kg/m2. These physiological effects of weight gain should be considered when interpreting PFTs and their effects on respiratory symptoms even in the absence of disease and may also exaggerate existing lung diseases.

Nano-fEM: protein localization using photo-activated localization microscopy and electron microscopy.

Mapping the distribution of proteins is essential for understanding the function of proteins in a cell. Fluorescence microscopy is extensively used for protein localization, but subcellular context is often absent in fluorescence images. Immuno-electron microscopy, on the other hand, can localize proteins, but the technique is limited by a lack of compatible antibodies, poor preservation of morphology and because most antigens are not exposed to the specimen surface. Correlative approaches can acquire the fluorescence image from a whole cell first, either from immuno-fluorescence or genetically tagged proteins. The sample is then fixed and embedded for electron microscopy, and the images are correlated (1-3). However, the low-resolution fluorescence image and the lack of fiducial markers preclude the precise localization of proteins. Alternatively, fluorescence imaging can be done after preserving the specimen in plastic. In this approach, the block is sectioned, and fluorescence images and electron micrographs of the same section are correlated (4-7). However, the diffraction limit of light in the correlated image obscures the locations of individual molecules, and the fluorescence often extends beyond the boundary of the cell. Nano-resolution fluorescence electron microscopy (nano-fEM) is designed to localize proteins at nano-scale by imaging the same sections using photo-activated localization microscopy (PALM) and electron microscopy. PALM overcomes the diffraction limit by imaging individual fluorescent proteins and subsequently mapping the centroid of each fluorescent spot (8-10). We outline the nano-fEM technique in five steps. First, the sample is fixed and embedded using conditions that preserve the fluorescence of tagged proteins. Second, the resin blocks are sectioned into ultrathin segments (70-80 nm) that are mounted on a cover glass. Third, fluorescence is imaged in these sections using the Zeiss PALM microscope. Fourth, electron dense structures are imaged in these same sections using a scanning electron microscope. Fifth, the fluorescence and electron micrographs are aligned using gold particles as fiducial markers. In summary, the subcellular localization of fluorescently tagged proteins can be determined at nanometer resolution in approximately one week.

The novel intestinal filament organizer IFO-1 contributes to epithelial integrity in concert with ERM-1 and DLG-1.

The nematode Caenorhabditis elegans is an excellent model system in which to study in vivo organization and function of the intermediate filament (IF) system for epithelial development and function. Using a transgenic ifb-2::cfp reporter strain, a mutagenesis screen was performed to identify mutants with aberrant expression patterns of the IF protein IFB-2, which is expressed in a dense network at the subapical endotube just below the microvillar brush border of intestinal cells. Two of the isolated alleles (kc2 and kc3) were mapped to the same gene, which we refer to as ifo-1 (intestinal filament organizer). The encoded polypeptide colocalizes with IF proteins and F-actin in the intestine. The apical localization of IFO-1 does not rely on IFB-2 but is dependent on LET-413, a basolateral protein involved in apical junction assembly and maintenance of cell polarity. In mutant worms, IFB-2 and IFC-2 are mislocalized in cytoplasmic granules and accumulate in large aggregates at the C. elegans apical junction (CeAJ) in a DLG-1-dependent fashion. Electron microscopy reveals loss of the prominent endotube and disordered but still intact microvilli. Semiquantitative fluorescence microscopy revealed a significant decrease of F-actin, suggesting a general role of IFO-1 in cytoskeletal organization. Furthermore, downregulation of the cytoskeletal organizer ERM-1 and the adherens junction component DLG-1, each of which leads to F-actin reduction on its own, induces a novel synthetic phenotype in ifo-1 mutants resulting in disruption of the lumen. We conclude that IFO-1 is a multipurpose linker between different cytoskeletal components of the C. elegans intestinal terminal web and contributes to proper epithelial tube formation.

Development and implementation of coral reef biocriteria in U.S. jurisdictions.

Coral reefs worldwide are declining at an alarming rate and are under continuous threat from both natural and anthropogenic environmental stressors. Warmer sea temperatures attributed to global climate change and numerous human activities at local scales place these valuable ecosystems at risk. Reefs provide numerous services, including shoreline protection, fishing, tourism and biological diversity, which are lost through physical damage, overfishing, and pollution. Pollution can be controlled under provisions of the Clean Water Act, but these options have not been fully employed to protect coral reefs. No U.S. jurisdiction has implemented coral reef biocriteria, which are narrative or quantitative water quality standards based on the condition of a biological resource or assemblage. The President's Ocean Action Plan directs the U.S. Environmental Protection Agency (EPA) to develop biological assessment methods and biological criteria for evaluating and maintaining the health of coral reef ecosystems. EPA has formed the Coral Reef Biocriteria Working Group (CRBWG) to foster development of coral reef biocriteria through focused research, evaluation and communication among Agency partners and U.S. jurisdictions. Ongoing CRBWG activities include development and evaluation of a rapid bioassessment protocol for application in biocriteria programs; development of a survey design and monitoring strategy for the U.S. Virgin Islands; comprehensive reviews of biocriteria approaches proposed by states and territories; and assembly of data from a variety of monitoring programs for additional metrics. Guidance documents are being prepared to assist U.S. jurisdictions in reaching protective and defensible biocriteria.

Evaluation of stony coral indicators for coral reef management.

Colonies of reef-building stony corals at 57 stations around St. Croix, US Virgin Islands were characterized by species, size and percentage of living tissue. Taxonomic, biological and physical indicators of coral condition were derived from these measurements and assessed for their response to gradients of human disturbance-a requirement for indicators used in regulatory assessments under authority of the Clean Water Act. At the most intensely disturbed location, five of eight primary indicators were highly correlated with distance from the source of disturbance: Coral taxa richness, average colony size, the coefficient of variation of colony size, total topographic coral surface area, and live coral surface area. An additional set of exploratory indicators related to rarity, reproductive and spawning mode and taxonomic identity were also screened. The primary indicators demonstrated sufficient precision to detect levels of change that would be applicable in a regional-scale regulatory program.

Phase II study of rubitecan in recurrent or metastatic head and neck cancer.

PURPOSE: Rubitecan is an oral camptothecin analogue that has shown activity against a broad spectrum of human tumor xenografts and has been tested in several diseases. PATIENTS AND METHODS: In the present study, 19 patients with incurable, recurrent or metastatic head and neck cancer were treated with rubitecan at the initial dose of 1.5 mg/m(2) x 5 days per week. An appropriate dose modification program was set up according to the observed toxicities. RESULTS: Thirteen out of the 19 treated patients were formally evaluable for tumor response. Ten patients had a disease progression and three patients had a stabilization of disease as their best response. The mean duration of stable disease was 141 days. Median survival was 16 weeks (range 2-22 weeks). Three patients died during the study or less than a month after their last dose of study medication. Hematologic toxicity was serious in this study since four patients discontinued their participation because of severe anemia. The drug was also associated with grade 1-4 neutropenia, and with 1-3 thrombocytopenia. CONCLUSION: We conclude that rubitecan is not effective as a single-agent in recurrent or metastatic head and neck cancer with the doses and schedule used in this study.

Source apportionment of fine particles in Tennessee using a source-oriented model.

Source apportionment of fine particles (PM2.5, particulate matter < 2 microm in aerodynamic diameter) is important to identify the source categories that are responsible for the concentrations observed at a particular receptor. Although receptor models have been used to do source apportionment, they do not fully take into account the chemical reactions (including photochemical reactions) involved in the formation of secondary fine particles. Secondary fine particles are formed from photochemical and other reactions involving precursor gases, such as sulfur dioxide, oxides of nitrogen, ammonia, and volatile organic compounds. This paper presents the results of modeling work aimed at developing a source apportionment of primary and secondary PM2.5. On-road mobile source and point source inventories for the state of Tennessee were estimated and compiled. The national emissions inventory for the year 1999 was used for the other states. U.S. Environmental Protection Agency Models3/Community Multi-Scale Air Quality modeling system was used for the photochemical/secondary particulate matter modeling. The modeling domain consisted of a nested 36-12-4-km domain. The 4-km domain covered the entire state of Tennessee. The episode chosen for the modeling runs was August 29 to September 9, 1999. This paper presents the approach used and the results from the modeling and attempts to quantify the contribution of major source categories, such as the on-road mobile sources (including the fugitive dust component) and coal-fired power plants, to observed PM2.5 concentrations in Tennessee. The results of this work will be helpful in policy issues targeted at designing control strategies to meet the PM2.5 National Ambient Air Quality Standards in Tennessee.

Proteomic and phototoxic characterization of melanolipofuscin: correlation to disease and model for its origin.

PURPOSE: Melanolipofuscin (MLF) is a complex granule, exhibiting properties of both melanosomes and lipofuscin (LF) granules, which accumulates in retinal pigment epithelial (RPE) cells and may contribute to the etiology of age-related macular degeneration (AMD). MLF accumulation has been reported by Feeney-Burns to more closely reflect the onset of AMD than the accumulation of lipofuscin. In an effort to assess the possible contribution MLF may have to the onset of AMD, we analyzed the phototoxicity and protein composition of MLF and compared those results to that of LF. METHODS: Specifically, we observed the accumulation of MLF in human RPE from different decades of life, and assessed the phototoxicity of these granules. We also employed fluorescence spectroscopy, atomic force microscopy, transmission and scanning electron microscopy and proteomic analysis to examine the composition of MLF granules in an effort to ascertain their origin. RESULTS: Our results show that MLF granules are phototoxic and their accumulation more closely reflects the onset of AMD than does LF accumulation. Our compositional analysis of MLF has shown that while these granules contain some similarities to LF granules, MLF is substantially different. Of significant interest is the finding that MLF, in contrast to LF, does not contain photoreceptor-specific proteins, suggesting that MLF may not originate from the phagocytosis of photoreceptor outer segments. Instead the presence of RPE- and melanosome-specific proteins would suggest that MLF accumulates as a result of the melanosomal autophagocytosis of RPE cells. CONCLUSIONS: Our results provide significant insight into understanding the formation and toxicity of MLF and suggest a possible contribution to the etiology of retinal diseases.

Ozone and PM2.5 exposure and acute pulmonary health effects: a study of hikers in the Great Smoky Mountains National Park.

To address the lack of research on the pulmonary health effects of ozone and fine particulate matter (

Prediction of the vertical profile of ozone based on ground-level ozone observations and cloud cover.

A number of statistical techniques have been used to develop models to predict high-elevation ozone (O3) concentrations for each discrete hour of day as a function of elevation based on ground-level O3 observations. The analyses evaluated the effect of exclusion/inclusion of cloud cover as a variable. It was found that a simple model, using the current maximum ground-level O3 concentration and no effect of cloud cover provided a reasonable prediction of the vertical profile of O3, based on data analyzed from O3 sites located in North Carolina and Tennessee. The simple model provided an approach that estimates the concentration of O3 as a function of elevation (up to 1800 m) based on the statistical results with a +/- 13.5 ppb prediction error, an R2 of 0.56, and an index of agreement, d1, of 0.66. The inclusion of cloud cover resulted in a slight improvement in the model over the simple regression model. The developed models, which consist of two matrices of 24 equations (one for each hour of day for clear to partly cloudy conditions and one for cloudy conditions), can be used to estimate the vertical O3 profile based on the inputs of the current day's 1-hr maximum ground-level O3 concentration and the level of cloud cover.

Development and evaluation of a Macroinvertebrate Biotic Integrity Index (MBII) for regionally assessing Mid-Atlantic Highlands Streams.

The Macroinvertebrate Biotic Integrity Index (MBII) was developed from data collected at 574 wadeable stream reaches in the Mid-Atlantic Highlands region (MAHR) by the U.S. Environmental Protection Agency's (USEPA) Environmental Monitoring and Assessment Program (EMAP). Over 100 candidate metrics were evaluated for range, precision, responsiveness to various disturbances, relationship to catchment area, and redundancy. Seven metrics were selected, representing taxa richness (Ephemeroptera richness, Plecoptera richness, Trichoptera richness), assemblage composition (percent non-insect individuals, percent 5 dominant taxa), pollution tolerance [Macroinvertebrate Tolerance Index (MTI)], and one functional feeding group (collector-filterer richness). We scored metrics and summed them, then ranked the resulting index through use of independently evaluated reference stream reaches. Although sites were classified into lowland and upland ecoregional groups, we did not need to develop separate scoring criteria for each ecoregional group. We were able to use the same metrics for pool and riffle composite samples, but we had to score them differently. Using the EMAP probability design, we inferred the results, with known confidence bounds, to the 167,797 kilometers of wadeable streams in the Mid-Atlantic Highlands. We classified 17% of the target stream length in the MAHR as good, 57% as fair, and 26% as poor. Pool-dominated reaches were relatively rare in the MAHR, and the usefulness of the MBII was more difficult to assess in these reaches. The process used for developing the MBII is widely applicable and resulted in an index effective in evaluating region-wide conditions and distinguishing good and impaired reaches among both upland and lowland streams dominated by riffle habitat.