Visual Data Analysis as an Integral Part of Environmental Management.

The U.S. Department of Energy's (DOE) Office of Environmental Management (DOE/EM) currently supports an effort to understand and predict the fate of nuclear contaminants and their transport in natural and engineered systems. Geologists, hydrologists, physicists and computer scientists are working together to create models of existing nuclear waste sites, to simulate their behavior and to extrapolate it into the future. We use visualization as an integral part in each step of this process. In the first step, visualization is used to verify model setup and to estimate critical parameters. High-performance computing simulations of contaminant transport produces massive amounts of data, which is then analyzed using visualization software specifically designed for parallel processing of large amounts of structured and unstructured data. Finally, simulation results are validated by comparing simulation results to measured current and historical field data. We describe in this article how visual analysis is used as an integral part of the decision-making process in the planning of ongoing and future treatment options for the contaminated nuclear waste sites. Lessons learned from visually analyzing our large-scale simulation runs will also have an impact on deciding on treatment measures for other contaminated sites.

Fluid shear influences on the performance of hydraulic flocculation systems.

Gravity driven hydraulic flocculators that operate in the absence of reliable electric power are better suited to meet the water treatment needs of green communities, resource-poor communities, and developing countries than conventional mechanical flocculators. However, current understanding regarding the proper design and operation of hydraulic flocculation systems is insufficient. Of particular interest is the optimal fluid shear level needed to produce low turbidity water. A hydraulic tube flocculator was used to study how fluid shear levels affect the settling properties of a flocculated alum-kaolin suspension. A Flocculation Residual Turbidity Analyzer (FReTA) was used to quantitatively compare the sedimentation velocity distributions and the post-sedimentation residual turbidities of the flocculated suspensions to see how they were affected by varying fluid shear, G, and hydraulic residence time, θ, while holding collision potential, Gθ, constant. Results show that floc breakup occurred at all velocity gradients evaluated. High floc settling velocities were correlated with low residual turbidities, both of which were optimized at low fluid shear levels and long fluid residence times. This study shows that, for hydraulic flocculation systems under the conditions described in this paper, low turbidity water is produced when fluid shear is kept at a minimum. Use of the product Gθ for design of laminar flow tube flocculators is insufficient if residual turbidity is used as the metric for performance. At any Gθ within the range tested in this study, best performance is obtained when G is small and θ is long.

Method for quantitative analysis of flocculation performance.

The sedimentation rate and the post-sedimentation residual turbidity of flocculated suspensions are properties central to the design and operation of unit processes following flocculation in a water treatment plant. A method for comparing flocculation performance based on these two properties is described. The flocculation residual turbidity analyzer (FReTA) records the turbidity of flocculent suspensions undergoing quiescent settling. The fixed distance across which flocs must travel to clear the measurement volume allows sedimentation velocity distributions of the flocculent suspension to be calculated from the raw turbidity data. By fitting the transformed turbidity data with a modified gamma distribution, the mean and variance of sedimentation velocity can be obtained along with the residual turbidity after a period of settling. This new analysis method can be used to quantitatively compare how differences in flocculator operating conditions affect the sedimentation velocity distribution of flocs as well as the post-sedimentation residual turbidity.

Flocculation model and collision potential for reactors with flows characterized by high Peclet numbers.

A mechanistically-based model is developed to characterize flocculation in the context of flow regimes with high Peclet numbers such as would occur in serpentine flow reactors. These flow conditions are obtained in gravity-driven hydraulic flocculators without mechanical agitation that are an important component of sustainable water treatment systems where energy efficiency and cost are receiving increasing emphasis. The model incorporates a fractal description of flocs, estimates of floc separation distances, estimates of relative velocities of floc particles dependent on the relevant flow regime, and provides an overall prediction of the required reaction time for formation of settleable flocs based on influent turbidity, alum dose, and energy dissipation rate. Viscosity is shown to be significant for the early stage of flocculation and turbulent eddies are shown to be significant for the final stage of flocculation. The collision potential defined as the product of the hydraulic residence time (θ) and the cube root of the energy dissipation rate (ɛ), i.e., ɛ(1/3)θ, is shown to be a better predictor of flocculator performance than the conventional product of θ and the velocity gradient (G), i.e., Gθ.

The role of aluminum in slow sand filtration.

Engineering enhancement of slow sand filtration has been an enigma in large part because the mechanisms responsible for particle removal have not been well characterized. The presumed role of biological processes in the filter ripening process nearly precluded the possibility of enhancing filter performance since interventions to enhance biological activity would have required decreasing the quality of the influent water. In previous work, we documented that an acid soluble polymer controls filter performance. The new understanding that particle removal is controlled in large part by physical chemical mechanisms has expanded the possibilities of engineering slow sand filter performance. Herein, we explore the role of naturally occurring aluminum as a ripening agent for slow sand filters and the possibility of using a low dose of alum to improve filter performance or to ripen slow sand filters.

Enhancing slow sand filter performance with an acid-soluble seston extract.

An acid-soluble extract was obtained from Cayuga Lake (Ithaca, NY) seston and applied to slow sand filters at different application rates. Biological activity in the filters was inhibited with 3mM sodium azide. The filters were challenged with a synthetic raw water containing Escherichia coli. The Cayuga Lake seston extract (CLSE) fed filters removed up to 99.9999% of the influent coliforms while the control filter (no CLSE) removed 50%. Filter performance was correlated with the amount of CLSE applied to the filters.

A phase II study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma.

We have previously demonstrated that the combination of tamoxifen and cisplatin has activity in patients with metastatic melanoma. In vitro studies have demonstrated that tamoxifen and cisplatin exhibit cytotoxic synergy in human melanoma cells and that this interaction is dependent on a tamoxifen effect. The mechanism of this effect is currently under investigation in in vitro studies. In an attempt to improve the complete response rate of this regimen, we initiated a phase II trial to determine the effect of the use of high dose tamoxifen and weekly cisplatin on the complete response rate, disease-free survival and overall survival. Tamoxifen was started on day 1 initially at a dose of 240 mg/day and continued until the patient was taken off treatment. This dose was subsequently lowered to 200 mg/day. Cisplatin (80 mg/m2) was begun on day 2 and repeated weekly for a total of 3 weeks. During week 4, the patient was not treated with cisplatin but was evaluated for response. If disease stabilization or regression was documented, the patient received a second 3 week cycle of cisplatin and was then re-evaluated for response. Patients with progressive disease at any evaluation were removed from the study. In 28 consecutive patients, the overall response rate was 32% (95% confidence interval 15.88-52.35%). One patient achieved a complete remission that lasted 22 months. All other responses were partial in nature. Toxicity was primarily nausea and vomiting. Two patients developed grade 2 renal toxicity. There were no episodes of deep venous thrombosis. This phase II study demonstrates that this combination has modest activity in patients with metastatic melanoma. However, this study failed to confirm our hypothesis that high dose tamoxifen would increase the complete response rate of this combination. While this combination has activity, the overall response rate is not significantly better that that observed with the original Dartmouth regimen and the toxicity is substantial. We do not recommend this dose and schedule for routine clinical use.

The effect of tamoxifen and cisplatin on the disease-free and overall survival of patients with high risk malignant melanoma.

The adjuvant treatment of high-risk malignant melanoma remains problematic. Previously we reported moderate success in the treatment of metastatic disease using tamoxifen, cisplatin, dacarbazine and carmustine. Based upon data that suggested tamoxifen and cisplatin were the active agents in this regimen, we initiated a phase II trial of this combination in the adjuvant setting. We treated 153 patients with 4 cycles of tamoxifen (160 mg day(-1), days 1-7) and cisplatin (100 mg m(-2), day 2) for 28-day intervals. Patients received an anti-nausea regimen of dexamethasone with ondansetron or granisetron. During the first 2 years of follow-up, patients were evaluated every 2 months with a history, physical exam, laboratory work and computed tomography scans of the chest, abdomen and pelvis every 4 months. Thereafter, patients were evaluated every 3 months and radiographic studies were performed if necessary. Currently, with a median follow-up of 36 months, the disease-free survival (DFS) is 68.4% and overall survival (OS) is 84.5%. Kaplan-Meier analysis predicts a 5-year DFS of 62% with an OS of 79%. Relapses after 20 months have been rare. No effect of gender or number of positive lymph nodes was noted, however, stage of disease prior treatment was a factor. The major toxicity proved to be gastrointestinal in nature with nausea the most prevalent symptom. Minimal renal, haematologic and neurologic toxicity occurred. These preliminary results suggest that there is a positive impact of tamoxifen and cisplatin on both the DFS and OS of high-risk malignant melanoma patients. The 5-year projected DFS and OS compare favourably with those reported for the ECOG 1684 trial and warrant confirmation in a prospective randomized trial.

Epican, a heparan/chondroitin sulfate proteoglycan form of CD44, mediates cell-cell adhesion.

Epican is a heparan/chondroitin sulfate proteoglycan form of CD44 and is expressed on the surface of keratinocytes from the basal layer to the granular layer of the epidermis. To analyze the adhesive properties of epican apart from the influence of other adhesive molecules found on keratinocytes, mouse L cell fibroblasts were transfected with CD44Epican cDNA. The epican expressed on the surface of transfected L cells was predominantly a heparan or chondroitin sulfate proteoglycan. The CD44Epican-transfected L cells acquired: (a) a self-aggregating phenotype that required hyaluronan but was calcium-independent; and (b) a new capacity to adhere to keratinocytes, a property that was blocked by an anti-epican antibody. Both aggregation and adhesion of CD44Epican-transfected cells were completely prevented by pretreatment with hyaluronidase, but were totally restored by the addition of exogenous hyaluronan. Aggregation of transfected L cells was minimally influenced by other glycosaminoglycans, but adhesion of transfected L cells to keratinocytes was substantially inhibited by heparin.

Relative transmission of ultrasound by media customarily used for phonophoresis.

The purpose of this study was to determine the relative transmission of ultrasound by the media commonly used by physical therapists to apply phonophoresis. The relative transmission of ultrasound energy through various phonophoresis media was compared with that of degassed water, which is the ideal standard. Transmission was assessed by placing a thin layer of the test medium on the transducer of a therapeutic ultrasound unit and measuring delivery of ultrasound with an ultrasound power meter. The media evaluated produced two significantly different groups of transmission results: (1) transmission greater than 80% of that of water and (2) transmission less than 40% of that of water. Media that optimize the therapeutic efficacy of phonophoresis in both clinical and experimental settings are discussed.

Quantitation of cross-linked protein: an alternative to counting cornified envelopes as an index of keratinocyte differentiation.

Covalently cross-linked protein is the key feature of the cornified envelope, an important marker of squamous differentiation. Enumeration of cornified envelopes is widely used to assess keratinocyte differentiation, but is tedious and subjective. We report here a rapid, objective, sensitive, and quantitative assay that measures total cross-linked protein in keratinocytes. The method is based on the resistance of cross-linked protein to solubilization in boiling SDS-beta ME, separation of cross-linked from soluble protein by collection of cross-linked protein on sheets of regenerated cellulose, binding of Coomassie blue to protein, and quantitation by scanning laser densitometry. There is excellent correlation between the cross-linked protein measured by this assay and the number of cornified envelopes.

Abuse potential of halazepam and of diazepam in patients recently treated for acute alcohol withdrawal.

Thirty men recently treated for alcohol withdrawal were enrolled in a three-way crossover double-blind study with a balanced incomplete block design. Patients received single doses of three of the following: halazepam, 320 mg; halazepam, 160 mg; diazepam, 40 mg; diazepam, 20 mg; and placebo. The doses of the drugs were approximately equivalent in anxiolytic effect. Patients rated themselves at baseline, 30 min after, and 1, 2, 3, 4, 6, and 8 hr after drug on the following: euphoria, sedation, "drug-liking," "feeling the drug," and drug identification. By 30 min both diazepam groups reported increases in euphoria, sedation, and feeling and liking the drug; halazepam groups reported little subjective change at 30 min, and at 1 hr subjective effects did not differ from placebo on any scale. At 2 and 3 hr, both halazepam doses induced subjective effects on several scales, but peak effects were lower than peak effects of high diazepam doses. Unlike diazepam, the higher halazepam dose did not appear to induce greater effects than the lower dose. At peak, more of the diazepam group correctly identified the drug than those in the halazepam groups. More in the halazepam groups identified it as placebo than either diazepam group. To the degree that abuse potential is related to peak intensity and to time of onset of those subjective effects described as pleasant or likable, halazepam should have a lower potential for abuse than diazepam.

Clinical utility of a two-site immunoradiometric assay for creatine kinase-MB in the detection of perioperative myocardial infarction.

In 144 patients, creatine kinase MB was measured serially at 0, 8, 16, 24, 48, and 72 hr using a two-site immunoradiometric assay (IRMA). Cardiac enzymes were also measured, including SGOT, LDH, total CPK, and CK-MB by electrophoresis. The presence of perioperative myocardial infarction (poMI) was established in 24 patients by the appearance of new electrocardiographic Q waves and/or new wall motion abnormalities detected by radionuclide ventriculography. In patients without poMI, CK-MB (IRMA) was elevated (6.4 +/- 4.9 equivalent units per liter) at 0-8 hr but decreased to 3.4 +/- 1.3 EU/l by 16 hr. In patients with poMI, peak values occurred at 16-24 hr (21.0 +/- 19.8 EU/l). Using a threshold value of 8.5 EU/l, patients with poMI could be distinguished from those without with 97% accuracy (sensitivity = 88%, specificity = 99%). The CK-MB (IRMA) was more reliable than the other enzyme assays, for which we used both empirically elevated threshold values based upon previous experience, and also threshold values retrospectively optimized for the study population. We conclude that the CK-MB (IRMA) can serve as a valuable postoperative screening test for poMI.

Radioligand assay: current trends in automation.

Using automatic equipment to perform routine RIA procedures can save time and money, improve precision, and free technologists to work on more-complex, non-routine assays. This article examines some of the instruments available for semiautomated and fully automated RIA testing. The pros and cons of automated testing are explored, and a framework for judging the true value and limitations of systems is presented.

Onset of insomnia: role of life-stress events.

During the year their insomnia began, chronic insomniacs experienced a greater number of stressful life events compared with previous or subsequent years and compared with good sleepers. In addition, among the life event categories assessed, insomniacs reported a greater number of undesirable events, particularly events related to losses and to ill health. They also had lifelong histories of more illnesses and somatic complaints, beginning with more childhood illnesses and more childhood problems related to eating and sleeping. During childhood, insomniacs reported more frequent discontent with their families, and prior to the onset of insomnia, they had less satisfying relationships with their parents as well as problems in other interpersonal relations and in their self-concepts. Currently, insomniacs felt considerably less satisfied with their lives, had lower self-concepts, and had greater difficulty with interpersonal relationships. Thus, stressful life events, mediated by certain predisposing factors of personal vulnerability, were found to be closely related to the onset of chronic insomnia.