Alluvial fans at Cala Gonone (Sardinia), a fast developing touristic village: origins, hazards and potential risks.

The study area of Cala Gonone in NE Sardinia (Italy) consists of a wide terraced re-entrance/valley crowned inland by carbonate hills and, near the coast bounded laterally and partly floored by thin basaltic lava lying over carbonate bedrock. In this re-entrance, several inland alluvial fans (500 m length by 700 m wide) have developed, and a local ~ 30 m high, about 10 m wide (thick), 400 m long scarp body-remnant of semi-consolidated alluvial fan deposits is exposed along the coast. The fans experience depositional events mostly developed during the late Pleistocene. They although nowadays dormant may be reactivated by major rainstorms during strong climate changes. In these last few decades, the touristic village of Cala Gonone has been rapidly expanding over the mid to lower parts of two coalescing alluvial fans (Stadium and Gustui) and along the coastal marine scarp edge (Palmasera alluvial fan system). The village thus may become exposed to natural hazards if extreme climatic conditions may re-occur. Moreover, rock falls and the instability of the costal scarp due to wave erosion may add addition hazards for habitations built near the scarp crest and visitors to the frontal replenished beach. As commonly occurring elsewhere since antiquity, the risk perception of such events is low because of the centennial, millennial of longer recurrence. Such perception does not negate the hazards but a long event recurrence may be accepted as a reasonable risk for the human's activity. Nevertheless, serious consideration should be given to potential problems and plan and build for amelioration and defense. The evidence of what environmentally did and could still happen in the Cala Gonone and similar other area is in part clearly imprinted on the landscape: geology, geomorphology, and relative details in the stratigraphy and sedimentology of the deposits.

A Scalable Cyberinfrastructure for Interactive Visualization of Terascale Microscopy Data.

The goal of the recently emerged field of connectomics is to generate a wiring diagram of the brain at different scales. To identify brain circuitry, neuroscientists use specialized microscopes to perform multichannel imaging of labeled neurons at a very high resolution. CLARITY tissue clearing allows imaging labeled circuits through entire tissue blocks, without the need for tissue sectioning and section-to-section alignment. Imaging the large and complex non-human primate brain with sufficient resolution to identify and disambiguate between axons, in particular, produces massive data, creating great computational challenges to the study of neural circuits. Researchers require novel software capabilities for compiling, stitching, and visualizing large imagery. In this work, we detail the image acquisition process and a hierarchical streaming platform, ViSUS, that enables interactive visualization of these massive multi-volume datasets using a standard desktop computer. The ViSUS visualization framework has previously been shown to be suitable for 3D combustion simulation, climate simulation and visualization of large scale panoramic images. The platform is organized around a hierarchical cache oblivious data layout, called the IDX file format, which enables interactive visualization and exploration in ViSUS, scaling to the largest 3D images. In this paper we showcase the VISUS framework used in an interactive setting with the microscopy data.

Generalized Topological Simplification of Scalar Fields on Surfaces.

We present a combinatorial algorithm for the general topological simplification of scalar fields on surfaces. Given a scalar field f, our algorithm generates a simplified field g that provably admits only critical points from a constrained subset of the singularities of f, while guaranteeing a small distance ||f - g||∞ for data-fitting purpose. In contrast to previous algorithms, our approach is oblivious to the strategy used for selecting features of interest and allows critical points to be removed arbitrarily. When topological persistence is used to select the features of interest, our algorithm produces a standard ϵ-simplification. Our approach is based on a new iterative algorithm for the constrained reconstruction of sub- and sur-level sets. Extensive experiments show that the number of iterations required for our algorithm to converge is rarely greater than 2 and never greater than 5, yielding O(n log(n)) practical time performances. The algorithm handles triangulated surfaces with or without boundary and is robust to the presence of multi-saddles in the input. It is simple to implement, fast in practice and more general than previous techniques. Practically, our approach allows a user to arbitrarily simplify the topology of an input function and robustly generate the corresponding simplified function. An appealing application area of our algorithm is in scalar field design since it enables, without any threshold parameter, the robust pruning of topological noise as selected by the user. This is needed for example to get rid of inaccuracies introduced by numerical solvers, thereby providing topological guarantees needed for certified geometry processing. Experiments show this ability to eliminate numerical noise as well as validate the time efficiency and accuracy of our algorithm. We provide a lightweight C++ implementation as supplemental material that can be used for topological cleaning on surface meshes.

Computing Morse-Smale Complexes with Accurate Geometry.

Topological techniques have proven highly successful in analyzing and visualizing scientific data. As a result, significant efforts have been made to compute structures like the Morse-Smale complex as robustly and efficiently as possible. However, the resulting algorithms, while topologically consistent, often produce incorrect connectivity as well as poor geometry. These problems may compromise or even invalidate any subsequent analysis. Moreover, such techniques may fail to improve even when the resolution of the domain mesh is increased, thus producing potentially incorrect results even for highly resolved functions. To address these problems we introduce two new algorithms: (i) a randomized algorithm to compute the discrete gradient of a scalar field that converges under refinement; and (ii) a deterministic variant which directly computes accurate geometry and thus correct connectivity of the MS complex. The first algorithm converges in the sense that on average it produces the correct result and its standard deviation approaches zero with increasing mesh resolution. The second algorithm uses two ordered traversals of the function to integrate the probabilities of the first to extract correct (near optimal) geometry and connectivity. We present an extensive empirical study using both synthetic and real-world data and demonstrates the advantages of our algorithms in comparison with several popular approaches.

Visualizing Network Traffic to Understand the Performance of Massively Parallel Simulations.

The performance of massively parallel applications is often heavily impacted by the cost of communication among compute nodes. However, determining how to best use the network is a formidable task, made challenging by the ever increasing size and complexity of modern supercomputers. This paper applies visualization techniques to aid parallel application developers in understanding the network activity by enabling a detailed exploration of the flow of packets through the hardware interconnect. In order to visualize this large and complex data, we employ two linked views of the hardware network. The first is a 2D view, that represents the network structure as one of several simplified planar projections. This view is designed to allow a user to easily identify trends and patterns in the network traffic. The second is a 3D view that augments the 2D view by preserving the physical network topology and providing a context that is familiar to the application developers. Using the massively parallel multi-physics code pF3D as a case study, we demonstrate that our tool provides valuable insight that we use to explain and optimize pF3D's performance on an IBM Blue Gene/P system.

Understanding the structure of the turbulent mixing layer in hydrodynamic instabilities.

When a heavy fluid is placed above a light fluid, tiny vertical perturbations in the interface create a characteristic structure of rising bubbles and falling spikes known as Rayleigh-Taylor instability. Rayleigh-Taylor instabilities have received much attention over the past half-century because of their importance in understanding many natural and man-made phenomena, ranging from the rate of formation of heavy elements in supernovae to the design of capsules for Inertial Confinement Fusion. We present a new approach to analyze Rayleigh-Taylor instabilities in which we extract a hierarchical segmentation of the mixing envelope surface to identify bubbles and analyze analogous segmentations of fields on the original interface plane. We compute meaningful statistical information that reveals the evolution of topological features and corroborates the observations made by scientists. We also use geometric tracking to follow the evolution of single bubbles and highlight merge/split events leading to the formation of the large and complex structures characteristic of the later stages. In particular we (i) Provide a formal definition of a bubble; (ii) Segment the envelope surface to identify bubbles; (iii) Provide a multi-scale analysis technique to produce statistical measures of bubble growth; (iv) Correlate bubble measurements with analysis of fields on the interface plane; (v) Track the evolution of individual bubbles over time. Our approach is based on the rigorous mathematical foundations of Morse theory and can be applied to a more general class of applications.

Advances in three-dimensional reconstruction of the experimental spinal cord injury.

Three-dimensional (3D) computer reconstruction is an ideal tool for evaluating the centralized pathology of mammalian spinal cord injury (SCI) where multiple anatomical features are embedded within each other. Here, we evaluate three different reconstruction algorithms to three-dimensionally visualize SCIs. We also show for the first time, that determination of the volume and surface area of pathological features is possible using the reconstructed 3D images themselves. We compare these measurements to those calculated by older morphometric approaches. Finally, we demonstrate dynamic navigation into a 3D spinal cord reconstruction.

Immunoscintigraphy with 111In-satumomab pendetide in patients with colorectal adenocarcinoma: performance and impact on clinical management.

PURPOSE: The role of immunoscintigraphy with 111In-satumomab pendetide in the medical and/or surgical management of colorectal cancer patients was evaluated in a multicenter trial. METHODS: This 103 patient study population included 46 individuals with rising serum carcinoembryonic antigen levels and otherwise negative diagnostic evaluation, 29 patients with known recurrence, presumed to be isolated and resectable, and 28 patients for whom standard diagnostic tests provided equivocal information. RESULTS: No adverse reactions were noted following intravenous administration of 1 mg of satumomab pendetide radiolabeled with approximately 5 mCi of 111In. Thirty percent of patients developed human anti-mouse antibodies postinfusion. In the 84 patients for whom correlation with histopathologic, diagnostic, and/or clinical findings was available, antibody imaging demonstrated a sensitivity of 73 percent in patients with confirmed tumor (36/49) and negative results for all 35 patients with no evidence of malignancy. Occult disease was detected in 18 patients. CONCLUSION: 111In-satumomab pendetide immunoscintigraphy was helpful in the medical and/or surgical management of 45 (44 percent) patients and provided information unavailable from other diagnostic modalities.

Immunoscintigraphy in patients with colorectal, ovarian, and prostate cancer. Results with site-specific immunoconjugates.

Application of monoclonal antibody (MoAb) technology to cancer management is discussed by reviewing the development and clinical evaluation of two MoAb-based immunoscintigraphic agents (111In-satumomab pendetide [OncoScint CR/OV-In] and 111In-CYT-356; Cytogen Corporation, Princeton, NJ). Both agents were prepared using a site-specific MoAb modification method that preserves the immunoreactivity of the radiolabeled immunoconjugate. 111In-satumomab pendetide is an 111In-labeled conjugate of the murine MoAb B72.3, which is directed to TAG-72, an antigen expressed by the majority of adenocarcinomas. By providing information that complements the results of standard radiographic diagnostic modalities, this imaging agent can aid in the treatment of patients with colorectal or ovarian cancer. Immunoscintigraphy with 111In-satumomab pendetide has been shown to assist in medical-surgical management by detecting occult extrahepatic lesions, clarifying equivocal results of other diagnostic imaging tests, and evaluating the extent and resectability of known tumor lesions. 111In-CYT-356 is an 111In-labeled conjugate of the murine MoAb 7E11-C5.3, which is reactive with prostatic carcinoma, benign prostatic hypertrophy, and, to a lesser extent, normal prostatic tissue. Results of preliminary clinical investigations suggest that 111In-CYT-356 immunoscintigraphy can be useful for the presurgical staging of prostatic carcinoma and for the detection of occult distant disease in patients with negative or equivocal results on standard imaging tests. Results with these site-specifically radiolabeled immunconjugates demonstrate the clinical utility of MoAb-based imaging agents in the treatment of patients with solid tumors.

Antihypertensive therapy with indoramin: risk-benefit profile in clinical practice.

In a multicenter, prospective study of step II antihypertensive therapy with indoramin, 1,847 hypertensive patients (773 men and 1,074 women) between the ages of 18 and 70 years were treated by 148 general practitioners. Patients whose blood pressure was inadequately controlled after 4 weeks of therapy with cyclopenthiazide (0.25 to 1.0 mg/day) had indoramin (25 to 200 mg/day) added to their treatment regimen. During cyclopenthiazide treatment, mean (+/- SD) blood pressure decreased from 176/105 +/- 20/7 mm Hg at baseline to 164/98 +/- 21/9 mm Hg (p less than 0.001), and only 447 (24%) patients obtained satisfactory blood pressure control. The addition of indoramin produced a further reduction in mean blood pressure from 169/102 +/- 18/6 to 152/89 +/- 18/8 mm Hg during the first 3 months of treatment (p less than 0.001); this response was maintained for up to 2 years. Satisfactory blood pressure reduction was achieved in 79% of the patients who received indoramin (mean dose, 68 mg/day) plus cyclopenthiazide. Only 25 patients (2%) discontinued indoramin treatment because of nonresponse, and 156 (12%) withdrew because of adverse effects, the most common being sedation, dizziness/giddiness, and headache. These results indicate that indoramin provides safe and effective blood pressure control when used as step II treatment for hypertensive patients who fail to respond to single-agent diuretic therapy.

Antihypertensive therapy with indoramin in the elderly.

The antihypertensive efficacy and safety of indoramin, an alpha 1-adrenergic antagonist, were evaluated in 215 elderly patients. Data were collected from patients aged 60 years and older who were treated under similar protocols with indoramin administered alone (n = 58) or in combination with a thiazide diuretic (n = 157). After at least 6 months of treatment, the mean daily dosage of indoramin was higher among patients who received indoramin alone (122 mg/day) than among those who received indoramin plus a diuretic (92 mg/day). Mean supine blood pressure decreased (p less than 0.001) from 174/105 to 152/191 mm Hg in indoramin-treated patients and from 179/101 to 150/91 mm Hg in patients who were treated with indoramin plus a diuretic. Clinically satisfactory blood pressure decreases occurred in the majority of the patients who received indoramin, either alone (69%) or with a diuretic (75%). Both treatments were well tolerated by elderly patients; only 15 patients (7%) discontinued therapy because of adverse effects. Drowsiness, fatigue, and dizziness were the most frequently reported side effects. The results of this analysis indicate that indoramin, administered alone or in combination with a thiazide diuretic, is a safe and effective therapeutic regimen for elderly hypertensive patients.

Pharmacokinetics of guanabenz in patients with impaired liver function.

The disposition of guanabenz, a centrally acting antihypertensive agent, was compared in 10 normotensive patients (eight males and two females) with chronic hepatic disease secondary to alcohol abuse and 10 healthy male volunteers after a 16 mg oral dose. Mean plasma concentrations of guanabenz were higher in patients with liver disease than in healthy subjects at every sampling time through 72 h after drug administration (p less than 0.05). In liver disease patients, the mean oral-dose clearance (2 L/h/kg) and terminal-phase volume of distribution (20 L/kg) were lower (p less than 0.001) than the respective values of 11 L/h/kg and 71 L/kg of healthy volunteers. The mean plasma half-life of patients with liver disease (6.4 h) was not significantly longer than that of healthy subjects (4.3 h). The mean fraction of unbound drug in the plasma was higher (p less than 0.01) in patients with liver disease (12.7%) than in healthy volunteers (10.5%). As guanabenz is eliminated predominantly via hepatic biotransformation and undergoes significant presystemic elimination after oral administration, the changes in guanabenz disposition in liver disease are not unexpected. They may be explained by enhanced oral bioavailability, owing to portosystemic shunting and/or reduced intrinsic clearance, combined with decreased hepatic clearance of guanabenz in liver disease. Individual dosage titration may be required when guanabenz is used for antihypertensive therapy of patients with chronic liver disease.

Effects of guanabenz on gastrointestinal absorption of hydrochlorothiazide.

The pharmacokinetics of guanabenz (16 mg) and hydrochlorothiazide (25 mg), administered separately and as a fixed-combination tablet (guanabenz 16 mg/hydrochlorothiazide 25 mg), were compared in a randomized three-period crossover study in 24 healthy men. Plasma concentrations were monitored for 48 h after each administration. No statistically significant differences between the two formulations were noted in mean plasma concentrations or the rate and extent of absorption of guanabenz. The relative bioavailability (Fr) of the combination tablet compared with guanabenz alone was 96%; thus the two formulations were bioequivalent with respect to guanabenz. For hydrochlorothiazide, mean plasma concentrations were similar for 3 h after administration but were higher for the combination tablet than for hydrochlorothiazide alone from 4 through 48 h (p less than 0.05). A significant increase in the extent, but not the rate, of absorption of hydrochlorothiazide was observed for the combination tablet (mean Fr, 120%), which is not considered clinically significant. We propose that this increase may have been due to increased systemic availability of hydrochlorothiazide in the presence of guanabenz, an alpha-adrenergic agonist, which may have delayed intestinal transport of hydrochlorothiazide, resulting in enhanced gastrointestinal absorption.

Antihypertensive therapy with guanabenz in patients with chronic obstructive pulmonary diseases.

The management of hypertension in patients with chronic obstructive pulmonary disease (COPD) may be complicated by the adverse effects of several antihypertensive agents on pulmonary function. The safety and antihypertensive efficacy of guanabenz, a centrally acting alpha-adrenergic agonist, were evaluated in 42 patients with asthma and 24 patients with other forms of COPD. Among the 64 patients with data evaluated for efficacy, pretreatment supine diastolic blood pressures (SDBP) were between 90 and 121 mm Hg (mean, 100 mm Hg). The patients were treated for 6 months with guanabenz as sole antihypertensive therapy in doses ranging from 8 to 64 mg/day (mean final dosage, 28 mg/day). At the end of the treatment period, a mean decrease in SDBP of 10 mm Hg was observed (p less than 0.001). Excellent or satisfactory blood pressure responses were obtained for 65% of the asthmatic patients and 83% of the patients with other forms of COPD. Mean supine pulse rate decreased by 7 beats/min (p less than 0.001), and mean body weight decreased by 2 lb. (p less than 0.05). Only one patient discontinued guanabenz treatment because of an exacerbation of asthma thought to be due to airway dryness. Because beta-adrenergic blocking agents, including the cardioselective drugs, have been known to exacerbate COPD, guanabenz treatment may be preferable as antiadrenergic antihypertensive therapy in patients with asthma and other forms of COPD.

Quantitation of ketoconazole in biological fluids using high-performance liquid chromatography.

A rapid, specific procedure is described for the quantitation of ketoconazole in biological fluids using high-performance liquid chromatography (HPLC). The procedure involves sample preparation using a reverse-phase C-18 cartridge prior to chromatography and quantitation using peak height ratios (UV absorbance detection, 231 nm) of ketoconazole to the internal standard, phenothiazine. A sensitivity of 0.2 micrograms/ml was achieved using a 0.5-ml sample. The mean recovery was 86.2%, and overall coefficient of variation of the procedure was 7.1%. This procedure has been used to determine ketoconazole levels in human serum, plasma, CSF, and synovial fluid. A comparison with a microbiological assay is presented, and adaptability of this procedure to quantitation by fluorescence to increase the sensitivity fivefold is discussed.

Quantitation of testolactone and 4,5-dihydrotestolactone in plasma and urine using high-performance liquid chromatography.

A rapid, sensitive, and selective assay is described for the quantitation of both testolactone and its recently identified metabolite, 4,5-dihydrotestolactone, in plasma and urine using high-performance liquid chromatography. The procedure includes a methylene chloride extraction prior to chromatography and quantitation using peak height ratios (ultraviolet absorbance detection, 242 nm) of testolactone and 4,5-dihydrotestolactone to the internal standard, testosterone. A sensitivity of 20 ng/ml for both testolactone and 4,5-dihydrotestolactone is easily achieved using only 0.5 ml of sample. Mean recoveries for testolactone and its metabolite are 95.0% and 81.8%, respectively, and the mean coefficient of variation of the procedure is 3.5% for the drug and 7.1% for the metabolite. This method is currently being used to study the pharmacokinetics of testolactone and 4,5-dihydrotestolactone in male patients. A steady-state plasma concentration versus time profile from a representative patient is included.

The effect of pregnancy on the metabolism of [14C]phenytoin in the isolated perfused rat liver.

The metabolism of [14C]phenytoin (DPH) was measured in isolated perfused livers from non-pregnant female rats and rats at 13, 15, 17, 19 and 21 days of gestation. The half-life of [14C]phenytoin in the perfusate was not significantly altered by pregnancy in livers perfused with 20% blood at 2 ml/min/g of liver but was increased from 38 min in control livers to 158 min in livers from rats at 21 days of gestation when livers were perfused with 10% blood at 1 ml/min/g of liver. Secretion of the glucuronide conjugate of 5-[14C]phenyl-5-parahydroxy-phenylhydantoin into the bile was markedly inhibited during the latter stages of pregnancy such that a 4-fold decrease in the cumulative secretion into the bile was present at 21 days of gestation. The bile/perfusate concentration ratio of the glucuronide after 30 min was 148 in control livers but decreased to 6 in livers from rats at 21 days gestation.