Mass-like peripheral zone enhancement on CT is predictive of higher-grade (Gleason 4 + 3 and higher) prostate cancer.

PURPOSE: To determine whether focal peripheral zone enhancement on routine venous-phase CT is predictive of higher-grade (Gleason 4 + 3 and higher) prostate cancer. MATERIALS AND METHODS: IRB approval was obtained and informed consent waived for this HIPAA-compliant retrospective study. Forty-three patients with higher-grade prostate cancer (≥Gleason 4 + 3) and 96 with histology-confirmed lower-grade (≤Gleason 3 + 4 [n = 47]) or absent (n = 49) prostate cancer imaged with venous-phase CT comprised the study population. CT images were reviewed by ten blinded radiologists (5 attendings, 5 residents) who scored peripheral zone enhancement on a scale of 1 (benign) to 5 (malignant). Mass-like peripheral zone enhancement was considered malignant. Likelihood ratios (LR) and specificities were calculated. Multivariate conditional logistic regression analyses were conducted. RESULTS: Scores of "5" were strongly predictive of higher-grade prostate cancer (pooled LR+ 9.6 [95% CI 5.8-15.8]) with rare false positives (pooled specificity: 0.98 [942/960, 95% CI 0.98-0.99]; all 10 readers had specificity ≥95%). Attending scores of "5" were more predictive than resident scores of "5" (LR+: 14.7 [95% CI 5.8-37.2] vs. 7.6 [95% CI 4.2-13.7]) with similar specificity (0.99 [475/480, 95% CI 0.98-1.00] vs. 0.97 [467/480, 95% CI 0.96-0.99]). Significant predictors of an assigned score of "5" included presence of a peripheral zone mass (p < 0.0001), larger size (p < 0.0001), and less reader experience (p = 0.0008). Significant predictors of higher-grade prostate cancer included presence of a peripheral zone mass (p = 0.0002) and larger size (p < 0.0001). CONCLUSION: Focal mass-like peripheral zone enhancement on routine venous-phase CT is specific and predictive of higher-grade (Gleason 4 + 3 and higher) prostate cancer.

The metabolic demands of endosymbiotic chemoautotrophic metabolism on host physiological capacities.

While chemoautotrophic endosymbioses of hydrothermal vents and other reducing environments have been well studied, little attention has been paid to the magnitude of the metabolic demands placed upon the host by symbiont metabolism and the adaptations necessary to meet such demands. Here we make the first attempt at such an evaluation, and show that moderate to high rates of chemoautotrophic or methanotrophic metabolism impose oxygen uptake and proton equivalent elimination demands upon the hosts that are much higher than is typical for the non-symbiotic annelid, bivalve and gastropod lineages to which they are related. The properties of the hosts are described and compared to determine which properties are associated with and predictive of the highest rates. We suggest that the high oxygen demand of these symbionts is perhaps the most limiting flux for the symbioses. Among the consequences of such demands has been the widespread presence of circulating and/or tissue hemoglobins in these symbioses that are necessary to support high metabolic rates in thioautotrophic endosymbioses. We also compare photoautotrophic with chemoautotrophic and methanotrophic endosymbioses to evaluate the differences and similarities in physiologies. These analyses suggest that the high demand for oxygen by chemoautotrophic and methanotrophic symbionts is likely a major factor precluding their endosymbiosis with cnidarians.

Nanoscale magnetic field detection using a spin torque oscillator.

Magnetic field detection with extremely high spatial resolution is crucial to applications in magnetic storage, biosensing, and magnetic imaging. Here, we present the concept of using a spin torque oscillator (STO) to detect magnetic fields by measuring the frequency of the oscillator. This sensor's performance relies predominantly on STO properties such as spectral linewidth and frequency dispersion with magnetic field, rather than signal amplitude as in conventional magnetoresistive sensors, and is shown in measured devices to achieve large signal to noise ratios. Using macrospin simulations, we describe oscillator designs for maximizing performance, making spin torque oscillators an attractive candidate to replace more commonly used sensors in nanoscale magnetic field sensing and future magnetic recording applications.

Imaging collective magnonic modes in 2D arrays of magnetic nanoelements.

We have used time resolved scanning Kerr microscopy to image collective spin wave modes within a 2D array of magnetic nanoelements. Long wavelength spin waves are confined within the array as if it was a continuous element of the same size but with effective material properties determined by the structure of the array and its constituent nanoelements. The array is an example of a magnonic metamaterial, the demonstration of which provides new opportunities within the emerging field of magnonics.

Rapid domain wall motion in permalloy nanowires excited by a spin-polarized current applied perpendicular to the nanowire.

We study domain wall dynamics in Permalloy nanowires excited by alternating spin-polarized current applied perpendicular to the nanowire. Spin torque ferromagnetic resonance measurements reveal that domain wall oscillations at a pinning site in the nanowire can be excited with velocities as high as 800 m/s at current densities below 10{7} A/cm{2}.

Resonant nonlinear damping of quantized spin waves in ferromagnetic nanowires: a spin torque ferromagnetic resonance study.

We use spin torque ferromagnetic resonance to measure the spectral properties of dipole-exchange spin waves in Permalloy nanowires. Our measurements reveal that geometric confinement has a profound effect on the damping of spin waves in the nanowire geometry. The damping parameter of the lowest-energy quantized spin-wave mode depends on applied magnetic field in a resonant way and exhibits a maximum at a field that increases with decreasing nanowire width. This enhancement of damping originates from a nonlinear resonant three-magnon confluence process allowed at a particular bias field value determined by quantization of the spin-wave spectrum in the nanowire geometry.

Characterization of liposomal vesicles encapsulating rhodanese for cyanide antagonism.

The major mechanism of removing cyanide from the body is its enzymatic conversion by a sulfurtransferase, e.g. rhodanese, to the less toxic thiocyanate in the presence of a sulfur donor. Earlier results demonstrated that externally administered encapsulated rhodanese significantly enhances the in vivo efficacy of the given sulfur donor. Present studies are focused on liposomal carrier systems encapsulating rhodanese. Physicochemical properties, e.g. membrane rigidity, size distribution, surface potential, osmolarity, and viscosity, were determined for various liposomal lipid compositions and hydrating buffers to establish in vitro stability and in vivo fate. Lipid composition was also optimized to achieve maximum encapsulation efficiency.

Public health ethics. Public justification and public trust.

Viewing public health as a political and social undertaking as well as a goal of this activity, the authors develop some key elements in a framework for public health ethics, with particular attention to the formation of public health policies and to decisions by public health officials that are not fully determined by established public policies. They concentrate on ways to approach ethical conflicts about public health interventions. These conflicts arise because, in addition to the value of public health, societies have a wide range of other values that sometimes constrain the selection of means to achieve public health goals. The authors analyze three approaches for resolving these conflicts (absolutist, contextualist, and presumptivist), argue for the superiority of the presumptivist approach, and briefly explicate five conditions for rebutting presumptions in a process of public justification. In a liberal, pluralistic, democratic society, a presumptivist approach that engages the public in the context of a variety of relationships can provide a foundation for public trust, which is essential to public health as a political and social practice as well as to achieving public health goals.

Effects of metabolite uptake on proton-equivalent elimination by two species of deep-sea vestimentiferan tubeworm, Riftia pachyptila and Lamellibrachia cf luymesi: proton elimination is a necessary adaptation to sulfide-oxidizing chemoautotrophic symbionts.

Intracellular symbiosis requires that the host satisfy the symbiont's metabolic requirements, including the elimination of waste products. The hydrothermal vent tubeworm Riftia pachyptila and the hydrocarbon seep worm Lamellibrachia cf luymesi are symbiotic with chemolithoautotrophic bacteria that produce sulfate and protons as end-products. In this report, we examine the relationship between symbiont metabolism and host proton equivalent elimination in R. pachyptila and L. cf luymesi, and the effects of sulfide exposure on proton-equivalent elimination by Urechis caupo, an echiuran worm that lacks intracellular symbionts (for brevity, we will hereafter refer to proton-equivalent elimination as 'proton elimination'). Proton elimination by R. pachyptila and L. cf luymesi constitutes the worms' largest mass-specific metabolite flux, and R. pachyptila proton elimination is, to our knowledge, the most rapid reported for any metazoan. Proton elimination rates by R. pachyptila and L. cf luymesi correlated primarily with the rate of sulfide oxidation. Prolonged exposure to low environmental oxygen concentrations completely inhibited the majority of proton elimination by R. pachyptila, demonstrating that proton elimination does not result primarily from anaerobic metabolism. Large and rapid increases in environmental inorganic carbon concentrations led to short-lived proton elimination by R. pachyptila, as a result of the equilibration between internal and external inorganic carbon pools. U. caupo consistently exhibited proton elimination rates 5-20 times lower than those of L. cf luymesi and R. pachyptila upon exposure to sulfide. Treatment with specific ATPase inhibitors completely inhibited a fraction of proton elimination and sulfide and inorganic carbon uptake by R. pachyptila, suggesting that proton elimination occurs in large part via K(+)/H(+)-ATPases and Na(+)/H(+)-ATPases. In the light of these results, we suggest that protons are the primary waste product of the symbioses of R. pachyptila and L. cf luymesi, and that proton elimination is driven by symbiont metabolism, and may be the largest energetic cost incurred by the worms.

A paradox resolved: sulfide acquisition by roots of seep tubeworms sustains net chemoautotrophy.

Vestimentiferan tubeworms, symbiotic with sulfur-oxidizing chemoautotrophic bacteria, dominate many cold-seep sites in the Gulf of Mexico. The most abundant vestimentiferan species at these sites, Lamellibrachia cf. luymesi, grows quite slowly to lengths exceeding 2 meters and lives in excess of 170-250 years. L. cf. luymesi can grow a posterior extension of its tube and tissue, termed a "root," down into sulfidic sediments below its point of original attachment. This extension can be longer than the anterior portion of the animal. Here we show, using methods optimized for detection of hydrogen sulfide down to 0.1 microM in seawater, that hydrogen sulfide was never detected around the plumes of large cold-seep vestimentiferans and rarely detectable only around the bases of mature aggregations. Respiration experiments, which exposed the root portions of L. cf. luymesi to sulfide concentrations between 51-561 microM, demonstrate that L. cf. luymesi use their roots as a respiratory surface to acquire sulfide at an average rate of 4.1 micromol x g(-1) x h(-1). Net dissolved inorganic carbon uptake across the plume of the tubeworms was shown to occur in response to exposure of the posterior (root) portion of the worms to sulfide, demonstrating that sulfide acquisition by roots of the seep vestimentiferan L. cf. luymesi can be sufficient to fuel net autotrophic total dissolved inorganic carbon uptake.

The failure to give: reducing barriers to organ donation.

Moral frameworks for evaluating non-donation strategies to increase the supply of cadaveric human organs for transplantation and ways to overcome barriers to organ donation are explored. Organ transplantation is a very complex area, because the human body evokes various beliefs, symbols, sentiments, and emotions as well as various rituals and social practices. From a rationalistic standpoint, some policies to increase the supply of a transplantable organs may appear to be quite defensible but then turn out to be ineffective and perhaps even counterproductive because of inadequate attention to these rich and complex features of human body parts. Excessively rationalistic policies neglect deep beliefs, symbols, sentiments, and emotions and the like, and that deficiency marks many actual and proposed policies. In addition, policies are often too individualistic and too legalistic.

Reduced enzymatic antioxidative defense in deep-sea fish.

Oxygen, while being an obligate fuel for aerobic life, has been shown to be toxic through its deleterious reactive species, which can cause oxidative stress and lead ultimately to cell and organism death. In marine organisms, reactive oxygen species (ROS), such as the superoxide anion and hydrogen peroxide, are generated within respiring cells and tissues and also by photochemical processes in sea water. Considering both the reduced metabolic rate of nektonic organisms thriving in the deep sea and the physico-chemical conditions of this dark, poorly oxygenated environment, the meso- and bathypelagic waters of the oceans might be considered as refuges against oxidative dangers. This hypothesis prompted us to investigate the activities of the three essential enzymes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX) constitutive of the antioxidative arsenal of cells in the tissues of 16 species of meso- and bathypelagic fishes occurring between the surface and a depth of 1300 m. While enzymatic activities were detected in all tissues from all species, the levels of SOD and GPX decreased in parallel with the exponential reduction in the metabolic activity as estimated by citrate synthase activity. In contrast, CAT was affected neither by the metabolic activity nor by the depth of occurrence of the fishes. High levels of metabolic and antioxidative enzymes were detected in the light organs of bioluminescent species. The adjustment of the activity of SOD and GPX to the decreased metabolic activity associated with deep-sea living suggests that these antioxidative defense mechanisms are used primarily against metabolically produced ROS, whereas the maintenance of CAT activity throughout all depths could be indicative of another role. The possible reasons for the occurrence of such a reduced antioxidative arsenal in deep-sea species are discussed.

Polypeptide chain composition diversity of hexagonal-bilayer haemoglobins within a single family of annelids, the alvinellidae.

Following previous analysis of the structure of Alvinella pompejana heaxagonal-bilayer haemoglobin (HBL Hb) [1], we report in this paper the structure of three other HBL Hbs belonging to Alvinella caudata, Paralvinella grasslei and Paralvinella palmiformis, members of the Alvinellidae, annelid family strictly endemic to deep-sea hydrothermal vents located on the ridge crests in the Pacific ocean. The multi-angle laser light scattering (MALLS) and fast protein liquid chromatography (FPLC) analysis revealed a broad range of molecular masses for the extracellular Hb molecules, 3517 +/- 14 kDa (A. caudata), 3822 +/- 28 kDa (P. grasslei) and 3750 +/- 150 kDa (P. palmiformis). Native and derivative Hbs (reduced, carbamidomethylated and deglycosylated) were analysed by electrospray ionization mass spectroscopy (ESI-MS) and the data was processed by the maximum entropy deconvolution system (MaxEnt). The most important difference between alvinellid HBL Hbs was the variation in their composition, from two to four monomeric globin chains, and from one to four linker chains. Therefore, despite the fact that all these species belong to a single family, notable differences in the polypeptide chain composition of their HBL Hbs were observed, probably accounting for their different functional properties as previously reported by this group Toulmond, A., El Idrissi Slitine, F., De Frescheville, J. & Jouin, C. (1990) Biol. Bull. 179, 366-373.

Fate of nitrate acquired by the tubeworm Riftia pachyptila.

The hydrothermal vent tubeworm Riftia pachyptila lacks a mouth and gut and lives in association with intracellular, sulfide-oxidizing chemoautotrophic bacteria. Growth of this tubeworm requires an exogenous source of nitrogen for biosynthesis, and, as determined in previous studies, environmental ammonia and free amino acids appear to be unlikely sources of nitrogen. Nitrate, however, is present in situ (K. Johnson, J. Childress, R. Hessler, C. Sakamoto-Arnold, and C. Beehler, Deep-Sea Res. 35:1723-1744, 1988), is taken up by the host, and can be chemically reduced by the symbionts (U. Hentschel and H. Felbeck, Nature 366:338-340, 1993). Here we report that at an in situ concentration of 40 microM, nitrate is acquired by R. pachyptila at a rate of 3.54 micromol g(-1) h(-1), while elimination of nitrite and elimination of ammonia occur at much lower rates (0. 017 and 0.21 micromol g(-1) h(-1), respectively). We also observed reduction of nitrite (and accordingly nitrate) to ammonia in the trophosome tissue. When R. pachyptila tubeworms are exposed to constant in situ conditions for 60 h, there is a difference between the amount of nitrogen acquired via nitrate uptake and the amount of nitrogen lost via nitrite and ammonia elimination, which indicates that there is a nitrogen "sink." Our results demonstrate that storage of nitrate does not account for the observed stoichiometric differences in the amounts of nitrogen. Nitrate uptake was not correlated with sulfide or inorganic carbon flux, suggesting that nitrate is probably not an important oxidant in metabolism of the symbionts. Accordingly, we describe a nitrogen flux model for this association, in which the product of symbiont nitrate reduction, ammonia, is the primary source of nitrogen for the host and the symbionts and fulfills the association's nitrogen needs via incorporation of ammonia into amino acids.

Light-limitation on predator-prey interactions: consequences for metabolism and locomotion of deep-sea cephalopods.

The present study attempts to correlate the metabolism and locomotory behavior of 25 species of midwater Cephalopoda from California and Hawaii with the maximal activities of key metabolic enzymes in various locomotory muscle tissues. Citrate synthase (CS) and octopine dehydrogenase (ODH) activities were used as indicators of aerobic and anaerobic metabolic potential respectively. CS activity in mantle muscle is highly correlated with whole-animal rates of oxygen consumption, whereas ODH activity in mantle muscle is significantly correlated with a species' ability to buffer the acidic end-products of anaerobic metabolism. Both CS and ODH activities in mantle muscle declined strongly with a species' habitat depth. For example, CS and ODH activities ranged respectively from 0.04 units g(-1) and 0.03 units g(-1) in the deep-living squid Joubiniteuthis portieri, to 8.13 units g(-1) and 420 units g(-1) in the epipelagic squid Sthenoteuthis oualaniensis. The relationships between enzymatic activities and depth are consistent with similar patterns observed for whole-animal oxygen consumption. This pattern is believed to result from a relaxation, among deep-living species, in the need for strong locomotory abilities for visual predator/prey interactions; the relaxation is due to light-limitation in the deep sea. Intraspecific scaling patterns for ODH activities may, for species that migrate ontogenetically to great depths, reflect the counteracting effects of body size and light on predator-prey detection distances. When scaled allometrically, enzymatic activities for the giant squid, Architeuthis sp., suggest a fairly active aerobic metabolism but little burst swimming capacity. Interspecific differences in the relative distributions of enzymatic activities in fin, mantle, and arm tissue suggest an increased reliance on fin and arm muscle for locomotion among deep-living species. We suggest that, where high-speed locomotion is not required, more efficient means of locomotion, such as fin swimming or medusoid arm propulsion, are more prevalent.