Radiotherapy, toxicity and dosimetry of copper-64-TETA-octreotide in tumor-bearing rats

The efficacy of 64Cu [T1/2 = 12.7 hr; beta+ (0.655 MeV; 19%); beta- (0.573 MeV; 40%)] as a radioisotope for radiotherapy has been recently established. Here we demonstrate that 64Cu-1,4,8,11 -tetraazacyclotetradecane-N,N',N",N'-tetraacetic acid (TETA)-octreotide, a somatostatin receptor ligand, inhibits the growth of CA20948 rat pancreatic tumors in Lewis rats at doses that cause minimal toxicity. METHODS: Tumor-bearing rats were administered a single 15 mCi (555 MBq) dose, a fractionated dose of 15 mCi given in 2-3 doses over 2-8 days, or control agents of buffer, unlabeled octreotide or 64Cu-labeled TETA. In certain experiments, blood was removed at times from 4-23 days post-treatment, and a complete blood count along with blood chemistry analyses were obtained. RESULTS: Tumor-growth inhibition was significantly greater in rats injected with a single 15 mCi dose than in rats injected with control agents (p < 0.05). Dose fractionation in two doses, either 1 or 2 days apart, induced significantly increased tumor-growth inhibition compared with rats given a single dose (p < 0.05). The only toxicity observed in treated rats was a decrease in the white blood cell count. This drop was more pronounced in rats treated with a single dose compared with those treated with a fractionated dose. Human absorbed doses of 64Cu-TETA-octreotide to normal organs were estimated from biodistribution data in Lewis rats, and these data indicate that radiotherapy with 64Cu-TETA-octreotide in humans would be feasible. CONCLUSION: Copper-64-TETA-octreotide is a promising radiopharmaceutical for targeted radiotherapy of somatostatin receptor-positive tumors.     

Predicting and presenting plausible future scenarios of wind power production from numerical weather prediction systems: a qualitative ex ante evaluation for decision making

This paper is concerned with evaluating techniques to forecast plausible future scenarios in wind power production for up to 48 h ahead, where the term scenario refers to a coherent chronological prediction including the timing, rapidity and size of large changes. Such predictions are of great interest in power systems with high regional wind penetration where a large rapid change in wind power may pose a threat to power system security. Numerous studies have evaluated wind power forecasting methods on ex post statistical measures of forecast accuracy such as root mean square error. Other work has assessed the forecast value by simulating automated decision making for bidding wind generation into particular electricity markets, and in some cases, the ex ante value of a perfect forecast has been assessed. The future, however, will always be uncertain, and decision making always takes place in an ex ante context. This paper discusses how numerical weather prediction (NWP) systems forecasts are produced, with a particular focus on uncertainty and how forecasters might visually present plausible future scenarios for wind power to electricity industry decision makers. It is difficult to quantify the ex ante value of visual wind power forecast information to the complex decision‐making process involved. Consequently, this paper explores qualitative assessments of ex ante value by proposing six desirable attributes for the techniques and the presentation of NWP forecasts to decision makers. It uses these attributes to assess four such methodologies, which include NWP ensemble methods and the recently introduced NWP spatial field approach. Copyright © 2011 John Wiley & Sons, Ltd.     

Synthetically programmable nanoparticle superlattices using a hollow three-dimensional spacer approach

Crystalline nanoparticle arrays and superlattices with well-defined geometries can be synthesized by using appropriate electrostatic, hydrogen-bonding or biological recognition interactions. Although superlattices with many distinct geometries can be produced using these approaches, the library of achievable lattices could be increased by developing a strategy that allows some of the nanoparticles within a binary lattice to be replaced with 'spacer' entities that are constructed to mimic the behaviour of the nanoparticles they replace, even though they do not contain an inorganic core. The inclusion of these spacer entities within a known binary superlattice would effectively delete one set of nanoparticles without affecting the positions of the other set. Here, we show how hollow DNA nanostructures can be used as 'three-dimensional spacers' within nanoparticle superlattices assembled through programmable DNA interactions. We show that this strategy can be used to form superlattices with five distinct symmetries, including one that has never before been observed in any crystalline material.     

Effect of Additives on the Activation Energy for Sintering of Silicon Carbide

The combined-stage sintering model was used to determine the activation energy, Q , of sintering for selected SiC-based materials. SiC densified with a liquid (1.65 wt% Al) had an activation energy of 842±79 kJ/mol, a value between those for a silicon carbide densified with 1 wt% C and 0.25 wt% B₄C ( Q =643±37 kJ/mol) and one densified with 2.5 wt% AlN ( Q =1022±122 kJ/mol), compositions which have no liquid phase below 1850°C. The SiC with Al additive began densification by 1500°C and the densification curve was offset by approximately 100°C compared with the other two materials below 1850°C. The choice and amount of additives not only affect densification and activation energy, but also influence microstructure and fracture mode, allowing engineering of mechanical properties.     

Randomized clinical trial of tetracycline hydrochloride bandage and paste treatments for resolution of lesions and pain associated with digital dermatitis in dairy cattle

Digital dermatitis is an infectious disease that causes lameness in dairy cattle, a primary welfare concern of the dairy industry. One of the common treatments for this painful hoof disease is through the application of an antibiotic bandage that must be removed following treatment. The objectives of this randomized clinical trial were to determine if topical application of tetracycline hydrochloride in a paste would be as therapeutically effective for the treatment of digital dermatitis as a powdered form of tetracycline hydrochloride held in place by a bandage, and to quantify pain associated with digital dermatitis lesions. Two hundred and fourteen Holstein cow hooves with digital dermatitis lesions were randomly assigned to 1 of 3 treatments: a tetracycline hydrochloride paste, tetracycline hydrochloride powder held in place with a bandage for 2 d, or a negative (untreated) control. Lesions were examined at 2 time periods: 3 to 7 d posttreatment and 8 to 12 d posttreatment to determine healing rates. Nociceptive thresholds were measured using a pressure algometer to quantify the pain at the lesion site. The tetracycline hydrochloride paste was as effective as the powdered bandage treatment in terms of healing rates, with 47.4 and 57.1% hooves healed at 8 to 12 d posttreatment, respectively. Both treatments were more effective than the control, in which no lesions healed 8 to 12 d following initial examination. Mean (±SE) nociceptive thresholds for active, healing, and healed lesions differed, with limb-withdrawal response occurring at 7.45 (±0.67) kg, 12.84 (±1.85) kg, and censored to 25 kg (maximum value of algometer) of force applied, respectively. However, active lesions were not consistently associated with pain, as maximum force was tolerated when applied to 19% of active lesions, perhaps due to variability in stoicism between individual cattle or due to changes in pain during the progression of infection. In conclusion, tetracycline hydrochloride paste was as effective as tetracycline hydrochloride bandage, eliminating the need for bandage removal following treatment application. Digital lesions can be painful during both active and healing stages, suggesting the need for treatment and husbandry interventions for pain mitigation.     

Cardiovascular disease prevention research at the National Heart, Lung, and Blood Institute

The morphology of endothelial cells in vivo depends on the local hemodynamic forces. Cells are polygonal and randomly oriented in areas of low shear stress, but they are elongated and aligned in the direction of fluid flow in regions of high shear stress. Endothelial cells in vitro also have a polygonal shape, but the application of shear stress orients and elongates the cells in the direction of fluid flow. The corresponding spatial reorganization of the cytoskeleton in response to the applied hemodynamic forces is unknown. In this study, we determined the spatial reorganization of the cytoskeleton throughout the volume of cultured bovine aortic endothelial cells after the cells had been exposed to a physiological level of shear stress for 0, 1.5, 3, 6, 12, or 24 h. The response of the monolayer to shear stress was not monotonic; it had three distinct phases. The first phase occurred within 3 h. The cells elongated and had more stress fibers, thicker intercellular junctions, and more apical microfilaments. After 6 h of exposure, the monolayer entered the second phase, where the cells exhibited characteristics of motility. The cells lost their dense peripheral bands and had more of their microtubule organizing centers and nuclei located in the upstream region of the cell. The third phase began after 12 h of exposure and was characterized by elongated cells oriented in the direction of fluid flow. The stress fibers in these cells were thicker and longer, and the heights of the intercellular junctions and microfilaments were increased. These results suggest that endothelial cells initially respond to shear stress by enhancing their attachments to the substrate and neighboring cells. The cells then demonstrate characteristics of motility as they realign. The cells eventually thicken their intercellular junctions and increase the amount of apical microfilaments. The time course of rearrangement can be described as a constrained motility that produces a new cytoskeletal organization that alters how the forces produced by fluid flow act on the cell and how the forces are transmitted to the cell interior and substrate.     

Competition in spoken word recognition: Spotting words in other words.

Although word boundaries are rarely clearly marked, listeners can rapidly recognize the individual words of spoken sentences. Some theories explain this in terms of competition between multiply activated lexical hypotheses; others invoke sensitivity to prosodic structure. A connectionist model, SHORTLIST, is described, in which recognition by activation and competition is successful with a realistically sized lexicon. Three experiments are then reported in which listeners detected real words embedded in nonsense strings, some of which were themselves the onsets of longer words. Effects both of competition between words and of prosodic structure were observed, suggesting that activation and competition alone are not sufficient to explain word recognition in continuous speech. However, the results can be accounted for by a version of SHORTLIST that is sensitive to prosodic structure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Witness confidence and witness accuracy: Assessing their forensic relation.

Jurors overbelieve eyewitnesses, have difficulty reliably differentiating accurate from inaccurate eyewitnesses, and are not adequately sensitive to aspects of witnessing and identification conditions. A major source of juror unreliability is reliance on witness confidence, a dubious indicator of eyewitness accuracy even when measured at the time an identification is made. Confidence appears to be influenced by postidentification factors such as repeated questioning, briefings in anticipation of cross-examination, and feedback about the behavior of other witnesses. Juror reliance on witness confidence appears to be unaffected by traditional safeguards such as cross-examination and judges' instructions in eyewitness cases. Expert psychological testimony on the factors that influence eyewitness memory, in contrast, appears to reduce juror reliance on confidence and enhance use of other factors known to affect memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)