Near-Monochromatic Tuneable Cryogenic Niobium Electron Field Emitter.

Creating, manipulating, and detecting coherent electrons is at the heart of future quantum microscopy and spectroscopy technologies. Leveraging and specifically altering the quantum features of an electron beam source at low temperatures can enhance its emission properties. Here, we describe electron field emission from a monocrystalline, superconducting niobium nanotip at a temperature of 5.9 K. The emitted electron energy spectrum reveals an ultranarrow distribution down to 16 meV due to tunable resonant tunneling field emission via localized band states at a nanoprotrusion's apex and a cutoff at the sharp low-temperature Fermi edge. This is an order of magnitude lower than for conventional field emission electron sources. The self-focusing geometry of the tip leads to emission in an angle of 3.7°, a reduced brightness of 3.8×10^{8} A/(m^{2} sr V), and a stability of hours at 4.1 nA beam current and 69 meV energy width. This source will decrease the impact of lens aberration and enable new modes in low-energy electron microscopy, electron energy loss spectroscopy, and high-resolution vibrational spectroscopy.

Beam shaping and probe characterization in the scanning electron microscope.

Here we demonstrate the use of nanofabricated grating holograms to diffract and shape electrons in a scanning electron microscope. The diffraction grating is placed in an aperture in the column. The entire diffraction pattern can be passed through the objective lens and projected onto the specimen, or an intermediate aperture can be used to select particular diffracted beams. We discuss several techniques for characterizing the diffraction pattern. The grating designs can incorporate features that can influence the phase and intensity of the diffracted SEM probe. We demonstrate this by producing electron vortex beams.

Train Traffic as a Powerful Noise Source for Monitoring Active Faults With Seismic Interferometry.

Laboratory experiments report that detectable seismic velocity changes should occur in the vicinity of fault zones prior to earthquakes. However, operating permanent active seismic sources to monitor natural faults at seismogenic depth is found to be nearly impossible to achieve. We show that seismic noise generated by vehicle traffic, and especially heavy freight trains, can be turned into a powerful repetitive seismic source to continuously probe the Earth's crust at a few kilometers depth. Results of an exploratory seismic experiment in Southern California demonstrate that correlations of train-generated seismic signals allow daily reconstruction of direct P body waves probing the San Jacinto Fault down to 4-km depth. This new approach may facilitate monitoring most of the San Andreas Fault system using the railway and highway network of California.

Why did that happen? Exploring the proliferation of barely usable software in healthcare systems.

Clinicians and support staff are faced with increasingly complex computer applications. This complexity stems partly from the integration of heterogeneous systems ranging from computerized patient records to theatre management and dosage planning applications, and also from the increased functionality offered by the new generation of IT systems. Many members of clinical staff are bewildered by the vast array of configuration options and operating modes supported by computer based systems, while manufacturers often feel compelled to offer more and more software features to retain market position. These factors combine to create "usability" problems that have had a direct impact on patient outcomes as well as a number of indirect effects-for example, the costs of replacing and upgrading inadequate computer systems carry significant opportunity costs in terms of services that might otherwise have been funded. In the future we need to educate staff to reject substandard computer interfaces early in the acquisition process; encourage the use of human computer interaction techniques in health care; and train staff to recognize the dangers of "working around" poor interface design.

How will we get the data and what will we do with it then? Issues in the reporting of adverse healthcare events.

Incident reporting has been proposed as an important means of identifying and addressing the causes of human error in medicine, and initiatives to implement these schemes have been set up in many countries. However, incident reporting has its limitations. Many people have been too ready to believe the overstated claims about the effectiveness of incident reporting in other domains. Others have not listened to the more limited claims made by the operators of existing systems in aviation and in organizational health and safety applications. This paper argues that more attention should be paid to the problems of eliciting incident reports from a broad spectrum of healthcare workers. It is also argued that more sophisticated computation support should be recruited so that clinicians do not have to learn complex command languages when they want to search for common factors in those incidents that are submitted.

Molecular markers linked to the blast resistance gene Pi-z in rice for use in marker-assisted selection.

Rice blast, caused by the fungal pathogen Pyricularia grisea, is a serious disease affecting rice-growing regions around the world. Current methods for identification of blast-resistant germplasm and progeny typically utilize phenotypic screening. However, phenotypic screens are influenced by environmental conditions and the presence of one resistance gene can sometimes phenotypically mask other genes conferring resistance to the same blast race. Pi-z is a dominant gene located on the short arm of chromosome 6 that confers complete resistance to five races of blast. Using sequence data found in public databases and degenerate primer pairs based on the P-loop, nucleotide binding sites and kinase domain motifs of previously cloned resistance genes, we have developed PCR-based DNA markers that cosegregate with the gene. These markers are polymorphic in a wide range of germplasm, including the narrow crosses characteristic of applied rice-breeding programs. They can now be used as a low cost, high-throughput alternative to conventional phenotypic screening for direct detection of blast resistance genes, allowing rapid introgression of genes into susceptible varieties as well as the incorporation of multiple genes into individual lines for more-durable blast resistance.

A method of indirect registration of the coordinates of condylar points with a six-degree-of-freedom jaw tracker.

Previous studies have indicated that the location of a condylar point can significantly influence its trajectory. The aim of this investigation was to develop a method of registering the location of radiographically defined condylar points in the coordinate system of a six-degree-of-freedom jaw-tracking device and to determine the accuracy of this method by using a perspex model in one experiment and a dry skull in another. A direct measurement ('the gold standard') of condylar point coordinates in the coordinate system of JAWS3D was done using a three-dimensional (3D) digitizer (MicroScribe-3DX). The indirect measurement used a distributed fiducial marker as the interface between the coordinate system of MicroScribe-3DX (which was used to register the fiducial marker and the JAWS3D coordinate system) and the coordinate system of the CT scans (used to define condyle anatomy and the relation with the fiducial marker). The coordinates of condylar points could then be calculated in the coordinate system of JAWS3D. The results showed that the indirect method could register condylar point coordinates on either side to an accuracy of approximately 0.5 mm.

Salvage cryotherapy using an argon based system for locally recurrent prostate cancer after radiation therapy: the Columbia experience.

PURPOSE: Cryosurgical ablation of the prostate has been reported as potential treatment for radioresistant clinically localized prostate cancer. We report our experience with the safety and efficacy of salvage cryosurgery using the argon based CRYOCare system (Endocare, Inc, Irvine, California). MATERIALS AND METHODS: Between October 1997 and September 2000, 38 men with a mean age of 71.9 years underwent salvage cryosurgery for recurrent prostate cancer after radiation therapy failed. All patients had biochemical disease recurrence, defined as an increase in prostate specific antigen (PSA) of greater than 0.3 ng./ml. above the post-radiation PSA nadir. Subsequently prostate biopsy was positive for cancer. Pre-cryosurgery bone scan demonstrated no evidence of metastatic disease. In addition, these patients received 3 months of neoadjuvant androgen deprivation therapy before cryotherapy. RESULTS: The PSA nadir was 0.1 or less, 1 or less and greater than 1 ng./ml. in 31 (81.5%), 5 (13.2%) and 2 (5.3%) patients, respectively. Biochemical recurrence-free survival calculated from Kaplan-Meier curves was 86% at 1 year and 74% at 2 years. Reported complications included rectal pain in 39.5% of cases, urinary tract infection in 2.6%, incontinence in 7.9%, hematuria in 7.9% and scrotal edema in 10.5%. The rate of rectourethral fistula, urethral sloughing and urinary retention was 0%. CONCLUSIONS: Our study supports cryosurgery of the prostate as safe and effective treatment in patients in whom radiation therapy fails. Using the CRYOCare machine resulted in a marked decrease in complications.

Flow cytometric enumeration of micronucleated reticulocytes: high transferability among 14 laboratories.

This laboratory previously described a single-laser flow cytometric method, which effectively resolves micronucleated erythrocyte populations in rodent peripheral blood samples. Even so, the rarity and variable size of micronuclei make it difficult to configure instrument settings consistently and define analysis regions rationally to enumerate the cell populations of interest. Murine erythrocytes from animals infected with the malaria parasite Plasmodium berghei contain a high prevalence of erythrocytes with a uniform DNA content. This biological model for micronucleated erythrocytes offers a means by which the micronucleus analysis regions can be rationally defined, and a means for controlling interexperimental variation. The experiments described herein were performed to extend these studies by testing whether malaria-infected erythrocytes could also be used to enhance the transferability of the method, as well as control intra- and interlaboratory variation. For these studies, blood samples from mice infected with malaria, or treated with vehicle or the clastogen methyl methanesulfonate, were fixed and shipped to collaborating laboratories for analysis. After configuring instrumentation parameters and guiding the position of analysis regions with the malaria-infected blood samples, micronucleated reticulocyte frequencies were measured (20,000 reticulocytes per sample). To evaluate both intra- and interlaboratory variation, five replicates were analyzed per day, and these analyses were repeated on up to five separate days. The data of 14 laboratories presented herein indicate that transferability of this flow cytometric technique is high when instrumentation is guided by the biological standard Plasmodium berghei.

The accuracy with which the human condyle can be expressed in the coordinate system of JAWS3D using a unilateral fiducial marker.

Previous studies have indicated that the selection of condylar referencing points can significantly influence condylar point trajectories, and the use of radiographically determined condylar points is essential for accurate representation of condylar movement. The aim of this investigation was to determine the accuracy with which the three-dimensional locations of condylar points could be determined in the coordinate system of the JAWS3D tracking device when an ipsilateral fiducial marker is used. A perspex mandible containing condylar radiographic markers was constructed. A JAWS3D target frame and a fiducial marker, supporting radiographic markers, were secured to the perspex mandible. The image data from computer tomography scans of the condyles and fiducial marker, together with photographs of the fiducial marker and the JAWS3D target frame were used to calculate condylar point coordinates in the JAWS3D coordinate system. These data were then compared with the data obtained by direct measurement of the condylar radiographic markers in the JAWS3D coordinates. The results suggest that a unilateral fiducial marker is sufficient to allow the registration of ipsilateral condylar point coordinates to an accuracy of approximately 1.0 mm.

Interstitial fibrosis of unilateral ureteral obstruction is exacerbated in kidneys of mice lacking the gene for inducible nitric oxide synthase.

Unilateral ureteral obstruction (UUO) is characterized by decreases in renal function and increases in interstitial fibrosis. Previous studies have indicated that pharmacologic manipulations that increase nitric oxide (NO) are beneficial to the obstructed kidneys. NO is produced from arginine by nitric oxide synthase (NOS), an enzyme that exists in both constitutive and inducible (iNOS) forms. To determine the role of the inducible form of NOS in UUO, we used mice with a targeted deletion of iNOS (iNOS -/- mice) and compared them with wild-type (WT) mice. Kidneys were obstructed for 2 weeks in both WT and iNOS -/- mice, and were then removed and bisected. Half of the kidney was embedded in paraffin and tissue sections were examined for interstitial volume or the presence of macrophages. The remainder was flash-frozen and samples were used to measure tissue collagen (hydroxyproline) or transforming growth factor-beta (TGF-beta). This study demonstrates that both cortex and medulla of obstructed kidneys of iNOS -/- mice exhibit significantly increased interstitial volume and interstitial macrophages as compared with their WT counterparts. Furthermore tissue collagen was increased to 9.2+/-1.3 microg/mg tissue in WT obstructed kidneys, whereas in iNOS -/- kidneys, collagen was increased to 13.2+/-0.8 microg/mg tissue. The profibrotic cytokine TGF-beta was also significantly increased in obstructed kidneys of iNOS -/- mice, as compared with WT mice. No differences were noted between the unobstructed kidneys of iNOS -/- mice compared with WT mice in any of the parameters examined. These results demonstrate that targeted deletion of the iNOS results in exacerbation of fibrotic events in the obstructed kidney. These results confirm previous pharmacologic studies, and suggest that NO produced via the inducible NOS normally serves a protective function in UUO.

Sensitivity of the SRBC PFC assay versus ELISA for detection of immunosuppression by TCDD and TCDD-like congeners.

The splenic antibody plaque forming cell (PFC) assay is a widely used assay in immunotoxicity testing. A recent revision of the Federal Insecticide, Fungicide and Rodenticide (FIFRA) Immunotoxicity test guidelines by the EPA recommended that either the PFC assay or the sheep red blood cell (SRBC) specific serum IgM enzyme-linked immunosorbent assay (ELISA) be used to assess the primary humoral response to SRBCs. The PFC assay quantifies the number of plasma cells in the spleen producing SRBC-specific antibody, while the ELISA measures SRBC-specific IgM antibody in the serum. Because these two assays measure different endpoints, there is a need for comparison of their sensitivity and reliability. The purpose of this project was to determine if these two assays are equally sensitive to suppression of the SRBC response in B6C3F1 female mice. Female B6C3F1 mice were given a single oral exposure to different doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or four TCDD-like congeners. One week later, two sets of mice were immunized with SRBC. The first set was evaluated for the PFC response and the second for the ELISA response, on day 4 or 5 post-immunization, respectively. The four TCDD-like congeners tested were: 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,2,3,4,7-pentachlorodibenzofuran (4PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB126) and 2,3',4,4',5-pentachlrorbiphenyl (PCB118). The results were used to generate dose-response curves for the determination of the ED(50) for TCDD and each TCDD-like congener. For all chemicals tested, measuring the level of SRBC-specific IgM antibody by ELISA was more sensitive than the PFC assay to detect immunosuppression, as indicated by lower ED(50) values. These results indicate that the SRBC-specific IgM ELISA is a more sensitive assay for detecting the T-cell mediated immunotoxicity of dioxin-like chemicals in this rodent model.

Quality of obturation in student cases instructed by endodontic versus general dentistry faculty.

Endodontic literature suggests that only about 60% of endodontic therapy meets current technical standards and that general dentists may be making a significant contribution to this compromised care. If so, where in the continuum of dental education does this begin. This study evaluated the quality of obturation in mandibular molars provided on the one hand by 3rd year dental students instructed by endodontic faculty, and on the other hand by 4th year students instructed by general dentistry faculty, versus the quality of obturation achieved by endodontic residents who served as a control for both groups. Final radiographs were chosen from students in all three groups so that there were 22 samples per group. Three evaluators rank-ordered the radiographs. In order of excellence, the results were: (a) residents, (b) 3rd year students, and (c) 4th year students. There was no significant difference between the 3rd year students or the residents, only between residents and 4th year students (p < 0.05). The reasons for this outcome may range from dental school objectives to the private practice procedures of the general dentists who instructed the 4th year students.

The effect of foot structure and range of motion on musculoskeletal overuse injuries.

The purpose of this prospective study was to determine whether an association exists between foot structure and the development of musculoskeletal overuse injuries. The study group was a well-defined cohort of 449 trainees at the Naval Special Warfare Training Center in Coronado, California. Before beginning training, measurements were made of ankle motion, subtalar motion, and the static (standing) and dynamic (walking) characteristics of the foot arch. The subjects were tracked prospectively for injuries throughout training. We identified risk factors that predispose people to lower extremity overuse injuries. These risk factors include dynamic pes planus, pes cavus, restricted ankle dorsiflexion, and increased hindfoot inversion, all of which are subject to intervention and possible correction.

Trajectories of condylar points during nonworking side and protrusive movements of the mandible.

STATEMENT OF PROBLEM: During lateral excursive and protrusive jaw movements, condylar points are distant from any instantaneous rotational center. Therefore, it is likely that different condylar points would follow similar trajectories during these movements. PURPOSE: This study evaluated the effect of changes in condylar point location on trajectories of condylar points on the nonworking side and during a protrusive jaw movement and compared these changes with the effects described for open-close and working-side condylar movements in the same group of subjects. METHODS: The movements of 5 clinically determined condylar points were recorded in 44 subjects during a contralateral excursion and during protrusion (7 radiographically determined condylar points in 2 subjects). RESULTS: During any single jaw movement, the trajectory of each condylar point was similar in form and dimension to the other condylar points within that subject. CONCLUSION: Changes in condylar point location had little effect on the trajectories of condylar points on the nonworking side and during protrusive jaw movement.

Issues in immunohistochemistry.

Immunohistochemistry is a powerful technique used to localize specific molecules in tissues. Literally thousands of immunoreagents specific for an incredibly diverse number of molecules are commercially available, and some of these immunoreagents will detect minute quantities of target molecule in tissues. However, like any powerful technique, the staining study design must be carefully conceived and controlled to avoid misinterpretation.

Trajectories of condylar points during working-side excursive movements of the mandible.

STATEMENT OF PROBLEM: Trajectories of different condylar points provide different interpretations of condylar movement during open-close jaw movements. Movement of the working-side condyle is often assessed clinically by recording the trajectory of a single arbitrary condylar point. PURPOSE: This study examined the effect of the differences in condylar point location on condylar point movement trajectories during a working-side movement. METHODS: Different points exhibited different trajectories during a single working-side movement in each of 44 subjects. RESULTS: Up to 40% of a point's displacement could be attributed simply to the location of the point. CONCLUSIONS: Interpretation of condylar movement on the working side within a subject depends on the point chosen.

Fiber-coupled high-power external-cavity semiconductor lasers for real-time Raman sensing.

High-power, external-cavity semiconductor lasers with narrow bandwidth and fiber-coupled output are designed and constructed. An output power of 540 mW is coupled out of a 100-mum multimode fiber with coupling efficiency of 72% when the laser is operated at 1.1 A. The emission linewidth is as narrow as 22 GHz, and the wavelength is tunable from 779.7 to 793.0 nm. Application of such lasers to remote real-time Raman sensing of materials is also demonstrated.

The effect of posterior tooth guidance on non-working side arbitrary condylar point movement.

Occlusal form is frequently modified in clinical practice and yet we do not have detailed knowledge of the possible effects of these changes on condylar movement. The aim of this study was to quantify the effects of an alteration in the occlusion on condylar movement during a lateral excursive jaw movement. Posterior tooth guidances (i.e. metal overlays) were attached to both maxillary first molars. The movement of arbitrary condylar points on the non-working side was recorded in seven subjects during lateral excursion under natural tooth guidance (control) and was compared with that after placement of the overlays (guidance). The guidance resulted in statistically significant changes to the displacement of the arbitrary condylar points on the non-working side. For example, at a standardized (3 mm) displacement along the mid-incisor point trajectory during the lateral excursion for both control and guidance in all subjects, the corresponding displacements of the condylar points were statistically significantly decreased under the guidance situation in comparison with the control situation. These data suggest that, for the same magnitude of mandibular displacement during lateral excursion, the introduction of a posterior tooth guidance limits condylar displacement on the non-working side.