Comparison of Time Series and Random-Vibration Theory Site-Response Methods

The random-vibration theory (RVT) approach to equivalent-linear site-response analysis is often used to simulate site amplification, particularly when large numbers of simulations are required for incorporation into probabilistic seismic-hazard analysis. The fact that RVT site-response analysis does not require the specification of input-time series makes it an attractive alternative to other site-response methods. However, some studies have indicated that the site amplification predicted by RVT site-response analysis systematically differs from that predicted by time-series approaches. This study confirms that RVT site-response analysis predicts site amplification at the natural site frequencies as much as 20%-50% larger than time-series analysis, with the largest overprediction occurring for sites with smaller natural frequencies and sites underlain by hard rock. The overprediction is caused by an increase in duration generated by the site response, which is not taken into account in the RVT calculation. Correcting for this change in duration brings the RVT results within 20% of the time-series results. A similar duration effect is observed for the RVT shear-strain calculation used to estimate the equivalent-linear strain-compatible soil properties. An alternative to applying a duration correction to improve the agreement between RVT and time-series analysis is the modeling of shear-wave velocity variability. It is shown that introducing shear-wave velocity variability through Monte Carlo simulation brings the RVT results consistently within +/- 20% of the time-series results.Nuclear Regulatory Commission NRC-04-07-122Civil, Architectural, and Environmental Engineerin

Clinical Practice Guidelines for Hand Therapy and Application of the Occupational Adaptation Model

The purpose of this capstone project was to gain advanced clinical practice skills in the hand therapy setting. The 14-week capstone project was completed at TRIA Orthopedics in Woodbury, MN with a primary focus on direct patient care while building the advanced clinical practice skills and knowledge needed to become a competent entry-level hand therapist. Overall, the student worked with a wide variety of diagnoses commonly seen in the hand therapy setting. The objectives for the project included (1) TRIA student objectives; (2) review of surgery videos of common hand therapy diagnoses; (3) PAMs/wound care/pre-posttests; (4) clinical practice guideline for swan neck and boutonniere deformity; (5) case study on poly-trauma patient emphasizing the occupational adaptation frame of reference; (6) handle a full caseload/fabricate custom splints and orthotics. Each objective had corresponding deliverables that were completed by the capstone student. These deliverables included proof of completed TRIA objectives, written reflections of hand surgery videos, proof of competencies in PAMs/wound care/pre-posttests, a completed clinical practice guideline on the swan neck and boutonniere deformities with a corresponding presentation, a completed case study of poly-trauma patient with a corresponding presentation, and a written summary/table of the capstone experience. Using the constructs of the occupational adaptation model, the student was able to treat with a more holistic and client-centered focus throughout this experience. This capstone project provided materials and knowledge for future use to guide practice along with developing skills needed for entry-level practice

Analysis of a turbine rotor containing a transverse crack at Oak Creek Unit 17

Transient increases in one, two and three per revolution vibration characteristics of a low pressure steam turbine were observed during steam temperature reduction operations. Vibration and fracture mechanics analyses suggested the presence of a transverse shaft crack which was eventually identified by ultrasonic inspection and confirmed by destructive sectioning. Signature analyses of vibration data recorded over a two-year period prior to crack identification are correlated with fatigue crack growth, which occurred intermittently during transient temperature decreases. The apparent increased response of the rotor to vibration is due to asymmetric stiffness changes introduced by the growing transverse crack. The vibration response is predicted to increase with increasing crack depths in excess of 10% of the shaft diameter. Fracture mechanics analyses predict that fatigue crack growth occurred during periods of steam temperature decrease, when high surface tensile stresses are present. These same transient thermal stresses are shown to have retarded and prevented subsequent fatigue crack growth during steady operation

Single-cycle viral gene expression, rather than progressive replication and oncolysis, is required for VSV therapy of B16 melanoma

A fully intact immune system would be expected to hinder the efficacy of oncolytic virotherapy by inhibiting viral replication. Simultaneously, however, it may also enhance antitumor therapy through initiation of proinflammatory, antiviral cytokine responses at the tumor site. The aim of this study was to investigate the role of a fully intact immune system on the antitumor efficacy of an oncolytic virus. In this respect, injection of oncolytic vesicular stomatitis virus (VSV) into subcutaneous B16ova melanomas in C57Bl/6 mice leads to tumor regression, but it is not associated with viral replicative burst in the tumor. In contrast, intratumoral delivery of VSV induces an acute proinflammatory reaction, which quickly resolves concomitantly with virus clearance. Consistent with the hypothesis that therapy may not be dependent on the ability of VSV to undergo progressive rounds of replication, a single-cycle VSV is equally effective as a fully replication-competent VSV, whereas inactivated viruses do not generate therapy. Even though therapy is dependent on host CD8+ and natural killer cells, these effects are not associated with interferon-γ-dependent responses against either the virus or tumor. There is, however, a strong correlation between viral gene expression, induction of proinflammatory reaction in the tumor and in vivo therapy. Overall, our results suggest that acute innate antiviral immune response, which rapidly clears VSV from B16ova tumors, is associated with the therapy observed in this model. Therefore, the antiviral immune response to an oncolytic virus mediates an intricate balance between safety, restriction of oncolysis and, potentially, significant immune-mediated antitumor therapy

Estimation of the frequency of isoform–genotype discrepancies at the apolipoprotein E locus in heterozygotes for the isoforms

Estimates of the impact of apolipoprotein E (apo E) alleles coding for the three common isoforms on plasma lipid levels assume genetic homogeneity among the genotype classes. To test this assumption, we have determined the apo E genotype at the two common polymorphic sites (amino acids 112 and 158) by DNA amplification and hybridisation with allele‐specific oligoprobes, in 195 unrelated Caucasian participants of the Rochester Family Heart Study previously classified as heterozygotes by isoelectric focusing (IEF). Fourteen discordant samples were initially detected. Repeat typing of these samples by both methods resolved nine discrepancies and analysis of additional blood samples from the remaining five individuals eliminated a further four discrepancies. The only truly discordant allele was found in a female subject who had an E3 isoform with the common E2 (Cys 112 , Cys 158 ) genotype. Transmission of this allele from the mother was demonstrated. From these results, we estimate the frequency of discrepancies between isoforms and common genotypes to be 0.25% in this population. Allele misclassification was caused by poor amplification of the DNA in six samples and superimposition of glycosylated and nonglycosylated apo E isoforms on isoelectric focusing gels in five samples. We conclude that the assumption of genetic homogeneity among genotype classes is valid and that misclassification due to technical difficulties is more frequent than true discordancies. © 1992 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101763/1/1370090403_ftp.pd

Perturbation theory for anisotropic dielectric interfaces, and application to sub-pixel smoothing of discretized numerical methods

We derive a correct first-order perturbation theory in electromagnetism for cases where an interface between two anisotropic dielectric materials is slightly shifted. Most previous perturbative methods give incorrect results for this case, even to lowest order, because of the complicated discontinuous boundary conditions on the electric field at such an interface. Our final expression is simply a surface integral, over the material interface, of the continuous field components from the unperturbed structure. The derivation is based on a "localized" coordinate-transformation technique, which avoids both the problem of field discontinuities and the challenge of constructing an explicit coordinate transformation by taking a limit in which a coordinate perturbation is infinitesimally localized around the boundary. Not only is our result potentially useful in evaluating boundary perturbations, e.g. from fabrication imperfections, in highly anisotropic media such as many metamaterials, but it also has a direct application in numerical electromagnetism. In particular, we show how it leads to a sub-pixel smoothing scheme to ameliorate staircasing effects in discretized simulations of anisotropic media, in such a way as to greatly reduce the numerical errors compared to other proposed smoothing schemes.Comment: 10 page

Combination therapy with reovirus and anti-PD-1 blockade controls tumor growth through innate and adaptive immune responses.

Oncolytic reovirus can be delivered both systemically and intratumorally, in both pre-clinical models and in early phase clinical trials. Reovirus has direct oncolytic activity against a variety of tumor types and anti-tumor activity is directly associated with immune activation by virus replication in tumors. Immune mechanisms of therapy include both innate immune activation against virally infected tumor cells, and the generation of adaptive anti-tumor immune responses as a result of in vivo priming against tumor-associated antigens. We tested the combination of local oncolytic reovirus therapy with systemic immune checkpoint inhibition. We show that treatment of subcutaneous B16 melanomas with a combination of intravenous (i.v.) anti-PD-1 antibody and intratumoral (i.t.) reovirus significantly enhanced survival of mice compared to i.t. reovirus (p<0.01) or anti-PD-1 therapy alone. In vitro immune analysis demonstrated that checkpoint inhibition improved the ability of NK cells to kill reovirus-infected tumor cells, reduced Treg activity, and increased the adaptive CD8(+) T cell dependent anti-tumor T cell response. PD-1 blockade also enhanced the anti-viral immune response but through effector mechanisms which overlapped with, but also differed from those affecting the antitumor response. Therefore, combination with checkpoint inhibition represents a readily translatable next step in the clinical development of reovirus

Testing for hereditary thrombophilia: a retrospective analysis of testing referred to a national laboratory

<p>Abstract</p> <p>Background</p> <p>Predisposition to venous thrombosis may be assessed through testing for defects and/or deficiencies of a number of hereditary factors. There is potential for confusion about which of these tests are appropriate in which settings. At least one set of recommendations has been published to guide such testing, but it is unclear how widely these have been disseminated.</p> <p>Methods</p> <p>We performed a retrospective analysis of laboratory orders and results at a national referral laboratory to gain insight into physicians' ordering practices, specifically comparing them against the ordering practices recommended by a 2002 College of American Pathologists (CAP) consensus conference on thrombophilia testing. Measurements included absolute and relative ordering volumes and positivity rates from approximately 200,000 thrombophilia tests performed from September 2005 through August 2006 at a national reference laboratory. Quality control data were used to estimate the proportion of samples that may have been affected by anticoagulant therapy. A sample of ordering laboratories was surveyed in order to assess potential measurement bias.</p> <p>Results</p> <p>Total antigen assays for protein C, protein S and antithrombin were ordered almost as frequently as functional assays for these analytes. The DNA test for factor V Leiden was ordered much more often than the corresponding functional assay. In addition, relative positivity rates coupled with elevations in prothrombin time (PT) in many of these patients suggest that these tests are often ordered in the setting of oral anticoagulant therapy.</p> <p>Conclusion</p> <p>In this real-world setting, testing for inherited thrombophilia is frequently at odds with the recommendations of the CAP consensus conference. There is a need for wider dissemination of concise thrombophilia testing guidelines.</p

Dose Reduction in Standard Head CT: First Results from a New Scanner Using Iterative Reconstruction and a New Detector Type in Comparison with Two Previous Generations of Multi-slice CT

Purpose: Computed tomography (CT) accounts for more than half of the total radiation exposure from medical procedures, which makes dose reduction in CT an effective means of reducing radiation exposure. We analysed the dose reduction that can be achieved with a new CT scanner [Somatom Edge (E)] that incorporates new developments in hardware (detector) and software (iterative reconstruction). Methods: We compared weighted volume CT dose index (CTDIvol) and dose length product (DLP) values of 25 consecutive patients studied with non-enhanced standard brain CT with the new scanner and with two previous models each, a 64-slice 64-row multi-detector CT (MDCT) scanner with 64 rows (S64) and a 16-slice 16-row MDCT scanner with 16 rows (S16). We analysed signal-to-noise and contrast-to-noise ratios in images from the three scanners and performed a quality rating by three neuroradiologists to analyse whether dose reduction techniques still yield sufficient diagnostic quality. Results: CTDIVol of scanner E was 41.5 and 36.4 % less than the values of scanners S16 and S64, respectively; the DLP values were 40 and 38.3 % less. All differences were statistically significant (p < 0.0001). Signal-to-noise and contrast-to-noise ratios were best in S64; these differences also reached statistical significance. Image analysis, however, showed "non-inferiority” of scanner E regarding image quality. Conclusions: The first experience with the new scanner shows that new dose reduction techniques allow for up to 40 % dose reduction while still maintaining image quality at a diagnostically usable level

Synthesis, in vitro, and in vivo evaluation of novel N-phenylindazolyl diarylureas as potential anti-cancer agents.

Novel N-phenylindazole based diarylureas have been designed, synthesized and evaluated as potential anticancer agents. In vitro cell viability studies of these derivatives illustrate good potency with IC50 values in the range of 0.4–50 μM in several cancer cell lines including murine metastatic breast cancer 4T1, murine glioblastoma GL261, human triple negative breast cancer MDA-MB-231, human pancreatic cancer MIAPaCa-2, and human colorectal cancer cell line WiDr. The ester group in the lead compound 8i was modified to incorporate amino-amides to increase solubility and stability while retaining biological activity. Further in vitro studies reveal that lead candidates inhibit tube length in HUVEC cells. In vivo systemic toxicity studies indicate that these candidate compounds are well tolerated in mice without any significant side effects. Anticancer efficacy studies in WiDr tumor xenograft and 4T1 tumor syngraft models demonstrate that the lead candidate 11 exhibits significant antitumor properties as a single agent in these tumor models