Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

INTRODUCTION: To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years. RESULTS: Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V(120) (urethral volume receiving > or =120% of the prescribed HDR-B dose) was associated with acute (P=.047) and late > or = grade 2 GU toxicities (P=.049). CONCLUSIONS: Late grades 3 and 4GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V(120) on GU toxicity should be validated in further studies.

Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy

PURPOSE: To determine the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and present short-term biochemical no evidence of disease (bNED) rates after high-dose-rate brachytherapy (HDR-B) monotherapy. METHODS AND MATERIALS: Between October 2003 and June 2006, 36 patients with low (28) and intermediate (8) risk prostate cancer (PCA) were treated by HDR-B monotherapy. All patients received one implant and four fractions of 9.5Gy within 48h for a total prescribed dose (PD) of 38Gy. Five patients received hormonal therapy (HT). Median age was 63.5 years and median followup was 3 years (range, 0.4-4 years). Toxicity was scored according to the CTCAE version 3.0. Biochemical failure was defined according to the Phoenix criteria. RESULTS: Acute and late Grade 3 GU toxicity was observed in 1 (3%) and 4 (11%) patients, respectively. Grade 3 GI toxicity was absent. The three- year bNED survival rate was 100%. The sexual preservation rate in patients without HT was 75%. Late Grade 3 GU toxicity was associated with the planning target volume (PTV) V(100) (% PTV receiving > or =100% of the PD; p=0.036), D(90) (dose delivered to 90% of the PTV; p=0.02), and the urethral V(120) (urethral volume receiving > or =120% of the PD; p=0.043). The urethral V(120) was associated with increased PTV V(100) (p<0.001) and D(90) (p=0.003). CONCLUSIONS: After HDR-B monotherapy, late Grade 3 GU toxicity is associated with the urethral V(120) and the V(100) and D(90) of the PTV. Decrease of the irradiated urethral volume may reduce the GU toxicity and potentially improve the therapeutic ratio of this treatment.

High failure rate of trochanteric fracture osteosynthesis with proximal femoral locking compression plate

INTRODUCTION Stable reconstruction of proximal femoral (PF) fractures is especially challenging due to the peculiarity of the injury patterns and the high load-bearing requirement. Since its introduction in 2007, the PF-locking compression plate (LCP) 4.5/5.0 has improved osteosynthesis for intertrochanteric and subtrochanteric fractures of the femur. This study reports our early results with this implant. METHODS Between January 2008 and June 2010, 19 of 52 patients (12 males, 7 females; mean age 59 years, range 19-96 years) presenting with fractures of the trochanteric region were treated at the authors' level 1 trauma centre with open reduction and internal fixation using PF-LCP. Postoperatively, partial weight bearing was allowed for all 19 patients. Follow-up included a thorough clinical and radiological evaluation at 1.5, 3, 6, 12, 24, 36 and 48 months. Failure analysis was based on conventional radiological and clinical assessment regarding the type of fracture, postoperative repositioning, secondary fracture dislocation in relation to the fracture constellation and postoperative clinical function (Merle d'Aubigné score). RESULTS In 18 patients surgery achieved adequate reduction and stable fixation without intra-operative complications. In one patient an ad latus displacement was observed on postoperative X-rays. At the third month follow-up four patients presented with secondary varus collapse and at the sixth month follow-up two patients had 'cut-outs' of the proximal fragment, with one patient having implant failure due to a broken proximal screw. Revision surgeries were performed in eight patients, one patient receiving a change of one screw, three patients undergoing reosteosynthesis with implantation of a condylar plate and one patient undergoing hardware removal with secondary implantation of a total hip prosthesis. Eight patients suffered from persistent trochanteric pain and three patients underwent hardware removal. CONCLUSIONS Early results for PF-LCP osteosynthesis show major complications in 7 of 19 patients requiring reosteosynthesis or prosthesis implantation due to secondary loss of reduction or hardware removal. Further studies are required to evaluate the limitations of this device.

Late toxicity and five year outcomes after high-dose-rate brachytherapy as a monotherapy for localized prostate cancer

BACKGROUND To determine the 5-year outcome after high-dose-rate brachytherapy (HDR-BT) as a monotherapy. METHODS Between 10/2003 and 06/2006, 36 patients with low (28) and intermediate (8) risk prostate cancer were treated by HDR-BT monotherapy. All patients received one implant and 4 fractions of 9.5 Gy within 48 hours for a total prescribed dose (PD) of 38 Gy. Five patients received concomitant androgen deprivation therapy (ADT). Toxicity was scored according to the common terminology criteria for adverse events from the National Cancer Institute (CTCAE) version 3.0. Biochemical recurrence was defined according to the Phoenix criteria and analyzed using the Kaplan Meier method. Predictors for late grade 3 GU toxicity were analyzed using univariate and multivariate Cox regression analyses. RESULTS The median follow-up was 6.9 years (range, 1.5-8.0 years). Late grade 2 and 3 genitourinary (GU) toxicity was observed in 10 (28%) and 7 (19%) patients, respectively. The actuarial proportion of patients with late grade 3 GU toxicity at 5 years was 17.7%. Late grade 2 and 3 gastrointestinal (GI) toxicities were not observed. The crude erectile function preservation rate in patients without ADT was 75%. The 5 year biochemical recurrence-free survival (bRFS) rate was 97%. Late grade 3 GU toxicity was associated with the urethral volume (p = 0.001) and the urethral V120 (urethral volume receiving ≥120% of the PD; p = 0.0005) after multivariate Cox regression. CONCLUSIONS After HDR-BT monotherapy late grade 3 GU was observed relatively frequently and was associated with the urethral V120. GI toxicity was negligible, the erectile function preservation rate and the bRFS rate was excellent.

DEVELOPMENT AND IMPLEMENTATION OF A REMOTE AUDIT TOOL FOR HIGH DOSE RATE (HDR) 192IR BRACHYTHERAPY USING OPTICALLY STIMULATED LUMINESCENCE DOSIMETRY

This work aimed to create a mailable and OSLD-based phantom with accuracy suitable for RPC audits of HDR brachytherapy sources at institutions participating in NCI-funded cooperative clinical trials. An 8 × 8 × 10 cm3 prototype with two slots capable of holding nanoDot Al2O3:C OSL dosimeters (Landauer, Glenwood, IL) was designed and built. The phantom has a single channel capable of accepting all 192Ir HDR brachytherapy sources in current clinical use in the United States. Irradiations were performed with an 192Ir HDR source to determine correction factors for linearity with dose, dose rate, and the combined effect of irradiation energy and phantom construction. The uncertainties introduced by source positioning in the phantom and timer resolution limitations were also investigated. It was found that the linearity correction factor was where dose is in cGy, which differed from that determined by the RPC for the same batch of dosimeters under 60Co irradiation. There was no significant dose rate effect. Separate energy+block correction factors were determined for both models of 192Ir sources currently in clinical use and these vendor-specific correction factors differed by almost 2.6%. For Nucletron sources, this correction factor was 1.026±0.004 (99% Confidence Interval) and for Varian sources it was 1.000±0.007 (99% CI). Reasonable deviations in source positioning within the phantom and the limited resolution of the source timer had insignificant effects on the ability to measure dose. Overall measurement uncertainty of the system was estimated to be ±2.5% for both Nucletron and Varian source audits (95% CI). This uncertainty was sufficient to establish a ±5% acceptance criterion for source strength audits under a formal RPC audit program. Trial audits of eight participating institutions resulted in an average RPC-to-institution dose ratio of 1.000 with a standard deviation of 0.011.

Exchange Rate Stabilization and IMF High Interest Rate Policy: A Critical Reconsideration Using a Dynamic Model

This paper examines whether the IMF high interest rate policy was suitable for crisis-ridden East Asian economies. Using an "overshoot" model similar to that of Dornbusch's (1976), it shows that this sort of policy might cause an unnecessary deflationary adjusting process and have no effect on containing the real depreciation of exchange rates in the long run. The study also demonstrates that Thai economic data coincides quite well with the model presented here. Finally, it points out that the high interest policy itself might provoke high risk-premium, the existence of which, in turn, justifies the policy. This means that the policy has a self-fulfilling property. In conclusion, a "one-size-fits-all" adaptation of high interest rate policy in a currency crisis is very dangerous in general, and was inappropriate for East Asia. The desirable policy would have been to let currencies depreciate and keep interest rates stable.

High data rate modulation of high power 1060-nm DBR tapered lasers with separate contacts

Direct optical modulation at 2.5 Gb/s with amplitude of more than 0.5 W has been demonstrated in single longitudinal mode distributed Bragg reflector tapered lasers emitting at 1060 nm with separated injection of the ridge waveguide and tapered sections. The modulating signal of ~110 mA peak to peak was applied to the ridge waveguide section, yielding a high modulation efficiency of ~5 W/A. The large-signal frequency response of the experimental set-up was limited by the bandwidth of the electrical amplifier rather than by the internal dynamics of the laser, indicating that higher bit rates could be achieved with improved driving electronics.

Design and optimization of optical, fiber based PSK demodulators for high-bit-rate optical networks

El objetivo principal de esta tesis ha sido el diseño y la optimización de receptores implementados con fibra óptica, para ser usados en redes ópticas de alta velocidad que empleen formatos de modulación de fase. En los últimos años, los formatos de modulación de fase (Phase Shift keying, PSK) han captado gran atención debido a la mejora de sus prestaciones respecto a los formatos de modulación convencionales. Principalmente, presentan una mejora de la eficiencia espectral y una mayor tolerancia a la degradación de la señal causada por la dispersión cromática, la dispersión por modo de polarización y los efectos no-lineales en la fibra óptica. En este trabajo, se analizan en detalle los formatos PSK, incluyendo sus variantes de modulación de fase diferencial (Differential Phase Shift Keying, DPSK), en cuadratura (Differential Quadrature Phase Shift Keying, DQPSK) y multiplexación en polarización (Polarization Multiplexing Differential Quadrature Phase Shift Keying, PM-DQPSK), con la finalidad de diseñar y optimizar los receptores que permita su demodulación. Para ello, se han analizado y desarrollado nuevas estructuras que ofrecen una mejora en las prestaciones del receptor y una reducción de coste comparadas con las actualmente disponibles. Para la demodulación de señales DPSK, en esta tesis, se proponen dos nuevos receptores basados en un interferómetro en línea Mach-Zehnder (MZI) implementado con tecnología todo-fibra. El principio de funcionamiento de los MZI todo-fibra propuestos se asienta en la interferencia modal que se produce en una fibra multimodo (MMF) cuando se situada entre dos monomodo (SMF). Este tipo de configuración (monomodo-multimodo-monomodo, SMS) presenta un buen ratio de extinción interferente si la potencia acoplada en la fibra multimodo se reparte, principal y equitativamente, entre dos modos dominantes. Con este objetivo, se han estudiado y demostrado tanto teórica como experimentalmente dos nuevas estructuras SMS que mejoran el ratio de extinción. Una de las propuestas se basa en emplear una fibra multimodo de índice gradual cuyo perfil del índice de refracción presenta un hundimiento en su zona central. La otra consiste en una estructura SMS con las fibras desalineadas y donde la fibra multimodo es una fibra de índice gradual convencional. Para las dos estructuras, mediante el análisis teórico desarrollado, se ha demostrado que el 80 – 90% de la potencia de entrada se acopla a los dos modos dominantes de la fibra multimodo y se consigue una diferencia inferior al 10% entre ellos. También se ha demostrado experimentalmente que se puede obtener un ratio de extinción de al menos 12 dB. Con el objeto de demostrar la capacidad de estas estructuras para ser empleadas como demoduladores de señales DPSK, se han realizado numerosas simulaciones de un sistema de transmisión óptico completo y se ha analizado la calidad del receptor bajo diferentes perspectivas, tales como la sensibilidad, la tolerancia a un filtrado óptico severo o la tolerancia a las dispersiones cromática y por modo de polarización. En todos los casos se ha concluido que los receptores propuestos presentan rendimientos comparables a los obtenidos con receptores convencionales. En esta tesis, también se presenta un diseño alternativo para la implementación de un receptor DQPSK, basado en el uso de una fibra mantenedora de la polarización (PMF). A través del análisi teórico y del desarrollo de simulaciones numéricas, se ha demostrado que el receptor DQPSK propuesto presenta prestaciones similares a los convencionales. Para complementar el trabajo realizado sobre el receptor DQPSK basado en PMF, se ha extendido el estudio de su principio de demodulación con el objeto de demodular señales PM-DQPSK, obteniendo como resultado la propuesta de una nueva estructura de demodulación. El receptor PM-DQPSK propuesto se basa en la estructura conjunta de una única línea de retardo junto con un rotador de polarización. Se ha analizado la calidad de los receptores DQPSK y PM-DQPSK bajo diferentes perspectivas, tales como la sensibilidad, la tolerancia a un filtrado óptico severo, la tolerancia a las dispersiones cromática y por modo de polarización o su comportamiento bajo condiciones no-ideales. En comparación con los receptores convencionales, nuestra propuesta exhibe prestaciones similares y además permite un diseño más simple que redunda en un coste potencialmente menor. En las redes de comunicaciones ópticas actuales se utiliza la tecnología de multimplexación en longitud de onda (WDM) que obliga al uso de filtros ópticos con bandas de paso lo más estrechas posibles y a emplear una serie de dispositivos que incorporan filtros en su arquitectura, tales como los multiplexores, demultiplexores, ROADMs, conmutadores y OXCs. Todos estos dispositivos conectados entre sí son equivalentes a una cadena de filtros cuyo ancho de banda se va haciendo cada vez más estrecho, llegando a distorsionar la forma de onda de las señales. Por esto, además de analizar el impacto del filtrado óptico en las señales de 40 Gbps DQPSK y 100 Gbps PM-DQPSK, este trabajo de tesis se completa estudiando qué tipo de filtro óptico minimiza las degradaciones causadas en la señal y analizando el número máximo de filtros concatenados que permiten mantener la calidad requerida al sistema. Se han estudiado y simulado cuatro tipos de filtros ópticos;Butterworth, Bessel, FBG y F-P. ABSTRACT The objective of this thesis is the design and optimization of optical fiber-based phase shift keying (PSK) demodulators for high-bit-rate optical networks. PSK modulation formats have attracted significant attention in recent years, because of the better performance with respect to conventional modulation formats. Principally, PSK signals can improve spectrum efficiency and tolerate more signal degradation caused by chromatic dispersion, polarization mode dispersion and nonlinearities in the fiber. In this work, many PSK formats were analyzed in detail, including the variants of differential phase modulation (Differential Phase Shift Keying, DPSK), in quadrature (Differential Quadrature Phase Shift Keying, DQPSK) and polarization multiplexing (Polarization Multiplexing Differential Quadrature Phase Shift Keying, PM-DQPSK), in order to design and optimize receivers enabling demodulations. Therefore, novel structures, which offer good receiver performances and a reduction in cost compared to the current structures, have been analyzed and developed. Two novel receivers based on an all-fiber in-line Mach-Zehnder interferometer (MZI) were proposed for DPSK signal demodulation in this thesis. The operating principle of the all-fiber MZI is based on the modal interference that occurs in a multimode fiber (MMF) when it is located between two single-mode fibers (SMFs). This type of configuration (Single-mode-multimode-single-mode, SMS) can provide a good extinction ratio if the incoming power from the SMF could be coupled equally into two dominant modes excited in the MMF. In order to improve the interference extinction ratio, two novel SMS structures have been studied and demonstrated, theoretically and experimentally. One of the two proposed MZIs is based on a graded-index multimode fiber (MMF) with a central dip in the index profile, located between two single-mode fibers (SMFs). The other one is based on a conventional graded-index MMF mismatch spliced between two SMFs. Theoretical analysis has shown that, in these two schemes, 80 – 90% of the incoming power can be coupled into the two dominant modes exited in the MMF, and the power difference between them is only ~10%. Experimental results show that interference extinction ratio of 12 dB could be obtained. In order to demonstrate the capacity of these two structures for use as DPSK signal demodulators, numerical simulations in a completed optical transmission system have been carried out, and the receiver quality has been analyzed under different perspectives, such as sensitivity, tolerance to severe optical filtering or tolerance to chromatic and polarization mode dispersion. In all cases, from the simulation results we can conclude that the two proposed receivers can provide performances comparable to conventional ones. In this thesis, an alternative design for the implementation of a DQPSK receiver, which is based on a polarization maintaining fiber (PMF), was also presented. To complement the work made for the PMF-based DQPSK receiver, the study of the demodulation principle has been extended to demodulate PM-DQPSK signals, resulting in the proposal of a novel demodulation structure. The proposed PM-DQPSK receiver is based on only one delay line and a polarization rotator. The quality of the proposed DQPSK and PM-DQPSK receivers under different perspectives, such as sensitivity, tolerance to severe optical filtering, tolerance to chromatic dispersion and polarization mode dispersion, or behavior under non-ideal conditions. Compared with the conventional receivers, our proposals exhibit similar performances but allow a simpler design which can potentially reduce the cost. The wavelength division multiplexing (WDM) technology used in current optical communications networks requires the use of optical filters with a passband as narrow as possible, and the use of a series of devices that incorporate filters in their architecture, such as multiplexers, demultiplexers, switches, reconfigurable add-drop multiplexers (ROADMs) and optical cross-connects (OXCs). All these devices connected together are equivalent to a chain of filters whose bandwidth becomes increasingly narrow, resulting in distortion to the waveform of the signals. Therefore, in addition to analyzing the impact of optical filtering on signal of 40 Gbps DQPSK and 100 Gbps PM-DQPSK, we study which kind of optical filter minimizes the signal degradation and analyze the maximum number of concatenated filters for maintaining the required quality of the system. Four types of optical filters, including Butterworth, Bessel, FBG and FP, have studied and simulated.

The cellulose-binding domain of the major cellobiohydrolase of Trichoderma reesei exhibits true reversibility and a high exchange rate on crystalline cellulose.

Cellulose-binding domains (CBDs) bind specifically to cellulose, and form distinct domains of most cellulose degrading enzymes. The CBD-mediated binding of the enzyme has a fundamental role in the hydrolysis of the solid cellulose substrate. In this work we have investigated the reversibility and kinetics of the binding of the CBD from Trichoderma reesei cellobiohydrolase I on microcrystalline cellulose. The CBD was produced in Escherichia coli, purified, and radioactively labeled by reductive alkylation with 3H. Sensitive detection of the labeled CBD allowed more detailed analysis of its behavior than has been possible before, and important novel features were resolved. Binding of the CBD was found to be temperature sensitive, with an increased affinity at lower temperatures. The interaction of the CBD with cellulose was shown to be fully reversible and the CBD could be eluted from cellulose by simple dilution. The rate of exchange measured for the CBD-cellulose interaction compares well with the hydrolysis rate of cellobiohydrolase I, which is consistent with its proposed mode of action as a processive exoglucanase.

High daily rate trickling filter performance : under the direction of the Board of State Health Commissioners, Upper Mississippi River Basin Sanitaton Agreement /

Includes bibliographical references.

Analysis of insurance premiums and payouts for 1983-1984 designated high theft rate passenger cars. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

HIgh repetition rate pulser for beam switching magnet /

"AEC Contract AT(04-3)-400."

Chipless machining; methods of cold forming ferrous metals, including heading, rolling, spinning, swaging, extruding, and high-energy-rate forming.

Includes bibliography.

Stable production of hyaluronic acid in Streptococcus zooppidemicus chemostats operated at high dilution rate

Hyaluronic acid is routinely produced through fermentation of both Group A and C streptococci. Despite significant production costs associated with short fermentations and removal of contaminating proteins released during entry into stationary phase, hyaluronic acid is typically produced in batch rather than continuous culture. The main reason is that hyaluronic acid synthesis has been found to be unstable in continuous culture except at very low dilution rates. Here, we investigated the mechanisms underlying this instability and developed a stable, high dilution rate (0.4 h(-1)) chemostat process for both chemically defined and complex media operating for more than 150 h of production. In chemically defined medium, the product yield was 25% higher in chemostat cultures than in conventional batch culture when arginine or glucose was the limiting substrate. In contrast, glutamine limitation resulted in higher ATP requirements and a yield similar to that observed in batch culture. In complex, glucose-limited medium, ATP requirements were greatly reduced but biomass synthesis was favored over hyaluronic acid and no improvement in hyaluronic acid yield was observed. The successful establishment of continuous culture at high dilution rate enables both commercial production at reduced cost and a more rational characterization and optimization of hyaluronic acid production in streptococci. (c) 2005 Wiley Periodicals, Inc.