Design, Calibration, and Evaluation of Depth-of-Interaction-Capable PET Detector Modules

High-resolution, small-bore PET systems suffer from a tradeoff between system sensitivity, and image quality degradation. In these systems long crystals allow mispositioning of the line of response due to parallax error and this mispositioning causes resolution blurring, but long crystals are necessary for high system sensitivity. One means to allow long crystals without introducing parallax errors is to determine the depth of interaction (DOI) of the gamma ray interaction within the detector module. While DOI has been investigated previously, newly available solid state photomultipliers (SSPMs) well-suited to PET applications and allow new modules for investigation. Depth of interaction in full modules is a relatively new field, and so even if high performance DOI capable modules were available, the appropriate means to characterize and calibrate the modules are not. This work presents an investigation of DOI capable arrays and techniques for characterizing and calibrating those modules. The methods introduced here accurately and reliably characterize and calibrate energy, timing, and event interaction positioning. Additionally presented is a characterization of the spatial resolution of DOI capable modules and a measurement of DOI effects for different angles between detector modules. These arrays have been built into a prototype PET system that delivers better than 2.0 mm resolution with a single-sided-stopping-power in excess of 95% for 511 keV g's. The noise properties of SSPMs scale with the active area of the detector face, and so the best signal-to-noise ratio is possible with parallel readout of each SSPM photodetector pixel rather than multiplexing signals together. This work additionally investigates several algorithms for improving timing performance using timing information from multiple SSPM pixels when light is distributed among several photodetectors.

Design, Synthesis and Development of Transporter Targeting Agents for Image-guided Therapy and Drug Delivery

The purpose of this study was to design, synthesize and develop novel transporter targeting agents for image-guided therapy and drug delivery. Two novel agents, N4-guanine (N4amG) and glycopeptide (GP) were synthesized for tumor cell proliferation assessment and cancer theranostic platform, respectively. N4amG and GP were synthesized and radiolabeled with 99mTc and 68Ga. The chemical and radiochemical purities as well as radiochemical stabilities of radiolabeled N4amG and GP were tested. In vitro stability assessment showed both 99mTc-N4amG and 99mTc-GP were stable up to 6 hours, whereas 68Ga-GP was stable up to 2 hours. Cell culture studies confirmed radiolabeled N4amG and GP could penetrate the cell membrane through nucleoside transporters and amino acid transporters, respectively. Up to 40% of intracellular 99mTc-N4amG and 99mTc-GP was found within cell nucleus following 2 hours of incubation. Flow cytometry analysis revealed 99mTc-N4amG was a cell cycle S phase-specific agent. There was a significant difference of the uptake of 99mTc-GP between pre- and post- paclitaxel-treated cells, which suggests that 99mTc-GP may be useful in chemotherapy treatment monitoring. Moreover, radiolabeled N4amG and GP were tested in vivo using tumor-bearing animal models. 99mTc-N4amG showed an increase in tumor-to-muscle count density ratios up to 5 at 4 hour imaging. Both 99mTc-labeled agents showed decreased tumor uptake after paclitaxel treatment. Immunohistochemistry analysis demonstrated that the uptake of 99mTc-N4amG was correlated with Ki-67 expression. Both 99mTc-N4amG and 99mTc-GP could differentiate between tumor and inflammation in animal studies. Furthermore, 68Ga-GP was compared to 18F-FDG in rabbit PET imaging studies. 68Ga-GP had lower tumor standardized uptake values (SUV), but similar uptake dynamics, and different biodistribution compared with 18F-FDG. Finally, to demonstrate that GP can be a potential drug carrier for cancer theranostics, several drugs, including doxorubicin, were selected to be conjugated to GP. Imaging studies demonstrated that tumor uptake of GP-drug conjugates was increased as a function of time. GP-doxorubicin (GP-DOX) showed a slow-release pattern in in vitro cytotoxicity assay and exhibited anti-cancer efficacy with reduced toxicity in in vivo tumor growth delay study. In conclusion, both N4amG and GP are transporter-based targeting agents. Radiolabeled N4amG can be used for tumor cell proliferation assessment. GP is a potential agent for image-guided therapy and drug delivery.

Organizational perspectives on the management and evaluation of large -scale multicenter controlled clinical trials: An exploratory study of participation in the beta -blocker heart attack trial

A review of literature related to appointment-keeping served as the basis for the development of an organizational paradigm for the study of appointment-keeping in the Beta-blocker Heart Attack Trial (BHAT). Features of the organizational environment, demographic characteristics of BHAT enrollees, organizational structure and processes and previous organizational performance variables were measured so as to provide exploratory information relating to the appointment-keeping behavior of 3,837 participants enrolled at thirty-two Clinical Centers. Results suggest that the social context of individual behavior is an important consideration for the understanding of patient compliance. In particular, the degree to which previous organizational performance--as measured by obtaining recruitment goals--and the ability to utilize resources had particularly strong bivariate associations with appointment-keeping. Implications for future theory development, research and practical implications were provided as was a suggestion for the development of multidisciplinary research efforts conducted within the context of Centers for the study and application of adherence behaviors. ^

Design, synthesis and cellular and molecular pharmacology of 2$\sp\prime$-bromo-4$\sp\prime$-epidaunorubicin (WP401): A novel non-cross-resistant anthracycline antibiotic with the intrinsic ability to circumvent P -glycoprotein-mediated drug resistance

We designed and synthesized a novel daunorubicin (DNR) analogue that effectively circumvents P-glycoprotein (P-gp)-mediated drug resistance. The fully protected carbohydrate intermediate 1,2-dibromoacosamine was prepared from acosamine and effectively coupled to daunomycinone in high yield. Deprotection under alkaline conditions yielded 2$\sp\prime$-bromo-4$\sp\prime$-epidaunorubicin (WP401). The in vitro cytotoxicity and cellular and molecular pharmacology of WP401 were compared with those of DNR in a panel of wild-type cell lines (KB-3-1, P388S, and HL60S) and their multidrug-resistant (MDR) counterparts (KB-V1, P388/DOX, and HL60/DOX). Fluorescent spectrophotometry, flow cytometry, and confocal laser scanning microscopy were used to measure intracellular accumulation, retention, and subcellular distribution of these agents. All MDR cell lines exhibited reduced DNR uptake that was restored, upon incubation with either verapamil (VER) or cyclosporin A (CSA), to the level found in sensitive cell lines. In contrast, the uptake of WP401 was essentially the same in the absence or presence of VER or CSA in all tested cell lines. The in vitro cytotoxicity of WP401 was similar to that of DNR in the sensitive cell lines but significantly higher in resistant cell lines (resistance index (RI) of 2-6 for WP401 vs 75-85 for DNR). To ascertain whether drug-mediated cytotoxicity and retention were accompanied by DNA strand breaks, DNA single- and double-strand breaks were assessed by alkaline elution. High levels of such breaks were obtained using 0.1-2 $\mu$g/mL of WP401 in both sensitive and resistant cells. In contrast, DNR caused strand breaks only in sensitive cells and not much in resistant cells. We also compared drug-induced DNA fragmentation similar to that induced by DNR. However, in P-gp-positive cells, WP401 induced 2- to 5-fold more DNA fragmentation than DNR. This increased DNA strand breakage by WP401 was correlated with its increased uptake and cytotoxicity in these cell lines. Overall these results indicate that WP401 is more cytotoxic than DNR in MDR cells and that this phenomenon might be related to the reduced basicity of the amino group and increased lipophilicity of WP401. ^

Abortion and Clinical Practice. Abortion Review Papers from the bpas conference: London, 25 - 26 June 2008

The groundbreaking bpas conference The Future of Abortion: Controversies and Care brought together clinicians, academics, policymakers and advocates from the UK, Europe and the USA for a discussion about all aspects of abortion provision. Taking place during a critical Parliamentary debate about the UK abortion law, the conference generated great excitement and presented a number of important research findings and policy suggestions.In order to maximise the strides made by The Future of Abortion conference in taking forward an international, interdisciplinary discussion, Abortion Review is producing a series of special editions in which we have published edited transcripts of the presentations. In this third edition, Abortion and Clinical Practice, the presentations examine developments in abortion research and practice, and what these might indicate for the kind of abortion service that should be provided.

Public management and regional development

Este trabajo tiene por objetivo analizar los elementos de la gestión pública del desarrollo regional a partir de las condiciones del desarrollo regional y las nociones de desarrollo local y desarrollo sustentable. Bajo estas premisas se avanzan planteamientos esquemáticos en torno a la gestión pública del desarrollo local

Subjectivity and professional vocational counselling

In this work, I shall deal with the psychodynamic approach to subjectivity in P.V.C.. To this effect, I want to develop the concept of subject and subjectivity, its variation and historical-social construction and its approach in counselling, from a psychodynamic conceptual framework in P.V.C. with a short reference to the theoretical sources on which this approach is founded.

Subjectivity and professional vocational counselling

In this work, I shall deal with the psychodynamic approach to subjectivity in P.V.C.. To this effect, I want to develop the concept of subject and subjectivity, its variation and historical-social construction and its approach in counselling, from a psychodynamic conceptual framework in P.V.C. with a short reference to the theoretical sources on which this approach is founded.

Public management and regional development

Este trabajo tiene por objetivo analizar los elementos de la gestión pública del desarrollo regional a partir de las condiciones del desarrollo regional y las nociones de desarrollo local y desarrollo sustentable. Bajo estas premisas se avanzan planteamientos esquemáticos en torno a la gestión pública del desarrollo local

Subjectivity and professional vocational counselling

In this work, I shall deal with the psychodynamic approach to subjectivity in P.V.C.. To this effect, I want to develop the concept of subject and subjectivity, its variation and historical-social construction and its approach in counselling, from a psychodynamic conceptual framework in P.V.C. with a short reference to the theoretical sources on which this approach is founded.

Public management and regional development

Este trabajo tiene por objetivo analizar los elementos de la gestión pública del desarrollo regional a partir de las condiciones del desarrollo regional y las nociones de desarrollo local y desarrollo sustentable. Bajo estas premisas se avanzan planteamientos esquemáticos en torno a la gestión pública del desarrollo local

Knowledge Management and Information Systems based on Workflow Technology

Knowledge management is critical for the success of virtual communities, especially in the case of distributed working groups. A representative example of this scenario is the distributed software development, where it is necessary an optimal coordination to avoid common problems such as duplicated work. In this paper the feasibility of using the workflow technology as a knowledge management system is discussed, and a practical use case is presented. This use case is an information system that has been deployed within a banking environment. It combines common workflow technology with a new conception of the interaction among participants through the extension of existing definition languages.

Differences and Relationship Between Standard and Specific Throwing Test in Handball According to the Competitive and Professional Level

The present study analyzed the differences in distance throwing with heavy and light medicine ball and throwing velocity between handball players of different competitive and professional level. Likewise, the relationship between the three throwing test of progressive specificity was analyzed: throwing with heavy medicinal ball (TH), throwing with light medicinal ball (TL) and throwing velocity (TV). For this purpose, sixty-five professional (P), semiprofessional (S) and non-professional (N) players were evaluated. El presente estudio analizó las diferencias en la distancia de lanzamiento realizado con balón medicinal pesado y ligero y en la velocidad de lanzamiento entre jugadores de balonmano de diferente nivel competitivo y profesional. Igualmente, la relación entre los tres test de lanzamiento, de progresiva especificidad, fue analizado: lanzamiento con balón medicinal pesado (TH), lanzamiento con balón medicinal ligero (TL) y velocidad de lanzamiento (TV). Para ello, sesenta y cinco jugadores profesionales (P), semi-profesionales (S) y no-profesionales (N) fueron evaluados.

Design, manufacturing and measurements of a metal-less V-groove RXI collimator

A metal-less RXI collimator has been designed. Unlike to the conventional RXI collimators, whose back surface and central part of the front surface have to be metalized, this collimator does not include any mirrored surface. The back surface is designed as a grooved surface providing two TIR reflections for all rays impinging on it. The main advantage of the presented design is lower manufacturing cost since there is no need for the expensive process of metalization. Also, unlike to the conventional RXI collimators this design performs good colour mixing. The first prototype of V-groove RXI collimator has been made of PMMA by direct cutting using a five axis diamond turning machine. The experimental measurements of the first prototype are presented.

FPGA Acceleration of Monte Carlo-based Financial Simulation: Design Challenges and Lessons Learnt

The simulation of interest rate derivatives is a powerful tool to face the current market fluctuations. However, the complexity of the financial models and the way they are processed require exorbitant computation times, what is in clear conflict with the need of a processing time as short as possible to operate in the financial market. To shorten the computation time of financial derivatives the use of hardware accelerators becomes a must.