Long-term follow-up of high-dose chemotherapy with autologous stem-cell transplantation and response-adapted whole-brain radiotherapy for newly diagnosed primary CNS lymphoma: results of the multicenter Ostdeutsche Studiengruppe Hamatologie und Onkologie OSHO-53 phase II study.

Background We previously reported the results of a phase II study for patients with newly diagnosed primary central nervous system lymphoma treated with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiotherapy (WBRT). Now, we update the initial results. Patients and methods From 1999 to 2004, 23 patients received high-dose methotrexate. In case of at least partial remission, high-dose busulfan/thiotepa (HD-BuTT) followed by aPBSCT was carried out. Patients refractory to induction or without complete remission after HD-BuTT received WBRT. Eight patients still alive in 2011 were contacted and Mini-Mental State Examination (MMSE) and the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 were carried out. Results Of eight patients still alive, median follow-up is 116.9 months. Only one of nine irradiated patients is still alive with a severe neurologic deficit. In seven of eight patients treated with HD-BuTT, health condition and quality of life are excellent. MMSE and QLQ-C30 showed remarkably good results in patients who did not receive WBRT. All of them have a Karnofsky score of 90%-100%. Conclusions Follow-up shows an overall survival of 35%. In six of seven patients where WBRT could be avoided, no long-term neurotoxicity has been observed and all patients have an excellent quality of life.

Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients.

PURPOSE: We conducted a phase I multicenter trial in naïve metastatic castrate-resistant prostate cancer patients with escalating inecalcitol dosages, combined with docetaxel-based chemotherapy. Inecalcitol is a novel vitamin D receptor agonist with higher antiproliferative effects and a 100-fold lower hypercalcemic activity than calcitriol. EXPERIMENTAL DESIGN: Safety and efficacy were evaluated in groups of three to six patients receiving inecalcitol during a 21-day cycle in combination with docetaxel (75 mg/m2 every 3 weeks) and oral prednisone (5 mg twice a day) up to six cycles. Primary endpoint was dose-limiting toxicity (DLT) defined as grade 3 hypercalcemia within the first cycle. Efficacy endpoint was ≥30% PSA decline within 3 months. RESULTS: Eight dose levels (40-8,000 μg) were evaluated in 54 patients. DLT occurred in two of four patients receiving 8,000 μg/day after one and two weeks of inecalcitol. Calcemia normalized a few days after interruption of inecalcitol. Two other patients reached grade 2, and the dose level was reduced to 4,000 μg. After dose reduction, calcemia remained within normal range and grade 1 hypercalcemia. The maximum tolerated dose was 4,000 μg daily. Respectively, 85% and 76% of the patients had ≥30% PSA decline within 3 months and ≥50% PSA decline at any time during the study. Median time to PSA progression was 169 days. CONCLUSION: High antiproliferative daily inecalcitol dose has been safely used in combination with docetaxel and shows encouraging PSA response (≥30% PSA response: 85%; ≥50% PSA response: 76%). A randomized phase II study is planned.

Material and Construction Optimization for Prevention of Premature Pavement Distress in PCC Pavements, Phase III Final Report, 2008

Mixture materials, mix design, and pavement construction are not isolated steps in the concrete paving process. Each affects the other in ways that determine overall pavement quality and long-term performance. However, equipment and procedures commonly used to test concrete materials and concrete pavements have not changed in decades, leaving gaps in our ability to understand and control the factors that determine concrete durability. The concrete paving community needs tests that will adequately characterize the materials, predict interactions, and monitor the properties of the concrete. The overall objectives of this study are (1) to evaluate conventional and new methods for testing concrete and concrete materials to prevent material and construction problems that could lead to premature concrete pavement distress and (2) to examine and refine a suite of tests that can accurately evaluate concrete pavement properties. The project included three phases. In Phase I, the research team contacted each of 16 participating states to gather information about concrete and concrete material tests. A preliminary suite of tests to ensure long-term pavement performance was developed. The tests were selected to provide useful and easy-to-interpret results that can be performed reasonably and routinely in terms of time, expertise, training, and cost. The tests examine concrete pavement properties in five focal areas critical to the long life and durability of concrete pavements: (1) workability, (2) strength development, (3) air system, (4) permeability, and (5) shrinkage. The tests were relevant at three stages in the concrete paving process: mix design, preconstruction verification, and construction quality control. In Phase II, the research team conducted field testing in each participating state to evaluate the preliminary suite of tests and demonstrate the testing technologies and procedures using local materials. A Mobile Concrete Research Lab was designed and equipped to facilitate the demonstrations. This report documents the results of the 16 state projects. Phase III refined and finalized lab and field tests based on state project test data. The results of the overall project are detailed herein. The final suite of tests is detailed in the accompanying testing guide.

Field Evaluation of Compaction Monitoring Technology: Phase I, 2004

This Phase I report describes a preliminary evaluation of a new compaction monitoring system developed by Caterpillar, Inc. (CAT), for use as a quality control and quality assurance (QC/QA) tool during earthwork construction operations. The CAT compaction monitoring system consists of an instrumented roller with sensors to monitor machine power output in response to changes in soil machine interaction and is fitted with a global positioning system (GPS) to monitor roller location in real time. Three pilot tests were conducted using CAT’s compaction monitoring technology. Two of the sites were located in Peoria, Illinois, at the Caterpillar facilities. The third project was an actual earthwork grading project in West Des Moines, Iowa. Typical construction operations for all tests included the following steps: (1) aerate/till existing soil; (2) moisture condition soil with water truck (if too dry); (3) remix; (4) blade to level surface; and (5) compact soil using the CAT CP-533E roller instrumented with the compaction monitoring sensors and display screen. Test strips varied in loose lift thickness, water content, and length. The results of the study show that it is possible to evaluate soil compaction with relatively good accuracy using machine energy as an indicator, with the advantage of 100% coverage with results in real time. Additional field trials are necessary, however, to expand the range of correlations to other soil types, different roller configurations, roller speeds, lift thicknesses, and water contents. Further, with increased use of this technology, new QC/QA guidelines will need to be developed with a framework in statistical analysis. Results from Phase I revealed that the CAT compaction monitoring method has a high level of promise for use as a QC/QA tool but that additional testing is necessary in order to prove its validity under a wide range of field conditions. The Phase II work plan involves establishing a Technical Advisor Committee, developing a better understanding of the algorithms used, performing further testing in a controlled environment, testing on project sites in the Midwest, and developing QC/QA procedures.

Post-switching beta synchronization reveals concomitant sensory reafferences and active inhibition processes

It is known that post-movement beta synchronization (PMBS) is involved both in active inhibition and in sensory reafferences processes. The aim of this study was examine the temporal and spatial dynamics of the PMBS involved during multi-limb coordination task. We investigated post-switching beta synchronization (assigned PMBS) using time-frequency and source estimations analyzes. Participants (n = 17) initiated an auditory-paced bimanual tapping. After a 1500 ms preparatory period, an imperative stimulus required to either selectively stop the left while maintaining the right unimanual tapping (Switch condition: SWIT) or to continue the bimanual tapping (Continue condition: CONT). PMBS significantly increased in SWIT compared to CONT with maximal difference within right central region in broad-band 14âeuro"30 Hz and within left central region in restricted-band 22âeuro"26 Hz. Source estimations localized these effects within right pre-frontal cortex and left parietal cortex, respectively. A negative correlation showed that participants with a low percentage of errors in SWIT had a large PMBS amplitude within right parietal and frontal cortices. This study shows for the first time simultaneous PMBS with distinct functions in different brain regions and frequency ranges. The left parietal PMBS restricted to 22âeuro"26 Hz could reflect the sensory reafferences of the right hand tapping disrupted by the switching. In contrast, the right pre-frontal PMBS in a broad-band 14âeuro"30 Hz is likely reflecting the active inhibition of the left hand stopped. Finally, correlations between behavioral performance and the magnitude of the PMBS suggest that beta oscillations can be viewed as a marker of successful active inhibition.

Electronic Construction Collaboration - Phase 1, 2009

Bridge construction projects are becoming increasingly complex as the demand for context-sensitive solutions, aesthetic designs, and accelerated bridge construction becomes more prevalent. In addition, the Iowa Department of Transportation (Iowa DOT) is entering a phase of design and construction of large border bridges, such as the I-80 (let 2008 for $56 million) and US 34 bridges over the Missouri River and I-74 over the Mississippi River. Compared to typical construction projects, these bridges generate more contractor Requests for Information (RFIs), Value Engineering (VE) proposals, Requests for Changes (RFCs), and shop drawings. Management of these submittals is a significant challenge for Resident Construction Engineers (RCEs) and other Iowa DOT staff. In addition, some submittals require cross-departmental and project consultant reviews. Commercially available software exists for managing submittals and project collaboration teams; in-house solutions may also be possible. Implementation is intended to speed construction submittal review time, reduce incidence of delay claims, and free up Iowa DOT staff from project management administrative tasks. Researchers from Iowa State University working with the Iowa DOT conducted a multi-pronged approach to indentify a web-based collaboration solution for Iowa DOT bridge projects. An investigation was launched to determine the functional needs of the Iowa DOT. Commercially available software programs were also evaluated to find what functionality is currently available. A Request for Proposals (RFP) was written to select a commercial web-based collaboration solution for pilot testing. In the second phase of research, a solution will be selected and implemented on two pilot projects. Lessons learned from these pilot projects will assist the Iowa DOT in developing and implementing a long-term solution to improve the management of Iowa DOT bridge projects.

Solid-Phase Synthesis of New Trp(Nps)-Containing Dipeptide Derivatives as TRPV1 Channel Blockers

Trp(Nps)-Lys-NH2 derivatives, bearing alkyl or guanidine groups either at the N-terminus or on the Lys side-chain or at both positions were conveniently prepared on solid-phase and evaluated as TRPV1 channel antagonists.

Study of OSEM with different subsets in grating-based X-ray differential phase-contrast imaging.

Impressive developments in X-ray imaging are associated with X-ray phase contrast computed tomography based on grating interferometry, a technique that provides increased contrast compared with conventional absorption-based imaging. A new "single-step" method capable of separating phase information from other contributions has been recently proposed. This approach not only simplifies data-acquisition procedures, but, compared with the existing phase step approach, significantly reduces the dose delivered to a sample. However, the image reconstruction procedure is more demanding than for traditional methods and new algorithms have to be developed to take advantage of the "single-step" method. In the work discussed in this paper, a fast iterative image reconstruction method named OSEM (ordered subsets expectation maximization) was applied to experimental data to evaluate its performance and range of applicability. The OSEM algorithm with different subsets was also characterized by comparison of reconstruction image quality and convergence speed. Computer simulations and experimental results confirm the reliability of this new algorithm for phase-contrast computed tomography applications. Compared with the traditional filtered back projection algorithm, in particular in the presence of a noisy acquisition, it furnishes better images at a higher spatial resolution and with lower noise. We emphasize that the method is highly compatible with future X-ray phase contrast imaging clinical applications.