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Background: Up to 50% of patients with uveal melanoma develop metastases (MUM) with a poor prognosis and median overall survival of approximately 1 year. Methods: This phase I study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the oral protein kinase C inhibitor LXS196 in 68 patients with MUM (NCT02601378). Patients received LXS196 doses ranging from 100–1000 mg once daily (QD; n = 38) and 200–400 mg twice daily (BID; n = 30). Results: First cycle dose-limiting toxicities (DLTs) were observed in 7/38 (18.4%) QD and 2/17 (11.8%) BID patients. Hypotension was the most common DLT, occurring at doses ≥500 mg/day, and manageable with LXS196 interruption and dose reduction. Median duration of exposure to LXS196 was 3.71 months (range: 1.81–15.28) for QD and 4.6 months (range: 0.33–58.32) for BID dosing. Clinical activity was observed in 6/66 (9.1%) evaluable patients achieving response (CR/PR), with a median duration of response of 10.15 months (range: 2.99–41.95); 45/66 had stable disease (SD) per RECIST v1.1. At 300 mg BID, the recommended dose for expansion, 2/18 (11.1%) evaluable patients achieved PR and 12/18 (66.7%) had SD. Conclusion: These results suggest manageable toxicity and encouraging clinical activity of single-agent LXS196 in patients with MUM. [ABSTRACT FROM AUTHOR]

Modular discrete and integrated implementations of a continuous-time analog rank-order N input filter are presented that uses one operational transconductance amplifier per input. Rank is programmable for all values from k=1 (min case) to k=N (max case). The implementation is based on transconductance cells with high transconductance gain and symmetrical output current saturating characteristics. Experimental results for both discrete and CMOS integrated implementations are presented that verify functionality and the high-frequency characteristics of the proposed implementations. [ABSTRACT FROM AUTHOR]

Many structural elements are exposed to conditions of load that are difficult to consider during the design stage, such as environment uncertainties, random impacts, overloads and inherent material idealization amongst others, hence, miss-estimating its life-time cycle. One way to test those designs is to construct a representative full-scale specimen and test it under the most critical load conditions in a controlled laboratory. Herein, we present a case of study of the fatigue test performed over a bolster beam redesigned in Universidad EAFIT belonging to a railway vehicle. The test was composed by three stages, each one testing a different load hypothesis. The bolster beam was instrumented at the most critical locations, following the results of a FEM analysis previously computed. As results, the most critical welds were identified and the total damage computed for an equivalent operation of eighteen-years, and also the behaviour of the specimen in presence of extreme longitudinal loads. [ABSTRACT FROM AUTHOR]

This paper presents a new mechanism for the management of mobile nodes fully compatible with IEEE 802.15.4 standard in non-beacon enabled mode. The proposed solution overcomes the problem related to the high association time of mobile nodes in this standard where continuous associations affect the activity time. A static structure supports the mobile nodes, and the procedure allows both data transmission from a mobile node and data reception from the static nodes with minimal activity time and high communication reliability. The approach reduces power consumption and packet loss. Experimental results have been measured on a network composed by a static structure of various hierarchical levels with multiple mobile nodes moving freely, and confirm the suitability of the proposed low activity mechanism. [ABSTRACT FROM AUTHOR]

A novel low voltage tunable linear transconductor is presented. The approach is based on quasi-floating gate transistors achieving higher transconductance and better dc common mode rejection than previous implementations. A dynamic biasing technique improves the sensibility of the linearity to process variations. Measurement results of the circuit, designed in a 0.5 μm CMOS process from 1.4 V power supply, confirm the advantages of the proposed approach with a very high speed operation of 50 MHz of gain-bandwidth product, a IM3 of −40 dB and a nominal power consumption of only 490 μW. [ABSTRACT FROM AUTHOR]

Background:Radiation-associated breast angiosarcoma (RT-AS) is an uncommon malignancy with an incidence of less than 1 % of all soft tissue sarcomas. The overall prognosis is quite dismal with high rates of recurrences and poor overall survival. There is an obvious paucity of data regarding clinical outcomes of patients with breast RT-AS.Methods:We identified all patients with RT-AS treated at the Memorial Sloan-Kettering Cancer Center between 1982-2011 and collected their correlative clinical information.Results:We identified 79 women with RT-AS with a median age of 68 (range 36-87). The median interval between radiation and development of RT-AS was 7 years (range 3-19). The median time to local and distant recurrence was 1.29 years (95 % CI 0.72-NA) and 2.48 years (95 % CI 1.29-NA), respectively. The median disease-specific survival was 2.97 years (95 % CI 2.21-NA). Independent predictors of worse disease-specific survival included age 68 years (HR 3.11, 95 % CI 1.20-8.08, P=0.020) and deep tumors (HR 3.23, 95 % CI 1.02-10.21, P=0.046.)Conclusion:RT-AS has high local/distant recurrence rates, limited duration on standard chemotherapy and poor disease-specific survival. [ABSTRACT FROM AUTHOR]

Primary care practitioners (PCPs) have been encouraged to screen all adults for obesity and to offer behavioral weight loss counseling to the affected individuals. However, there is limited research and guidance on how to provide such intervention in primary care settings. This led the National Heart, Lung and Blood Institute in 2005 to issue a request for applications to investigate the management of obesity in routine clinical care. Three institutions were funded under a cooperative agreement to undertake the practice-based opportunities for weight reduction (POWER) trials. The present article reviews selected randomized controlled trials, published before the initiation of POWER, and then provides a detailed overview of the rationale, methods and results of the POWER trial conducted at the University of Pennsylvania (POWER-UP). POWER-UP's findings are briefly compared with those from the two other POWER trials, conducted at Johns Hopkins University and Harvard University/Washington University. The methods of delivering behavioral weight loss counseling differed markedly across the three trials, as captured by an algorithm presented in the article. Delivery methods ranged from having medical assistants and PCPs from the practices provide counseling to using a commercially available call center, coordinated with an interactive website. Evaluation of the efficacy of primary care-based weight loss interventions must be considered in light of costs, as discussed in relation to the recent treatment model proposed by the Centers for Medicare and Medicaid Services. [ABSTRACT FROM AUTHOR]

A novel automatic frequency tuning circuit for continuous-time filters is presented. Based on the switched-capacitor technique, the circuit offers an advantage in terms of simplicity resulting from the use of only two matched current sources, an operational amplifier with relaxed specifications and a transconductor that is a replica of the filter transconductors. Despite the simplicity of the scheme, the accuracy of the system is less than 1 % of frequency error. The circuit has been designed in a 0.5 μm CMOS technology with a 3.3 V power supply and simulation results confirm the suitability of the proposed approach. [ABSTRACT FROM AUTHOR]

A CMOS highly linear voltage-controlled transconductor suitable for Gm-C filter design is presented. The control loop to program the transconductance maintains the input transistors in triode region with a compact topology. Measurement results for the transconductor fabricated in a 0.5-μm CMOS technology feature a spurious-free dynamic range (SFDR) of 72 dB for 1 V differential inputs at 1 MHz. The voltage to current converter ensures a high linearity level for a wide transconductance range. Functionality of the transconductor is shown in a fifth-order Gm-C tunable complex filter well suited for a dual-mode Bluetooth/Zigbee transceiver. [ABSTRACT FROM AUTHOR]

Matching accuracy of capacitors at the first stage of the residue amplifier limits the overall resolution in pipelined analog-to-digital converters. A new residue amplifier is presented in this paper which is inherently insensitive not only to capacitor ratio but also to amplifier offset voltage and gain errors. Experimental and simulation results are provided to show how the proposed technique senses and compensates these errors. [ABSTRACT FROM AUTHOR]

compact DC offset correction circuit based on the intrinsic properties of quasi-floating gate (QFG) transistors is presented. The proposed scheme uses a tuning mechanism to make its initial response faster improving the traditional large settling time of these circuits. A zero-IF baseband receiver chain suitable for Bluetooth that includes the proposed dc offset correction has been designed in a 0.18 μm CMOS technology at 1.2 V supply voltage. [ABSTRACT FROM AUTHOR]

This paper presents a new technique for programming SC circuits using a single time-multiplexed capacitor bank, achieving a significant reduction in capacitance area. Simulation and experimental results obtained with a programmable biquad low pass filter show the validity of the proposed method. [ABSTRACT FROM AUTHOR]

Cell-mediated immunity against an extract of homologous normal lung connective tissue was determined in vitro in spleen cells from CD1 mice with bleomycin-induced pulmonary fibrosis. Blastoid transformation and macrophage migration inhibitory factor (MIF) were measured at intervals in spleen lymphocytes for a total of seven weeks after the initiation of the fibrogenic process. MIF production was evident from the third week and progressively increased during the experimental period, while blastoid transformation was observed only after the fifth week. There was no immune response to bleomycin, but a decrease in DNA synthesis was found. Because of its relatively delayed onset, this autoimmune phenomenon does not appear to be associated with the etiology of the fibrosis, but rather with the maintenance of the inflammatory response. [ABSTRACT FROM AUTHOR]