Building an Energy-efficient Uplink and Downlink Delay Aware TDM-PON System

NASA Astrophysics Data System (ADS)

Newaz, S. H. Shah; Jang, Min Seok; Alaelddin, Fuad Yousif Mohammed; Lee, Gyu Myoung; Choi, Jun Kyun

2016-05-01

With the increasing concern over the energy expenditure due to rapid ICT expansion and growth of Internet traffic volume, there is a growing trend towards developing energy-efficient ICT solutions. Passive Optical Network (PON), which is regarded as a key enabler to facilitate high speed broadband connection to individual subscribers, is considered as one of the energy-efficient access network technologies. However, an immense amount of research effort can be noticed in academia and industries to make PON more energy-efficient. In this paper, we aim at improving energy saving performance of Time Division Multiplexing (TDM)-PON, which is the most widely deployed PON technology throughout the world. A commonly used approach to make TDM-PON energy-efficient is to use sleep mode in Optical Network Units (ONUs), which are the customer premises equipment of a TDM-PON system. However, there is a strong trade-off relationship between traffic delay performance of an ONU and its energy saving (the longer the sleep interval length of an ONU, the lower its energy consumption, but the higher the traffic delay, and vice versa). In this paper, we propose an Energy-efficient Uplink and Downlink Delay Aware (EUDDA) scheme for TDM-PON system. The prime object of EUDDA is to meet both downlink and uplink traffic delay requirement while maximizing energy saving performance of ONUs as much as possible. In EUDDA, traffic delay requirement is given more priority over energy saving. Even so, it still can improve energy saving of ONUs noticeably. We evaluate performance of EUDDA in front of two existing solutions in terms of traffic delay, jitter, and ONU energy consumption. The performance results show that EUDDA significantly outperforms the other existing solutions.

TDM in psychiatry and neurology: A comprehensive summary of the consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology, update 2017; a tool for clinicians^.

PubMed

Schoretsanitis, Georgios; Paulzen, Michael; Unterecker, Stefan; Schwarz, Markus; Conca, Andreas; Zernig, Gerald; Gründer, Gerhard; Haen, Ekkerhard; Baumann, Pierre; Bergemann, Niels; Clement, Hans Willi; Domschke, Katharina; Eckermann, Gabriel; Egberts, Karin; Gerlach, Manfred; Greiner, Christine; Havemann-Reinecke, Ursula; Hefner, Gudrun; Helmer, Renate; Janssen, Ger; Jaquenoud-Sirot, Eveline; Laux, Gerd; Messer, Thomas; Mössner, Rainald; Müller, Matthias J; Pfuhlmann, Bruno; Riederer, Peter; Saria, Alois; Schoppek, Bernd; Silva Gracia, Margarete; Stegmann, Benedikt; Steimer, Werner; Stingl, Julia C; Uhr, Manfred; Ulrich, Sven; Waschgler, Roland; Zurek, Gabriela; Hiemke, Christoph

2018-04-01

Therapeutic drug monitoring (TDM) combines the quantification of drug concentrations in blood, pharmacological interpretation and treatment guidance. TDM introduces a precision medicine tool in times of increasing awareness of the need for personalized treatment. In neurology and psychiatry, TDM can guide pharmacotherapy for patient subgroups such as children, adolescents, pregnant women, elderly patients, patients with intellectual disabilities, patients with substance use disorders, individuals with pharmacokinetic peculiarities and forensic patients. Clear indications for TDM include lack of clinical response in the therapeutic dose range, assessment of drug adherence, tolerability issues and drug-drug interactions. Based upon existing literature, recommended therapeutic reference ranges, laboratory alert levels, and levels of recommendation to use TDM for dosage optimization without specific indications, conversion factors, factors for calculation of dose-related drug concentrations and metabolite-to-parent ratios were calculated. This summary of the updated consensus guidelines by the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie offers the practical and theoretical knowledge for the integration of TDM as part of pharmacotherapy with neuropsychiatric agents into clinical routine. The present guidelines for TDM application for neuropsychiatric agents aim to assist clinicians in enhancing safety and efficacy of treatment.

Two-dimensional priority-based dynamic resource allocation algorithm for QoS in WDM/TDM PON networks

NASA Astrophysics Data System (ADS)

Sun, Yixin; Liu, Bo; Zhang, Lijia; Xin, Xiangjun; Zhang, Qi; Rao, Lan

2018-01-01

Wavelength division multiplexing/time division multiplexing (WDM/TDM) passive optical networks (PON) is being viewed as a promising solution for delivering multiple services and applications. The hybrid WDM / TDM PON uses the wavelength and bandwidth allocation strategy to control the distribution of the wavelength channels in the uplink direction, so that it can ensure the high bandwidth requirements of multiple Optical Network Units (ONUs) while improving the wavelength resource utilization. Through the investigation of the presented dynamic bandwidth allocation algorithms, these algorithms can't satisfy the requirements of different levels of service very well while adapting to the structural characteristics of mixed WDM / TDM PON system. This paper introduces a novel wavelength and bandwidth allocation algorithm to efficiently utilize the bandwidth and support QoS (Quality of Service) guarantees in WDM/TDM PON. Two priority based polling subcycles are introduced in order to increase system efficiency and improve system performance. The fixed priority polling subcycle and dynamic priority polling subcycle follow different principles to implement wavelength and bandwidth allocation according to the priority of different levels of service. A simulation was conducted to study the performance of the priority based polling in dynamic resource allocation algorithm in WDM/TDM PON. The results show that the performance of delay-sensitive services is greatly improved without degrading QoS guarantees for other services. Compared with the traditional dynamic bandwidth allocation algorithms, this algorithm can meet bandwidth needs of different priority traffic class, achieve low loss rate performance, and ensure real-time of high priority traffic class in terms of overall traffic on the network.

[TDM management system for contribution to proper use of anti-mRSA drugs--establishment of cooperation support system between pharmacy and clinical laboratory in hospital].

PubMed

Yodoshi, Masahiro; Iwasaki, Naomi; Satoh, Kaori; Nomura, Morihiro; Morishima, Yoshiyuki; Nakae, Kenichi; Yamazoe, Yuzuru

2013-02-01

In team medicine, highly specialized pharmacists have recently been in demand. As one of the specialties, there is therapeutic drug monitoring (TDM). It is important for the optimal dosing of a wide range of drugs. In our hospital, a TDM service was started in 1987 at the clinical laboratory. A clinical laboratory technologist with the license of a pharmacist has performed administration plans for anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs, vancomycin, teicoplanin, and arbekacin. In particular, the pharmacist in charge of TDM services, a TDM-specialized pharmacist, plays a central role in administration plans for anti MRSA drugs. Furthermore, we examined the active use of the TDM service to expand pharmaceutical care. Therefore, at first, we have worked in partnership with the clinical laboratory, as it is called the "Cooperation Support System", since September 2010. As a result, after the introduction of this system, from August 2011 to July 2012, the rate that the doctor referred to the administration plan was markedly improved by approximately 90%. We have been able to enhance TDM in practical training for pharmacology as an extension of this system. We thought that drug therapy can be performed more appropriately by increasing the number of executions of TDM in the future. For drug therapy to be done more appropriately, efforts made through cooperation with the clinical laboratory are essential for an effective TDM system. Naturally, an effective TDM process requires a collaborative, multidisciplinary approach with input from doctors, nurses, and clinical pharmacists.

High accuracy demodulation for twin-grating based sensor network with hybrid TDM/FDM

NASA Astrophysics Data System (ADS)

Ai, Fan; Sun, Qizhen; Cheng, Jianwei; Luo, Yiyang; Yan, Zhijun; Liu, Deming

2017-04-01

We demonstrate a high accuracy demodulation platform with a tunable Fabry-Perot filter (TFF) for twin-grating based fiber optic sensing network with hybrid TDM/FDM. The hybrid TDM/FDM scheme can improve the spatial resolution to centimeter but increases the requirement of high spectrum resolution. To realize the demodulation of the complex twin-grating spectrum, we adopt the TFF demodulation method and compensate the environmental temperature change and nonlinear effect through calibration FBGs. The performance of the demodulation module is tested by a temperature experiment. Spectrum resolution of 1pm is realized with precision of 2.5pm while the environmental temperature of TFF changes 9.3°C.

An integrated multiple-analyte pharmacokinetic model to characterize trastuzumab emtansine (T-DM1) clearance pathways and to evaluate reduced pharmacokinetic sampling in patients with HER2-positive metastatic breast cancer.

PubMed

Lu, Dan; Joshi, Amita; Wang, Bei; Olsen, Steve; Yi, Joo-Hee; Krop, Ian E; Burris, Howard A; Girish, Sandhya

2013-08-01

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate recently approved by the US Food and Drug Administration for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer previously treated with trastuzumab and taxane chemotherapy. It comprises the microtubule inhibitory cytotoxic agent DM1 conjugated to the HER2-targeted humanized monoclonal antibody trastuzumab via a stable linker. To characterize the pharmacokinetics of T-DM1 in patients with metastatic breast cancer, concentrations of multiple analytes were quantified, including serum concentrations of T-DM1 conjugate and total trastuzumab (the sum of conjugated and unconjugated trastuzumab), as well as plasma concentrations of DM1. The clearance of T-DM1 conjugate is approximately 2 to 3 times faster than its parent antibody, trastuzumab. However, the clearance pathways accounting for this faster clearance rate are unclear. An integrated population pharmacokinetic model that simultaneously fits the pharmacokinetics of T-DM1 conjugate and total trastuzumab can help to elucidate the clearance pathways of T-DM1. The model can also be used to predict total trastuzumab pharmacokinetic profiles based on T-DM1 conjugate pharmacokinetic data and sparse total trastuzumab pharmacokinetic data, thereby reducing the frequency of pharmacokinetic sampling. T-DM1 conjugate and total trastuzumab serum concentration data, including baseline trastuzumab concentrations prior to T-DM1 treatment, from phase I and II studies were used to develop this integrated population pharmacokinetic model. Based on a hypothetical T-DM1 catabolism scheme, two-compartment models for T-DM1 conjugate and trastuzumab were integrated by assuming a one-step deconjugation clearance from T-DM1 conjugate to trastuzumab. The ability of the model to predict the total trastuzumab pharmacokinetic profile based on T-DM1 conjugate pharmacokinetics and various sampling schemes of total trastuzumab

T-DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo

PubMed Central

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-01-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody–drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. PMID:24890382

Multi-granularity Bandwidth Allocation for Large-Scale WDM/TDM PON

NASA Astrophysics Data System (ADS)

Gao, Ziyue; Gan, Chaoqin; Ni, Cuiping; Shi, Qiongling

2017-12-01

WDM (wavelength-division multiplexing)/TDM (time-division multiplexing) PON (passive optical network) is being viewed as a promising solution for delivering multiple services and applications, such as high-definition video, video conference and data traffic. Considering the real-time transmission, QoS (quality of services) requirements and differentiated services model, a multi-granularity dynamic bandwidth allocation (DBA) in both domains of wavelengths and time for large-scale hybrid WDM/TDM PON is proposed in this paper. The proposed scheme achieves load balance by using the bandwidth prediction. Based on the bandwidth prediction, the wavelength assignment can be realized fairly and effectively to satisfy the different demands of various classes. Specially, the allocation of residual bandwidth further augments the DBA and makes full use of bandwidth resources in the network. To further improve the network performance, two schemes named extending the cycle of one free wavelength (ECoFW) and large bandwidth shrinkage (LBS) are proposed, which can prevent transmission from interruption when the user employs more than one wavelength. The simulation results show the effectiveness of the proposed scheme.

Ethnic sensitivity assessment of the antibody-drug conjugate trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer.

PubMed

Li, Chunze; Wang, Bei; Lu, Dan; Jin, Jin Y; Gao, Yuying; Matsunaga, Kiyoshi; Igawa, Yuriko; Nijem, Ihsan; Lu, Michael; Strasak, Alexander; Chernyukhin, Nataliya; Girish, Sandhya

2016-09-01

Trastuzumab emtansine (T-DM1) is indicated for previously treated HER2-positive metastatic breast cancer. Ethnic sensitivity assessment of T-DM1 was conducted using data from eight clinical studies to ensure that the clinically recommended dose is appropriate across ethnicities. Four approaches were used: (1) non-compartmental analysis (NCA) comparing pharmacokinetic parameters of T-DM1 and relevant analytes across ethnic groups, (2) population pharmacokinetic (popPK) analysis assessing the impact of ethnicity on pharmacokinetics, (3) comparison of T-DM1 pharmacokinetics in Japanese patients versus the global population, and (4) exposure-response analyses assessing the impact of ethnicity on safety and efficacy. NCA pharmacokinetic parameters (T-DM1, total trastuzumab, DM1) were comparable across ethnic groups; mean cycle 1 T-DM1 AUCinf was 475, 442, and 518 day µg/mL for white (n = 461), Asian (n = 68), and others (n = 57), respectively. PopPK analysis showed that ethnicity (white, Asian, and others) was not a significant covariate for T-DM1 pharmacokinetics (n = 671). Additionally, visual predictive check plots indicated that observed pharmacokinetic profiles in Japanese patients (n = 42) were within the prediction interval generated from the final PopPK model. Exposure-response analyses showed that ethnicity was not a significant covariate impacting efficacy or hepatotoxicity risk, but there was a trend of greater thrombocytopenia risk among Asians versus non-Asians, which could not be explained by similar exposure between the ethnic groups. Most Asians with thrombocytopenia were able to continue T-DM1 using dose-adjustment rules recommended for the global population. These results suggest that T-DM1 pharmacokinetics are comparable across ethnic groups and that use of the current dosing regimen is appropriate across ethnicities.

Impact of transportation demand management (TDM) elements on managed lanes toll prices.

DOT National Transportation Integrated Search

2015-03-01

This research involved a simulation comparing three days of actual traffic data for the I-95 Express : Lanes and General Purpose Lanes in Miami, Florida to a hypothetical scenario where all transportation : demand management (TDM) activities and toll...

A novel protection scheme for a hybrid WDM/TDM PON

NASA Astrophysics Data System (ADS)

Chen, Jiajia; Wosinska, Lena; He, Sailing

2007-11-01

This paper proposes a novel protection scheme based on the cyclic property of an array waveguide grating (AWG) and neighboring connection pattern between two adjacent optical network units (ONUs) for the hybrid WDM/TDM passive optical networks (PONs). Our scheme uses 50% fewer wavelengths while offering one order of magnitude better connection availability than the existing scheme.

T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.

PubMed

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-10-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Improving the cost effectiveness of financial incentives in managing travel demand management (TDM).

DOT National Transportation Integrated Search

2013-10-01

Providing financial incentives to commuters to use alternative modes is a common element of managing transportation demand. Although these incentives have become common during the past two decades as elements of transportation demand management (TDM)...

DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase I inhibitor, overcomes HER2-positive gastric cancer T-DM1 resistance.

PubMed

Takegawa, Naoki; Nonagase, Yoshikane; Yonesaka, Kimio; Sakai, Kazuko; Maenishi, Osamu; Ogitani, Yusuke; Tamura, Takao; Nishio, Kazuto; Nakagawa, Kazuhiko; Tsurutani, Junji

2017-10-15

Anti-HER2 therapies are beneficial for patients with HER2-positive breast or gastric cancer. T-DM1 is a HER2-targeting antibody-drug conjugate (ADC) comprising the antibody trastuzumab, a linker, and the tubulin inhibitor DM1. Although effective in treating advanced breast cancer, all patients eventually develop T-DM1 resistance. DS-8201a is a new ADC incorporating an anti-HER2 antibody, a newly developed, enzymatically cleavable peptide linker, and a novel, potent, exatecan-derivative topoisomerase I inhibitor (DXd). DS-8201a has a drug-to-antibody-ratio (DAR) of 8, which is higher than that of T-DM1 (3.5). Owing to these unique characteristics and unlike T-DM1, DS-8201a is effective against cancers with low-HER2 expression. In the present work, T-DM1-resistant cells (N87-TDMR), established using the HER2-positive gastric cancer line NCI-N87 and continuous T-DM1 exposure, were shown to be susceptible to DS-8201a. The ATP-binding cassette (ABC) transporters ABCC2 and ABCG2 were upregulated in N87-TDMR cells, but HER2 overexpression was retained. Furthermore, inhibition of ABCC2 and ABCG2 by MK571 restored T-DM1 sensitivity. Therefore, resistance to T-DM1 is caused by efflux of its payload DM1, due to aberrant expression of ABC transporters. In contrast to DM1, DXd payload of DS-8201a inhibited the growth of N87-TDMR cells in vitro. This suggests that either DXd may be a poor substrate of ABCC2 and ABCG2 in comparison to DM1, or the high DAR of DS-8201a relative to T-DM1 compensates for increased efflux. Notably, N87-TDMR xenograft tumor growth was prevented by DS-8201a. In conclusion, the efficacy of DS-8201a as a treatment for patients with T-DM1-resistant breast or gastric cancer merits investigation. © 2017 UICC.

Potential of Surface Enhanced Raman Spectroscopy (SERS) in Therapeutic Drug Monitoring (TDM). A Critical Review

PubMed Central

Jaworska, Aleksandra; Fornasaro, Stefano; Sergo, Valter; Bonifacio, Alois

2016-01-01

Surface-Enhanced Raman Spectroscopy (SERS) is a label-free technique that enables quick monitoring of substances at low concentrations in biological matrices. These advantages make it an attractive tool for the development of point-of-care tests suitable for Therapeutic Drug Monitoring (TDM) of drugs with a narrow therapeutic window, such as chemotherapeutic drugs, immunosuppressants, and various anticonvulsants. In this article, the current applications of SERS in the field of TDM for cancer therapy are discussed in detail and illustrated according to the different strategies and substrates. In particular, future perspectives are provided and special concerns regarding the standardization of self-assembly methods and nanofabrication procedures, quality assurance, and technology readiness are critically evaluated. PMID:27657146

FDMA/TDM satellite communication systems for domestic/business services

NASA Astrophysics Data System (ADS)

Perrotta, G.; Losquadro, G.; Giubilei, R.

A design concept is presented for a Ka-band satellite communication system for domestic business applications, based on FDMA uplinks and time-domain-multiplexed (TDM) downlinks. The single-hop modular-design regenerative/processing repeaters employed are capable of handling up to 16 2-Mb/s uplink carriers each. The internal (short-block) and external (Reed-Solomon) coding techniques, frequency relations and symbol synchronization, and optional mini-TDMA implementation are explained, and the results of numerical simulations of subcomponent performance are presented graphically.

Physical-Layer Network Coding for VPN in TDM-PON

NASA Astrophysics Data System (ADS)

Wang, Qike; Tse, Kam-Hon; Chen, Lian-Kuan; Liew, Soung-Chang

2012-12-01

We experimentally demonstrate a novel optical physical-layer network coding (PNC) scheme over time-division multiplexing (TDM) passive optical network (PON). Full-duplex error-free communications between optical network units (ONUs) at 2.5 Gb/s are shown for all-optical virtual private network (VPN) applications. Compared to the conventional half-duplex communications set-up, our scheme can increase the capacity by 100% with power penalty smaller than 3 dB. Synchronization of two ONUs is not required for the proposed VPN scheme

Power Budget Analysis of Colorless Hybrid WDM/TDM-PON Scheme Using Downstream DPSK and Re-modulated Upstream OOK Data Signals

NASA Astrophysics Data System (ADS)

Khan, Yousaf; Afridi, Muhammad Idrees; Khan, Ahmed Mudassir; Rehman, Waheed Ur; Khan, Jahanzeb

2014-09-01

Hybrid wavelength-division multiplexed/time-division multiplexed passive optical access networks (WDM/TDM-PONs) combine the advance features of both WDM and TDM PONs to provide a cost-effective access network solution. We demonstrate and analyze the transmission performances and power budget issues of a colorless hybrid WDM/TDM-PON scheme. A 10-Gb/s downstream differential phase shift keying (DPSK) and remodulated upstream on/off keying (OOK) data signals are transmitted over 25 km standard single mode fiber. Simulation results show error free transmission having adequate power margins in both downstream and upstream transmission, which prove the applicability of the proposed scheme to future passive optical access networks. The power budget confines both the PON splitting ratio and the distance between the Optical Line Terminal (OLT) and Optical Network Unit (ONU).

QoS support over ultrafast TDM optical networks

NASA Astrophysics Data System (ADS)

Narvaez, Paolo; Siu, Kai-Yeung; Finn, Steven G.

1999-08-01

HLAN is a promising architecture to realize Tb/s access networks based on ultra-fast optical TDM technologies. This paper presents new research results on efficient algorithms for the support of quality of service over the HLAN network architecture. In particular, we propose a new scheduling algorithm that emulates fair queuing in a distributed manner for bandwidth allocation purpose. The proposed scheduler collects information on the queue of each host on the network and then instructs each host how much data to send. Our new scheduling algorithm ensures full bandwidth utilization, while guaranteeing fairness among all hosts.

A TDM link with channel coding and digital voice.

NASA Technical Reports Server (NTRS)

Jones, M. W.; Tu, K.; Harton, P. L.

1972-01-01

The features of a TDM (time-division multiplexed) link model are described. A PCM telemetry sequence was coded for error correction and multiplexed with a digitized voice channel. An all-digital implementation of a variable-slope delta modulation algorithm was used to digitize the voice channel. The results of extensive testing are reported. The measured coding gain and the system performance over a Gaussian channel are compared with theoretical predictions and computer simulations. Word intelligibility scores are reported as a measure of voice channel performance.

OSD1 promotes meiotic progression via APC/C inhibition and forms a regulatory network with TDM and CYCA1;2/TAM.

PubMed

Cromer, Laurence; Heyman, Jefri; Touati, Sandra; Harashima, Hirofumi; Araou, Emilie; Girard, Chloe; Horlow, Christine; Wassmann, Katja; Schnittger, Arp; De Veylder, Lieven; Mercier, Raphael

2012-01-01

Cell cycle control is modified at meiosis compared to mitosis, because two divisions follow a single DNA replication event. Cyclin-dependent kinases (CDKs) promote progression through both meiosis and mitosis, and a central regulator of their activity is the APC/C (Anaphase Promoting Complex/Cyclosome) that is especially required for exit from mitosis. We have shown previously that OSD1 is involved in entry into both meiosis I and meiosis II in Arabidopsis thaliana; however, the molecular mechanism by which OSD1 controls these transitions has remained unclear. Here we show that OSD1 promotes meiotic progression through APC/C inhibition. Next, we explored the functional relationships between OSD1 and the genes known to control meiotic cell cycle transitions in Arabidopsis. Like osd1, cyca1;2/tam mutation leads to a premature exit from meiosis after the first division, while tdm mutants perform an aberrant third meiotic division after normal meiosis I and II. Remarkably, while tdm is epistatic to tam, osd1 is epistatic to tdm. We further show that the expression of a non-destructible CYCA1;2/TAM provokes, like tdm, the entry into a third meiotic division. Finally, we show that CYCA1;2/TAM forms an active complex with CDKA;1 that can phosphorylate OSD1 in vitro. We thus propose that a functional network composed of OSD1, CYCA1;2/TAM, and TDM controls three key steps of meiotic progression, in which OSD1 is a meiotic APC/C inhibitor.

La ponction biopsie hépatique à Dakar: indications, complications et apport diagnostique - à propos de 70 cas

PubMed Central

Touré, Papa Souleymane; Léye, Abdoulaye; Diop, Madoky Maguette; Gueye, Mame Daouda; Léye, Yakham Mohamed; Berthé, Adama; Mourtalla Ka, Mamadou

2014-01-01

Introduction Les objectifs de notre travail étaient de déterminer les indications, les complications et l'apport diagnostique de la ponction biopsie hépatique (PBH) transpariétale. Méthodes Il s'agissait d'une étude rétrospective descriptive allant du janvier 2006 à décembre 2010, réalisée dans le service de Médecine Interne de l'hôpital de Pikine de Dakar. Etaient inclus, tous les malades ayant subi une biopsie hépatique, en ambulatoire ou en hospitalisation. Etaient exclus, tous les patients qui ont bénéficié d'une PBH dont les résultats n'ont pas été retrouvés. Les données suivantes étaient étudié: l’âge, le sexe, les indications, la taille du fragment biopsique, Le nombre de carottes, les complications, la comparaison des diagnostics pré biopsiques avec les comptes rendus histologiques. Résultats Ont été colligées 70 patients atteints d'hépatopathie chronique ayant bénéficiés d'une PBH. Il s'agissait de 46 hommes (65.71%) et 24 femmes (34.29%). L’âge moyen des patients était de 36 ans. Les PBH étaient réalisées en ambulatoire chez 58 patients (82.86%) et chez 12 malades hospitalisés (17,14%). Les indications étaient dominées par les hépatites virales chroniques dans 62,86% (44cas), suivi des processus tumoraux du foie dans 24.29% (17 cas). Les complications survenues chez 15 patients (21.43%) étaient représentées de 14 cas de douleur (20%) et d'un cas de malaise vagal (1.43%). Les 70 PBH effectuées ont ramené une carotte dans 35,71% des cas, 2 à 6 carottes dans 32,87% des cas. La longueur moyenne des fragments biopsiques était de 22 ±8 mm. Soixante-six résultats étaient interprétables et 4 non interprétables soit une performance diagnostique de 94,29%. Conclusion La PBH est de pratique sure, avec un respect des contres indications et une bonne maitrise de la technique. Son acceptabilité a été bonne dans notre pratique et sa rentabilité diagnostique excellente. Elle devrait être beaucoup plus

Ridesharing, Technology, and TDM in University Campus Settings : Lessons for State, Regional, and Local Agencies

DOT National Transportation Integrated Search

2016-05-01

This report examines how university campus transportation departments are using new technologies and supportive polices to advance ridesharing and transportation demand management (TDM) as alternatives to driving alone to campus. It looks at universi...

Effects of Modulation Techniques (Manchester Code, NRZ or RZ) on the Operation of Hybrid WDM/TDM Passive Optical Networks

PubMed Central

Nyachionjeka, Kumbirayi

2014-01-01

In this paper, the performance and feasibility of a hybrid wavelength division multiplexing/time division multiplexing passive optical network (WDM/TDM PON) system with 128 optical network units (ONUs) is analysed. In this system, triple play services (video, voice and data) are successfully communicated through a distance of up to 28 km. Moreover, we analysed and compared the performance of various modulation formats for different distances in the proposed hybrid WDM/TDM PON. NRZ rectangular emerged as the most appropriate modulation format for triple play transmission in the proposed hybrid PON. PMID:27382633

Efficacy and safety of trastuzumab emtansine (T-DM1) in the treatment of HER2-positive metastatic breast cancer (MBC): a meta-analysis of randomized controlled trial

PubMed Central

Yan, Hongjing; Yu, Kewei; Zhang, Kaile; Liu, Linxia; Li, Yue

2017-01-01

Aims Trastuzumab emtansine (T-DM1), an antibody-drug conjugate against human epidermal growth factor receptor 2 (HER2), has been used in the treatment of patients with HER2-positive metastatic breast cancer (MBC). We conducted a meta-analysis to evaluate the efficacy and toxicity of T-DM1 for the treatment of patients with HER2-positive MBC. Materials and Methods Randomized controlled trials (RCTs), published in Pubmed, Embase, and Web of Science were systematically reviewed to assess the survival benefits and toxicity profile of HER2-positive patients with MBC who were treated with T-DM1. Outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and toxicities. Results were expressed as the hazard ratio (HR) with 95% confidence intervals (CIs). Results A total of 5 RCTs involving 3,720 patients met the inclusion criteria and were included in this meta-analysis. T-DM1 significantly prolonged PFS (HR = 0.73, 95% CI: 0.61, 0.86; P < 0.05), OS (HR = 0.68, 95% CI: 0.62, 0.74; P < 0.05), but it did not increase ORR (RR = 1.25, 95% CI: 0.94, 1.66; P = 0.148). Subgroup analysis indicated that T-DM1 significantly improved PFS when it was used as first-line (HR = 0.86, 95% CI: 0.74, 1.00; P < 0.05) or non-first-line treatment (HR = 0.65, 95% CI: 0.53, 0.81; P < 0.05). T-DM1 was associated with more frequent adverse events, including fatigue, elevated ALT, elevated AST, and thrombocytopenia, than other anti-HER2 therapies. Conclusions Based on the current evidence, T-DM1 significantly prolonged PFS and OS with a tolerated toxicity than other anti-HER2 therapies in patients with HER2-positive MBC. These findings confirm the use of T-DM1 for the treatment of patients with HER2-positive MBC. Further well-designed, multi-center RCTs needed to identify these findings. PMID:29254261

A Randomized Clinical Trial Evaluating Therapeutic Drug Monitoring (TDM) for Protease Inhibitor–Based Regimens in Antiretroviral-Experienced HIV-Infected Individuals: Week 48 Results of the A5146 Study

PubMed Central

Albrecht, Mary; Mukherjee, A. Lisa; Tierney, Camlin; Morse, Gene D.; Dykes, Carrie; Klingman, Karin L.; Demeter, Lisa M.

2012-01-01

Background We devised an open-label, randomized trial to evaluate whether therapeutic drug monitoring (TDM) of protease inhibitors (PIs) and dose escalation based upon a normalized inhibitory quotient (NIQ), which integrates PI trough concentration and drug resistance, could improve virologic outcome in PI-experienced patients with treatment failure. Secondary analyses through 48 weeks are presented. Methods Eligible HIV-infected subjects with a screening viral load of ≥1000 copies/mL initiated a new PI-based regimen at entry and had NIQ performed at week 2. Subjects with an NIQ ≤1 were randomized at week 4 to a standard-of-care (SOC) arm or TDM arm featuring PI dose escalation. Results One hundred and eighty-three subjects were randomized. There was no significant treatment difference in change from randomization to week 48 in HIV-1 RNA [P = .13, median (25th, 75th percentile log10 copies/mL change): −0.03 (−0.74, 0.62) with TDM and 0.11 (−2.3, 0.82) with SOC]. In subgroup analysis, patients with ≥0.69 active PIs benefited from TDM compared to those with <0.69 active PIs (P = .05). Conclusions While the TDM strategy of PI dose escalation did not improve virologic response at week 48 overall, in subgroup analysis, TDM favorably impacted virologic outcome in subjects taking PI-based regimens with moderate antiviral activity. PMID:22044856

An enhanced DWBA algorithm in hybrid WDM/TDM EPON networks with heterogeneous propagation delays

NASA Astrophysics Data System (ADS)

Li, Chengjun; Guo, Wei; Jin, Yaohui; Sun, Weiqiang; Hu, Weisheng

2011-12-01

An enhanced dynamic wavelength and bandwidth allocation (DWBA) algorithm in hybrid WDM/TDM PON is proposed and experimentally demonstrated. In addition to the fairness of bandwidth allocation, this algorithm also considers the varying propagation delays between ONUs and OLT. The simulation based on MATLAB indicates that the improved algorithm has a better performance compared with some other algorithms.

Circuit-switch architecture for a 30/20-GHz FDMA/TDM geostationary satellite communications network

NASA Technical Reports Server (NTRS)

Ivancic, William D.

1992-01-01

A circuit switching architecture is described for a 30/20 GHz frequency division, multiple access uplink/time division multiplexed downlink (FDMA/TDM) geostationary satellite communications network. Critical subsystems and problem areas are identified and addressed. Work was concentrated primarily on the space segment; however, the ground segment was considered concurrently to ensure cost efficiency and realistic operational constraints.

Destination-directed, packet-switching architecture for 30/20-GHz FDMA/TDM geostationary communications satellite network

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Shalkhauser, Mary JO

1992-01-01

A destination-directed packet switching architecture for a 30/20-GHz frequency division multiple access/time division multiplexed (FDMA/TDM) geostationary satellite communications network is discussed. Critical subsystems and problem areas are identified and addressed. Efforts have concentrated heavily on the space segment; however, the ground segment has been considered concurrently to ensure cost efficiency and realistic operational constraints.

Vaccination with liposomal leishmanial antigens adjuvanted with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) confers long-term protection against visceral leishmaniasis through a human administrable route.

PubMed

Ravindran, Rajesh; Maji, Mithun; Ali, Nahid

2012-01-01

The development of a long-term protective subunit vaccine against visceral leishmaniasis depends on antigens and adjuvants that can induce an appropriate immune response. The immunization of leishmanial antigens alone shows limited efficacy in the absence of an appropriate adjuvant. Earlier we demonstrated sustained protection against Leishmania donovani with leishmanial antigens entrapped in cationic liposomes through an intraperitoneal route. However, this route is not applicable for human administration. Herein, we therefore evaluated the immune response and protection induced by liposomal soluble leishmanial antigen (SLA) formulated with monophosphoryl lipid-trehalose dicorynomycolate (MPL-TDM) through a subcutaneous route. Subcutaneous immunization of BALB/c mice with SLA entrapped in liposomes or with MPL-TDM elicited partial protection against experimental visceral leishmaniasis. In contrast, liposomal SLA adjuvanted with MPL-TDM induced significantly higher levels of protection in liver and spleen in BALB/c mice challenged 10 days post-vaccination. Protection conferred by this formulation was sustained up to 12 weeks of immunization, and infection was controlled for at least 4 months of the challenge, similar to liposomal SLA immunization administered intraperitoneally. An analysis of cellular immune responses of liposomal SLA + MPL-TDM immunized mice demonstrated the induction of IFN-γ and IgG2a antibody production not only 10 days or 12 weeks post-vaccination but also 4 months after the challenge infection and a down regulation of IL-4 production after infection. Moreover, long-term immunity elicited by this formulation was associated with IFN-γ production also by CD8⁺ T cells. Taken together, our results suggest that liposomal SLA + MPL-TDM represent a good vaccine formulation for the induction of durable protection against L. donovani through a human administrable route.

Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastuzumab emtansine (T-DM1) vs. treatment of physician's choice in previously treated HER2-positive advanced breast cancer.

PubMed

Kim, Sung-Bae; Wildiers, Hans; Krop, Ian E; Smitt, Melanie; Yu, Ron; Lysbet de Haas, Sanne; Gonzalez-Martin, Antonio

2016-11-15

In the phase III TH3RESA study (NCT01419197), 602 patients with HER2-positive advanced breast cancer who received prior taxane therapy and ≥2 HER2-directed regimens, including trastuzumab and lapatinib (advanced setting), were randomized to trastuzumab emtansine (T-DM1) or treatment of physician's choice (TPC). A statistically significant progression-free survival (PFS) benefit favoring T-DM1 was demonstrated. Here, we examine the relationship between HER2-related biomarkers and PFS in an exploratory analysis. Biomarkers assessed included HER2 (n = 505) and HER3 (n = 505) mRNA expression, PIK3CA mutation status (n = 410) and PTEN protein expression (n = 358). For biomarkers with continuous data (HER2, HER3, PTEN), subgroups were defined using median values (>median and ≤median). For all biomarker subgroups, median PFS was longer with T-DM1 vs. TPC. The PFS benefit favoring T-DM1 vs. TPC was numerically greater in the HER2 mRNA >median subgroup (7.2 vs. 3.4 months; unstratified hazard ratio [HR], 0.40; 95% CI, 0.28-0.59; p < 0.0001) vs. ≤median subgroup (5.5 vs. 3.9 months; HR, 0.68; 95% CI, 0.49-0.92; p = 0.0131). The PFS benefit with T-DM1 was similar among HER3, PIK3CA and PTEN subgroups. Consistent with other reports, benefit was seen with T-DM1 regardless of PIK3CA mutation status. In a multivariate analysis including an interaction term (treatment group by log2-transformed HER2 mRNA), patients with higher HER2 mRNA levels benefited more from receiving T-DM1 (HR, 0.84; 95% CI, 0.75-0.94; interaction p value = 0.0027). In summary, T-DM1 prolonged median PFS in all biomarker subgroups analyzed, including activating PIK3CA mutations, with numerically greater benefit in patients with tumors expressing HER2 mRNA >median vs. ≤median. © 2016 UICC.

Destination directed packet switch architecture for a 30/20 GHz FDMA/TDM geostationary communication satellite network

NASA Technical Reports Server (NTRS)

Ivancic, William D.; Shalkhauser, Mary JO

1991-01-01

Emphasis is on a destination directed packet switching architecture for a 30/20 GHz frequency division multiplex access/time division multiplex (FDMA/TDM) geostationary satellite communication network. Critical subsystems and problem areas are identified and addressed. Efforts have concentrated heavily on the space segment; however, the ground segment was considered concurrently to ensure cost efficiency and realistic operational constraints.

Upstream capacity upgrade in TDM-PON using RSOA based tunable fiber ring laser.

PubMed

Yi, Lilin; Li, Zhengxuan; Dong, Yi; Xiao, Shilin; Chen, Jian; Hu, Weisheng

2012-04-23

An upstream multi-wavelength shared (UMWS) time division multiplexing passive optical network (TDM-PON) is presented by using a reflective semiconductor amplifier (RSOA) and tunable optical filter (TOF) based directly modulated fiber ring laser as upstream laser source. The stable laser operation is easily achieved no matter what the bandwidth and shape of the TOF is and it can be directly modulated when the RSOA is driven at its saturation region. In this UMWS TDM-PON system, an individual wavelength can be assigned to the user who has a high bandwidth demand by tuning the central wavelength of the TOF in its upgraded optical network unit (ONU), while others maintain their traditional ONU structure and share the bandwidth via time slots, which greatly and dynamically upgrades the upstream capacity. We experimentally demonstrated the bidirectional transmission of downstream data at 10-Gb/s and upstream data at 1.25-Gb/s per wavelength over 25-km single mode fiber (SMF) with almost no power penalty at both ends. A stable performance is observed for the upstream wavelength tuned from 1530 nm to 1595 nm. Moreover, due to the high extinction ratio (ER) of the upstream signal, the burst-mode transmitting is successfully presented and a better time-division multiplexing performance can be obtained by turning off the unused lasers thanks to the rapid formation of the laser in the fiber ring. © 2012 Optical Society of America

Evolution of Antibody-Drug Conjugate Tumor Disposition Model to Predict Preclinical Tumor Pharmacokinetics of Trastuzumab-Emtansine (T-DM1).

PubMed

Singh, Aman P; Maass, Katie F; Betts, Alison M; Wittrup, K Dane; Kulkarni, Chethana; King, Lindsay E; Khot, Antari; Shah, Dhaval K

2016-07-01

A mathematical model capable of accurately characterizing intracellular disposition of ADCs is essential for a priori predicting unconjugated drug concentrations inside the tumor. Towards this goal, the objectives of this manuscript were to: (1) evolve previously published cellular disposition model of ADC with more intracellular details to characterize the disposition of T-DM1 in different HER2 expressing cell lines, (2) integrate the improved cellular model with the ADC tumor disposition model to a priori predict DM1 concentrations in a preclinical tumor model, and (3) identify prominent pathways and sensitive parameters associated with intracellular activation of ADCs. The cellular disposition model was augmented by incorporating intracellular ADC degradation and passive diffusion of unconjugated drug across tumor cells. Different biomeasures and chemomeasures for T-DM1, quantified in the companion manuscript, were incorporated into the modified model of ADC to characterize in vitro pharmacokinetics of T-DM1 in three HER2+ cell lines. When the cellular model was integrated with the tumor disposition model, the model was able to a priori predict tumor DM1 concentrations in xenograft mice. Pathway analysis suggested different contribution of antigen-mediated and passive diffusion pathways for intracellular unconjugated drug exposure between in vitro and in vivo systems. Global and local sensitivity analyses revealed that non-specific deconjugation and passive diffusion of the drug across tumor cell membrane are key parameters for drug exposure inside a cell. Finally, a systems pharmacokinetic model for intracellular processing of ADCs has been proposed to highlight our current understanding about the determinants of ADC activation inside a cell.

The Chromatin Protein DUET/MMD1 Controls Expression of the Meiotic Gene TDM1 during Male Meiosis in Arabidopsis

PubMed Central

Andreuzza, Sébastien; Nishal, Bindu; Singh, Aparna; Siddiqi, Imran

2015-01-01

Meiosis produces haploid cells essential for sexual reproduction. In yeast, entry into meiosis activates transcription factors which trigger a transcriptional cascade that results in sequential co-expression of early, middle and late meiotic genes. However, these factors are not conserved, and the factors and regulatory mechanisms that ensure proper meiotic gene expression in multicellular eukaryotes are poorly understood. Here, we report that DUET/MMD1, a PHD finger protein essential for Arabidopsis male meiosis, functions as a transcriptional regulator in plant meiosis. We find that DUET-PHD binds H3K4me2 in vitro, and show that this interaction is critical for function during meiosis. We also show that DUET is required for proper microtubule organization during meiosis II, independently of its function in meiosis I. Remarkably, DUET protein shows stage-specific expression, confined to diplotene. We identify two genes TDM1 and JAS with critical functions in cell cycle transitions and spindle organization in male meiosis, as DUET targets, with TDM1 being a direct target. Thus, DUET is required to regulate microtubule organization and cell cycle transitions during male meiosis, and functions as a direct transcription activator of the meiotic gene TDM1. Expression profiling showed reduced expression of a subset comprising about 12% of a known set of meiosis preferred genes in the duet mutant. Our results reveal the action of DUET as a transcriptional regulator during male meiosis in plants, and suggest that transcription of meiotic genes is under stagewise control in plants as in yeast. PMID:26348709

The Chromatin Protein DUET/MMD1 Controls Expression of the Meiotic Gene TDM1 during Male Meiosis in Arabidopsis.

PubMed

Andreuzza, Sébastien; Nishal, Bindu; Singh, Aparna; Siddiqi, Imran

2015-09-01

Meiosis produces haploid cells essential for sexual reproduction. In yeast, entry into meiosis activates transcription factors which trigger a transcriptional cascade that results in sequential co-expression of early, middle and late meiotic genes. However, these factors are not conserved, and the factors and regulatory mechanisms that ensure proper meiotic gene expression in multicellular eukaryotes are poorly understood. Here, we report that DUET/MMD1, a PHD finger protein essential for Arabidopsis male meiosis, functions as a transcriptional regulator in plant meiosis. We find that DUET-PHD binds H3K4me2 in vitro, and show that this interaction is critical for function during meiosis. We also show that DUET is required for proper microtubule organization during meiosis II, independently of its function in meiosis I. Remarkably, DUET protein shows stage-specific expression, confined to diplotene. We identify two genes TDM1 and JAS with critical functions in cell cycle transitions and spindle organization in male meiosis, as DUET targets, with TDM1 being a direct target. Thus, DUET is required to regulate microtubule organization and cell cycle transitions during male meiosis, and functions as a direct transcription activator of the meiotic gene TDM1. Expression profiling showed reduced expression of a subset comprising about 12% of a known set of meiosis preferred genes in the duet mutant. Our results reveal the action of DUET as a transcriptional regulator during male meiosis in plants, and suggest that transcription of meiotic genes is under stagewise control in plants as in yeast.

An All-Optical Access Metro Interface for Hybrid WDM/TDM PON Based on OBS

NASA Astrophysics Data System (ADS)

Segarra, Josep; Sales, Vicent; Prat, Josep

2007-04-01

A new all-optical access metro network interface based on optical burst switching (OBS) is proposed. A hybrid wavelength-division multiplexing/time-division multiplexing (WDM/TDM) access architecture with reflective optical network units (ONUs), an arrayed-waveguide-grating outside plant, and a tunable laser stack at the optical line terminal (OLT) is presented as a solution for the passive optical network. By means of OBS and a dynamic bandwidth allocation (DBA) protocol, which polls the ONUs, the available access bandwidth is managed. All the network intelligence and costly equipment is located at the OLT, where the DBA module is centrally implemented, providing quality of service (QoS). To scale this access network, an optical cross connect (OXC) is then used to attain a large number of ONUs by the same OLT. The hybrid WDM/TDM structure is also extended toward the metropolitan area network (MAN) by introducing the concept of OBS multiplexer (OBS-M). The network element OBS-M bridges the MAN and access networks by offering all-optical cross connection, wavelength conversion, and data signaling. The proposed innovative OBS-M node yields a full optical data network, interfacing access and metro with a geographically distributed access control. The resulting novel access metro architectures are nonblocking and, with an improved signaling, provide QoS, scalability, and very low latency. Finally, numerical analysis and simulations demonstrate the traffic performance of the proposed access scheme and all-optical access metro interface and architectures.

Optical chaos and hybrid WDM/TDM based large capacity quasi-distributed sensing network with real-time fiber fault monitoring.

PubMed

Luo, Yiyang; Xia, Li; Xu, Zhilin; Yu, Can; Sun, Qizhen; Li, Wei; Huang, Di; Liu, Deming

2015-02-09

An optical chaos and hybrid wavelength division multiplexing/time division multiplexing (WDM/TDM) based large capacity quasi-distributed sensing network with real-time fiber fault monitoring is proposed. Chirped fiber Bragg grating (CFBG) intensity demodulation is adopted to improve the dynamic range of the measurements. Compared with the traditional sensing interrogation methods in time, radio frequency and optical wavelength domains, the measurand sensing and the precise locating of the proposed sensing network can be simultaneously interrogated by the relative amplitude change (RAC) and the time delay of the correlation peak in the cross-correlation spectrum. Assisted with the WDM/TDM technology, hundreds of sensing units could be potentially multiplexed in the multiple sensing fiber lines. Based on the proof-of-concept experiment for axial strain measurement with three sensing fiber lines, the strain sensitivity up to 0.14% RAC/με and the precise locating of the sensors are achieved. Significantly, real-time fiber fault monitoring in the three sensing fiber lines is also implemented with a spatial resolution of 2.8 cm.

Profil diagnostique et évolutif du myélome multiple au Sénégal: étude monocentrique de 2005 à 2016

PubMed Central

Fall, Seynabou; Dieng, Fatma; Diouf, Coumba; Djiba, Boundia; Ndao, Awa Cheikh; Ndiaye, Fatou Samba Diago

2017-01-01

Introduction Les thérapeutiques innovantes du myélome multiple sont peu accessibles en Afrique subsaharienne. Le but de cette étude est de décrire les particularités diagnostiques et évolutives observées dans notre pratique de prise en charge des myélomateux. Méthodes Une étude rétrospective (2005 - 2016) descriptive à visée analytique, mené à l’hôpital Le Dantec (Sénégal) a concerné les myélomateux inclus selon les critères de l’International Myeloma Working Group (2003, 2014). Résultats Ont été colligés 136 dossiers (69 hommes, 67 femmes) de patients d’âge moyen 59 ans ± 10,1 ans et qui ont un âge inférieur à 65 ans dans 69,1% des cas. Les signes révélateurs ont été des douleurs osseuses (96,3%), une insuffisance rénale (36,8%), une infection (23,5%), une fracture pathologique (17,6%), une compression médullaire (16,9%), et une hypercalcémie maligne (16,2%). L’isotype a été IgG dans 61,3% des cas et Kappa dans 65% des cas. Les malades ont été classés stade III (59,4%) et I-II (40,6%) de l’index staging system. Sous traitement conventionnel (Méphalan-Prédnisone: 67,6%, innovant: 5,9%), la survie médiane a été de 20 mois (1-78 mois). La survie est meilleure, en l’absence de complications neurologiques, infectieuses et au score I-II de l’Index Staging System. Conclusion Dans notre étude, le myélome multiple est fréquemment diagnostiqué avant 65 ans, au stade de forte masse tumorale. La survie globale peut être améliorée par un dépistage précoce et un accès aux thérapeutiques adéquates. PMID:29187931

A large capacity time division multiplexed (TDM) laser beam combining technique enabled by nanosecond speed KTN deflector

NASA Astrophysics Data System (ADS)

Yin, Stuart (Shizhuo); Chao, Ju-Hung; Zhu, Wenbin; Chen, Chang-Jiang; Campbell, Adrian; Henry, Michael; Dubinskiy, Mark; Hoffman, Robert C.

2017-08-01

In this paper, we present a novel large capacity (a 1000+ channel) time division multiplexing (TDM) laser beam combining technique by harnessing a state-of-the-art nanosecond speed potassium tantalate niobate (KTN) electro-optic (EO) beam deflector as the time division multiplexer. The major advantages of TDM approach are: (1) large multiplexing capability (over 1000 channels), (2) high spatial beam quality (the combined beam has the same spatial profile as the individual beam), (3) high spectral beam quality (the combined beam has the same spectral width as the individual beam, and (4) insensitive to the phase fluctuation of individual laser because of the nature of the incoherent beam combining. The quantitative analyses show that it is possible to achieve over one hundred kW average power, single aperture, single transverse mode solid state and/or fiber laser by pursuing this innovative beam combining method, which represents a major technical advance in the field of high energy lasers. Such kind of 100+ kW average power diffraction limited beam quality lasers can play an important role in a variety of applications such as laser directed energy weapons (DEW) and large-capacity high-speed laser manufacturing, including cutting, welding, and printing.

Performance Analysis of Hybrid PON (WDM-TDM) with Equal and Unequal Channel Spacing

NASA Astrophysics Data System (ADS)

Sharma, Ramandeep; Dewra, Sanjeev; Rani, Aruna

2016-06-01

In this hybrid WDM-TDM PON has been evaluated and compared the downstream wavelengths with equal and unequal channel spacing at 5 Gbit/s per wavelength in the scenario of triple play services with 128 optical network units (ONUs). The triple play services: data, voice and video signals are transmitted up to 50 km distance having Q factor of 6.68 and BER of 3.64e-012 with unequal channel spacing and 45 km distance having Q factor of 6.33 and BER of 2.40e-011 with equal channel spacing in downstream direction. It has been observed that downstream wavelengths with unequal channel spacing provide better results than equal channel spacing.

Hybrid WDM/TDM PON Using the AWG FSR and Featuring Centralized Light Generation and Dynamic Bandwidth Allocation

NASA Astrophysics Data System (ADS)

Bock, Carlos; Prat, Josep; Walker, Stuart D.

2005-12-01

A novel time/space/wavelength division multiplexing (TDM/WDM) architecture using the free spectral range (FSR) periodicity of the arrayed waveguide grating (AWG) is presented. A shared tunable laser and a photoreceiver stack featuring dynamic bandwidth allocation (DBA) and remote modulation are used for transmission and reception. Transmission tests show correct operation at 2.5 Gb/s to a 30-km reach, and network performance calculations using queue modeling demonstrate that a high-bandwidth-demanding application could be deployed on this network.

Assessment of Two Desk-Top Computer Simulations Used to Train Tactical Decision Making (TDM) of Small Unit Infantry Leaders

DTIC Science & Technology

2007-04-01

judgmental self-doubt, depression, and causal uncertainty, tend to take fewer risks, and have lower self-esteem. Results from two studies (Nygren, 2000...U.S. Army Research Institute for the Behavioral and Social Sciences Research Report 1869 Assessment of Two Desk-Top Computer Simulations Used to...SUBTITLE 5a. CONTRACT OR GRANT NUMBER Assessment of Two Desk-Top Computer Simulations Used to Train Tactical Decision Making (TDM) of Small Unit

Optical power equalization for upstream traffic with injection-locked Fabry-Perot lasers in TDM-PON

NASA Astrophysics Data System (ADS)

Huang, Ting-Tsan; Sheu, Lih-Gen; Chi, Sien

2010-10-01

An optical power equalization of upstream traffic in time-division-multiplexed passive optical network (TDM-PON) based on injection-locked Fabry-Perot lasers has been experimentally investigated. The upstream transmitters with stable spectrum are achieved by using an external injection light source in the optical line terminal (OLT). The different upstream powers can be equalized by injection locking a Fabry-Perot laser diode (FP-LD) biased below threshold current in OLT. The dynamic upstream power range from - 8.5 to - 19.5 db m is reduced to a 1.6 dB maximal power variation, when the uplink signal is directly modulated at 1.25 Gb/s.

DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1.

PubMed

Ogitani, Yusuke; Aida, Tetsuo; Hagihara, Katsunobu; Yamaguchi, Junko; Ishii, Chiaki; Harada, Naoya; Soma, Masako; Okamoto, Hiromi; Oitate, Masataka; Arakawa, Shingo; Hirai, Takehiro; Atsumi, Ryo; Nakada, Takashi; Hayakawa, Ichiro; Abe, Yuki; Agatsuma, Toshinori

2016-10-15

An anti-HER2 antibody-drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its preclinical pharmacologic profile was assessed. In vitro and in vivo pharmacologic activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX) models. The mechanism of action for the efficacy was also evaluated. Pharmacokinetics in cynomolgus monkeys and the safety profiles in rats and cynomolgus monkeys were assessed. DS-8201a exhibited a HER2 expression-dependent cell growth-inhibitory activity and induced tumor regression with a single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87 model. Binding activity to HER2 and ADCC activity of DS-8201a were comparable with unconjugated anti-HER2 antibody. DS-8201a also showed an inhibitory activity to Akt phosphorylation. DS-8201a induced phosphorylation of Chk1 and Histone H2A.X, the markers of DNA damage. Pharmacokinetics and safety profiles of DS-8201a were favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys, supporting DS-8201a as being well tolerated in humans. DS-8201a was effective in a T-DM1-insensitive PDX model with high HER2 expression. DS-8201a, but not T-DM1, demonstrated antitumor efficacy against several breast cancer PDX models with low HER2 expression. DS-8201a exhibited a potent antitumor activity in a broad selection of HER2-positive models and favorable pharmacokinetics and safety profiles. The results demonstrate that DS-8201a will be a valuable therapy with a great potential to respond to T-DM1-insensitive HER2-positive cancers and low HER2-expressing cancers. Clin Cancer Res; 22(20); 5097-108. ©2016 AACR. ©2016 American Association for Cancer Research.

TDM interrogation of intensity-modulated USFBGs network based on multichannel lasers.

PubMed

Rohollahnejad, Jalal; Xia, Li; Cheng, Rui; Ran, Yanli; Rahubadde, Udaya; Zhou, Jiaao; Zhu, Lin

2017-01-23

We report a large-scale multi-channel fiber sensing network, where ultra-short FBGs (USFBGs) instead of conventional narrow-band ultra-weak FBGs are used as the sensors. In the time division multiplexing scheme of the network, each grating response is resolved as three adjacent discrete peaks. The central wavelengths of USFBGs are tracked with the differential detection, which is achieved by calculating the peak-to-peak ratio of two maximum peaks. Compared with previous large-scale hybrid multiplexing sensing networks (e.g., WDM/TDM) which typically have relatively low interrogation speed and very high complexity, the proposed system can achieve interrogation of all channel sensors through very fast and simple intensity measurements with a broad dynamic range. A proof-of-concept experiment with twenty USFBGs, at two wavelength channels, was performed and a fast static strain measurements were demonstrated, with a high average sensitivity of ~0.54dB/µƐ and wide dynamic range of over ~3000µƐ. The channel to channel switching time was 10ms and total network interrogation time was 50ms.

Multi-PON access network using a coarse AWG for smooth migration from TDM to WDM PON

NASA Astrophysics Data System (ADS)

Shachaf, Y.; Chang, C.-H.; Kourtessis, P.; Senior, J. M.

2007-06-01

An interoperable access network architecture based on a coarse array waveguide grating (AWG) is described, displaying dynamic wavelength assignment to manage the network load across multiple PONs. The multi-PON architecture utilizes coarse Gaussian channels of an AWG to facilitate scalability and smooth migration path between TDM and WDM PONs. Network simulations of a cross-operational protocol platform confirmed successful routing of individual PON clusters through 7 nm-wide passband windows of the AWG. Furthermore, polarization-dependent wavelength shift and phase errors of the device proved not to impose restrain on the routing performance. Optical transmission tests at 2.5 Gbit/s for distances up to 20 km are demonstrated.

WDM/TDM PON experiments using the AWG free spectral range periodicity to transmit unicast and multicast data

NASA Astrophysics Data System (ADS)

Bock, Carlos; Prat, Josep

2005-04-01

A hybrid WDM/TDM PON architecture implemented by means of two cascaded Arrayed Waveguide Gratings (AWG) is presented. Using the Free Spectral Range (FSR) periodicity of AWGs we transmit unicast and multicast traffic on different wavelengths to each Optical Network Unit (ONU). The OLT is equipped with two laser stacks, a tunable one for unicast transmission and a fixed one for multicast transmission. We propose the ONU to be reflective in order to avoid any light source at the Costumer Premises Equipment (CPE). Optical transmission tests demonstrate correct transmission at 2.5 Gbps up to 30 km.

Enhanced optical gain clamping for upstream packet based traffic on hybrid WDM/TDM-PON using fiber Bragg grating

NASA Astrophysics Data System (ADS)

Neto, B.; Klingler, A.; Reis, C.; Dionísio, R. P.; Nogueira, R. N.; Teixeira, A. L. J.; André, P. S.

2011-03-01

In this paper, we propose a method to mitigate the temporal power transients arising from Erbium doped fiber amplifiers (EDFAs) on packeted/bursty scenario. The technique, applicable on hybrid WDM/TDM-PON for extended reach, is based on a low power clamping provided by a distributed feedback (DFB) laser and a fiber Bragg grating (FBG). An improvement in the data signal Q factor was achieved keeping the clamping control signal with a low power, accompanied by a maximum reduction in the gain excursion of 1.12 dB.

High performance architecture design for large scale fibre-optic sensor arrays using distributed EDFAs and hybrid TDM/DWDM

NASA Astrophysics Data System (ADS)

Liao, Yi; Austin, Ed; Nash, Philip J.; Kingsley, Stuart A.; Richardson, David J.

2013-09-01

A distributed amplified dense wavelength division multiplexing (DWDM) array architecture is presented for interferometric fibre-optic sensor array systems. This architecture employs a distributed erbium-doped fibre amplifier (EDFA) scheme to decrease the array insertion loss, and employs time division multiplexing (TDM) at each wavelength to increase the number of sensors that can be supported. The first experimental demonstration of this system is reported including results which show the potential for multiplexing and interrogating up to 4096 sensors using a single telemetry fibre pair with good system performance. The number can be increased to 8192 by using dual pump sources.

LC-MS/MS method for the simultaneous determination of Lys-MCC-DM1, MCC-DM1 and DM1 as potential intracellular catabolites of the antibody-drug conjugate trastuzumab emtansine (T-DM1).

PubMed

Liu, Yazhong; Zhou, Fang; Sang, Hua; Ye, Hui; Chen, Qianying; Yao, Lan; Ni, Ping; Wang, Guangji; Zhang, Jingwei

2017-04-15

Lysine-MCC-DM1, MCC-DM1 and DM1 are potential catabolites of trastuzumab emtansine (T-DM1). A convenient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to detect these catabolites simultaneously in in vitro investigations for the first time. Protein precipitation was utilized to prepare the samples. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with mobile-phase gradient elution. The calibration curves of each analyte ranging from 1 to 100nM showed good linearity (r 2 >0.995). The method was validated successfully and applied to the intracellular catabolism and regulation of T-DM1. Copyright © 2017 Elsevier B.V. All rights reserved.

A Wideband Satcom Based Avionics Network with CDMA Uplink and TDM Downlink

NASA Technical Reports Server (NTRS)

Agrawal, D.; Johnson, B. S.; Madhow, U.; Ramchandran, K.; Chun, K. S.

2000-01-01

The purpose of this paper is to describe some key technical ideas behind our vision of a future satcom based digital communication network for avionics applications The key features of our design are as follows: (a) Packetized transmission to permit efficient use of system resources for multimedia traffic; (b) A time division multiplexed (TDM) satellite downlink whose physical layer is designed to operate the satellite link at maximum power efficiency. We show how powerful turbo codes (invented originally for linear modulation) can be used with nonlinear constant envelope modulation, thus permitting the satellite amplifier to operate in a power efficient nonlinear regime; (c) A code division multiple access (CDMA) satellite uplink, which permits efficient access to the satellite from multiple asynchronous users. Closed loop power control is difficult for bursty packetized traffic, especially given the large round trip delay to the satellite. We show how adaptive interference suppression techniques can be used to deal with the ensuing near-far problem; (d) Joint source-channel coding techniques are required both at the physical and the data transport layer to optimize the end-to-end performance. We describe a novel approach to multiple description image encoding at the data transport layer in this paper.

Cryogenic Propellant Storage and Transfer (CPST) Technology Maturation: Establishing a Foundation for a Technology Demonstration Mission (TDM)

NASA Technical Reports Server (NTRS)

Doherty, Michael P.; Meyer, Michael L.; Motil, Susan M.; Ginty, Carol A.

2014-01-01

As part of U.S. National Space Policy, NASA is seeking an innovative path for human space exploration, which strengthens the capability to extend human and robotic presence throughout the solar system. NASA is laying the groundwork to enable humans to safely reach multiple potential destinations, including asteroids, Lagrange points, the Moon and Mars. In support of this, NASA is embarking on the Technology Demonstration Mission Cryogenic Propellant Storage and Transfer (TDM CPST) Project to test and validate key cryogenic capabilities and technologies required for future exploration elements, opening up the architecture for large cryogenic propulsion stages (CPS) and propellant depots. The TDM CPST project will provide an on-orbit demonstration of the capability to store, transfer, and measure cryogenic propellants for a duration which is relevant to enable long term human space exploration missions beyond low Earth orbit (LEO). Recognizing that key cryogenic fluid management technologies anticipated for on-orbit (flight) demonstration needed to be matured to a readiness level appropriate for infusion into the design of the flight demonstration, the NASA Headquarters Space Technology Mission Directorate authorized funding for a one-year (FY12) ground based technology maturation program. The strategy, proposed by the CPST Project Manager, focused on maturation through modeling, studies, and ground tests of the storage and fluid transfer Cryogenic Fluid Management (CFM) technology sub-elements and components that were not already at a Technology Readiness Level (TRL) of 5. A technology maturation plan (TMP) was subsequently approved which described: the CFM technologies selected for maturation, the ground testing approach to be used, quantified success criteria of the technologies, hardware and data deliverables, and a deliverable to provide an assessment of the technology readiness after completion of the test, study or modeling activity. This paper will present

Cryogenic Propellant Storage and Transfer (CPST) Technology Maturation: Establishing a Foundation for a Technology Demonstration Mission (TDM)

NASA Technical Reports Server (NTRS)

Doherty, Michael P.; Meyer, Michael L.; Motil, Susan M.; Ginty, Carol A.

2013-01-01

As part of U.S. National Space Policy, NASA is seeking an innovative path for human space exploration, which strengthens the capability to extend human and robotic presence throughout the solar system. NASA is laying the groundwork to enable humans to safely reach multiple potential destinations, including asteroids, Lagrange points, the Moon and Mars. In support of this, NASA is embarking on the Technology Demonstration Mission Cryogenic Propellant Storage and Transfer (TDM CPST) Project to test and validate key cryogenic capabilities and technologies required for future exploration elements, opening up the architecture for large cryogenic propulsion stages (CPS) and propellant depots. The TDM CPST project will provide an on-orbit demonstration of the capability to store, transfer, and measure cryogenic propellants for a duration which is relevant to enable long term human space exploration missions beyond low Earth orbit (LEO). Recognizing that key cryogenic fluid management technologies anticipated for on-orbit (flight) demonstration needed to be matured to a readiness level appropriate for infusion into the design of the flight demonstration, the NASA Headquarters Space Technology Mission Directorate authorized funding for a one-year (FY12) ground based technology maturation program. The strategy, proposed by the CPST Project Manager, focused on maturation through modeling, studies, and ground tests of the storage and fluid transfer Cryogenic Fluid Management (CFM) technology sub-elements and components that were not already at a Technology Readiness Level (TRL) of 5. A technology maturation plan (TMP) was subsequently approved which described: the CFM technologies selected for maturation, the ground testing approach to be used, quantified success criteria of the technologies, hardware and data deliverables, and a deliverable to provide an assessment of the technology readiness after completion of the test, study or modeling activity. This paper will present

Aspects épidémiologiques, diagnostiques et thérapeutiques des ostéosarcomes de l'enfant au CHU Aristide le Dantec de Dakar: à propos de 16 cas

PubMed Central

Ndour, Oumar; Alumeti, Desire Munyali; Fall, Mbaye; Fall, Aimée Faye; Diouf, Cheikh; Ndoye, Ndeye Aby; Ngom, Gabriel; Ndoye, Mamadou

2013-01-01

Le but de cette étude était de décrire les aspects épidémiologiques, diagnostiques et thérapeutiques des ostéosarcomes de l'enfant. Il s'agissait d'une étude rétrospective sur dix ans qui a colligé 16 dossiers d'ostéosarcome pris en charge au service de Chirurgie Pédiatrique de l'hôpital Aristide Le Dantec de Dakar. Les paramètres étudiés étaient le niveau d'instruction et le niveau socioprofessionnel des parents, l'origine géographique, l’âge, le sexe, les antécédents particuliers, le délai de consultation, les motifs de consultation, les signes physiques, les signes radiologiques, la biologie, les modalités thérapeutiques et l’évolution. Tous les patients avaient bénéficié d'un examen anatomopathologique qui a confirmé le diagnostic d'ostéosarcome. Pour la majeure partie de nos patients (58% des cas) les parents avaient un niveau d'instruction bas. L’âge moyen était de 11ans. Une prédominance masculine était retrouvée avec un sex-ratio de 3,25:1. Le délai de consultation moyen était de 16 mois. Le principal motif de consultation était la tuméfaction (10 cas). Huit patients avaient bénéficié d'un traitement traditionnel. La taille de la tumeur était supérieure à 10cm dans 14 cas. La localisation la plus fréquente était le genou (14 cas). La radiographie standard retrouvait dans 15 cas des images d'ostéolyse. Le bilan d'extension n'avait pas retrouvé de métastases. Les options thérapeutiques étaient dominées par l'amputation seule (43,75% des cas). La survie à 2 ans était de 17%. L'ostéosarcome atteint le plus souvent le garçon après l’âge de 10 ans. Sa prise en charge au Sénégal se heurte à d’énormes difficultés liées au retard diagnostique. La solution repose essentiellement sur une collaboration pluridisciplinaire. PMID:23720705

Addressing BI Transactional Flows in the Real-Time Enterprise Using GoldenGate TDM

NASA Astrophysics Data System (ADS)

Pareek, Alok

It's time to visit low latency and reliable real-time (RT) infrastructures to support next generation BI applications instead of continually debating the need and notion of real-time. The last few years have illuminated some key paradigms affecting data management. The arguments put forth to move away from traditional DBMS architectures have proven persuasive - and specialized architectural data stores are being adopted in the industry [1]. The change from traditional database pull methods towards intelligent routing/push models is underway, causing applications to be redesigned, redeployed, and re-architected. One direct result of this is that despite original warnings about replication [2] - enterprises continue to deploy multiple replicas to support both performance, and high availability of RT applications, with an added complexity around manageability of heterogeneous computing systems. The enterprise is overflowing with data streams that require instantaneous processing and integration, to deliver faster visibility and invoke conjoined actions for RT decision making, resulting in deployment of advanced BI applications as can be seen by stream processing over RT feeds from operational systems for CEP [3]. Given these various paradigms, a multitude of new challenges and requirements have emerged, thereby necessitating different approaches to management of RT applications for BI. The purpose of this paper is to offer a viewpoint on how RT affects critical operational applications, evolves the weight of non-critical applications, and pressurizes availability/data-movement requirements in the underlying infrastructure. I will discuss how the GoldenGate TDM platform is being deployed within the RTE to manage some of these challenges particularly around RT dissemination of transactional data to reduce latency in data integration flows, to enable real-time reporting/DW, and to increase availability of underlying operational systems. Real world case studies will be

Technology Maturation in Preparation for the Cryogenic Propellant Storage and Transfer (CPST) Technology Demonstration Mission (TDM)

NASA Technical Reports Server (NTRS)

Meyer, Michael L.; Doherty, Michael P.; Moder, Jeffrey P.

2014-01-01

In support of its goal to find an innovative path for human space exploration, NASA embarked on the Cryogenic Propellant Storage and Transfer (CPST) Project, a Technology Demonstration Mission (TDM) to test and validate key cryogenic capabilities and technologies required for future exploration elements, opening up the architecture for large in-space cryogenic propulsion stages and propellant depots. Recognizing that key Cryogenic Fluid Management (CFM) technologies anticipated for on-orbit (flight) demonstration would benefit from additional maturation to a readiness level appropriate for infusion into the design of the flight demonstration, the NASA Headquarters Space Technology Mission Directorate (STMD) authorized funding for a one-year technology maturation phase of the CPST project. The strategy, proposed by the CPST Project Manager, focused on maturation through modeling, concept studies, and ground tests of the storage and fluid transfer of CFM technology sub-elements and components that were lower than a Technology Readiness Level (TRL) of 5. A technology maturation plan (TMP) was subsequently approved which described: the CFM technologies selected for maturation, the ground testing approach to be used, quantified success criteria of the technologies, hardware and data deliverables, and a deliverable to provide an assessment of the technology readiness after completion of the test, study or modeling activity. The specific technologies selected were grouped into five major categories: thick multilayer insulation, tank applied active thermal control, cryogenic fluid transfer, propellant gauging, and analytical tool development. Based on the success of the technology maturation efforts, the CPST project was approved to proceed to flight system development.

Definition of technology development missions for early space station, orbit transfer vehicle servicing. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1983-01-01

Orbital Transfer Vehicle (OTV) servicing study scope, propellant transfer, storage and reliquefaction technology development missions (TDM), docking and berthing TDM, maintenance TDM, OTV/payload integration TDM, combined TDMS design, summary space station accomodations, programmatic analysis, and TDM equipment operational usage are discussed.

Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study.

PubMed

Perez, Edith A; Barrios, Carlos; Eiermann, Wolfgang; Toi, Masakazu; Im, Young-Hyuck; Conte, Pierfranco; Martin, Miguel; Pienkowski, Tadeusz; Pivot, Xavier; Burris, Howard; Petersen, Jennifer A; Stanzel, Sven; Strasak, Alexander; Patre, Monika; Ellis, Paul

2017-01-10

Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast

Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2–Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study

PubMed Central

Perez, Edith A.; Barrios, Carlos; Eiermann, Wolfgang; Toi, Masakazu; Im, Young-Hyuck; Conte, Pierfranco; Martin, Miguel; Pienkowski, Tadeusz; Pivot, Xavier; Burris, Howard; Petersen, Jennifer A.; Stanzel, Sven; Strasak, Alexander; Patre, Monika; Ellis, Paul

2017-01-01

Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) –targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast

Neutrophils Promote Mycobacterial Trehalose Dimycolate-Induced Lung Inflammation via the Mincle Pathway

PubMed Central

Lee, Wook-Bin; Kang, Ji-Seon; Yan, Ji-Jing; Lee, Myeong Sup; Jeon, Bo-Young; Cho, Sang-Nae; Kim, Young-Joon

2012-01-01

Trehalose 6,6′-dimycolate (TDM), a cord factor of Mycobacterium tuberculosis (Mtb), is an important regulator of immune responses during Mtb infections. Macrophages recognize TDM through the Mincle receptor and initiate TDM-induced inflammatory responses, leading to lung granuloma formation. Although various immune cells are recruited to lung granulomas, the roles of other immune cells, especially during the initial process of TDM-induced inflammation, are not clear. In this study, Mincle signaling on neutrophils played an important role in TDM-induced lung inflammation by promoting adhesion and innate immune responses. Neutrophils were recruited during the early stage of lung inflammation following TDM-induced granuloma formation. Mincle expression on neutrophils was required for infiltration of TDM-challenged sites in a granuloma model induced by TDM-coated-beads. TDM-induced Mincle signaling on neutrophils increased cell adherence by enhancing F-actin polymerization and CD11b/CD18 surface expression. The TDM-induced effects were dependent on Src, Syk, and MAPK/ERK kinases (MEK). Moreover, coactivation of the Mincle and TLR2 pathways by TDM and Pam3CSK4 treatment synergistically induced CD11b/CD18 surface expression, reactive oxygen species, and TNFα production by neutrophils. These synergistically-enhanced immune responses correlated with the degree of Mincle expression on neutrophil surfaces. The physiological relevance of the Mincle-mediated anti-TDM immune response was confirmed by defective immune responses in Mincle−/− mice upon aerosol infections with Mtb. Mincle-mutant mice had higher inflammation levels and mycobacterial loads than WT mice. Neutrophil depletion with anti-Ly6G antibody caused a reduction in IL-6 and monocyte chemotactic protein-1 expression upon TDM treatment, and reduced levels of immune cell recruitment during the initial stage of infection. These findings suggest a new role of Mincle signaling on neutrophils during anti

Intact molecular characterization of cord factor (trehalose 6,6'-dimycolate) from nine species of mycobacteria by MALDI-TOF mass spectrometry.

PubMed

Fujita, Yukiko; Naka, Takashi; McNeil, Michael R; Yano, Ikuya

2005-10-01

Cord factor (trehalose 6,6'-dimycolate, TDM) is an unique glycolipid with a trehalose and two molecules of mycolic acids in the mycobacterial cell envelope. Since TDM consists of two molecules of very long branched-chain 3-hydroxy fatty acids, the molecular mass ranges widely and in a complex manner. To characterize the molecular structure of TDM precisely and simply, an attempt was made to determine the mycolic acid subclasses of TDM and the molecular species composition of intact TDM by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for the first time. The results showed that less than 1 microg mycolic acid methyl ester of TDM from nine representative species of mycobacteria and TDM from the same species was sufficient to obtain well-resolved mass spectra composed of pseudomolecular ions [M+Na]+. Although the mass ion distribution was extremely diverse, the molecular species of each TDM was identified clearly by constructing a molecular ion matrix consisting of the combination of two molecules of mycolic acids. The results showed a marked difference in the molecular structure of TDM among mycobacterial species and subspecies. TDM from Mycobacterium tuberculosis (H37Rv and Aoyama B) showed a distinctive mass pattern and consisted of over 60 molecular ions with alpha-, methoxy- and ketomycolate. TDM from Mycobacterium bovis BCG Tokyo 172 similarly showed over 35 molecular ions, but that from M. bovis BCG Connaught showed simpler molecular ion clusters consisting of less than 35 molecular species due to a complete lack of methoxymycolate. Mass ions due to TDM from M. bovis BCG Connaught and Mycobacterium kansasii showed a biphasic distribution, but the two major peaks of TDM from M. kansasii were shifted up two or three carbon units higher compared with M. bovis BCG Connaught. Within the rapid grower group, in TDM consisting of alpha-, keto- and wax ester mycolate from Mycobacterium phlei and Mycobacterium flavescens, the

Patch testing to a textile dye mix by the international contact dermatitis research group.

PubMed

Isaksson, Marléne; Ale, Iris; Andersen, Klaus E; Diepgen, Thomas; Goh, Chee-Leok; Goossens R, An; Jerajani, Hemangi; Maibach, Howard I; Sasseville, Denis; Bruze, Magnus

2015-01-01

Disperse dyes are well-known contact sensitizers not included in the majority of commercially available baseline series. To investigate the outcome of patch testing to a textile dye mix (TDM) consisting of 8 disperse dyes. Two thousand four hundred ninety-three consecutive dermatitis patients in 9 dermatology clinics were patch tested with a TDM 6.6%, consisting of Disperse (D) Blue 35, D Yellow 3, D Orange 1 and 3, D Red 1 and 17, all 1.0% each, and D Blue 106 and D Blue 124, each 0.3%. 90 reacted positively to the TDM. About 92.2% of the patients allergic to the TDM were also tested with the 8 separate dyes. Contact allergy to TDM was found in 3.6% (1.3-18.2) Simultaneous reactivity to p-phenylenediamine was found in 61.1% of the TDM-positive patients. Contact allergy to TDM and not to other p-amino-substituted sensitizers was diagnosed in 1.2%. The most frequent dye allergen in the TDM-positive patients was D Orange 3. Over 30% of the TDM allergic patients had been missed if only the international baseline series was tested. Contact allergy to TDM could explain or contribute to dermatitis in over 20% of the patients. Textile dye mix should be considered for inclusion into the international baseline series.

Textilome abdominal, à propos d'un cas

PubMed Central

Erguibi, Driss; Hassan, Robleh; Ajbal, Mohamed; Kadiri, Bouchaib

2015-01-01

Le textilome, également appelé gossybipomas, est une complication postopératoire très rare. Il peut s'agir d'un corps étranger composé de compresse(s) ou champ(s) chirurgicaux oubliés au niveau d'un foyer opératoire. Ils sont plus souvent asymptomatiques, et difficile à diagnostiquer. En particulier, les cas chroniques ne présentent pas de signes cliniques et radiologiques spécifiques pour le diagnostic différentiel. L'anamnèse est donc indispensable pour le diagnostic vu que les signes cliniques ne sont pas concluants. Le cliché d'abdomen sans préparation est peu contributif, l’échographie est fiable. La tomodensitométrie permet un diagnostic topographique précis, mais ce n'est pas toujours le cas. Certaines équipes proposent des explorations par IRM. Nous rapportons un cas de textilome intra abdominal, chez une patiente de 31 ans opérée il y a 8 ans pour grossesse extra-utérine, chez qui la TDM abdomino-pelvienne a évoqué un kyste hydatique péritonéale sans localisation du foie. Traitée par extrait d'un petit champ de 25x15cm et adhérant au sigmoïde. Le but de ce travail est de mettre en évidence le problème de diagnostic de cette pathologie et l'importance de la laparotomie exploratrice. PMID:26523184

Association of pellicle growth morphological characteristics and clinical presentation of Mycobacterium tuberculosis isolates.

PubMed

Arora, Ranjana; Armitige, Lisa; Wanger, Audrey; Hunter, Robert L; Hwang, Shen-An

2016-12-01

Trehalose 6,6'dimycolate (TDM) is a glycolipid found in nearly pure form on the surface of virulent Mycobacterium tuberculosis (MTB). This manuscript investigated the production of TDM, growth rate and colony morphology of multiple strains of MTB, each of which had been isolated from both pulmonary (sputum) and extrapulmonary sites of multiple patients. Since sputum contains MTB primarily from cavities and extrapulmonary biopsies are typically granulomas, this provided an opportunity to compare the behavior of single strains of MTB that had been isolated from cavities and granulomas. The results demonstrated that MTB isolated from pulmonary sites produced more TDM (3.23 ± 1.75 μg TDM/mg MTB), grew more rapidly as thin spreading pellicles, demonstrated early cording, and climbed culture well walls. In contrast, extrapulmonary isolates produced less TDM (1.42 ± 0.58 μg TDM/mg MTB) (p < 0.001) and grew as discrete patches with little tendency to spread or climb. Both Beijing pulmonary isolates and the non-Beijing pulmonary isolates produced significantly more TDM (1.64 ± 0.46 μg TDM/mg MTB) and grew faster than the Beijing and non-Beijing extrapulmonary isolates (1.14 ± 0.63 μg TDM/mg MTB) (p < 0.001 and p < 0.005 respectively). These results indicate that MTB from pulmonary sites (cavities) grows faster and produces more TDM than strains isolated from extrapulmonary sites (granulomas). This report suggests a critical role for TDM in cavitary TB. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Therapeutic drug monitoring in epileptology and psychiatry].

PubMed

Brandt, C; Baumann, P; Eckermann, G; Hiemke, C; May, T W; Rambeck, B; Pohlmann-Eden, B

2008-02-01

Experts from epileptology and psychiatry reviewed the current significance of therapeutic drug monitoring (TDM) of antiepileptic drugs and psychiatric drugs in a workshop at Bethel Epilepsy Centre in December 2005. TDM has been essential in epileptology for about 30 years, and it is also increasingly important in psychiatry, in which consensus recommendations were published recently. With regard to cost-cutting in the health system, there are discussions about the financial effect of TDM and outsourcing it to bigger laboratories. In psychiatry it has however been shown that sensibly used TDM may lead to reduced costs. Many issues in TDM require the knowledge and experience of specialised laboratories. The use of TDM data for scientific purposes was discussed at the workshop as well.

A Critical Commentary on the 2017 AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology.

PubMed

de Leon, Jose

2018-01-01

In 2004, 2011, and 2017, the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP), a group of German-speaking psychiatric researchers and psychiatrists, published successive versions of therapeutic drug monitoring (TDM) expert group consensus guidelines. The 2017 version has as a major strength its encyclopedic nature, including 1358 references. The guideline has 3 major sections: 1) theoretical aspects of TDM, 2) drug concentration levels in blood to guide neuropsychopharmacotherapy, and 3) practical aspects of TDM in psychiatry and neurology. The writer hopes the time is right for a TDM guideline in psychiatry, which is indicated for: 1) psychiatric researchers ready to value how TDM can contribute to moving psychopharmacology forward, 2) flexible clinicians ready to improve their patient care by personalizing dosing, and 3) today's psychiatry residents prepared as a new generation ready to be trained in TDM and willing to continue incorporating TDM as new psychiatric drugs are marketed. © Georg Thieme Verlag KG Stuttgart · New York.

Antipsychotic therapeutic drug monitoring: psychiatrists’ attitudes and factors predicting likely future use

PubMed Central

Law, Suzanne; Haddad, Peter M.; Chaudhry, Imran B.; Husain, Nusrat; Drake, Richard J.; Flanagan, Robert J.; David, Anthony S.

2015-01-01

Background: This study aimed to explore predictive factors for future use of therapeutic drug monitoring (TDM) and to further examine psychiatrists’ current prescribing practices and perspectives regarding antipsychotic TDM using plasma concentrations. Method: A cross-sectional study for consultant psychiatrists using a postal questionnaire was conducted in north-west England. Data were combined with those of a previous London-based study and principal axis factor analysis was conducted to identify predictors of future use of TDM. Results: Most of the 181 participants (82.9%, 95% confidence interval 76.7–87.7%) agreed that ‘if TDM for antipsychotics were readily available, I would use it’. Factor analysis identified five factors from the original 35 items regarding TDM. Four of the factors significantly predicted likely future use of antipsychotic TDM and together explained 40% of the variance in a multivariate linear regression model. Likely future use increased with positive attitudes and expectations, and decreased with potential barriers, negative attitudes and negative expectations. Scientific perspectives of TDM and psychiatrist characteristics were not significant predictors. Conclusion: Most senior psychiatrists indicated that they would use antipsychotic TDM if available. However, psychiatrists’ attitudes and expectations and the potential barriers need to be addressed, in addition to the scientific evidence, before widespread use of antipsychotic TDM is likely in clinical practice. PMID:26301077

Definition of technology development missions for early space station, orbit transfer vehicle servicing, volume 2

NASA Technical Reports Server (NTRS)

1983-01-01

Propellant transfer, storage, and reliquefaction TDM; docking and berthing technology development mission; maintenance technology development mission; OTV/payload integration, space station interface/accommodations; combined TDM conceptual design; programmatic analysis; and TDM equipment usage are discussed.

Treatment decision-making in the medical encounter: comparing the attitudes of French surgeons and their patients in breast cancer care.

PubMed

Nguyen, Florence; Moumjid, Nora; Charles, Cathy; Gafni, Amiram; Whelan, Tim; Carrère, Marie-Odile

2014-02-01

To explore attitudes of French surgeons and their patients towards treatment decision-making (TDM) in the medical encounter. Surgeons involved in early stage breast cancer and their patients treated in a French cancer care network received a cross-sectional survey questionnaire containing examples of four different approaches to TDM: paternalistic, "some sharing", informed TDM and, shared TDM. Surgeons' interaction styles were clearly distributed among paternalistic, shared and mixed. The paternalistic approach seemed to be associated with private rather than public practice and with less professional experience. Patients reported a rather low level of participation in TDM, varying by socio-demographic characteristics. One third of patients were dissatisfied with the way their treatment decision had been made. Most surgeons reported adopting the "some sharing" approach. However, one patient out of three reported that they would have liked to participate more in the TDM process. Surgeons need to ask patients what their preferences for involvement in TDM are and then think about ways to accommodate both their own and patients' preferences regarding the TDM process to be used in each encounter. In addition, decision aids could be offered to surgeons to help them discuss treatment options with their patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017.

PubMed

Hiemke, C; Bergemann, N; Clement, H W; Conca, A; Deckert, J; Domschke, K; Eckermann, G; Egberts, K; Gerlach, M; Greiner, C; Gründer, G; Haen, E; Havemann-Reinecke, U; Hefner, G; Helmer, R; Janssen, G; Jaquenoud, E; Laux, G; Messer, T; Mössner, R; Müller, M J; Paulzen, M; Pfuhlmann, B; Riederer, P; Saria, A; Schoppek, B; Schoretsanitis, G; Schwarz, M; Gracia, M Silva; Stegmann, B; Steimer, W; Stingl, J C; Uhr, M; Ulrich, S; Unterecker, S; Waschgler, R; Zernig, G; Zurek, G; Baumann, P

2018-01-01

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs. © Georg Thieme Verlag KG Stuttgart · New York.

Therapeutic drug monitoring in the past 40 years of the Journal of Antimicrobial Chemotherapy.

PubMed

Reeves, David; Lovering, Andrew; Thomson, Alison

2016-12-01

Since the Journal of Antimicrobial Chemotherapy was first published in 1975, papers addressing therapeutic drug monitoring (TDM) have been a regular feature. Initially they focused on laboratory aspects of drug concentration measurement then they changed more to the application of TDM in a clinical setting. Over its history, the Journal has provided its readership with the latest technological and scientific advances in TDM and has helped to drive changes in TDM that have directly impacted on patient care. These have varied from improvement in the quality of antimicrobial measurements through better identification of dosage regimens and TDM targets that help predict outcome and adverse events. Despite these advances in our understanding of the science and practice of TDM, there remain many areas of uncertainty. As we move into the next 40 years, it is clear that the Journal will continue to provide the readership with the latest science and opinion in this important area. © Crown copyright 2016.

Gambling with your life: the process of breast cancer treatment decision making in Chinese women.

PubMed

Lam, Wendy Wt; Fielding, Richard; Chan, Miranda; Chow, Louis; Or, Amy

2005-01-01

Treatment decision making (TDM) studies have primarily focused on assessing TDM quality and predominantly presume rational analytic processes as the gold standard. In a grounded theory study of 22 Hong Kong Chinese women following breast surgery who completed an in-depth interview exploring the process of TDM in breast cancer (BC), narrative data showed that discovery of a breast abnormality and emotional responses to BC diagnosis influence the TDM process. Lack of guidance from surgeons impaired TDM. Decisions were, for the most part, made using intuitive, pragmatic and emotionally driven criteria in the absence of complete information. The experience of TDM, which was likened to gambling, did not end once the decision was made but unfolded while waiting for surgery and the post-operative report. In this waiting period, women were emotionally overwhelmed by fear of death and the uncertainty of the surgical outcome, and equivocated over whether they had made the 'right' choice. This suggests that Chinese women feel they are gambling with their lives during TDM. These women are particularly emotionally vulnerable whilst waiting for their surgery and the post-surgical clinical pathology results. Providing emotional support is particularly important at this time when these women are overwhelmed by uncertainty. 2004 John Wiley & Sons, Ltd.

Atmospheric modeling to assess wind dependence in tracer dilution method measurements of landfill methane emissions.

PubMed

Taylor, Diane M; Chow, Fotini K; Delkash, Madjid; Imhoff, Paul T

2018-03-01

The short-term temporal variability of landfill methane emissions is not well understood due to uncertainty in measurement methods. Significant variability is seen over short-term measurement campaigns with the tracer dilution method (TDM), but this variability may be due in part to measurement error rather than fluctuations in the actual landfill emissions. In this study, landfill methane emissions and TDM-measured emissions are simulated over a real landfill in Delaware, USA using the Weather Research and Forecasting model (WRF) for two emissions scenarios. In the steady emissions scenario, a constant landfill emissions rate is prescribed at each model grid point on the surface of the landfill. In the unsteady emissions scenario, emissions are calculated at each time step as a function of the local surface wind speed, resulting in variable emissions over each 1.5-h measurement period. The simulation output is used to assess the standard deviation and percent error of the TDM-measured emissions. Eight measurement periods are simulated over two different days to look at different conditions. Results show that standard deviation of the TDM- measured emissions does not increase significantly from the steady emissions simulations to the unsteady emissions scenarios, indicating that the TDM may have inherent errors in its prediction of emissions fluctuations. Results also show that TDM error does not increase significantly from the steady to the unsteady emissions simulations. This indicates that introducing variability to the landfill emissions does not increase errors in the TDM at this site. Across all simulations, TDM errors range from -15% to 43%, consistent with the range of errors seen in previous TDM studies. Simulations indicate diurnal variations of methane emissions when wind effects are significant, which may be important when developing daily and annual emissions estimates from limited field data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Therapeutic Drug Monitoring Guides the Management of Crohn's Patients with Secondary Loss of Response to Adalimumab.

PubMed

Restellini, Sophie; Chao, Che-Yung; Lakatos, Peter L; Aruljothy, Achuthan; Aziz, Haya; Kherad, Omar; Bitton, Alain; Wild, Gary; Afif, Waqqas; Bessissow, Talat

2018-04-13

Managing loss of response (LOR) in Crohn's disase (CD) patients remains challenging. Compelling evidence supports therapeutic drug monitoring (TDM) to guide management in patients on infliximab, but data for other biologics are less robust. We aimed to asses if empiric dose escalation led to improved clinical outcome in addition to TDM-guided optimization in CD patients with LOR to adalimumab (ADA). Retrospective chart review of patients followed between 2014 and 2016 at McGill IBD Center with index TDM for LOR to ADA was performed. Primary outcomes were composite remission at 3, 6, and 12 months in those with empiric adjustments versus TDM-guided optimization. There were 104 patients (54.8% men) who were included in the study. Of this group, 81 patients (77.9%) had serum level (SL) ≥5µg/ml at index TDM with a median value of 12µg/ml (IQR 6.1-16.5). There were 10 patients (9.6%) who had undetectable SL with high anti-ADA antibodies and 48 (46.2%) received empiric escalation. TDM led to change in treatment in 58 patients (55.8%). Among them, 28 (48.3%) had discontinued ADA, 12 (21.7%) had addition of immunomodulator or steroid, and 18 (31%) had ADA dose escalation. Empiric dose escalation before TDM-based optimization was not associated with improved outcomes at 3, 6, and 12 months, irrespective of SL levels. Clear SL cutoff associated with composite remission was not identified. Our data do not support empiric dose adjustment beyond that based on the result of the TDM in patients with LOR to ADA. TDM limits unnecessary dose escalation and provides appropriate treatment strategy without compromising clinical outcomes. 10.1093/ibd/izy044_video1izy044.video15768828880001.

Who is at risk of death from nephrectomy? An analysis of thirty-day mortality after 21 380 nephrectomies in 3 years of the British Association of Urological Surgeons (BAUS) National Nephrectomy Audit.

PubMed

Fernando, Archie; Fowler, Sarah; Van Hemelrijck, Mieke; O'Brien, Tim

2017-09-01

To ascertain contemporary overall and differential thirty-day mortality (TDM) rates after all types of nephrectomy in the UK, and to identify potential new risk factors for death. We conducted a retrospective analysis of the 110 deaths that occurred within 30 days of surgery out of the total of 21 380 nephrectomies performed, and calculated the odds ratio (OR) and 95% confidence interval (CI) for TDM based on peri-operative characteristics. The overall TDM rate was 110/21380 (0.5%). The TDM rates after radical, partial, simple nephrectomy and nephro-ureterectomy were 0.6% (63/11057), 0.1% (4/3931), 0.4% (11/2819) and 0.9% (28/3091), respectively. TDM increased with age, stage, estimated blood loss (EBL), operating time and performance status. EBL of 1-2 L was associated with a greater risk of TDM than EBL of 2-5 L (OR 1.38; 95% CI 1.03-2.24). Conversion from minimally invasive surgery was associated with higher risk than non-conversion (OR 2.53; 95% CI 1.14-4.51. Curative surgery was safer than cytoreductive surgery (OR 0.31; 95% CI 0.18-0.54). There was an association between surgical volume and TDM. This study provides contemporary insights into the true risks of all types of nephrectomy. The TDM rate after nephrectomy in the UK appears acceptably low at 0.5%. Established risk factors were confirmed and the following novel risk factors were identified: modest EBL (1-2 L) and conversion from minimally invasive surgery. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Coronary bypass graft patency in patients with diabetes in the Bypass Angioplasty Revascularization Investigation (BARI).

PubMed

Schwartz, Leonard; Kip, Kevin E; Frye, Robert L; Alderman, Edwin L; Schaff, Hartzell V; Detre, Katherine M

2002-11-19

Few studies have compared long-term status of bypass grafts between patients with and without diabetes, and uncertainty exists as to whether diabetes independently predicts poor clinical outcome after CABG. Among 1526 patients in BARI who underwent CABG as initial revascularization, 99 of 292 (34%) with treated diabetes mellitus (TDM) (those on insulin or oral hypoglycemic agents) and 469 of 1234 (38%) without TDM had follow-up angiography. Angiograms with the longest interval from initial surgery and before any percutaneous graft intervention (mean 3.9 years) were reviewed. An average of 3.0 grafts were placed at initial CABG for patients with TDM (n=297; internal mammary artery [IMA], 33%) and 2.9 grafts for patients without TDM (n=1347; IMA, 34%). Patients with TDM were more likely than those without to have small (<1.5 mm) grafted distal vessels (29% versus 22%) and vessels of poor quality (9% versus 6%). On follow-up angiography, 89% of IMA grafts were free of stenoses > or =50% among patients with TDM versus 85% among patients without TDM (P=0.23). For vein grafts, the corresponding percentages were 71% versus 75% (P=0.40). After statistical adjustment, TDM was unrelated to having a graft stenosis > or =50% (adjusted odds ratio, 0.87; 95% CI, 0.58 to 1.32). Despite diabetic patients' having smaller distal vessels and vessels judged to be of poorer quality, diabetes does not appear to adversely affect patency of IMA or vein grafts over an average of 4-year follow-up. Previously observed differences in survival between CABG-treated patients with and without diabetes may be largely a result of differential risk of mortality from noncardiac causes.

Therapeutic drug monitoring of antitubercular agents for disseminated Mycobacterium tuberculosis during intermittent haemodialysis and continuous venovenous haemofiltration.

PubMed

Sin, J H; Elshaboury, R H; Hurtado, R M; Letourneau, A R; Gandhi, R G

2018-04-01

There is a lack of data regarding therapeutic drug monitoring (TDM) of antitubercular agents in the setting of continuous venovenous haemofiltration (CVVH). We describe TDM results of numerous antitubercular agents in a critically ill patient during CVVH and haemodialysis. A 49-year-old man was initiated on treatment for disseminated Mycobacterium tuberculosis. During hospital admission, the patient developed critical illness and required renal replacement therapy. TDM results and pharmacokinetic calculations showed adequate serum concentrations of rifampin, ethambutol and amikacin during CVVH and of rifampin, pyrazinamide, ethambutol and levofloxacin during intermittent haemodialysis. The presence of critical illness and renal replacement therapy can induce pharmacokinetic changes that may warrant vigilant TDM to ensure optimal therapy. To our knowledge, this is the first report to describe TDM for several antitubercular agents during CVVH in a critically patient with disseminated M. tuberculosis. © 2017 John Wiley & Sons Ltd.

Développement d’un programme multidisciplinaire de diagnostic de l’adrénoleucodystrophie liée à l’X au Maroc: résultats de la mise en œuvre du programme de diagnostic clinique et biologique

PubMed Central

Benjelloun, Fatima-Zohra Madani; Chabraoui, Layachi; Kriouile, Yamna

2017-01-01

Introduction L'adrénoleucodystrophie liée à l'X (X-ALD) est une maladie neurodégénérative sévère, due à des mutations du gène ABCD1. Elle se manifeste par une atteinte du système nerveux central et périphérique, une insuffisance surrénalienne et une atteinte des testicules chez le garçon. Son diagnostic repose sur le dosage des Acides Gras à Très Longue Chaine. Le diagnostic précoce est d'une grande importance puisque il définit l'accessibilité aux traitements selon le stage de la maladie. Méthodes Nous avons mis en place un programme de diagnostic de l'X-ALD au Maroc au niveau de l'Hôpital d'enfants et du Laboratoire centrale des maladies héréditaires et du métabolisme de Rabat. Le programme s'articule sur trois axes à savoir : le recrutement des patients, le diagnostic et la sensibilisation. Le diagnostic s'effectue selon trois protocoles : un protocole pour les cas symptomatiques, un deuxième pour les cas asymptomatiques et un troisième pour les femmes hétérozygotes. Résultats Durant trois ans après la mise en place de notre programme de diagnostic de l'Adrénoleucodystrophie liée à l'X, nous avons diagnostiqué la maladie chez sept familles, avec neuf garçons et trois femmes hétérozygotes. Tous les enfants diagnostiqués présentaient la forme cérébrale démyélinisante. Toutes les femmes hétérozygotes étaient asymptomatiques. Une prise en charge thérapeutique a été mise place selon la symptomatologie de chaque cas. Conclusion l'X-ALD est une maladie rare. Notre programme de diagnostique a permis de diagnostiquer un nombre important de cas, ce qui montre son importance. Les compagnes de sensibilisation auprès des professionnels permettront de mieux comprendre la maladie et mieux la diagnostiquer et ainsi donner accès à un nombre plus élevé de patients. PMID:29599883

Large-Scale Variability of Inpatient Tacrolimus Therapeutic Drug Monitoring at an Academic Transplant Center: a Retrospective Study.

PubMed

Strohbehn, Garth W; Pan, Warren W; Petrilli, Christopher M; Heidemann, Lauren; Larson, Sophia; Aaronson, Keith D; Johnson, Matt; Ellies, Tammy; Heung, Michael

2018-04-30

Inpatient tacrolimus therapeutic drug monitoring (TDM) lacks standardized guidelines. In this study, the authors analyzed variability in the pre-analytical phase of the inpatient tacrolimus TDM process at their institution. Patients receiving tacrolimus (twice-daily formulation) and tacrolimus laboratory analysis were included in the study. Times of tacrolimus administration and laboratory study collection were extracted and time distribution plots for each step in the inpatient TDM process were generated. Trough levels were drawn appropriately in 25.9% of the cases. Timing between doses was consistent, with 91.9% of the following dose administrations occurring 12 +/- 2 hours after the previous dose. Only 38.1% of the drug administrations occurred within one hour of laboratory study collection. Tacrolimus-related patient safety events were reported at a rate of 1.9 events per month while incorrect timing of TDM sample collection occurred approximately 200 times per month. Root cause analysis identified a TDM process marked by a lack of communication and coordination of drug administration and TDM sample collection. Extrapolating findings nationwide, we estimate $22 million in laboratory costs wasted annually. Based on this large single-center study, the authors concluded that the inpatient TDM process is prone to timing errors, thus is financially wasteful, and at its worst harmful to patients due to clinical decisions being made on the basis of unreliable data. Further work is needed on systems solutions to better align the laboratory study collection and drug administration processes.

Therapeutic drug monitoring of anti-infective agents in critically ill patients.

PubMed

Jager, Nynke G L; van Hest, Reinier M; Lipman, Jeffrey; Taccone, Fabio S; Roberts, Jason A

2016-07-01

Initial adequate anti-infective therapy is associated with significantly improved clinical outcomes for patients with severe infections. However, in critically ill patients, several pathophysiological and/or iatrogenic factors may affect the pharmacokinetics of anti-infective agents leading to suboptimal drug exposure, in particular during the early phase of therapy. Therapeutic drug monitoring (TDM) may assist to overcome this problem. We discuss the available evidence on the use of TDM in critically ill patient populations for a number of anti-infective agents, including aminoglycosides, β-lactams, glycopeptides, antifungals and antivirals. Also, we present the available evidence on the practices of anti-infective TDM and describe the potential utility of TDM to improve treatment outcome in critically ill patients with severe infections. For aminoglycosides, glycopeptides and voriconazole, beneficial effects of TDM have been established on both drug effectiveness and potential side effects. However, for other drugs, therapeutic ranges need to be further defined to optimize treatment prescription in this setting.

Leveraging the trusted clinician: documenting disease management program enrollment.

PubMed

Frazee, Sharon Glave; Kirkpatrick, Patricia; Fabius, Raymond; Chimera, Joseph

2007-02-01

The objective of this study was to test the hypothesis that an integrated disease management (IDM) protocol (patent-pending), which combines telephonic-delivered disease management (TDM) with a worksite-based primary care center and pharmacy delivery, would yield higher contact and enrollment rates than traditional remote disease management alone. IDM is characterized by the combination of standard TDM with a worksite-based primary care and pharmacy delivery protocol led by trusted clinicians. This prospective cohort study tracks contact and enrollment rates for persons assigned to either IDM or traditional TDM protocols, and compares them on contact and enrollment efficiency. The IDM protocol showed a significant improvement in contact and enrollment rates over traditional TDM. Integrating a worksite-based primary care and pharmacy delivery system led by trusted clinicians with traditional TDM increases contact and enrollment rates, resulting in higher patient engagement. The IDM protocol should be adopted by employers seeking higher returns on their investment in disease management programming.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McChesney, D.G.; Ledney, G.D.; Madonna, G.S.

The survival of B6D2F1 female mice exposed to lethal doses of fission neutron radiation is increased when trehalose dimycolate (TDM) preparations are given either 1 h after exposure or 1 day before exposure to radiation. TDM in an emulsion of squalene, Tween 80, and saline was the most effective formulation for increasing the 30-day survival of mice when given 1 day before (90%) or 1 h after (88%) exposure to radiation. An aqueous suspension of a synthetic analog of TDM was less effective at increasing 30-day survival (60%) when given 1 day prior to radiation exposure and not effective whenmore » given 1 h after radiation. Mice receiving a sublethal dose (3.5 Gy) of fission neutron radiation and either the TDM emulsion or synthetic TDM 1 h after irradiation were substantially more resistant to challenge with 10, 100, 1000, or 5000 times the LD50/30 dose of Klebsiella pneumoniae than untreated mice.« less

Trastuzumab emtansine delays and overcomes resistance to the third-generation EGFR-TKI osimertinib in NSCLC EGFR mutated cell lines.

PubMed

La Monica, Silvia; Cretella, Daniele; Bonelli, Mara; Fumarola, Claudia; Cavazzoni, Andrea; Digiacomo, Graziana; Flammini, Lisa; Barocelli, Elisabetta; Minari, Roberta; Naldi, Nadia; Petronini, Pier Giorgio; Tiseo, Marcello; Alfieri, Roberta

2017-12-04

Osimertinib is a third-generation EGFR-TKI with a high selective potency against T790M-mutant NSCLC patients. Considering that osimertinib can lead to enhanced HER-2 expression on cell surface and HER-2 overexpression is a mechanism of resistance to osimertinib, this study was addressed to investigate the potential of combining osimertinib with trastuzumab emtansine (T-DM1) in order to improve the efficacy of osimertinib and delay or overcome resistance in NSCLC cell lines with EGFR activating mutation and with T790M mutation or HER-2 amplification. The effects of osimertinib combined with T-DM1 on cell proliferation, cell cycle, cell death, antibody-dependent cell-mediated cytotoxicity (ADCC), and acquisition of osimertinib resistance was investigated in PC9, PC9-T790M and H1975 cell lines. The potential of overcoming osimertinib resistance with T-DM1 was tested in a PC9/HER2c1 xenograft model. T-DM1 exerted an additive effect when combined with osimertinib in terms of inhibition of cell proliferation, cell death and ADCC induction in PC9, PC9-T790M and H1975 cell lines. Combining osimertinib and T-DM1 using different schedules in long-term growth experiments revealed that the appearance of osimertinib-resistance was prevented in PC9-T790M and delayed in H1975 cells when the two drugs were given together. By contrast, when osimertinib was followed by T-DM1 an antagonistic effect was observed on cell proliferation, cell death and resistance acquisition. In xenograft models, we demonstrated that HER-2 amplification was associated with osimertinib-resistance and that T-DM1 co-administration is a potential strategy to overcome this resistance. Our data suggest that concomitant treatment with osimertinib and T-DM1 may be a promising therapeutic strategy for EGFR-mutant NSCLC.

Pulmonary granulomas of guinea pigs induced by inhalation exposure of heat-treated BCG Pasteur, purified trehalose dimycolate and methyl ketomycolate.

PubMed

Sugawara, I; Udagawa, T; Hua, S C; Reza-Gholizadeh, M; Otomo, K; Saito, Y; Yamada, H

2002-02-01

This study was designed to determine the identity of granulomatogenic substances in Mycobacterium bovis BCG Pasteur. When heat-treated BCG Pasteur bacilli were introduced into the lungs of guinea-pigs by an inhalation exposure apparatus, pulmonary granulomas without necrosis developed. Furthermore, when four kinds of mycolates derived from M. tuberculosis Aoyama B strain were introduced into the lungs by the same method, only trehalose 6,6'-dimycolate (TDM) and methyl ketomycolate induced pulmonary granulomas without central necrosis. The pulmonary granulomas consisted of epithelioid macrophages and lymphocytes. When a mixture of TDM and anti-TDM antibody was introduced into the lungs, development of granulomatous lesions was reduced. These data indicate that TDM and methyl ketomycolate are potent granulomatogenic reagents.

Characterization of the receptors for mycobacterial cord factor in Guinea pig.

PubMed

Toyonaga, Kenji; Miyake, Yasunobu; Yamasaki, Sho

2014-01-01

Guinea pig is a widely used animal for research and development of tuberculosis vaccines, since its pathological disease process is similar to that present in humans. We have previously reported that two C-type lectin receptors, Mincle (macrophage inducible C-type lectin, also called Clec4e) and MCL (macrophage C-type lectin, also called Clec4d), recognize the mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). Here, we characterized the function of the guinea pig homologue of Mincle (gpMincle) and MCL (gpMCL). gpMincle directly bound to TDM and transduced an activating signal through ITAM-bearing adaptor molecule, FcRγ. Whereas, gpMCL lacked C-terminus and failed to bind to TDM. mRNA expression of gpMincle was detected in the spleen, lymph nodes and peritoneal macrophages and it was strongly up-regulated upon stimulation of zymosan and TDM. The surface expression of gpMincle was detected on activated macrophages by a newly established monoclonal antibody that also possesses a blocking activity. This antibody potently suppressed TNF production in BCG-infected macrophages. Collectively, gpMincle is the TDM receptor in the guinea pig and TDM-Mincle axis is involved in host immune responses against mycobacteria.

Therapeutic drug monitoring for drugs used in the treatment of substance-related disorders: literature review using a therapeutic drug monitoring appropriateness rating scale.

PubMed

Brünen, Sonja; Vincent, Philippe D; Baumann, Pierre; Hiemke, Christoph; Havemann-Reinecke, Ursula

2011-10-01

The efficacy of drugs for the treatment of substance-related disorders is moderate at best. Therapeutic drug monitoring (TDM) could be an instrument to improve outcomes. Because TDM for most of those drugs is not established, the authors reviewed the literature and built a rating scale to detect the potential added value of TDM for these pharmacologic agents. A literature search was performed for acamprosate, bupropion, buprenorphine, clomethiazole, disulfiram, methadone, naltrexone, and varenicline. The rating scale included 22 items and was divided in five categories: efficacy, toxicity, pharmacokinetics, patient characteristics, and cost-effectiveness. Three reference substances with established TDM were similarly assessed for comparison: clozapine, lithium, and nortriptyline. The three reference substances achieved scores of 15, 12, and 14 points, respectively. Drugs for treatment of substance-related disorders achieved 3 to 17 points, 17 for methadone, 11 for buprenorphine, 10 for disulfiram, also 10 for naltrexone for the indication opioid-dependence and 9 for the indication alcohol dependence as well as bupropion, 7 points for acamprosate, 6 points for clomethiazole, and 3 for varenicline. It is concluded that systematic evaluation of drug- and patient-related variables with the new rating scale can estimate the appropriateness of TDM. Because their rating revealed similar scores as the three reference drugs, it is proposed that TDM should be established for bupropion, buprenorphine, disulfiram or a metabolite, methadone, and naltrexone. An objective rating of drug- and patient-related characteristics could help laboratories focus their method development on the most likely drugs to require TDM along with a thorough drug use evaluation.

Applied Space Systems Engineering. Chapter 17; Manage Technical Data

NASA Technical Reports Server (NTRS)

Kent, Peter

2008-01-01

Effective space systems engineering (SSE) is conducted in a fully electronic manner. Competitive hardware, software, and system designs are created in a totally digital environment that enables rapid product design and manufacturing cycles, as well as a multitude of techniques such as modeling, simulation, and lean manufacturing that significantly reduce the lifecycle cost of systems. Because the SSE lifecycle depends on the digital environment, managing the enormous volumes of technical data needed to describe, build, deploy, and operate systems is a critical factor in the success of a project. This chapter presents the key aspects of Technical Data Management (TDM) within the SSE process. It is written from the perspective of the System Engineer tasked with establishing the TDM process and infrastructure for a major project. Additional perspectives are reflected from the point of view of the engineers on the project who work within the digital engineering environment established by the TDM toolset and infrastructure, and from the point of view of the contactors who interface via the TDM infrastructure. Table 17.1 lists the TDM process as it relates to SSE.

Design of a surface plasmon resonance immunoassay for therapeutic drug monitoring of amikacin.

PubMed

Losoya-Leal, Adrian; Estevez, M-Carmen; Martínez-Chapa, Sergio O; Lechuga, Laura M

2015-08-15

The therapeutic drug monitoring (TDM) of pharmaceutical drugs with narrow therapeutic ranges is of great importance in the clinical setting. It provides useful information towards the enhancement of drug therapies, aiding in dosage control and toxicity risk management. Amikacin is an aminoglycoside antibiotic commonly used in neonatal therapies that is indicated for TDM due to the toxicity risks inherent in its use. Current techniques for TDM such as high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) are costly, time consuming, and cannot be performed at the site of action. Over the last decades, surface plasmon resonance (SPR) biosensors have become increasingly popular in clinical diagnostics due to their ability to detect biomolecular interactions in real-time. We present an SPR-based competitive immunoassay for the detection of the antibiotic amikacin, suitable for TDM in both adults and neonates. We have obtained high specificity and sensitivity levels with an IC50 value of 1.4ng/mL and a limit of detection of 0.13ng/mL, which comfortably comply with the drug's therapeutic range. Simple dilution of serum can therefore be sufficient to analyze low-volume real samples from neonates, increasing the potential of the methodology for TDM. Compared to current TDM conventional methods, this SPR-based immunoassay can provide advantages such as simplicity, potential portability, and label-free measurements with the possibility of high throughput. This work is the foundation towards the development of an integrated, simple use, highly sensitive, fast, and point-of-care sensing platform for the opportune TDM of antibiotics and other drugs in a clinical setting. Copyright © 2015 Elsevier B.V. All rights reserved.

The role of patients' families in treatment decision-making among adult cancer patients in the Sultanate of Oman.

PubMed

Al-Bahri, A; Al-Moundhri, M; Al-Mandhari, Z; Al-Azri, M

2018-04-17

There are limited numbers of studies available in Middle Eastern Arabic countries regarding participation of family ‎members in cancer treatment decision-making (TDM). The aim of this study was to evaluate the role of family members' ‎in TDM among ‎adult Omani cancer ‎patients. A cross-sectional study was conducted in two main teaching hospitals. All adult Omani patients who were diagnosed with cancer and their nominated family members were invited to ‎participate. A tool developed by Cancer Care Outcomes Research and ‎Surveillance Consortium was used to identify the level of family involvement in TDM. A weighted kappa (k) was significant (p < .001) and showed almost full agreement between the patients' experiences and their preferences ‎(‎k = .98) and between family members' experiences and their preferences ‎(‎k = .96) ‎‎of family involvement in TDM. Binary logistic regression showed significant family-controlled TDM if the patient communicated‎ less with oncologists (OR = 9.89; 95% CI: 3.79-25.81); financial dependence of the patient on their families ‎(OR = 6.21; 95% CI: 2.19-17.10‎); and advanced stages of cancer at the time of diagnosis ‎(OR = 3.10; 95% CI: 1.37-7.03). Oncologists in Oman should be aware of the strong family involvement in TDM to allow a successful cancer treatment. © 2018 John Wiley & Sons Ltd.

Physician‐related facilitators and barriers to patient involvement in treatment decision making in early stage breast cancer: perspectives of physicians and patients

PubMed Central

O’Brien, Mary Ann; Ellis, Peter M.; Whelan, Timothy J.; Charles, Cathy; Gafni, Amiram; Lovrics, Peter; Mukherjee, Som D.; Hodgson, Nicole

2011-01-01

Abstract Objective  To identify patients’ and physicians’ perceptions of physician‐related verbal and nonverbal facilitators and barriers to patient involvement in treatment decision making (TDM) occurring during clinical encounters for women with early stage breast cancer (ESBC). Methods  Eligible women were offered treatment options including surgery and adjuvant therapy. Eligible physicians provided care for women with ESBC in either a teaching hospital or an academic cancer centre. In Phase 1, women were interviewed 1–2 weeks after their initial consultation. In Phase 2, women and their physicians were interviewed separately while watching their own consultation on a digital video disk. All interviews were audiotaped, transcribed and analysed. Results  Forty women with ESBC and six physicians participated. Patients and physicians identified thirteen categories of physician facilitators of women’s involvement. Of these, seven categories were frequently identified by women: conveyed a rationale for patient involvement in TDM; explained the risk of cancer recurrence; explained treatment options; enhanced patient understanding of information; gave time for TDM; offered a treatment recommendation; and made women feel comfortable. Physicians described similar information‐giving facilitators but less often mentioned other facilitators. Few physician barriers to women’s involvement in TDM were identified. Conclusions  Women with ESBC and cancer physicians shared some views of how physicians involve patients in TDM, although there were important differences. Physicians may underestimate the importance that women’s place on understanding the rationale for their involvement in TDM and on feeling comfortable during the consultation. PMID:21923813

Application of time-division-multiplexed lasers for measurements of gas temperature and CH4 and H2O concentrations at 30 kHz in a high-pressure combustor.

PubMed

Caswell, Andrew W; Kraetschmer, Thilo; Rein, Keith; Sanders, Scott T; Roy, Sukesh; Shouse, Dale T; Gord, James R

2010-09-10

Two time-division-multiplexed (TDM) sources based on fiber Bragg gratings were applied to monitor gas temperature, H(2)O mole fraction, and CH(4) mole fraction using line-of-sight absorption spectroscopy in a practical high-pressure gas turbine combustor test article. Collectively, the two sources cycle through 14 wavelengths in the 1329-1667 nm range every 33 μs. Although it is based on absorption spectroscopy, this sensing technology is fundamentally different from typical diode-laser-based absorption sensors and has many advantages. Specifically, the TDM lasers allow efficient, flexible acquisition of discrete-wavelength information over a wide spectral range at very high speeds (typically 30 kHz) and thereby provide a multiplicity of precise data at high speeds. For the present gas turbine application, the TDM source wavelengths were chosen using simulated temperature-difference spectra. This approach is used to select TDM wavelengths that are near the optimum values for precise temperature and species-concentration measurements. The application of TDM lasers for other measurements in high-pressure, turbulent reacting flows and for two-dimensional tomographic reconstruction of the temperature and species-concentration fields is also forecast.

Therapeutic drug monitoring in pregnancy.

PubMed

Matsui, Doreen M

2012-10-01

Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

Cost evaluation of therapeutic drug monitoring of gentamicin at a teaching hospital in Malaysia

PubMed Central

Ibrahim, Mohamed Izham Mohamed; Abdelrahim, Hisham Elhag Ahmed; Ab Rahman, Ab Fatah

Background Therapeutic drug monitoring (TDM) makes use of serum drug concentrations as an adjunct to decision-making. Preliminary data in our hospital showed that approximately one-fifth of all drugs monitored by TDM service were gentamicin. Objective In this study, we evaluated the costs associated with providing the service in patients with bronchopneumonia and treated with gentamicin. Methods We retrospectively collected data from medical records of patients admitted to the Hospital Universiti Sains Malaysia over a 5-year period. These patients were diagnosed with bronchopneumonia and were on gentamicin as part of their treatment. Five hospitalisation costs were calculated; (i) cost of laboratory and clinical investigations, (ii) cost associated with each gentamicin dose, (iii) fixed and operating costs of TDM service, (iv) cost of providing medical care, and (v) cost of hospital stay during gentamicin treatment. Results There were 1920 patients admitted with bronchopneumonia of which 67 (3.5%) had TDM service for gentamicin. Seventy-three percent (49/67) patients were eligible for final analysis. The duration of gentamicin therapy ranged from 3 to 15 days. The cost of providing one gentamicin assay was MYR25, and the average cost of TDM service for each patient was MYR104. The average total hospitalisation cost during gentamicin treatment for each patient was MYR442 (1EUR approx. MYR4.02). Conclusions Based on the hospital perspective, in patients with bronchopneumonia and treated with gentamicin, the provision of TDM service contributes to less than 25% of the total cost of hospitalization. PMID:24644520

The combination use of platelet-rich fibrin and treated dentin matrix for tooth root regeneration by cell homing.

PubMed

Ji, Baohui; Sheng, Lei; Chen, Gang; Guo, Shujuan; Xie, Li; Yang, Bo; Guo, Weihua; Tian, Weidong

2015-01-01

Endogenous regeneration through cell homing provides an alternative approach for tissue regeneration, except cell transplantation, especially considering clinical translation. However, tooth root regeneration through cell homing remains a provocative approach in need of intensive study. Both platelet-rich fibrin (PRF) and treated dentin matrix (TDM) are warehouses of various growth factors, which can promote cell homing. We hypothesized that endogenous stem cells are able to sense biological cues from PRF membrane and TDM, and contribute to the regeneration of tooth root, including soft and hard periodontal tissues. Therefore, the biological effects of canine PRF and TDM on periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMSCs) were evaluated respectively in vitro. Beagle dogs were used as orthotopic transplantation model. It was found that PRF significantly recruited and stimulated the proliferation of PDLSCs and BMSCs in vitro. Together, PRF and TDM induced cell differentiation by upregulating the mineralization-related gene expression of bone sialoprotein (BSP) and osteopotin (OPN) after 7 days coculture. In vivo, transplantation of autologous PRF and allogeneic TDM into fresh tooth extraction socket achieved successful root regeneration 3 months postsurgery, characterized by the regeneration of cementum and periodontal ligament (PDL)-like tissues with orientated fibers, indicative of functional restoration. The results suggest that tooth root connected to the alveolar bone by cementum-PDL complex can be regenerated through the implantation of PRF and TDM in a tooth socket microenvironment, probably by homing of BMSCs and PDLSCs. Furthermore, bioactive cues and inductive microenvironment are key factors for endogenous regeneration. This approach provides a tangible pathway toward clinical translation.

Decision making and distress among individuals diagnosed with follicular lymphoma.

PubMed

Poe, Jennifer K; Hayslip, John W; Studts, Jamie L

2012-01-01

Follicular lymphoma (FL) is an indolent lymphoma that generally responds well to treatment. However, individuals with FL commonly face multiple complex treatment decision-making (TDM) experiences because it frequently follows a relapsing and remitting course. This study explored TDM and distress among individuals with FL (N = 32). Results indicated that most participants reported little decisional conflict or regret and wanted to be actively involved in TDM. However, more than 25% of participants reported clinically-relevant cancer-specific distress, and 60% indicated moderate or higher anxiety symptoms. Research is needed to clarify the cause and course of the psychological distress revealed in this study.

Variation in Prescribing Patterns and Therapeutic Drug Monitoring of Intravenous Busulfan in Pediatric Hematopoietic Cell Transplant Recipients

PubMed Central

McCune, Jeannine S.; Baker, K. Scott; Blough, David K.; Gamis, Alan; Bemer, Meagan J.; Kelton-Rehkopf, Megan C.; Winter, Laura; Barrett, Jeffrey S.

2016-01-01

Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package insert dose. The initial busulfan dose achieved the target exposure in only 24.3% of children. A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained. Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors’ group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children. PMID:23444282

Level of evidence for therapeutic drug monitoring of taxanes.

PubMed

Gerritsen-van Schieveen, Pauline; Royer, Bernard

2011-08-01

Taxanes are anticancer drugs on the market for more than 10 years that are thought to be interesting for therapeutic drug monitoring (TDM): high inter- and intra-patient variability, relationship between exposure and efficacy and especially toxicity. Nevertheless, the paclitaxel and docetaxel characteristics result in different conclusions for these two molecules with respect to their TDM. For paclitaxel, the nonlinear pharmacokinetics makes that the parameter which seems the more reliable to toxicity or outcome is the time during which the plasma concentration exceeds 0.05 μm. Concentration controlled studies using Bayesian adaptation showed that the TDM of paclitaxel is feasible in routine. However, this target needs to be prospectively validated with new weekly schedules of administration, leading to a balance between 'recommended' and 'potentially useful'. For docetaxel, the 3-weekly administration, which is the more effective scheme, is also the more toxic. However, neutropenia can be individually modeled and efficiently predicted without using plasma drug concentrations. The docetaxel TDM using this docetaxel-related neutropenia modeling however needs to be prospectively validated in routine. The level of evidence of TDM thus 'needs to be assessed'. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Trehalose 6,6′-Dimycolate and Lipid in the Pathogenesis of Caseating Granulomas of Tuberculosis in Mice

PubMed Central

Hunter, Robert L.; Olsen, Margaret; Jagannath, Chinnaswamy; Actor, Jeffrey K.

2006-01-01

Trehalose 6,6′-dimycolate (TDM) is the most abundant, most granulomagenic, and most toxic lipid extractable from the surface of virulent Mycobacterium tuberculosis (MTB). We further examined its toxicity, which requires activation by oily surfaces. Injections of MTB and/or TDM into sensitized mice induced caseating granulomas that centered on oil droplets. If large doses of MTB were injected in saline, caseating granulomas developed in adipose tissue, but MTB with surface TDM removed induced only acute inflammation that did not persist. Variations in protocols produced several variants of caseating granulomas, each with characteristics of human tuberculosis. In each instance, MTB were localized in fat cells or oil drops during initiation of caseating granulomas suggesting that necrosis was caused by activation of the toxicity of TDM toxicity. Evidence extending these findings to the lung was derived from the observation that in sensitized mice, as in humans, tuberculosis development stimulates accumulation of lipid selectively in alveoli. MTB preferentially associated with lipid droplets in developing necrotic foci in late-stage murine tuberculosis. This supports the hypothesis that pulmonary tuberculosis sequesters MTB in a protected environment that accumulates lipid until it is able to activate the toxicity of TDM and initiate necrosis that results in caseating granulomas. PMID:16565499

Practices associated with serum antiepileptic drug level monitoring at a pediatric neurology clinic: a Malaysian experience.

PubMed

Salih, Muhannad R M; Bahari, Mohd Baidi; Hassali, Mohamed Azmi Ahmad; Shafie, Asrul Akmal; Al-Lela, Omer Qutaiba B; Abd, Arwa Y; Ganesan, Vigneswari

2013-06-01

To assess the practices associated with the application of therapeutic drug monitoring (TDM) for antiepileptic drugs (AEDs) in the management of children with structural-metabolic epilepsy. It was a retrospective chart review and included children aged ≥2 years old with structural-metabolic epilepsy, treated with AEDs, and received TDM. The data were extracted from the medical records. Thirty-two patients were identified with 50 TDM assays. In two thirds of the assays, "check level" and "recheck level" were the reasons behind the requesting of serum level monitoring of AEDs. Knowledge of serum AED levels led to alterations in the management in 60% of the assays. Thirty-two (76%) pediatrician's actions were consistent with the recommendation of TDM pharmacist. Forty-nine (98%) levels were appropriately indicated. In relation to the appropriateness of sampling time, 9 (18%) levels were not assessed due to missing data. Twenty-seven (54%) levels were appropriately sampled. More studies should be designed to improve the component of the current TDM request form, especially in the reason section. By the same token, the number of pointless assays and the costs to the health care system can be reduced both by enhancing and improving the educational standards of the requesting neurologists.

Genetic parameters of milk production traits in response to a short once-daily milking period in crossbred Holstein × Normande dairy cows.

PubMed

Charton, C; Guinard-Flament, J; Lefebvre, R; Barbey, S; Gallard, Y; Boichard, D; Larroque, H

2018-03-01

Despite its potential utility for predicting cows' milk yield responses to once-daily milking (ODM), the genetic basis of cow milk trait responses to ODM has been scarcely if ever described in the literature, especially for short ODM periods. This study set out to (1) estimate the genetic determinism of milk yield and composition during a 3-wk ODM period, (2) estimate the genetic determinism of milk yield responses (i.e., milk yield loss upon switching cows to ODM and milk yield recovery upon switching them back to twice-daily milking; TDM), and (3) seek predictors of milk yield responses to ODM, in particular using the first day of ODM. Our trial used 430 crossbred Holstein × Normande cows and comprised 3 successive periods: 1 wk of TDM (control), 3 wk of ODM, and 2 wk of TDM. Implementing ODM for 3 wk reduced milk yield by 27.5% on average, and after resuming TDM cows recovered on average 57% of the milk lost. Heritability estimates in the TDM control period and 3-wk ODM period were, respectively, 0.41 and 0.35 for milk yield, 0.66 and 0.61 for milk fat content, 0.60 and 0.80 for milk protein content, 0.66 and 0.36 for milk lactose content, and 0.20 and 0.15 for milk somatic cell score content. Milk yield and composition during 3-wk ODM and TDM periods were genetically close (within-trait genetic correlations between experimental periods all exceeding 0.80) but were genetically closer within the same milking frequency. Heritabilities of milk yield loss observed upon switching cows to ODM (0.39 and 0.34 for milk yield loss in kg/d and %, respectively) were moderate and similar to milk yield heritabilities. Milk yield recovery (kg/d) upon resuming TDM was a trait of high heritability (0.63). Because they are easy to measure, TDM milk yield and composition and milk yield responses on the first day of ODM were investigated as predictors of milk yield responses to a 3-wk ODM to easily detect animals that are well adapted to ODM. Twice-daily milking milk yield and

Le syndrome des enfants battus: aspects cliniques et radiologiques

PubMed Central

Jlalia, Zied; Znaigui, Talel; Smida, Mahmoud

2016-01-01

La maltraitance physique des enfants ou le syndrome des enfants battus est responsable de plus de 75.000 décès par an en France. Ce problème de santé publique reste sous diagnostiqué en Tunisie et dans le monde. Le chemin a été laborieux pour la reconnaissance du syndrome des enfants battus dans certaines sociétés même occidentales. Nous avons voulus exposer ce problème aux praticiens afin qu'il soit mieux diagnostiqué et pris en charge. La maltraitance physique des enfants est appelée à tort syndrome de Silverman qui ne regroupe en fait que les lésions squelettiques chez ces enfants tels que les fractures. Mots clés: Fracture, maltraitance, enfant, neuro-radiologie PMID:27642408

Aductive laser iridoplasty and laser goniopuncture after non-perforating trabeculectomy.

PubMed

D, Lawrence F Jindra M

2013-03-01

Successful non-perforating trabeculectomy (NPT) results in filtration of aqueous humor out of the anterior chamber and into a filtration bleb, without surgical excision of tissue from the anterior chamber angle, and without penetration into the anterior chamber. The complications of perforating trabeculectomy, due to early postoperative hypotony (shallow anterior chamber, hyphema, macular folds, suprachoroidal effusion, and ciliochoroidal hemorrhage) (3, 4, 5, 6, 7, 8, 9) are regarded by many surgeons as significant risks. Nonperforating surgery has been reported to reduce the incidence of early hypotony-related complications (10), because it has the advantage of creating gradual filtration of aqueous humor, through a thin trabeculodescemetic membrane (TDM), which markedly reduces postoperative complications seen after a conventional trabeculectomy (11), and also has been reported to provide better long-term intraocular pressure (IOP) control (12, 13). NPT is reported to be a procedure with a significant learning curve, sometimes necessitating conversion to perforating trabeculectomy, and requiring careful postoperative monitoring (14, 15, 16, 17). Zimmerman et al. reported filtration of aqueous humor under a filtering bleb, by resecting the roof of Schlemms canal and removing corneal stroma overlying the trabecular meshwork (18) Mermoud et al. reported filtration of aqueous humor under a filtering, bleb by unroofing Schlemms canal and removing corneal stroma overlying the trabecular meshwork as well Descemets membrane (19); he found that resistance across the TDM sometimes increased with time. When this resistance to aqueous humor outflow occurred, Mermoud found TDM resistance could be eliminated by performance of goniopuncture (ab interno Nd:YAG laser membranotomy via gonioprism), to enhance aqueous humor outflow into the filtration bleb. Failure to filter adequately through the TDM is a potential complication following NPT which can result in a rise in

Hierarchical zwitterionic modification of a SERS substrate enables real-time drug monitoring in blood plasma

NASA Astrophysics Data System (ADS)

Sun, Fang; Hung, Hsiang-Chieh; Sinclair, Andrew; Zhang, Peng; Bai, Tao; Galvan, Daniel David; Jain, Priyesh; Li, Bowen; Jiang, Shaoyi; Yu, Qiuming

2016-11-01

Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive analytical technique with molecular specificity, making it an ideal candidate for therapeutic drug monitoring (TDM). However, in critical diagnostic media including blood, nonspecific protein adsorption coupled with weak surface affinities and small Raman activities of many analytes hinder the TDM application of SERS. Here we report a hierarchical surface modification strategy, first by coating a gold surface with a self-assembled monolayer (SAM) designed to attract or probe for analytes and then by grafting a non-fouling zwitterionic polymer brush layer to effectively repel protein fouling. We demonstrate how this modification can enable TDM applications by quantitatively and dynamically measuring the concentrations of several analytes--including an anticancer drug (doxorubicin), several TDM-requiring antidepressant and anti-seizure drugs, fructose and blood pH--in undiluted plasma. This hierarchical surface chemistry is widely applicable to many analytes and provides a generalized platform for SERS-based biosensing in complex real-world media.

Hierarchical zwitterionic modification of a SERS substrate enables real-time drug monitoring in blood plasma

PubMed Central

Sun, Fang; Hung, Hsiang-Chieh; Sinclair, Andrew; Zhang, Peng; Bai, Tao; Galvan, Daniel David; Jain, Priyesh; Li, Bowen; Jiang, Shaoyi; Yu, Qiuming

2016-01-01

Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive analytical technique with molecular specificity, making it an ideal candidate for therapeutic drug monitoring (TDM). However, in critical diagnostic media including blood, nonspecific protein adsorption coupled with weak surface affinities and small Raman activities of many analytes hinder the TDM application of SERS. Here we report a hierarchical surface modification strategy, first by coating a gold surface with a self-assembled monolayer (SAM) designed to attract or probe for analytes and then by grafting a non-fouling zwitterionic polymer brush layer to effectively repel protein fouling. We demonstrate how this modification can enable TDM applications by quantitatively and dynamically measuring the concentrations of several analytes—including an anticancer drug (doxorubicin), several TDM-requiring antidepressant and anti-seizure drugs, fructose and blood pH—in undiluted plasma. This hierarchical surface chemistry is widely applicable to many analytes and provides a generalized platform for SERS-based biosensing in complex real-world media. PMID:27834380

Cross-platform normalization of microarray and RNA-seq data for machine learning applications

PubMed Central

Thompson, Jeffrey A.; Tan, Jie

2016-01-01

Large, publicly available gene expression datasets are often analyzed with the aid of machine learning algorithms. Although RNA-seq is increasingly the technology of choice, a wealth of expression data already exist in the form of microarray data. If machine learning models built from legacy data can be applied to RNA-seq data, larger, more diverse training datasets can be created and validation can be performed on newly generated data. We developed Training Distribution Matching (TDM), which transforms RNA-seq data for use with models constructed from legacy platforms. We evaluated TDM, as well as quantile normalization, nonparanormal transformation, and a simple log2 transformation, on both simulated and biological datasets of gene expression. Our evaluation included both supervised and unsupervised machine learning approaches. We found that TDM exhibited consistently strong performance across settings and that quantile normalization also performed well in many circumstances. We also provide a TDM package for the R programming language. PMID:26844019

The Theory of Dyadic Morality: Reinventing Moral Judgment by Redefining Harm.

PubMed

Schein, Chelsea; Gray, Kurt

2018-02-01

The nature of harm-and therefore moral judgment-may be misunderstood. Rather than an objective matter of reason, we argue that harm should be redefined as an intuitively perceived continuum. This redefinition provides a new understanding of moral content and mechanism-the constructionist Theory of Dyadic Morality (TDM). TDM suggests that acts are condemned proportional to three elements: norm violations, negative affect, and-importantly-perceived harm. This harm is dyadic, involving an intentional agent causing damage to a vulnerable patient (A→P). TDM predicts causal links both from harm to immorality (dyadic comparison) and from immorality to harm (dyadic completion). Together, these two processes make the "dyadic loop," explaining moral acquisition and polarization. TDM argues against intuitive harmless wrongs and modular "foundations," but embraces moral pluralism through varieties of values and the flexibility of perceived harm. Dyadic morality impacts understandings of moral character, moral emotion, and political/cultural differences, and provides research guidelines for moral psychology.

Current status of therapeutic drug monitoring in Australia and New Zealand: a need for improved assay evaluation, best practice guidelines, and professional development.

PubMed

Norris, Ross L; Martin, Jennifer H; Thompson, Erin; Ray, John E; Fullinfaw, Robert O; Joyce, David; Barras, Michael; Jones, Graham R; Morris, Raymond G

2010-10-01

The measurement of drug concentrations, for clinical purposes, occurs in many diagnostic laboratories throughout Australia and New Zealand. However, the provision of a comprehensive therapeutic drug monitoring (TDM) service requires the additional elements of pre- and postanalytical advice to ensure that concentrations reported are meaningful, interpretable, and clinically applicable to the individual patient. The aim of this project was to assess the status of TDM services in Australia and New Zealand. A range of professions involved in key aspects of TDM was surveyed by questionnaire in late 2007. Information gathered included: the list of drugs assayed; analytical methods used; interpretation services offered; interpretative methods used; and further monitoring advice provided. Fifty-seven responses were received, of which 42% were from hospitals (public and/or private); 11% a hospital (public and/or private) and pathology provider; and 47% a pathology provider only (public and/or private). Results showed that TDM is applied to a large number of different drugs. Poorly performing assay methods were used in some cases, even when published guidelines recommended alternative practices. Although there was a wide array of assays available, the evidence suggested a need for better selection of assay methods. In addition, only limited advice and/or interpretation of results was offered. Of concern, less than 50% of those providing advice on aminoglycoside dosing in adults used pharmacokinetic tools with six of 37 (16.2%) respondents using Bayesian pharmacokinetic tools, the method recommended in the Australian Therapeutic Guidelines: Antibiotic. In conclusion, the survey highlighted deficiencies in the provision of TDM services, in particular assay method selection and both quality and quantity of postanalytical advice. A range of recommendations, some of which may have international implications, are discussed. There is a need to include measures of impact on clinical

Drug persistence and need for dose intensification to adalimumab therapy; the importance of therapeutic drug monitoring in inflammatory bowel diseases.

PubMed

Gonczi, Lorant; Kurti, Zsuzsanna; Rutka, Mariann; Vegh, Zsuzsanna; Farkas, Klaudia; Lovasz, Barbara D; Golovics, Petra A; Gecse, Krisztina B; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

2017-08-08

Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients. One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France). Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 μg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5-24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4-9.5). ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR.

Prognostic value of gonioscopy after deep sclerectomy.

PubMed

Moreno-Montañés, J; Rebolleda, G; Muñoz-Negrete, F J

2007-01-01

To ascertain gonioscopic characteristics and identify prognostic indicators related to intraocular pressure (IOP) after deep sclerectomy (DS). A transversal, prospective, and nonselected study was performed in 106 eyes (95 patients) after DS. Three surgeons performed all the surgeries and the gonioscopic examination, using the same protocol including 13 gonioscopic data. These data were evaluated for an association with postoperative IOP and time after surgery. A subscleral space was found in 91 eyes (85.8%), with visualization of the line of scleral flap in 48 eyes (45.3%). The trabeculo-Descemet membrane (TDM) was transparent in 46 eyes (43.4%), opaque in 4 cases, and pigmented in 18 eyes. This TDM was broken using Nd:YAG laser goniopuncture in 38 eyes(35.8%). Thin vessels around TDM were found in 58 eyes (54.7%), and blood remained in 25 eyes (23.5%). Gonioscopic variables significantly positively related with postoperative IOP were as follows: presence of subscleral space, scleral flap line view, and a Schwalbe line depressed. A narrow anterior chamber angle and iris synechia in TDM had a statistically significant negative effect on the postoperative IOP control. Similarly, eyes requiring Nd:YAG goniopuncture had a worse IOP control. The frequency of eyes with visible subscleral space and transparent TDM decreases with time after surgery (p=0.001). A visible subscleral space was a gonioscopic sign positively related to IOP control after surgery, although it decreased with follow-up. Eyes with goniopuncture, postoperative narrow angle, and iris synechia had worse postoperative IOP control. Although new vessels in TDM were a common finding after DS, the authors did not find any association with postoperative IOP.

De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor-Positive Phase II Randomized Trial-Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET.

PubMed

Harbeck, Nadia; Gluz, Oleg; Christgen, Matthias; Kates, Ronald Ernest; Braun, Michael; Küemmel, Sherko; Schumacher, Claudia; Potenberg, Jochem; Kraemer, Stefan; Kleine-Tebbe, Anke; Augustin, Doris; Aktas, Bahriye; Forstbauer, Helmut; Tio, Joke; von Schumann, Raquel; Liedtke, Cornelia; Grischke, Eva-Maria; Schumacher, Johannes; Wuerstlein, Rachel; Kreipe, Hans Heinrich; Nitz, Ulrike Anneliese

2017-09-10

Purpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen

Trastuzumab Emtansine for Treating HER2-Positive, Unresectable, Locally Advanced or Metastatic Breast Cancer After Treatment with Trastuzumab and a Taxane: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

PubMed

Squires, Hazel; Stevenson, Matt; Simpson, Emma; Harvey, Rebecca; Stevens, John

2016-07-01

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of trastuzumab emtansine (T-DM1) (Kadcyla(®); Roche) to submit evidence of its clinical and cost-effectiveness for treating human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced or metastatic breast cancer after treatment with trastuzumab and a taxane. The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield were the independent Evidence Review Group (ERG) who produced a critical review of the company's submission to NICE. The ERG also independently searched for relevant evidence and modified the submitted decision analytic model to produce a revised estimate of cost-effectiveness and examine the impact of altering some of the key assumptions. The clinical effectiveness data were taken from two randomised controlled trials that reported a significant advantage in progression-free survival (PFS) for T-DM1 over lapatinib in combination with capecitabine (EMILIA trial), and over the treatment of physician's choice (TH3RESA trial). A network meta-analysis suggested T-DM1 was the best treatment in terms of both overall survival and PFS compared with lapatinib in combination with capecitabine; trastuzumab in combination with capecitabine; and capecitabine monotherapy. Adverse event (AE) data were taken from a pooled analysis of additional trials of T-DM1 as a single agent. The most common grade 3 or greater AEs for T-DM1 were thrombocytopenia and hepatotoxicity. Following the clarification process, the manufacturer reported a deterministic incremental cost-effectiveness ratio (ICER) for T-DM1 compared with lapatinib in combination with capecitabine of £167,236, the latter of which was estimated to have an ICER of £49,798 compared with capecitabine monotherapy. The ERG produced similar values of £166,429 and £50,620 respectively. All other comparators were dominated. During the appraisal, the

Use of anti-TNF drug levels to optimise patient management

PubMed Central

Papamichael, Konstantinos; Cheifetz, Adam S

2016-01-01

Anti-tumour necrosis factor (TNF) therapies, such as infliximab, adalimumab, certolizumab pegol and golimumab, have been proven to be effective for the treatment of patients with Crohn's disease and ulcerative colitis. However, 10%–30% of patients with inflammatory bowel disease (IBD) show no initial clinical benefit to anti-TNF therapy (primary non-response), and over 50% after an initial favourable outcome will lose response over time (secondary loss of response (SLR)). Numerous recent studies in IBD have revealed an exposure–response relationship suggesting a positive correlation between high serum anti-TNF concentrations and favourable therapeutic outcomes including clinical, biomarker and endoscopic remission, whereas antidrug antibodies have been associated with SLR and infusion reactions. Currently, therapeutic drug monitoring (TDM) is typically performed when treatment failure occurs either for SLR, drug intolerance (potential immune-mediated reaction) or infusion reaction (reactive TDM). Nevertheless, recent data demonstrate that proactive TDM and a treat-to-target (trough) therapeutic approach may more effectively optimise anti-TNF therapy efficacy, safety and cost. However, implementing TDM in real-life clinical practice is currently limited by the diversity in study design, therapeutic outcomes and assays used, which have hindered the identification of robust clinically relevant concentration thresholds. This review will focus mainly on the pharmacodynamic properties of anti-TNF therapy and the role of TDM in guiding therapeutic decisions in IBD. PMID:28839870

Sophora flavescens protects against mycobacterial Trehalose Dimycolate-induced lung granuloma by inhibiting inflammation and infiltration of macrophages.

PubMed

Liu, Dehua; Chan, Ben Chung-Lap; Cheng, Ling; Tsang, Miranda Sin-Man; Zhu, Jing; Wong, Chun-Wai; Jiao, Delong; Chan, Helen Yau-Tsz; Leung, Ping Chung; Lam, Christopher Wai-Kei; Wong, Chun Kwok

2018-03-02

The immune system responds to Mycobacterium tuberculosis (MTB) infection by forming granulomas to quarantine the bacteria from spreading. Granuloma-mediated inflammation is a cause of lung destruction and disease transmission. Sophora flavescens (SF) has been demonstrated to exhibit bactericidal activities against MTB. However, its immune modulatory activities on MTB-mediated granulomatous inflammation have not been reported. In the present study, we found that flavonoids from Sophora flavescens (FSF) significantly suppressed the pro-inflammatory mediators released from mouse lung alveolar macrophages (MH-S) upon stimulation by trehalose dimycolate (TDM), the most abundant lipoglycan on MTB surface. Moreover, FSF reduced adhesion molecule (LFA-1) expression on MH-S cells after TDM stimulation. Furthermore, FSF treatment on TDM-activated lung epithelial (MLE-12) cells significantly downregulated macrophage chemoattractant protein (MCP-1/CCL2) expression, which in turn reduced the in vitro migration of MH-S to MLE-12 cells. In addition, FSF increased the clearance of mycobacterium bacteria (Mycobacterium aurum) in macrophages. FSF mainly affected the Mincle-Syk-Erk signaling pathway in TDM-activated MH-S cells. In TDM-induced mouse granulomas model, oral administration with FSF significantly suppressed lung granulomas formation and inflammation. These findings collectively implicated an anti-inflammatory role of FSF on MTB-mediated granulomatous inflammation, thereby providing evidence of FSF as an efficacious adjunct treatment during mycobacterial infection.

TDM Status Report - Telecommuting

DOT National Transportation Integrated Search

1992-08-01

Experience with telecommuting suggests it can be an effective strategy for : reducing commuter traffic. However, home based and satellite strategies deserve : careful planning, assessment and evaluation in future applications. Specific : effectivenes...

Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer.

PubMed

Baselga, José; Lewis Phillips, Gail D; Verma, Sunil; Ro, Jungsil; Huober, Jens; Guardino, Alice E; Samant, Meghna K; Olsen, Steve; de Haas, Sanne L; Pegram, Mark D

2016-08-01

HER2-positive breast cancer is heterogeneous. Some tumors express mutations, like activating PIK3CA mutations or reduced PTEN expression, that negatively correlate with response to HER2-targeted therapies. In this exploratory analysis, we investigated whether the efficacy of trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprised of the cytotoxic agent DM1 linked to the HER2-targeted antibody trastuzumab, was correlated with the expression of specific biomarkers in the phase III EMILIA study. Tumors were evaluated for HER2 (n = 866), EGFR (n = 832), and HER3 (n = 860) mRNA expression by quantitative reverse transcriptase PCR; for PTEN protein expression (n = 271) by IHC; and for PIK3CA mutations (n = 259) using a mutation detection kit. Survival outcomes were analyzed by biomarker subgroups. T-DM1 was also tested on cell lines and in breast cancer xenograft models containing PIK3CA mutations. Longer progression-free survival (PFS) and overall survival (OS) were observed with T-DM1 compared with capecitabine plus lapatinib in all biomarker subgroups. PIK3CA mutations were associated with shorter median PFS (mutant vs. wild type: 4.3 vs. 6.4 months) and OS (17.3 vs. 27.8 months) in capecitabine plus lapatinib-treated patients, but not in T-DM1-treated patients (PFS, 10.9 vs. 9.8 months; OS, not reached in mutant or wild type). T-DM1 showed potent activity in cell lines and xenograft models with PIK3CA mutations. Although other standard HER2-directed therapies are less effective in tumors with PI3KCA mutations, T-DM1 appears to be effective in both PI3KCA-mutated and wild-type tumors. Clin Cancer Res; 22(15); 3755-63. ©2016 AACR. ©2016 American Association for Cancer Research.

Clinical usefulness of therapeutic drug monitoring of voriconazole in a university hospital.

PubMed

Cabral-Galeano, Evelyn; Ruiz-Camps, Isabel; Len-Abad, Oscar; Pou-Clavé, Leonor; Sordé-Masip, Roger; Meije-Castillo, Yolanda; Blanco-Grau, Albert; Barba-Suñol, Pere; Monforte-Torres, Victor; Román-Broto, Antonio; Pahissa-Berga, Albert; Gavaldà-Santapau, Joan

2015-05-01

The aim of this study was to assess the clinical usefulness of therapeutic drug monitoring (TDM) of voriconazole (VOR) in a university hospital. A retrospective review was conducted on the clinical records of 52 patients treated with VOR and on whom TDM was performed. Steady-state trough plasma VOR concentration was measured at least 5 days after starting treatment. The therapeutic range of plasma VOR concentration was defined as 1-5.5μg/mL. The most frequent underlying conditions in the study population were lung transplant (48.1%) and hematological malignancies (26.9%). At the first TDM in each patient, VOR levels were outside the therapeutic range in 16 (30.7%) cases: <1μg/mL in 10 (19.2%) and >5.5μg/mL in 6 (11.5%). Eleven patients (21.2%) experienced severe muscle weakness and had considerable difficulty walking. All these patients were receiving concomitant treatment with corticosteroids. Age younger than 30 years (p=.005) and cystic fibrosis as the underlying disease (p=.04) were factors associated with low VOR levels. Almost all patients who had VOR concentrations >1μg/mL at the first TDM had a successful outcome (96%). Plasma VOR concentrations were outside the therapeutic range at the first TDM in 30% (16/52) of patients. Age younger than 30 years and cystic fibrosis were factors associated with low VOR levels. The potential interactions between corticosteroids and VOR should be highlighted, as they could be responsible for a high rate of muscle weakness observed in our patients. Prospective trials are needed to investigate VOR TDM and corticosteroid pharmacokinetics. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Watching excitons move: the time-dependent transition density matrix

NASA Astrophysics Data System (ADS)

Ullrich, Carsten

2012-02-01

Time-dependent density-functional theory allows one to calculate excitation energies and the associated transition densities in principle exactly. The transition density matrix (TDM) provides additional information on electron-hole localization and coherence of specific excitations of the many-body system. We have extended the TDM concept into the real-time domain in order to visualize the excited-state dynamics in conjugated molecules. The time-dependent TDM is defined as an implicit density functional, and can be approximately obtained from the time-dependent Kohn-Sham orbitals. The quality of this approximation is assessed in simple model systems. A computational scheme for real molecular systems is presented: the time-dependent Kohn-Sham equations are solved with the OCTOPUS code and the time-dependent Kohn-Sham TDM is calculated using a spatial partitioning scheme. The method is applied to show in real time how locally created electron-hole pairs spread out over neighboring conjugated molecular chains. The coupling mechanism, electron-hole coherence, and the possibility of charge separation are discussed.

Safety Evaluation of Trastuzumab Emtansine in Japanese Patients with HER2-Positive Advanced Breast Cancer

PubMed Central

WATANABE, JUNICHIRO; ITO, YOSHINORI; SAEKI, TOSHIAKI; MASUDA, NORIKAZU; TAKANO, TOSHIMI; TAKAO, SHINTARO; NAKAGAMI, KAZUHIKO; TSUGAWA, KOICHIRO; NAKAGAWA, SHINTARO; KANATANI, KAZUMITSU; NAKAYAMA, TAKAHIRO

2017-01-01

Background/Aim: Tolerability and safety of trastuzumab emtansine (T-DM1) was investigated in Japanese patients with HER2-positive advanced breast cancer who were previously treated with chemotherapy and trastuzumab. Patients and Methods: Patients with inoperable or recurrent breast cancer who were previously treated with chemotherapy and trastuzumab in adjuvant and/or metastatic disease were included. T-DM1 3.6 mg/kg was administered intravenously every 21 days. The administration dosage or schedule of T-DM1 was modified based on laboratory tests on the administration day. Results: Among 232 patients analyzed, adverse events were reported in 228 patients (98.3%); five patients (2.2%) discontinued due to adverse events and twenty patients (8.6%) had serious adverse events. The most commonly reported grade ≥3 adverse event of special interest was thrombocytopenia (69 patients; 29.7%), followed by hepatotoxicity (26 patients; 11.2%). Conclusion: T-DM1 was well tolerated in Japanese patients with HER2-positive advanced breast cancer and no new safety signals were observed. PMID:28438884

Participation in treatment decision-making among Chinese-Australian women with breast cancer.

PubMed

Kwok, Cannas; Koo, Fung Kuen

2017-03-01

Using Confucian philosophy as a conceptual framework, this article examines the extent to which cultural values and language affect the participation preferences and experiences of the breast cancer treatment decision-making (TDM) process among Chinese women with breast cancer in Australia. Three focus groups were conducted with 23 Chinese-Australian women diagnosed with breast cancer in their native language (Mandarin and Cantonese). Each interview was translated and transcribed. Content analysis was used to uncover the major themes. Four typologies emerged: the patient as an active decision maker, the patient as a passive decision maker, the patient as a reluctant decision maker and the patient as a reluctant passive decision maker. Language barriers, cultural expectation of doctor's role and family role in Chinese culture appear as influential factors in TDM process among this group of women. Intervention to improve doctors' cultural sensitivities in order to help them assess women's role preferences in TDM and the ability of doctors to communicate in a culturally appropriate manner, may improve the process of breast cancer TDM among women from Chinese background.

Fistule vesico-sigmoïdienne compliquant une hydatidose intestinale: à propos d'un cas rare

PubMed Central

Lahyani, Mounir; Jabbour, Younes; Karmouni, Tarik; Elkhader, Khalid; Koutani, Abdellatif; Andaloussi, Ahmed Ibn attya

2014-01-01

La fistule colo-vésicale sur une hydatidose sigmoidienne est une entité pathologique exceptionnelle. Nous rapportions une nouvelle observation, ou seront rappelées les principales données diagnostique et thérapeutique de cette affection. PMID:25722790

Isavuconazole Concentration in Real-world Practice: Consistency with Results from Clinical Trials.

PubMed

Andes, David; Kovanda, Laura; Desai, A; Kitt, Theresa; Zhao, M; Walsh, Thomas J

2018-05-07

Clinical use of voriconazole, posaconazole, and itraconazole revealed the need for therapeutic drug monitoring (TDM) of plasma concentrations of these antifungal agents. This need for TDM was not evident from clinical trials of these drugs. In order to establish if this requirement also applies to isavuconazole, we examined the plasma concentrations of 283 samples receiving isavuconazole in clinical practice and compared the values to those from clinical trials. The concentration distributions from real-world use and clinical trials were nearly identical (>1 μg/mL in 90% of patients). These findings suggest that routine TDM may not be required for isavuconazole in most instances. Copyright © 2018 American Society for Microbiology.

Time-dependent transition density matrix for visualizing charge-transfer excitations in photoexcited organic donor-acceptor systems

NASA Astrophysics Data System (ADS)

Li, Yonghui; Ullrich, Carsten

2013-03-01

The time-dependent transition density matrix (TDM) is a useful tool to visualize and interpret the induced charges and electron-hole coherences of excitonic processes in large molecules. Combined with time-dependent density functional theory on a real-space grid (as implemented in the octopus code), the TDM is a computationally viable visualization tool for optical excitation processes in molecules. It provides real-time maps of particles and holes which gives information on excitations, in particular those that have charge-transfer character, that cannot be obtained from the density alone. Some illustration of the TDM and comparison with standard density difference plots will be shown for photoexcited organic donor-acceptor molecules. This work is supported by NSF Grant DMR-1005651

Comparison between three adjuvants for a vaccine against canine leishmaniasis: In vitro evaluation of macrophage killing ability.

PubMed

Trotta, T; Fasanella, A; Scaltrito, D; Gradoni, L; Mitolo, V; Brandonisio, O; Acquafredda, A; Panaro, M A

2010-03-01

The aim of this study was to evaluate, in terms of dog macrophage killing ability in vitro, a vaccine based on Leishmania infantum promastigote soluble antigen (LSA) formulated with three different adjuvants (BCG, AdjuPrime, MPL/TDM/CWS). A significant increase of the macrophage killing ability was observed in dogs vaccinated with LSA+MPL/TDM/CWS after 1 month from vaccination. A similar increase of macrophage parasitocidal ability was present only after 5 months in dogs vaccinated with LSA+BCG or LSA+AdjuPrime. In all dogs the augmented killing percentage was still present after 12 months from vaccination. Therefore, in particular LSA+MPL/TDM/CWS vaccine seems promising for further studies in dogs. 2009 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McChesney, D.G.; Landauer, M.R.; Davis, H.D.

The biological response modifier, S-TDM, administered in doses of 100, 200, 400 and 800 ug/mouse 24 hours before a LD80/30 dose (5.6 Gy at 0.4 Gy-MLT/minute) of radiation (neutron:gamma {double bond} 1) resulted in survival of 100%, 60%, 89% and 20% respectively. Because of the radioprotective efficacy of this immunomodulator, the behavioral effects of S-TDM were investigated. Locomotor activity, food intake, water consumption, and body weight were examined using female B6D2F1 mice. At doses of 100-400 ug/mouse locomotor activity decreased within 4 hours of administration and returned to control values by 2.5 days postinjection. Food and water intake were significantlymore » depressed at doses of 100, 200, and 400 ug/mouse on the day following drug administration and recovered in 1 day. Body weight was significantly decreased in the 100 and 200 ug/mouse groups for 2 days and in the 400 ug/mouse for 3 days following injection of S-TDM. These results indicate that there is short-term reversible toxicity in mice administered S-TDM at doses of 100, 200, and 400 ug/mouse.« less

Paper-basd surface enhanced Raman spectroscopy of pnenobarbital sodium for point-of-care therapeutic drug monitoring

NASA Astrophysics Data System (ADS)

Yokoyama, Moe; Yamada, Kenji; Nishimura, Takahiro; Kido, Michiko; Jeong, Hieyong; Ohno, Yuko

2015-03-01

Therapeutic drug monitoring (TDM) contributes to safe and effective pharmacotherapy in clinical fields. A simple, rapid, low-cost, and minimally-invasive drug measurement method attracts much interest for point-of-care TDM. Tear fluids can be collected minimally-invasively compared to blood sampling and there is a correlation between a drug concentration in tears and that in bloods. Surface enhanced Raman spectroscopy (SERS) with paper-based substrate is useful for point-of-care TDM owing to inexpensiveness and high-sensitivity. Paper is also a safe tear collection tool. Then we are studying on a paper-based SERS of tear specimen for point-of-care TDM. In this paper, to improve sensitivity in measuring drug concentration in tear fluids, we fabricated a SERS substrate by coating gold nano-rods on a paper substrate and evaluated whether the fabricated substrate can enhance Raman scattering. Sodium phenobarbital (PB), an anti-convulsant agent, was used as a target. In experiment, the fabricated substrate indicated the lower detection limit of PB in a solution than a plain paper substrate. This result showed the potential of the paper based SERS substrate to measure drug concentration in tears simply and inexpensively.

Clinical utility of therapeutic drug monitoring in biological disease modifying anti-rheumatic drug treatment of rheumatic disorders: a systematic narrative review.

PubMed

Van Herwaarden, Noortje; Van Den Bemt, Bart J F; Wientjes, Maike H M; Kramers, Cornelis; Den Broeder, Alfons A

2017-08-01

Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have improved the treatment outcomes of inflammatory rheumatic diseases including Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of bDMARDs could potentially help in optimizing treatment for the individual patient. Areas covered: Evidence of clinical utility of TDM in bDMARD treatment is reviewed. Different clinical scenarios will be discussed, including: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity. Expert opinion: The limited available evidence does often not report important outcomes for diagnostic studies, such as sensitivity and specificity. In most clinical relevant scenarios, predictive value of serum (anti-) drug levels is absent, therefore the use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies should be done to further investigate the promising scenarios to determine the place of TDM in clinical practice.

Improvement of signal to noise ratio of time domain mutliplexing fiber Bragg grating sensor network with Golay complementary codes

NASA Astrophysics Data System (ADS)

Elgaud, M. M.; Zan, M. S. D.; Abushagur, A. G.; Bakar, A. Ashrif A.

2017-07-01

This paper reports the employment of autocorrelation properties of Golay complementary codes (GCC) to enhance the performance of the time domain multiplexing fiber Bragg grating (TDM-FBG) sensing network. By encoding the light from laser with a stream of non-return-to-zero (NRZ) form of GCC and launching it into the sensing area that consists of the FBG sensors, we have found that the FBG signals can be decoded correctly with the autocorrelation calculations, confirming the successful demonstration of coded TDM-FBG sensor network. OptiGrating and OptiSystem simulators were used to design customized FBG sensors and perform the coded TDM-FBG sensor simulations, respectively. Results have substantiated the theoretical dependence of SNR enhancement on the code length of GCC, where the maximum SNR improvement of about 9 dB is achievable with the use of 256 bits of GCC compared to that of 4 bits case. Furthermore, the GCC has also extended the strain exposure up to 30% higher compared to the maximum of the conventional single pulse case. The employment of GCC in the TDM-FBG sensor system provides overall performance enhancement over the conventional single pulse case, under the same conditions.

AERMOD as a Gaussian dispersion model for planning tracer gas dispersion tests for landfill methane emission quantification.

PubMed

Matacchiera, F; Manes, C; Beaven, R P; Rees-White, T C; Boano, F; Mønster, J; Scheutz, C

2018-02-13

The measurement of methane emissions from landfills is important to the understanding of landfills' contribution to greenhouse gas emissions. The Tracer Dispersion Method (TDM) is becoming widely accepted as a technique, which allows landfill emissions to be quantified accurately provided that measurements are taken where the plumes of a released tracer-gas and landfill-gas are well-mixed. However, the distance at which full mixing of the gases occurs is generally unknown prior to any experimental campaign. To overcome this problem the present paper demonstrates that, for any specific TDM application, a simple Gaussian dispersion model (AERMOD) can be run beforehand to help determine the distance from the source at which full mixing conditions occur, and the likely associated measurement errors. An AERMOD model was created to simulate a series of TDM trials carried out at a UK landfill, and was benchmarked against the experimental data obtained. The model was used to investigate the impact of different factors (e.g. tracer cylinder placements, wind directions, atmospheric stability parameters) on TDM results to identify appropriate experimental set ups for different conditions. The contribution of incomplete vertical mixing of tracer and landfill gas on TDM measurement error was explored using the model. It was observed that full mixing conditions at ground level do not imply full mixing over the entire plume height. However, when full mixing conditions were satisfied at ground level, then the error introduced by variations in mixing higher up were always less than 10%. Copyright © 2018. Published by Elsevier Ltd.

Attitudes Toward Family Involvement in Cancer Treatment Decision Making: The Perspectives of Patients, Family Caregivers, and Their Oncologists.

PubMed

Shin, Dong Wook; Cho, Juhee; Roter, Debra L; Kim, So Young; Yang, Hyung Kook; Park, Keeho; Kim, Hyung Jin; Shin, Hee-Young; Kwon, Tae Gyun; Park, Jong Hyock

2017-06-01

To investigate how cancer patients, family caregiver, and their treating oncologist view the risks and benefits of family involvement in cancer treatment decision making (TDM) or the degree to which these perceptions may differ. A nationwide, multicenter survey was conducted with 134 oncologists and 725 of their patients and accompanying caregivers. Participant answered to modified Control Preferences Scale and investigator-developed questionnaire regarding family involvement in cancer TDM. Most participants (>90%) thought that family should be involved in cancer TDM. When asked if the oncologist should allow family involvement if the patient did not want them involved, most patients and caregivers (>85%) thought they should. However, under this circumstance, only 56.0% of oncologists supported family involvement. Patients were significantly more likely to skew their responses toward patient rather than family decisional control than were their caregivers (P < .003); oncologists were more likely to skew their responses toward patient rather than family decisional control than caregivers (P < .001). Most respondents thought that family involvement is helpful and neither hamper patient autonomy nor complicate cancer TDM process. Oncologists were largely positive, but less so in these ratings than either patients or caregivers (P < .002). Patients, family caregivers, and, to a lesser degree, oncologists expect and valued family involvement in cancer TDM. These findings support a reconsideration of traditional models focused on protection of patient autonomy to a more contextualized form of relational autonomy, whereby the patient and family caregivers can be seen as a unit for autonomous decision. Copyright © 2016 John Wiley & Sons, Ltd.

A descriptive systematic review of salivary therapeutic drug monitoring in neonates and infants.

PubMed

Hutchinson, Laura; Sinclair, Marlene; Reid, Bernadette; Burnett, Kathryn; Callan, Bridgeen

2018-06-01

Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates. Databases were searched up to and including September 2016. Studies were included based on PICO as follows: P: infants and neonates being treated with any medication, I: salivary TDM vs. C: traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data. Twenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent/very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Any compound with an acid dissociation constant (pKa) within physiological range (pH 6-8) gave a more varied response. There is significant potential for infantile saliva testing and in particular for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude, any compound with a pKa within physiological range (pH 6-8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis. © 2018 The British Pharmacological Society.

Chronic Iron Overload Results in Impaired Bacterial Killing of THP-1 Derived Macrophage through the Inhibition of Lysosomal Acidification

PubMed Central

Kao, Jun-Kai; Wang, Shih-Chung; Ho, Li-Wei; Huang, Shi-Wei; Chang, Shu-Hao; Yang, Rei-Cheng; Ke, Yu-Yuan; Wu, Chun-Ying; Wang, Jiu-Yao; Shieh, Jeng-Jer

2016-01-01

Iron is essential for living organisms and the disturbance of iron homeostasis is associated with altered immune function. Additionally, bacterial infections can cause major complications in instances of chronic iron overload, such as patients with transfusion-dependent thalassemia. Monocytes and macrophages play important roles in maintaining systemic iron homoeostasis and in defense against invading pathogens. However, the effect of iron overload on the function of monocytes and macrophages is unclear. We elucidated the effects of chronic iron overload on human monocytic cell line (THP-1) and THP-1 derived macrophages (TDM) by continuously exposing them to high levels of iron (100 μM) to create I-THP-1 and I-TDM, respectively. Our results show that iron overload did not affect morphology or granularity of I-THP-1, but increased the granularity of I-TDM. Bactericidal assays for non-pathogenic E. coli DH5α, JM109 and pathogenic P. aeruginosa all revealed decreased efficiency with increasing iron concentration in I-TDM. The impaired P. aeruginosa killing ability of human primary monocyte derived macrophages (hMDM) was also found when cells are cultured in iron contained medium. Further studies on the bactericidal activity of I-TDM revealed lysosomal dysfunction associated with the inhibition of lysosomal acidification resulting in increasing lysosomal pH, the impairment of post-translational processing of cathepsins (especially cathepsin D), and decreased autophagic flux. These findings may explain the impaired innate immunity of thalassemic patients with chronic iron overload, suggesting the manipulation of lysosomal function as a novel therapeutic approach. PMID:27244448

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System.

PubMed

Piwko, Charles; Prady, Catherine; Yunger, Simon; Pollex, Erika; Moser, Aurelie

2015-08-01

Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers. An Excel-based model was utilized to estimate the relevant costs. Clinical data were obtained from the EMILIA trial. Cost information was obtained from the literature, clinical experts, and standard cost sources. The analysis was conducted from the Canadian public-payer perspective and reported in 2014 Canadian dollars (CAD). The management of included treatment-related AEs resulted in higher estimated per-patient costs of CAD6901 for CAP + LAP versus CAD3380 for T-DM1, resulting in savings of CAD3521. From a Canadian perspective, this analysis demonstrated that utilizing T-DM1 for the management of HER2-positive metastatic breast cancer results in substantial savings to the public health-care system when considering the costs of treatment-related AEs, due to fewer amount of toxicities compared with CAP + LAP. Results of various sensitivity analyses investigating changes in number and costs of AEs confirmed the findings; however, the magnitude of cost savings varied. Further analyses are necessary to determine whether these cost savings would occur in other countries and health-care systems.

NASA Technology Demonstrations Missions Program Overview

NASA Technical Reports Server (NTRS)

Turner, Susan

2011-01-01

The National Aeronautics and Space Administration (NASA) Fiscal Year 2010 (FY10) budget introduced a new strategic plan that placed renewed emphasis on advanced missions beyond Earth orbit. This supports NASA s 2011 strategic goal to create innovative new space technologies for our exploration, science, and economic future. As a result of this focus on undertaking many and more complex missions, NASA placed its attention on a greater investment in technology development, and this shift resulted in the establishment of the Technology Demonstrations Missions (TDM) Program. The TDM Program, within the newly formed NASA Office of the Chief Technologist, supports NASA s grand challenges by providing a steady cadence of advanced space technology demonstrations (Figure 1), allowing the infusion of flexible path capabilities for future exploration. The TDM Program's goal is to mature crosscutting capabilities to flight readiness in support of multiple future space missions, including flight test projects where demonstration is needed before the capability can transition to direct mission The TDM Program has several unique criteria that set it apart from other NASA program offices. For instance, the TDM Office matures a small number of technologies that are of benefit to multiple customers to flight technology readiness level (TRL) 6 through relevant environment testing on a 3-year development schedule. These technologies must be crosscutting, which is defined as technology with potential to benefit multiple mission directorates, other government agencies, or the aerospace industry, and they must capture significant public interest and awareness. These projects will rely heavily on industry partner collaboration, and funding is capped for all elements of the flight test demonstration including planning, hardware development, software development, launch costs, ground operations, and post-test assessments. In order to inspire collaboration across government and industry

Centaur operations at the space station

NASA Technical Reports Server (NTRS)

Porter, J.; Thompson, W.; Bennett, F.; Holdridge, J.

1987-01-01

A study was conducted on the feasibility of using a Centaur vehicle as a testbed to demonstrate critical OTV technologies at the Space Station. Two Technology Demonstration Missions (TDMs) were identified: (1) Accommodations, and (2) Operations. The Accommodations TDM contained: (1) berthing, (2) checkout, maintenance and safing, and (3) payload integration missions. The Operations TDM contained: (1) a cryogenic propellant resupply mission, and (2) Centaur deployment activities. A modified Space Station Co-Orbiting Platform (COP) was selected as the optimum refueling and launch node due to safety and operational considerations. After completion of the TDMs, the fueled Centaur would carry out a mission to actually test deployment and help offset TDM costs. From the Station, the Centaur could carry a single payload in excess of 20,000 pounds to geosynchronous orbit or multiple payloads.

Use of First-phase Insulin Secretion in Early Diagnosis of Thyroid Diabetes and Type 2 Diabetes Mellitus

PubMed Central

Meng, Li-Heng; Huang, Yao; Zhou, Jia; Liang, Xing-Huan; Xian, Jing; Li, Li; Qin, Ying-Fen

2017-01-01

Background: A relationship between hyperthyroidism and insulin secretion in type 2 diabetes mellitus (T2DM) has been reported. Therefore, this study explored the use of first-phase insulin secretion in the differential diagnosis of thyroid diabetes (TDM) and T2DM. Methods: In total, 101 patients with hyperthyroidism were divided into hyperthyroidism with normal glucose tolerance (TNGT), hyperthyroidism with impaired glucose regulation (TIGR), and diabetes (TDM) groups. Furthermore, 96 patients without hyperthyroidism were recruited as control groups (normal glucose tolerance [NGT], impaired glucose regulation [IGR], and T2DM). The following parameters were evaluated: homeostasis model assessment (HOMA)-IR, HOMA-β, modified β-cell function index (MBCI), peak insulin/fasting insulin (IP/I0), AUCins-OGTT, and AUCins-OGTT/AUCglu-OGTT from the oral glucose tolerance test (OGTT) insulin release test were utilized to assess the second-phase insulin secretion, while the IP/I0, AIR0′~10′, and AUCins-IVGTT from the intravenous glucose tolerance test (IVGTT) insulin release test were used to assess the first-phase insulin secretion. Results: In the OGTT, the HOMA-β values of the TNGT and TDM groups were higher than those of the NGT and T2DM groups (all P < 0.05). In the hyperthyroidism groups, the MBCI of the TDM group was lower than that of the TNGT and TIGR groups (all P < 0.05). Among the control groups, the MBCI values of the IGR and T2DM groups were lower than that of the normal glucose tolerance (NGT) group (all P < 0.05). In the IVGTT, insulin secretion peaked for all groups at 2–4 min, except for the T2DM group, which showed a low plateau and no secretion peak. The IP values of the TNGT, TIGR, and TDM groups were higher than those of the NGT, IGR, and T2DM groups (all P < 0.05). The Ip/I0, AIR0′~10′, and AUCins-IVGTT values of the TDM group were higher than those of the T2DM group but were lower than those of the TNGT, TIGR, NGR, and IGR groups (all P < 0

[Therapeutic monitoring: analytic, pharmacokinetic and clinical aspects].

PubMed

Marquet, P

1999-01-01

This paper gives an overview of present aspects and future prospects of therapeutic drug monitoring (TDM). The main aims of TDM are to avoid therapeutic failures due to bad compliance or too low dose of a given drug, as well as adverse or toxic effects due to an excessive dose. The therapeutic drugs frequently monitored depend on the country, but are generally few. For some of these drugs or for others, only patients at risk or belonging to particular sub-populations for a given drug, need TDM. A pre-analytical management is necessary, comprising a correct information of the physician, concerning the nature of the sample to collect and the clinical data necessary to the interpretation, as well as their recording; the control of the sample routing and storing conditions. Nowadays, drug analyses are essentially performed using immunochemical techniques, rapid and easy to operate but limited to a small number of drugs, and chromatographic methods, more specific and adaptable to almost any therapeutic drug and financially and technically more and more accessible. The interpretation of analytical results is a most important part of TDM, which requires knowledge of clinical data, precise collection time, co-administered treatments, and to dispose of a previously defined therapeutic range or target concentration, adapted to the population to which the patient belongs; the limitations of the analytical technique used must also be considered. Clinical pharmacokinetics is a further step in the use of analytical results, allowing the prediction of an efficient dose and administration schedule in one step, using a limited number of blood samples and generally a Bayesian estimation algorithm, readily available through commercial software dedicated to a few drugs in different reference populations. The pharmacokinetic characteristics of different populations and the validation of bayesian estimation have also been published for a number of drugs, sometimes by pharmaceutical

Trehalose Dimycolate Enhances Survival of Fission Neutron-Irradiated Mice and Klebsiella pneumoniae-Challenged Irradiated Mice

DTIC Science & Technology

1990-01-01

SR90-5 Trehalose Dimycolate Enhances Survival of Fission Neutron-Irradiated Mice and Kiebsiella pneumoniae-Challenged Irradiated Mice 1’ 2 D. (. M...doses kines and immunomodulators of nonspecific resistance to of fission neutron radiation is increased when trehalose dimycol- infection might have... trehalose day before exposure to radiation. TDM in an emulsion of squa- dimycolate (TDM) have been shown to be effective in in- lene. Tween 80, and saline

Therapeutic Drug Monitoring of Lacosamide in Norway: Focus on Pharmacokinetic Variability, Efficacy and Tolerability.

PubMed

Svendsen, Torleiv; Brodtkorb, Eylert; Baftiu, Arton; Burns, Margrete Larsen; Johannessen, Svein I; Johannessen Landmark, Cecilie

2017-07-01

Lacosamide (LCM) is a new antiepileptic drug (AED). Experience from therapeutic drug monitoring (TDM) in clinical practice is limited. The purpose of this study is to evaluate the pharmacokinetic variability of LCM in relation to efficacy and tolerability in patients with refractory epilepsy in a real-life setting. Variables included age, gender, daily doses and serum concentrations of LCM and other AEDs from the TDM-database at the National Center for Epilepsy in Norway. Clinical data regarding efficacy and tolerability were collected from medical records. The Norwegian Prescription Database (NorPD) was used to include population-based numbers of users. TDM-data from 344 patients were included. The median dose, serum concentration, and concentration/dose (C/D)-ratio of LCM was 350 (range 25-700) mg/day, 19.7 (range 8.1-56.2) µmol/L, and 0.06 (0.02-0.82) µmol/L/mg, respectively. Serum concentrations were reduced by 28% by concomitant use of enzyme inducers and increased by 30% in patients aged >65 years. Efficacy and tolerability were assessed in 227 patients: 29% had >50% seizure reduction (eight seizure free), 30% had no effect, and 44% reported adverse effects. In Norway, there were on average 500 patients per year using LCM in this period based on NorPD. The study demonstrated pharmacokinetic variability and use of TDM of LCM in Norway. Data were collected from multiple sources for improved pharmacovigilance. Serum concentrations were influenced by enzyme inducers and ageing, indicating the usefulness of TDM. Effect and tolerability were favorable within a suggested reference range of 10-40 µmol/L given drug-fasting conditions.

An audit of therapeutic drug monitoring services of anticonvulsants at a tertiary care hospital in India.

PubMed

Taur, Santosh R; Kulkarni, Namrata B; Gogtay, Nithya J; Thatte, Urmila M

2013-04-01

Therapeutic drug monitoring (TDM) is an important adjunct to the treatment of epilepsy. However, few studies have actually correlated plasma levels of antiepileptic drugs (AEDs) with treatment response. The present audit aimed to study (i) the association between seizure control and number of AEDs, plasma AED concentration, and concomitant use of antitubercular drugs; (ii) the pattern of indications for TDM requisitions; and (iii) the association between referral for toxicity and plasma AED concentration. This observational and retrospective study was carried out to analyze the TDM data of patients referred between January 2008 and December 2011. As per the International League Against Epilepsy Task Force 2009, patients were categorized into responders and nonresponders. Plasma AED levels were interpreted as below, within, and above the reference range. Of 3206 TDM requisitions, 67% were monotherapy and 33% were 2 or more AEDs. Only 8% were responders as against 92% nonresponders. Of 95 patients on concomitant antituberculosis treatment, 72 were nonresponders, with odds ratio (95% confidence interval) 3.71 [2.19 to 6.23]. Breakthrough seizure (37%) was the most common indication followed by suspected toxicity and routine monitoring in 22% each and suspected nonadherence in 11% of the total requests. In 52% of patients, plasma levels were below the reference range, and they were equally distributed amongst responders and nonresponders. Among patients referred for suspected phenytoin toxicity, only 59% (50.6 to 67.8) had plasma concentrations above the reference range. TDM continues to remain an important tool to support dose individualization when the patient is receiving multiple AEDs or other drugs such as antitubercular medicines, to assess compliance, and to monitor and treat toxicity.

Cost-effectiveness of drug monitoring of anti-TNF therapy in inflammatory bowel disease and rheumatoid arthritis: a systematic review.

PubMed

Martelli, Laura; Olivera, Pablo; Roblin, Xavier; Attar, Alain; Peyrin-Biroulet, Laurent

2017-01-01

Therapeutic drug monitoring (TDM) of anti-TNF is increasingly used to manage inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA). The cost-effectiveness of this strategy is debated. All studies comparing the cost-effectiveness of a TDM-based strategy and an empirical dose management of anti-TNF in IBD or RA were screened. Studies were identified through the MEDLINE electronic database (up to July 2016), and annual international meeting abstracts were also manually reviewed. Seven studies were included: two randomized controlled trials (RCTs) enrolling 332 patients [247 Crohn's disease (CD) and 85 ulcerative colitis (UC)] and five modeling approaches. Four studies included only CD patients, one included both CD and UC patients, and two included only RA patients. Three studies compared the cost-effectiveness of the two strategies in patients with secondary infliximab (IFX) failure (dose-escalation strategy), one in patients in remission on optimized IFX (de-escalation strategy), one in patients starting adalimumab, and two in patients with clinical response to maintenance anti-TNF therapy. The two RCTs demonstrated that a TDM strategy led to major cost savings, ranging from 28 to 34 %. The three modeling approaches with regard to CD patients demonstrated cost savings ranging from $5396 over a 1-year period to €13,130 per patient at 5 years of follow-up. A TDM strategy also led to major cost savings in the two modeling approaches in RA patients. Available evidence indicates that a TDM strategy leads to major cost savings related to anti-TNF therapy in both IBD and RA patients, with no negative impact on efficacy.

Team Development Measure in Interprofessional Graduate Education: A Pilot Study.

PubMed

Beebe, Lora Humphrey; Roman, Marian; Skolits, Gary; Raynor, Hollie; Thompson, Dixie; Franks, Andrea

2018-04-01

A faculty team developed the 4-week Recovery-Based Interprofessional Distance Education (RIDE) rotation for graduate students in their disciplines. The evaluation team identified the Team Development Measure (TDM) as a potential alternative to reflect team development during the RIDE rotation. The TDM, completed anonymously online, was piloted on the second student cohort (N = 18) to complete the RIDE rotation. The overall pretest mean was 60.73 points (SD = 11.85) of a possible 100 points, indicating that students anticipated their RIDE team would function at a moderately high level during the 4-week rotation. The overall posttest mean, indicating student perceptions of actual team functioning, was 72.71 points (SD = 23.31), an average increase of 11.98 points. Although not statistically significant, Cohen's effect size (d = 0.43) indicates an observed difference of large magnitude. No other published work has used the TDM as a pre-/posttest measure of team development. The authors believe the TDM has several advantages as a measure of student response to interprofessional education offerings, particularly in graduate students with prior experience on health care teams. Further work is needed to validate and extend the findings of this pilot study. [Journal of Psychosocial Nursing and Mental Health Services, 56(4), 18-22.]. Copyright 2018, SLACK Incorporated.

Cancers biliaires: aspects épidémiologiques cliniques et thérapeutiques à propos de 20 cas

PubMed Central

Ka, Ibrahima; Faye, Magatte; Diop, Papa Saloum; Faye, Amadou Bocar Niang Aliou Coly; Ndoye, Jean Marc; Fall, Babacar

2018-01-01

Les cancers des voies biliaires se répartissent en deux localisations principales: les cancers de la vésicule biliaire qui sont des adénocarcinomes et les cholangiocarcinomes de localisations intra et extra-hépatiques. Il s'agit étude rétrospective portant sur 20 cas de cancers biliaires entre Janvier 2006 et Octobre 2014 à la clinique chirurgicale de l'Hôpital Général de Grand- Yoff. Il s'agissait de 40% de cancer de la vésicule biliaire, 60% de cancer de la voie biliaire principale. Le sex-ratio était de 1. L'âge moyen de nos patients était de 58,1 ans. Le délai diagnostique moyen était de 3,77 mois. La symptomatologie était dominée par le syndrome ictérique et les douleurs de l'hypochondre droit. Tous les patients avaient présenté un syndrome de cholestase biologique. L'échographie abdominale a été réalisée dans 65% des cas, la TDM abdominale dans 85% des cas et L'IRM dans 35% des cas. Les formes avancées étaient prédominantes dans notre série (n=19).La majorité de nos patients a bénéficié d'une chirurgie palliative. Le geste le plus pratiqué était la dérivation biliaire chez 50% des patients. On notait une prédominance des cholangiocarcinomes. La morbidité opératoire globale était de 43,75%. La mortalité globale toutes localisations confondues était de 31,25%. La moyenne de survie est de 4 mois et demi. Les cancers des voies biliaires sont d'expression multiforme, se différenciant essentiellement en un cholangiocarcinome intra, extrahépatique et adénocarcinome de la vésicule biliaire dont l'évolution est globalement différente mais le pronostic spontanément mauvais. PMID:29662598

TDM Status Report: Transportation Allowances

DOT National Transportation Integrated Search

1992-08-01

The status report discusses the following travel allowance programs that provide subsidies to employees in one form or another: transit fare allowances or subsidies; vanpool fare allowances; parking allowances or free parking; and general travel allo...

Nitrogen and plant population change radiation capture and utilization capacity of sunflower in semi-arid environment.

PubMed

Awais, Muhammad; Wajid, Aftab; Bashir, Muhammad Usman; Habib-Ur-Rahman, Muhammad; Raza, Muhammad Aown Sammar; Ahmad, Ashfaq; Saleem, Muhammad Farrukh; Hammad, Hafiz Mohkum; Mubeen, Muhammad; Saeed, Umer; Arshad, Muhammad Naveed; Fahad, Shah; Nasim, Wajid

2017-07-01

The combination of nitrogen and plant population expresses the spatial distribution of crop plants. The spatial distribution influences canopy structure and development, radiation capture, accumulated intercepted radiation (Sa), radiation use efficiency (RUE), and subsequently dry matter production. We hypothesized that the sunflower crop at higher plant populations and nitrogen (N) rates would achieve early canopy cover, capture more radiant energy, utilize radiation energy more efficiently, and ultimately increase economic yield. To investigate the above hypothesis, we examined the influences of leaf area index (LAI) at different plant populations (83,333, 66,666, and 55,555 plants ha -1 ) and N rates (90, 120, and 150 kg ha -1 ) on radiation interception (Fi), photosynthetically active radiation (PAR) accumulation (Sa), total dry matter (TDM), achene yield (AY), and RUE of sunflower. The experimental work was conducted during 2012 and 2013 on sandy loam soil in Punjab, Pakistan. The sunflower crop captured more than 96% of incident radiant energy (mean of all treatments), 98% with a higher plant population (83,333 plants ha -1 ), and 97% with higher N application (150 kg ha -1 ) at the fifth harvest (60 days after sowing) during both study years. The plant population of 83,333 plants ha -1 with 150 kg N ha -1 ominously promoted crop, RUE, and finally productivity of sunflower (AY and TDM). Sunflower canopy (LAI) showed a very close and strong association with Fi (R 2  = 0.99 in both years), PAR (R 2  = 0.74 and 0.79 in 2012 and 2013, respectively), TDM (R 2  = 0.97 in 2012 and 0.91 in 2013), AY (R 2  = 0.95 in both years), RUE for TDM (RUE TDM ) (R 2  = 0.63 and 0.71 in 2012 and 2013, respectively), and RUE for AY (RUE AY ) (R 2  = 0.88 and 0.87 in 2012 and 2013, respectively). Similarly, AY (R 2  = 0.73 in 2012 and 0.79 in 2013) and TDM (R 2  = 0.75 in 2012 and 0.84 in 2013) indicated significant dependence on PAR accumulation of

Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity.

PubMed

Ogitani, Yusuke; Hagihara, Katsunobu; Oitate, Masataka; Naito, Hiroyuki; Agatsuma, Toshinori

2016-07-01

Antibody-drug conjugates deliver anticancer agents selectively and efficiently to tumor tissue and have significant antitumor efficacy with a wide therapeutic window. DS-8201a is a human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate prepared using a novel linker-payload system with a potent topoisomerase I inhibitor, exatecan derivative (DX-8951 derivative, DXd). It was effective against trastuzumab emtansine (T-DM1)-insensitive patient-derived xenograft models with both high and low HER2 expression. In this study, the bystander killing effect of DS-8201a was evaluated and compared with that of T-DM1. We confirmed that the payload of DS-8201a, DXd (1), was highly membrane-permeable whereas that of T-DM1, Lys-SMCC-DM1, had a low level of permeability. Under a coculture condition of HER2-positive KPL-4 cells and negative MDA-MB-468 cells in vitro, DS-8201a killed both cells, whereas T-DM1 and an antibody-drug conjugate with a low permeable payload, anti-HER2-DXd (2), did not. In vivo evaluation was carried out using mice inoculated with a mixture of HER2-positive NCI-N87 cells and HER2-negative MDA-MB-468-Luc cells by using an in vivo imaging system. In vivo, DS-8201a reduced the luciferase signal of the mice, indicating suppression of the MDA-MB-468-Luc population; however, T-DM1 and anti-HER2-DXd (2) did not. Furthermore, it was confirmed that DS-8201a was not effective against MDA-MB-468-Luc tumors inoculated at the opposite side of the NCI-N87 tumor, suggesting that the bystander killing effect of DS-8201a is observed only in cells neighboring HER2-positive cells, indicating low concern in terms of systemic toxicity. These results indicated that DS-8201a has a potent bystander effect due to a highly membrane-permeable payload and is beneficial in treating tumors with HER2 heterogeneity that are unresponsive to T-DM1. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer

Interventions et techniques de diagnostic prénatal visant l'obtention d'un prélèvement fœtal à des fins diagnostiques : Risques et avantages pour la mère et le fœtus.

PubMed

Wilson, R Douglas; Gagnon, Alain; Audibert, François; Campagnolo, Carla; Carroll, June

2016-12-01

Offrir aux fournisseurs de soins de maternité et à leurs patientes des lignes directrices factuelles contemporaines en ce qui concerne les services de counseling traitant des risques et des avantages maternels propres à la tenue des interventions diagnostiques prénatales orientées par échographie (et/ou des techniques permettant l'établissement d'un diagnostic génétique) nécessaires dans les cas où il a été établi pendant la période prénatale que la grossesse serait exposée à des risques, ainsi qu'en ce qui concerne la prise de décisions subséquentes quant à la prise en charge de la grossesse (questions abordant des aspects tels que le niveau du fournisseur de soins obstétricaux, la surveillance prénatale, le lieu où devraient se dérouler les soins et l'accouchement, et la décision de poursuivre ou d'interrompre la grossesse). La présente directive clinique se limite aux services de counseling traitant des risques et des avantages maternels, et aux décisions en matière de prise en charge de la grossesse pour les femmes qui nécessitent (ou qui envisagent) la mise en œuvre d'une intervention ou d'une technique effractive orientée par échographie aux fins de l'établissement d'un diagnostic prénatal. Femmes enceintes identifiées, à la suite de la mise en œuvre de protocoles établis de dépistage prénatal (taux sériques maternels ± imagerie, résultats d'analyse de l'ADN acellulaire indiquant des risques élevés, résultats anormaux au moment de l'imagerie fœtale diagnostique ou antécédents familiaux de troubles héréditaires), comme étant exposées à un risque accru d'anomalie génétique fœtale. Ces femmes pourraient nécessiter ou demander des services de counseling au sujet des risques et des avantages pour la grossesse de la tenue d'une intervention effractive orientée par échographie visant à déterminer l'étiologie, le diagnostic, et/ou la pathologie de possibles anomalies fœtales. RéSULTATS: La litt

Pharmacokinetic variability, efficacy and tolerability of eslicarbazepine acetate-A national approach to the evaluation of therapeutic drug monitoring data and clinical outcome.

PubMed

Svendsen, Torleiv; Brodtkorb, Eylert; Reimers, Arne; Molden, Espen; Sætre, Erik; Johannessen, Svein I; Johannessen Landmark, Cecilie

2017-01-01

Eslicarbazepine acetate (ESL) is a new antiepileptic drug (AED), still insufficiently studied regarding pharmacokinetic variability, efficacy and tolerability. The purpose of this study was to evaluate therapeutic drug monitoring (TDM) data in Norway and relate pharmacokinetic variability to clinical efficacy and tolerability in a long-term clinical setting in patients with refractory epilepsy. This retrospective observational study included TDM-data from the main laboratories and population data from the Norwegian Prescription Database in Norway, in addition to clinical data from medical records of adult patients using ESL for up to three years, whenever possible. TDM-data from 168 patients were utilized for assessment of pharmacokinetic variability, consisting of 71% of the total number of patients in Norway using ESL, 2011-14. Median daily dose of ESL was 800mg (range 400-1600mg), and median serum concentration of ESL was 53μmol/L (range 13-132μmol/L). Inter-patient variability of ESL was extensive, with 25-fold variability in concentration/dose ratios. Additional clinical data were available from 104 adult patients out of the 168, all with drug resistant focal epilepsy. After 1, 2 and 3 years follow-up, the retention rate of ESL was 83%, 72% and 64%, respectively. ESL was generally well tolerated as add-on treatment, but sedation, cognitive impairment and hyponatremia were reported. Hyponatremia (sodium <137mmol/L) was present in 36% of the patients, and lead to discontinuation in three. Pharmacokinetic variability of ESL was extensive and the demonstration of usefulness of TDM requires further studies. In patients with drug resistant focal Epilepsy, the high retention rate indicated good efficacy and tolerability. Hyponatremia was observed in one third of the patients. The present results point to a need for individualization of treatment and TDM may be useful. Copyright © 2016 Elsevier B.V. All rights reserved.

Improved accuracy and precision in δ15 NAIR measurements of explosives, urea, and inorganic nitrates by elemental analyzer/isotope ratio mass spectrometry using thermal decomposition.

PubMed

Lott, Michael J; Howa, John D; Chesson, Lesley A; Ehleringer, James R

2015-08-15

Elemental analyzer systems generate N(2) and CO(2) for elemental composition and isotope ratio measurements. As quantitative conversion of nitrogen in some materials (i.e., nitrate salts and nitro-organic compounds) is difficult, this study tests a recently published method - thermal decomposition without the addition of O(2) - for the analysis of these materials. Elemental analyzer/isotope ratio mass spectrometry (EA/IRMS) was used to compare the traditional combustion method (CM) and the thermal decomposition method (TDM), where additional O(2) is eliminated from the reaction. The comparisons used organic and inorganic materials with oxidized and/or reduced nitrogen and included ureas, nitrate salts, ammonium sulfate, nitro esters, and nitramines. Previous TDM applications were limited to nitrate salts and ammonium sulfate. The measurement precision and accuracy were compared to determine the effectiveness of converting materials containing different fractions of oxidized nitrogen into N(2). The δ(13) C(VPDB) values were not meaningfully different when measured via CM or TDM, allowing for the analysis of multiple elements in one sample. For materials containing oxidized nitrogen, (15) N measurements made using thermal decomposition were more precise than those made using combustion. The precision was similar between the methods for materials containing reduced nitrogen. The %N values were closer to theoretical when measured by TDM than by CM. The δ(15) N(AIR) values of purchased nitrate salts and ureas were nearer to the known values when analyzed using thermal decomposition than using combustion. The thermal decomposition method addresses insufficient recovery of nitrogen during elemental analysis in a variety of organic and inorganic materials. Its implementation requires relatively few changes to the elemental analyzer. Using TDM, it is possible to directly calibrate certain organic materials to international nitrate isotope reference materials without off

Dried Blood Spots Combined With Ultra-High-Performance Liquid Chromatography-Mass Spectrometry for the Quantification of the Antipsychotics Risperidone, Aripiprazole, Pipamperone, and Their Major Metabolites.

PubMed

Tron, Camille; Kloosterboer, Sanne M; van der Nagel, Bart C H; Wijma, Rixt A; Dierckx, Bram; Dieleman, Gwen C; van Gelder, Teun; Koch, Birgit C P

2017-08-01

Risperidone, aripiprazole, and pipamperone are antipsychotic drugs frequently prescribed for the treatment of comorbid behavioral problems in children with autism spectrum disorders. Therapeutic drug monitoring (TDM) could be useful to decrease side effects and to improve patient outcome. Dried blood spot (DBS) sample collection seems to be an attractive technique to develop TDM of these drugs in a pediatric population. The aim of this work was to develop and validate a DBS assay suitable for TDM and home sampling. Risperidone, 9-OH risperidone, aripiprazole, dehydroaripiprazole, and pipamperone were extracted from DBS and analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry using a C18 reversed-phase column with a mobile phase consisting of ammonium acetate/formic acid in water or methanol. The suitability of DBS for TDM was assessed by studying the influence of specific parameters: extraction solution, EDTA carryover, hematocrit, punching location, spot volume, and hemolysis. The assay was validated with respect to conventional guidelines for bioanalytical methods. The method was linear, specific without any critical matrix effect, and with a mean recovery around 90%. Accuracy and imprecision were within the acceptance criteria in samples with hematocrit values from 30% to 45%. EDTA or hemolysis did not skew the results, and no punching carryover was observed. No significant influence of the spot volume or the punch location was observed. The antipsychotics were all stable in DBS stored 10 days at room temperature and 1 month at 4 or -80°C. The method was successfully applied to quantify the 3 antipsychotics and their metabolites in patient samples. A UHPLC-MS/MS method has been successfully validated for the simultaneous quantification of risperidone, 9-OH risperidone, aripiprazole, dehydroaripiprazole, and pipamperone in DBS. The assay provided good analytical performances for TDM and clinical research applications.

CGDM: collaborative genomic data model for molecular profiling data using NoSQL.

PubMed

Wang, Shicai; Mares, Mihaela A; Guo, Yi-Ke

2016-12-01

High-throughput molecular profiling has greatly improved patient stratification and mechanistic understanding of diseases. With the increasing amount of data used in translational medicine studies in recent years, there is a need to improve the performance of data warehouses in terms of data retrieval and statistical processing. Both relational and Key Value models have been used for managing molecular profiling data. Key Value models such as SeqWare have been shown to be particularly advantageous in terms of query processing speed for large datasets. However, more improvement can be achieved, particularly through better indexing techniques of the Key Value models, taking advantage of the types of queries which are specific for the high-throughput molecular profiling data. In this article, we introduce a Collaborative Genomic Data Model (CGDM), aimed at significantly increasing the query processing speed for the main classes of queries on genomic databases. CGDM creates three Collaborative Global Clustering Index Tables (CGCITs) to solve the velocity and variety issues at the cost of limited extra volume. Several benchmarking experiments were carried out, comparing CGDM implemented on HBase to the traditional SQL data model (TDM) implemented on both HBase and MySQL Cluster, using large publicly available molecular profiling datasets taken from NCBI and HapMap. In the microarray case, CGDM on HBase performed up to 246 times faster than TDM on HBase and 7 times faster than TDM on MySQL Cluster. In single nucleotide polymorphism case, CGDM on HBase outperformed TDM on HBase by up to 351 times and TDM on MySQL Cluster by up to 9 times. The CGDM source code is available at https://github.com/evanswang/CGDM. y.guo@imperial.ac.uk. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.

PubMed

Cilliers, Cornelius; Menezes, Bruna; Nessler, Ian; Linderman, Jennifer; Thurber, Greg M

2018-02-01

Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo , yet improves the effectiveness of T-DM1 in vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758-68. ©2017 AACR . ©2017 American Association for Cancer Research.

Developments in Time-Division Multiplexing of X-ray Transition-Edge Sensors

NASA Astrophysics Data System (ADS)

Doriese, W. B.; Morgan, K. M.; Bennett, D. A.; Denison, E. V.; Fitzgerald, C. P.; Fowler, J. W.; Gard, J. D.; Hays-Wehle, J. P.; Hilton, G. C.; Irwin, K. D.; Joe, Y. I.; Mates, J. A. B.; O'Neil, G. C.; Reintsema, C. D.; Robbins, N. O.; Schmidt, D. R.; Swetz, D. S.; Tatsuno, H.; Vale, L. R.; Ullom, J. N.

2016-07-01

Time-division multiplexing (TDM) is a mature scheme for the readout of arrays of transition-edge sensors (TESs). TDM is based on superconducting-quantum-interference-device (SQUID) current amplifiers. Multiple spectrometers based on gamma-ray and X-ray microcalorimeters have been operated with TDM readout, each at the scale of 200 sensors per spectrometer, as have several astronomical cameras with thousands of sub-mm or microwave bolometers. Here we present the details of two different versions of our TDM system designed to read out X-ray TESs. The first has been field-deployed in two 160-sensor (8 columns × 20 rows) spectrometers and four 240-sensor (8 columns × 30 rows) spectrometers. It has a three-SQUID-stage architecture, switches rows every 320 ns, and has total readout noise of 0.41 μ Φ 0 / surd Hz. The second, which is presently under development, has a two-SQUID-stage architecture, switches rows every 160 ns, and has total readout noise of 0.19 μ Φ 0 / surd Hz. Both quoted noise values are non-multiplexed and referred to the first-stage SQUID. In a demonstration of this new architecture, a multiplexed 1-column × 32-row array of NIST TESs achieved average energy resolution of 2.55± 0.01 eV at 6 keV.

Xenogeneic Bio-Root Prompts the Constructive Process Characterized by Macrophage Phenotype Polarization in Rodents and Nonhuman Primates.

PubMed

Li, Hui; Sun, Jingjing; Li, Jie; Yang, Hefeng; Luo, Xiangyou; Chen, Jinlong; Xie, Li; Huo, Fangjun; Zhu, Tian; Guo, Weihua; Tian, Weidong

2017-03-01

Tissue or organ regeneration using xenogeneic matrices is a promising approach to address the shortage of donor matrices for allotransplantation. Success of such approach has been demonstrated to correlate with macrophage-mediated fibrotic homeostasis and tissue remodeling. The previous studies have demonstrated that treated dentin matrix (TDM) could be a suitable bioactive substrate for allogeneic tooth root regeneration. This study constructed xenogeneic bioengineered tooth root (bio-root) via a combination of porcine TDM (pTDM) with allogeneic dental follicle cells (DFCs). Macrophage phenotypes are used to evaluate the remodeling process of xenogeneic bio-roots in vitro and in vivo. pTDM can facilitate odontoblast differentiation of human derived DFCs. Xenogeneic bio-roots in rat subcutaneous tissue prompt constructive response via M1 macrophage infiltration during early postimplantation stages and increase restorative M2 phenotype at later stages. After implantation of bio-roots into jaws of rhesus monkeys for six months, periodontal ligament-like fibers accompanied by macrophage polarization are observed, which are positive for COL-1, Periostin, βIII-tubulin and display such structures as fibroblasts and blood vessels. The reconstructed bio-root possesses biomechanical properties for the dissipation of masticatory forces. These results support that xenogeneic bio-root could maintain fibrotic homeostasis during remodeling process and highlight the potential application of xenogeneic matrices in regenerative medicine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymorphisme de l'apolipoprotéine E dans la population du nord du Maroc: fréquence et influence sur les paramètres lipidiques

PubMed Central

Benyahya, Fatiha; Barakat, Amina; Ghailani, Naima; Bennani, Mohcine

2013-01-01

Introduction L'objectif de ce travail est de déterminer les fréquences alléliques et génotypiques des sites polymorphes situés dans le gène de l'apolipoprotéine E (apo E) ainsi que leur impact sur les paramètres cliniques et lipidiques dans un échantillon de la population du nord du Maroc cliniquement diagnostiqué ADH. Méthodes Le génotype de l'apo E a été analysé par séquençage direct chez 46 patients cliniquement diagnostiqués ADH selon les critères standards. Résultats Les fréquences des allèles epsilon 3, epsilon 2 et epsilon 4 ont été respectivement 78.3%, 2.2% et 19.6%. La fréquence de l'allèle epsilon 4 est très élevée chez la population du nord du Maroc en comparaison avec les populations des autres régions marocaines. Elle est similaire à celle rapportée dans les pays de l'Europe du nord. Les taux du cholestérol total, du cholestérol LDL ainsi que la présence des xanthomes et les maladies cardiovasculaires ne différent pas entre les génotypes de l'apoE. En revanche, les résultats ont montré une influence de l'allèle epsilon4 sur le taux des triglycérides chez les sujets obèses. Conclusion Le génotype de l'apoE ne peut expliquer le phénotype clinique et biochimique présenté par des patients du Nord du Maroc cliniquement diagnostiqués ADH. PMID:24396563

Therapeutic drug monitoring of psychotropic medications

PubMed Central

Mitchell, Philip B

2000-01-01

Therapeutic drug monitoring (TDM) of a number of psychotropic medications has proven to be of value, enabling minimization of the limitations of considerable genetic variability in their metabolism and the high rates of poor compliance with many psychiatric disorders. Therapeutic ranges have been established for lithium, some of the tricyclic antidepressants, and clozapine. TDM has also been shown to be useful in avoiding toxicity (as many psychotropics have narrow therapeutic indices), particularly that due to interactions with other compounds. PMID:10759685

Effect of Shot Noise on Simultaneous Sensing in Frequency Division Multiplexed Diffuse Optical Tomographic Imaging Process.

PubMed

Jang, Hansol; Lim, Gukbin; Hong, Keum-Shik; Cho, Jaedu; Gulsen, Gultekin; Kim, Chang-Seok

2017-11-28

Diffuse optical tomography (DOT) has been studied for use in the detection of breast cancer, cerebral oxygenation, and cognitive brain signals. As optical imaging studies have increased significantly, acquiring imaging data in real time has become increasingly important. We have developed frequency-division multiplexing (FDM) DOT systems to analyze their performance with respect to acquisition time and imaging quality, in comparison with the conventional time-division multiplexing (TDM) DOT. A large tomographic area of a cylindrical phantom 60 mm in diameter could be successfully reconstructed using both TDM DOT and FDM DOT systems. In our experiment with 6 source-detector (S-D) pairs, the TDM DOT and FDM DOT systems required 6.18 and 1 s, respectively, to obtain a single tomographic data set. While the absorption coefficient of the reconstruction image was underestimated in the case of the FDM DOT, we experimentally confirmed that the abnormal region can be clearly distinguished from the background phantom using both methods.

Centaur operations at the space station: Cost and transportation analysis

NASA Technical Reports Server (NTRS)

1988-01-01

A study was conducted to expand on the results of an initial study entitled Centaur Operations at the Space Station. The previous study developed technology demonstration missions (TDMs) that utilized the Centaur G-prime upper stage to advance OTV technologies required for accomodations and operations at the Space Station. An initial evaluation was performed of the cost to NASA for TDM implementation. Due to the potential for commercial communication satellite operation utilizing the TDM hardware, an evaluation of the Centaur's transportation potential was also performed.

Equivalence of time-multiplexed and frequency-multiplexed signals in digital communications.

NASA Technical Reports Server (NTRS)

Timor, U.

1972-01-01

In comparing different techniques for multiplexing N binary data signals into a single channel, time-division multiplexing (TDM) is known to have a theoretic efficiency of 100 percent (neglecting sync power) and thus seems to outperform frequency-division multiplexing systems (FDM). By considering more general FDM systems, we will show that both TDM and FDM are equivalent and have an efficiency of 100 percent. The difference between the systems is in the multiplexing and demultiplexing subsystems, but not in the performance or in the generated waveforms.

Therapeutic Drug Monitoring of Phenytoin by Simple, Rapid, Accurate, Highly Sensitive and Novel Method and Its Clinical Applications.

PubMed

Shaikh, Abdul S; Guo, Ruichen

2017-01-01

Phenytoin has very challenging pharmacokinetic properties. To prevent its toxicity and ensure efficacy, continuous therapeutic monitoring is required. It is hard to get a simple, accurate, rapid, easily available, economical and highly sensitive assay in one method for therapeutic monitoring of phenytoin. The present study is directed towards establishing and validating a simpler, rapid, an accurate, highly sensitive, novel and environment friendly liquid chromatography/mass spectrometry (LC/MS) method for offering rapid and reliable TDM results of phenytoin in epileptic patients to physicians and clinicians for making immediate and rational decision. 27 epileptics patients with uncontrolled seizures or suspected of non-compliance or toxicity of phenytoin were selected and advised for TDM of phenytoin by neurologists of Qilu Hospital Jinan, China. The LC/MS assay was used for performing of therapeutic monitoring of phenytoin. The Agilent 1100 LC/MS system was used for TDM. The mixture of Ammonium acetate 5mM: Methanol at (35: 65 v/v) was used for the composition of mobile phase. The Diamonsil C18 (150mm×4.6mm, 5μm) column was used for the extraction of analytes in plasma. The samples were prepared with one step simple protein precipitation method. The technique was validated with the guidelines of International Conference on Harmonisation (ICH). The calibration curve demonstrated decent linearity within (0.2-20 µg/mL) concentration range with linearity equation, y= 0.0667855 x +0.00241785 and correlation coefficient (R2) of 0.99928. The specificity, recovery, linearity, accuracy, precision and stability results were within the accepted limits. The concentration of 0.2 µg/mL was observed as lower limit of quantitation (LLOQ), which is 12.5 times lower than the currently available enzyme-multiplied immunoassay technique (EMIT) for measurement of phenytoin in epilepsy patients. A rapid, simple, economical, precise, highly sensitive and novel LC/MS assay has been

Aminoglycosides in septic shock: an overview, with specific consideration given to their nephrotoxic risk.

PubMed

Boyer, Alexandre; Gruson, Didier; Bouchet, Stéphane; Clouzeau, Benjamin; Hoang-Nam, Bui; Vargas, Frédéric; Gilles, Hilbert; Molimard, Mathieu; Rogues, Anne-Marie; Moore, Nicholas

2013-04-01

Aminoglycoside nephrotoxicity has been reported in patients with sepsis, and several risk factors have been described. Once-daily dosing and shorter treatment have reduced nephrotoxicity risk, and simplified aminoglycoside monitoring. This review focuses on nephrotoxicity associated with aminoglycosides in the subset of patients with septic shock or severe sepsis. These patients are radically different from those with less severe sepsis. They may have, for instance, renal impairment due to the shock per se, sepsis-related acute kidney injury, frequent association with pre-existing risk factors for renal failure such as diabetes, dehydration and other nephrotoxic treatments. In this category of patients, these risk factors might modify substantially the benefit-risk ratio of aminoglycosides. In addition, aminoglycoside administration in critically ill patients with sepsis is complicated by an extreme inter- and intra-individual variability in drug pharmacokinetic/pharmacodynamic characteristics: the volume of distribution (Vd) is frequently increased while the elimination constant can be either increased or decreased. Consequently, and although its effect on nephrotoxicity has not been explored, a different administration schedule, i.e. a high-dose once daily (HDOD), and several therapeutic drug monitoring (TDM) options have been proposed in these patients. This review describes the historical perspective of these different options, including those applying to subsets of patients in which aminoglycoside administration is even more complex (obese intensive care unit [ICU] patients, patients needing continuous or discontinuous renal replacement therapy [CRRT/DRRT]). A simple linear dose adjustment according to aminoglycoside serum concentration can be classified as low-intensity TDM. Nomograms have also been proposed, based on the maximum (peak) plasma concentration (Cmax) objectives, weight and creatinine clearance. The Sawchuk and Zaske method (based on the

Time Division Multiplexing of Semiconductor Qubits

NASA Astrophysics Data System (ADS)

Jarratt, Marie Claire; Hornibrook, John; Croot, Xanthe; Watson, John; Gardner, Geoff; Fallahi, Saeed; Manfra, Michael; Reilly, David

Readout chains, comprising resonators, amplifiers, and demodulators, are likely to be precious resources in quantum computing architectures. The potential to share readout resources is contingent on realising efficient means of time-division multiplexing (TDM) schemes that are compatible with quantum computing. Here, we demonstrate TDM using a GaAs quantum dot device with multiple charge sensors. Our device incorporates chip-level switches that do not load the impedance matching network. When used in conjunction with frequency multiplexing, each frequency tone addresses multiple time-multiplexed qubits, vastly increasing the capacity of a single readout line.

Evaluating the road safety effects of a fuel cost increase measure by means of zonal crash prediction modeling.

PubMed

Pirdavani, Ali; Brijs, Tom; Bellemans, Tom; Kochan, Bruno; Wets, Geert

2013-01-01

Travel demand management (TDM) consists of a variety of policy measures that affect the transportation system's effectiveness by changing travel behavior. The primary objective to implement such TDM strategies is not to improve traffic safety, although their impact on traffic safety should not be neglected. The main purpose of this study is to evaluate the traffic safety impact of conducting a fuel-cost increase scenario (i.e. increasing the fuel price by 20%) in Flanders, Belgium. Since TDM strategies are usually conducted at an aggregate level, crash prediction models (CPMs) should also be developed at a geographically aggregated level. Therefore zonal crash prediction models (ZCPMs) are considered to present the association between observed crashes in each zone and a set of predictor variables. To this end, an activity-based transportation model framework is applied to produce exposure metrics which will be used in prediction models. This allows us to conduct a more detailed and reliable assessment while TDM strategies are inherently modeled in the activity-based models unlike traditional models in which the impact of TDM strategies are assumed. The crash data used in this study consist of fatal and injury crashes observed between 2004 and 2007. The network and socio-demographic variables are also collected from other sources. In this study, different ZCPMs are developed to predict the number of injury crashes (NOCs) (disaggregated by different severity levels and crash types) for both the null and the fuel-cost increase scenario. The results show a considerable traffic safety benefit of conducting the fuel-cost increase scenario apart from its impact on the reduction of the total vehicle kilometers traveled (VKT). A 20% increase in fuel price is predicted to reduce the annual VKT by 5.02 billion (11.57% of the total annual VKT in Flanders), which causes the total NOCs to decline by 2.83%. Copyright © 2012 Elsevier Ltd. All rights reserved.

Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection

PubMed Central

Mazumder, Saumyabrata; Maji, Mithun; Ali, Nahid

2011-01-01

Background Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice. Methodology/Principal Findings Towards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo. Conclusion Our results define the

DNA methylation and transcription in a distal region upstream from the bovine AlphaS1 casein gene after once or twice daily milking.

PubMed

Nguyen, Minh; Boutinaud, Marion; Pétridou, Barbara; Gabory, Anne; Pannetier, Maëlle; Chat, Sophie; Bouet, Stephan; Jouneau, Luc; Jaffrezic, Florence; Laloë, Denis; Klopp, Christophe; Brun, Nicolas; Kress, Clémence; Jammes, Hélène; Charlier, Madia; Devinoy, Eve

2014-01-01

Once daily milking (ODM) induces a reduction in milk production when compared to twice daily milking (TDM). Unilateral ODM of one udder half and TDM of the other half, enables the study of underlying mechanisms independently of inter-individual variability (same genetic background) and of environmental factors. Our results show that in first-calf heifers three CpG, located 10 kb upstream from the CSN1S1 gene were methylated to 33, 34 and 28%, respectively, after TDM but these levels were higher after ODM, 38, 38 and 33%, respectively. These methylation levels were much lower than those observed in the mammary gland during pregnancy (57, 59 and 50%, respectively) or in the liver (74, 78 and 61%, respectively). The methylation level of a fourth CpG (CpG4), located close by (29% during TDM) was not altered after ODM. CpG4 methylation reached 39.7% and 59.5%, during pregnancy or in the liver, respectively. CpG4 is located within a weak STAT5 binding element, arranged in tandem with a second high affinity STAT5 element. STAT5 binding is only marginally modulated by CpG4 methylation, but it may be altered by the methylation levels of the three other CpG nearby. Our results therefore shed light on mechanisms that help to explain how milk production is almost, but not fully, restored when TDM is resumed (15.1 ± 0.2 kg/day instead of 16.2 ± 0.2 kg/day, p<0.01). The STAT5 elements are 100 bp away from a region transcribed in the antisense orientation, in the mammary gland during lactation, but not during pregnancy or in other reproductive organs (ovary or testes). We now need to clarify whether the transcription of this novel RNA is a consequence of STAT5 interacting with the CSN1S1 distal region, or whether it plays a role in the chromatin structure of this region.

Morphometric analysis of erythrocytes from patients with thalassemia using tomographic diffractive microscopy

NASA Astrophysics Data System (ADS)

Lin, Yang-Hsien; Huang, Shin-Shyang; Wu, Shang-Ju; Sung, Kung-Bin

2017-11-01

Complete blood count is the most common test to detect anemia, but it is unable to obtain the abnormal shape of erythrocytes, which highly correlates with the hematologic function. Tomographic diffractive microscopy (TDM) is an emerging technique capable of quantifying three-dimensional (3-D) refractive index (RI) distributions of erythrocytes without labeling. TDM was used to characterize optical and morphological properties of 172 erythrocytes from healthy volunteers and 419 erythrocytes from thalassemic patients. To efficiently extract and analyze the properties of erythrocytes, we developed an adaptive region-growing method for automatically delineating erythrocytes from 3-D RI maps. The thalassemic erythrocytes not only contained lower hemoglobin content but also showed doughnut shape and significantly lower volume, surface area, effective radius, and average thickness. A multi-indices prediction model achieved perfect accuracy of diagnosing thalassemia using four features, including the optical volume, surface-area-to-volume ratio, sphericity index, and surface area. The results demonstrate the ability of TDM to provide quantitative, hematologic measurements and to assess morphological features of erythrocytes to distinguish healthy and thalassemic erythrocytes.

Design considerations of a hollow microneedle-optofluidic biosensing platform incorporating enzyme-linked assays

NASA Astrophysics Data System (ADS)

Ranamukhaarachchi, Sahan A.; Padeste, Celestino; Häfeli, Urs O.; Stoeber, Boris; Cadarso, Victor J.

2018-02-01

A hollow metallic microneedle is integrated with microfluidics and photonic components to form a microneedle-optofluidic biosensor suitable for therapeutic drug monitoring (TDM) in biological fluids, like interstitial fluid, that can be collected in a painless and minimally-invasive manner. The microneedle inner lumen surface is bio-functionalized to trap and bind target analytes on-site in a sample volume as small as 0.6 nl, and houses an enzyme-linked assay on its 0.06 mm2 wall. The optofluidic components are designed to rapidly quantify target analytes present in the sample and collected in the microneedle using a simple and sensitive absorbance scheme. This contribution describes how the biosensor components were optimized to detect in vitro streptavidin-horseradish peroxidase (Sav-HRP) as a model analyte over a large detection range (0-7.21 µM) and a very low limit of detection (60.2 nM). This biosensor utilizes the lowest analyte volume reported for TDM with microneedle technology, and presents significant avenues to improve current TDM methods for patients, by potentially eliminating blood draws for several drug candidates.

Emission quantification using the tracer gas dispersion method: The influence of instrument, tracer gas species and source simulation.

PubMed

Delre, Antonio; Mønster, Jacob; Samuelsson, Jerker; Fredenslund, Anders M; Scheutz, Charlotte

2018-09-01

The tracer gas dispersion method (TDM) is a remote sensing method used for quantifying fugitive emissions by relying on the controlled release of a tracer gas at the source, combined with concentration measurements of the tracer and target gas plumes. The TDM was tested at a wastewater treatment plant for plant-integrated methane emission quantification, using four analytical instruments simultaneously and four different tracer gases. Measurements performed using a combination of an analytical instrument and a tracer gas, with a high ratio between the tracer gas release rate and instrument precision (a high release-precision ratio), resulted in well-defined plumes with a high signal-to-noise ratio and a high methane-to-tracer gas correlation factor. Measured methane emission rates differed by up to 18% from the mean value when measurements were performed using seven different instrument and tracer gas combinations. Analytical instruments with a high detection frequency and good precision were established as the most suitable for successful TDM application. The application of an instrument with a poor precision could only to some extent be overcome by applying a higher tracer gas release rate. A sideward misplacement of the tracer gas release point of about 250m resulted in an emission rate comparable to those obtained using a tracer gas correctly simulating the methane emission. Conversely, an upwind misplacement of about 150m resulted in an emission rate overestimation of almost 50%, showing the importance of proper emission source simulation when applying the TDM. Copyright © 2018 Elsevier B.V. All rights reserved.

Mindfulness for Novice Pediatric Nurses: Smartphone Application Versus Traditional Intervention.

PubMed

Morrison Wylde, Chelsey; Mahrer, Nicole E; Meyer, Rika M L; Gold, Jeffrey I

The current study compares the effects of a traditionally delivered mindfulness (TDM) intervention to a smartphone delivered mindfulness (SDM) intervention, Headspace, an audio-guided mindfulness meditation program, in a group of novice nurses. Novice nurses participating in a pediatric nurse residency program were asked to participate in either a TDM or SDM intervention. Participants (N=95) completed self-administered pencil and paper questionnaires measuring mindfulness skills, and risk and protective factors at the start of their residency and three months after entering the program. Nurses in the SDM group reported significantly more "acting with awareness" and marginally more "non-reactivity to inner experience" skills compared to the TDM group. The smartphone intervention group also showed marginally more compassion satisfaction and marginally less burnout. Additionally, nurses in the SDM group had lower risk for compassion fatigue compared to the TDM group, but only when the nurses had sub-clinical posttraumatic symptoms at the start of the residency training program. Smartphone delivered mindfulness interventions may provide more benefits for novice nurses than traditionally delivered mindfulness interventions. However, the smart-phone intervention may be better indicated for nurses without existing symptoms of posttraumatic stress. Mindfulness interventions delivered through smartphone applications show promise in equipping nurses with important coping skills to manage stress. Because of the accessibility of smartphone applications, more nurses can benefit from the intervention as compared to a therapist delivered intervention. However, nurses with existing stress symptoms may require alternate interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring.

PubMed

Dolton, Michael J; Ray, John E; Marriott, Deborah; McLachlan, Andrew J

2012-06-01

Posaconazole has become an important part of the antifungal armamentarium in the prophylaxis and salvage treatment of invasive fungal infections (IFIs). Structurally related to itraconazole, posaconazole displays low oral bioavailability due to poor solubility, with significant drug interactions and gastrointestinal disease also contributing to the generally low posaconazole plasma concentrations observed in patients. While therapeutic drug monitoring (TDM) of plasma concentrations is widely accepted for other triazole antifungal agents such as voriconazole, the utility of TDM for posaconazole is controversial due to debate over the relationship between posaconazole exposure in plasma and clinical response to therapy. This review examines the available evidence for a relationship between plasma concentration and clinical efficacy for posaconazole, as well as evaluating the utility of TDM and providing provisional target concentrations for posaconazole therapy. Increasing evidence supports an exposure-response relationship for plasma posaconazole concentrations for prophylaxis and treatment of IFIs; a clear relationship has not been identified between posaconazole concentration and toxicity. Intracellular and intrapulmonary concentrations have been studied for posaconazole but have not been correlated to clinical outcomes. In view of the high mortality and cost associated with the treatment of IFIs, increasing evidence of an exposure-response relationship for posaconazole efficacy in the prevention and treatment of IFIs, and the common finding of low posaconazole concentrations in patients, TDM for posaconazole is likely to be of significant clinical utility. In patients with subtherapeutic posaconazole concentrations, increased dose frequency, administration with high-fat meals, and withdrawal of interacting medications from therapy are useful strategies to improve systemic absorption.

Assays for therapeutic drug monitoring of β-lactam antibiotics: A structured review.

PubMed

Carlier, Mieke; Stove, Veronique; Wallis, Steven C; De Waele, Jan J; Verstraete, Alain G; Lipman, Jeffrey; Roberts, Jason A

2015-10-01

In some patient groups, including critically ill patients, the pharmacokinetics of β-lactam antibiotics may be profoundly disturbed due to pathophysiological changes in distribution and elimination. Therapeutic drug monitoring (TDM) is a strategy that may help to optimise dosing. The aim of this review was to identify and analyse the published literature on the methods used for β-lactam quantification in TDM programmes. Sixteen reports described methods for the simultaneous determination of three or more β-lactam antibiotics in plasma/serum. Measurement of these antibiotics, due to low frequency of usage relative to some other tests, is generally limited to in-house chromatographic methods coupled to ultraviolet or mass spectrometric detection. Although many published methods state they are fit for TDM, they are inconvenient because of intensive sample preparation and/or long run times. Ideally, methods used for routine TDM should have a short turnaround time (fast run-time and fast sample preparation), a low limit of quantification and a sufficiently high upper limit of quantification. The published assays included a median of 6 analytes [interquartile range (IQR) 4-10], with meropenem and piperacillin being the most frequently measured β-lactam antibiotics. The median run time was 8 min (IQR 5.9-21.3 min). There is also a growing number of methods measuring free concentrations. An assay that measures antibiotics without any sample preparation would be the next step towards real-time monitoring; no such method is currently available. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

[Increased glucose uptake by seborrheic keratosis on PET scan].

PubMed

Merklen-Djafri, C; Truntzer, P; Hassler, S; Cribier, B

2017-05-01

Positron emission tomography (PET) is an examination based upon the uptake of a radioactive tracer by hypermetabolic cells. It is primarily used in tandem with tomodensitometry (PET-TDM) for cancer staging because of its high sensitivity and specificity for the detection of metastases. However, unusually high uptake may occur with benign tumours, including skin tumours. Herein, we report an extremely rare case of pathological uptake levels resulting from seborrhoeic keratosis. A 55-year-old male patient with oesophageal squamous-cell carcinoma was referred to us following the discovery of an area of high marker uptake following PET-TDM and corresponding to a pigmented skin lesion. No other areas of suspect high uptake were seen. The lesion was surgically excised and histological examination indicated seborrhoeic keratosis. The histological appearance was that of standard seborrhoeic keratosis without any notable mitotic activity. PET-TDM is an examination that enables diagnosis of malignancy. However, rare cases have been described of increased marker uptake by benign cutaneous tumours such as histiocytofibroma, pilomatricoma and condyloma. To date, there have only been only very few cases of increased uptake due to seborrhoeic keratosis. This extremely unusual case of increased glucose uptake in PET-TDM due to seborrhoeic keratosis confirms that the hypermetabolic activity detected by this examination is not necessarily synonymous with malignancy and that confirmation by clinical and histological findings is essential. The reasons for increased metabolic activity within such benign tumours are not known. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

TDM Status Report: Parking Cash Out

DOT National Transportation Integrated Search

1994-02-01

Employers often provide employees with subsidized parking. Employers may provide free parking to employees in parking spaces they own or lease, or provide parking at rates below market value in the area. The parking subsidy is the difference between ...

TDM Status Report: Variable Work Hours

DOT National Transportation Integrated Search

1992-08-01

Work hour policies established by employers govern when employees travel to and from work. The policies influence not only the volume of employees traveling during peak traffic periods, but employee propensity to consider transit, carpooling and othe...

TDM Status Report: Guaranteed Ride Home

DOT National Transportation Integrated Search

1992-08-01

Guaranteed Ride Home (GRH) is TSM program providing car and vanpool patrons a ride to home or to other destination in an emergency. The intent of the program is to overcome one of the barriers to ridesharing--need of a vehicle to get home, to school,...

Les masques trompeurs de la bipolarité: étude de 100 cas

PubMed Central

Nabih, Fadoua Oueriagli; Benali, Abdesslam; Adali, Imane; Manoudi, Fatiha; Asri, Fatima

2015-01-01

Le trouble bipolaire (TB) est une pathologie dont la prévalence est estimée à 1-2%. Le diagnostic précoce du trouble constitue un enjeu thérapeutique majeur. L'objectif de ce travail est de déterminer les différents diagnostiques attribués aux patients bipolaires avant de recevoir le diagnostic adéquat et de préciser le délai moyen du retard diagnostique. C'est une étude descriptive transversale portant sur 100 patients atteints de TB, inclus selon les critères du DSM V, qui ont été vus en consultation ou bien hospitalisés dans le service de psychiatrie de l'hôpital Militaire Avicenne de Marrakech, durant une période de deux ans. L’âge moyen des patients était de 29,5 ans avec une prédominance masculine (80%). 40% de nos patients ont reçu au début un autre diagnostic que celui du TB et le premier diagnostic retenu était celui de l’épisode dépressif majeur dans 36% des cas, suivi de l'accès psychotique aigu dans 28% des cas, la schizophrénie dans 16,8% et le trouble de personnalité dans 10,2%. Le délai moyen du retard diagnostic était de 64 mois. 50% des patients ayant reçu un autre diagnostic avaient consulté au moins un psychiatre et 60% des patients avaient été hospitalisés au moins une fois avant le diagnostic du TB. Les errances diagnostiques du TB sont bien établies, conduisant forcément à un retard de prise en charge adéquate. Ces données devraient alerter les psychiatres pour favoriser un meilleur dépistage de la manie et de l'hypomanie qui restent les éléments clé du diagnostic du TB. PMID:26587161

Multilayered Electrospun Scaffolds for Tendon Tissue Engineering

PubMed Central

Chainani, Abby; Hippensteel, Kirk J.; Kishan, Alysha; Garrigues, N. William; Ruch, David S.; Guilak, Farshid

2013-01-01

Full-thickness rotator cuff tears are one of the most common causes of shoulder pain in people over the age of 65. High retear rates and poor functional outcomes are common after surgical repair, and currently available extracellular matrix scaffold patches have limited abilities to enhance new tendon formation. In this regard, tissue-engineered scaffolds may provide a means to improve repair of rotator cuff tears. Electrospinning provides a versatile method for creating nanofibrous scaffolds with controlled architectures, but several challenges remain in its application to tissue engineering, such as cell infiltration through the full thickness of the scaffold as well as control of cell growth and differentiation. Previous studies have shown that ligament-derived extracellular matrix may enhance differentiation toward a tendon or ligament phenotype by human adipose stem cells (hASCs). In this study, we investigated the use of tendon-derived extracellular matrix (TDM)-coated electrospun multilayered scaffolds compared to fibronectin (FN) or phosphate-buffered saline (PBS) coating for use in rotator cuff tendon tissue engineering. Multilayered poly(ɛ-caprolactone) scaffolds were prepared by sequentially collecting electrospun layers onto the surface of a grounded saline solution into a single scaffold. Scaffolds were then coated with TDM, FN, or PBS and seeded with hASCs. Scaffolds were maintained without exogenous growth factors for 28 days in culture and evaluated for protein content (by immunofluorescence and biochemical assay), markers of tendon differentiation, and tensile mechanical properties. The collagen content was greatest by day 28 in TDM-scaffolds. Gene expression of type I collagen, decorin, and tenascin C increased over time, with no effect of scaffold coating. Sulfated glycosaminoglycan and dsDNA contents increased over time in culture, but there was no effect of scaffold coating. The Young's modulus did not change over time, but yield strain

Pharmacokinetics and therapeutic drug monitoring of psychotropic drugs in pediatrics.

PubMed

Pichini, Simona; Papaseit, Esther; Joya, Xavier; Vall, Oriol; Farré, Magí; Garcia-Algar, Oscar; de laTorre, Rafael

2009-06-01

Therapeutic drug monitoring (TDM) in pediatrics (0-14 years) is especially important because the absorption, distribution, metabolism, and excretion of drugs and drug pharmacokinetic profiles can be different from that of the adult population. In this context, several parameters like half-life of drug elimination from the body (t(1/2)), peak plasma concentration (Cmax), area under the curve, clearance (CL), Tmax, and dose/concentration relationship in children may differ from adults. Hence, the knowledge of pharmacokinetic parameters and therapeutic and toxic ranges of drug concentrations may help the clinicians to optimize drug treatment regimens in the pediatric population. TDM of psychotropic drugs requires particular attention for the pharmacological and clinical consequences of nonadequate dose use, lack in the compliance, and overdoses with possible toxic effects. Psychoactive drugs such as benzodiazepines, antiepileptic drugs, tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotic drugs, psychostimulants (attention-deficit hyperactivity disorder drugs), opioid analgesics, and antimigraine drugs are a heterogeneous group. These drugs are subject to interindividual variability, and therefore, the usefulness of TDM for these drugs has to be assessed individually. Because of the occurrence of comorbid pathologies, including psychiatric disorders, the use of combined pharmacotherapy is not uncommon. As a consequence, these patients may be at risk from a number of potential drug-drug interactions. The implementation of TDM in pediatric population is more difficult than in adults because some sampling procedures are invasive and cause discomfort in children, and additionally, they require the cooperation of the patient. Several examples will be provided where the use of alternative matrices, such as saliva, is proposed to minimize inconvenience and patient discomfort.

Modulation of the humoral and cellular immune response in Abeta immunotherapy by the adjuvants monophosphoryl lipid A (MPL), cholera toxin B subunit (CTB) and E. coli enterotoxin LT(R192G).

PubMed

Maier, Marcel; Seabrook, Timothy J; Lemere, Cynthia A

2005-10-25

Abeta vaccination or passive transfer of human-specific anti-Abeta antibodies are approaches under investigation to prevent and/or treat Alzheimer's disease (AD). Successful active Abeta vaccination requires a strong and safe adjuvant to induce anti-Abeta antibody formation. We compared the adjuvants monophosphoryl lipid A (MPL)/trehalose dicorynomycolate (TDM), cholera toxin B subunit (CTB) and Escherichia coli heat-labile enterotoxin LT(R192G) for their ability to induce a humoral and cellular immune reaction, using fibrillar Abeta1-40/42 as a common immunogen in wildtype B6D2F1 mice. Subcutaneous (s.c.) administration with MPL/TDM resulted in anti-Abeta antibodies levels up to four times higher compared to s.c. LT(R192G). Using MPL/TDM, the anti-Abeta antibodies induced were mainly IgG2b, IgG1 and lower levels of IgG2a and IgM, with a moderate splenocyte proliferation and IFN-gamma production in vitro upon stimulation with Abeta1-40/42. LT(R192G), previously shown by us to induce robust titers of anti-Abeta antibodies, generated predominantly IgG2b and IgG1 anti-Abeta antibodies with very low splenocyte proliferation and IFN-gamma production. Weekly intranasal (i.n.) administration over 11 weeks of Abeta40/42 with CTB induced only moderate levels of antibodies. All immunogens generated antibodies that recognized mainly the Abeta1-7 epitope and specifically detected amyloid plaques on AD brain sections. In conclusion, MPL/TDM, in addition to LT(R192G), is an effective adjuvant when combined with Abeta40/42 and may aid in the design of Abeta immunotherapy.

C-Type Lectin Receptor MCL Facilitates Mincle Expression and Signaling through Complex Formation.

PubMed

Miyake, Yasunobu; Masatsugu, Oh-hora; Yamasaki, Sho

2015-06-01

C-type lectin receptors expressed in APCs are recently defined pattern recognition receptors that play a crucial role in immune responses against pathogen-associated molecular patterns. Among pathogen-associated molecular patterns, cord factor (trehalose-6,6'-dimycolate [TDM]) is the most potent immunostimulatory component of the mycobacterial cell wall. Two C-type lectin receptors, macrophage-inducible C-type lectin (Mincle) and macrophage C-type lectin (MCL), are required for immune responses against TDM. Previous studies indicate that MCL is required for TDM-induced Mincle expression. However, the mechanism by which MCL induces Mincle expression has not been fully understood. In this study, we demonstrate that MCL interacts with Mincle to promote its surface expression. After LPS or zymosan stimulation, MCL-deficient bone marrow-derived dendritic cells (BMDCs) had a lower level of Mincle protein expression, although mRNA expression was comparable with wild-type BMDCs. Meanwhile, BMDCs from MCL transgenic mice showed an enhanced level of Mincle expression on the cell surface. MCL was associated with Mincle through the stalk region and this region was necessary and sufficient for the enhancement of Mincle expression. This interaction appeared to be mediated by the hydrophobic repeat of MCL, as substitution of four hydrophobic residues within the stalk region with serine (MCL(4S)) abolished the function to enhance the surface expression of Mincle. MCL(4S) mutant failed to restore the defective TDM responses in MCL-deficient BMDCs. These results suggest that MCL positively regulates Mincle expression through protein-protein interaction via its stalk region, thereby magnifying Mincle-mediated signaling. Copyright © 2015 by The American Association of Immunologists, Inc.

Preliminary Assessment of Microwave Readout Multiplexing Factor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Croce, Mark Philip; Koehler, Katrina Elizabeth; Rabin, Michael W.

2017-01-23

Ultra-high resolution microcalorimeter gamma spectroscopy is a new non-destructive assay technology for measurement of plutonium isotopic composition, with the potential to reduce total measurement uncertainty to a level competitive with destructive analysis methods [1-4]. Achieving this level of performance in practical applications requires not only the energy resolution now routinely achieved with transition-edge sensor microcalorimeter arrays (an order of magnitude better than for germanium detectors) but also high throughput. Microcalorimeter gamma spectrometers have not yet achieved detection efficiency and count rate capability that is comparable to germanium detectors, largely because of limits from existing readout technology. Microcalorimeter detectors must bemore » operated at low temperature to achieve their exceptional energy resolution. Although the typical 100 mK operating temperatures can be achieved with reliable, cryogen-free systems, the cryogenic complexity and heat load from individual readout channels for large sensor arrays is prohibitive. Multiplexing is required for practical systems. The most mature multiplexing technology at present is time-division multiplexing (TDM) [3, 5-6]. In TDM, the sensor outputs are switched by applying bias current to one SQUID amplifier at a time. Transition-edge sensor (TES) microcalorimeter arrays as large as 256 pixels have been developed for X-ray and gamma-ray spectroscopy using TDM technology. Due to bandwidth limits and noise scaling, TDM is limited to a maximum multiplexing factor of approximately 32-40 sensors on one readout line [8]. Increasing the size of microcalorimeter arrays above the kilopixel scale, required to match the throughput of germanium detectors, requires the development of a new readout technology with a much higher multiplexing factor.« less

Spin-wave stiffness in the Dzyaloshinskii-Moriya helimagnets Mn1 -xFexSi

NASA Astrophysics Data System (ADS)

Grigoriev, S. V.; Altynbaev, E. V.; Siegfried, S.-A.; Pschenichnyi, K. A.; Menzel, D.; Heinemann, A.; Chaboussant, G.

2018-01-01

The small-angle neutron scattering is used to measure the spin-wave stiffness in the field-polarized state of the Dzyaloshinskii-Moriya helimagnets Mn1 -xFexSi with x =0.03 , 0.06, 0.09, and 0.10. The Mn1 -xFexSi compounds are helically ordered below Tc and show a helical fluctuation regime above Tc in a wide range up to TDM. The critical temperatures Tc and TDM decrease with x and tend to 0 at x =0.11 and 0.17, respectively. We have found that the spin-wave stiffness A change weakly with temperature for each individual Fe-doped compound. On the other hand, the spin-wave stiffness A decreases with x duplicating the TDM dependence on x , rather than Tc(x ) . These findings classify the thermal phase transition in all Mn1 -xFexSi compounds as an abrupt change in the spin state caused, most probably, by the features of an electronic band structure. Moreover, the criticality in these compounds is not related to the value of the ferromagnetic interaction but demonstrates the remarkable role of the Dzyaloshinskii-Moriya interaction as a factor destabilizing the magnetic order.

A metro-access integrated network with all-optical virtual private network function using DPSK/ASK modulation format

NASA Astrophysics Data System (ADS)

Tian, Yue; Leng, Lufeng; Su, Yikai

2008-11-01

All-optical virtual private network (VPN), which offers dedicated optical channels to connect users within a VPN group, is considered a promising approach to efficient internetworking with low latency and enhanced security implemented in the physical layer. On the other hand, time-division multiplexed (TDM) / wavelength-division multiplexed (WDM) network architecture based on a feeder-ring with access-tree topology, is considered a pragmatic migration scenario from current TDM-PONs to future WDM-PONs and a potential convergence scheme for access and metropolitan networks, due to its efficiently shared hardware and bandwidth resources. All-optical VPN internetworking in such a metro-access integrated structure is expected to cover a wider service area and therefore is highly desirable. In this paper, we present a TDM/WDM metro-access integrated network supporting all-optical VPN internetworking among ONUs in different sub- PONs based on orthogonal differential-phase-shift keying (DPSK) / amplitude-shift keying (ASK) modulation format. In each ONU, no laser but a single Mach-Zehnder modulator (MZM) is needed for the upstream and VPN signal generation, which is cost-effective. Experiments and simulations are performed to verify its feasibility as a potential solution to the future access service.

Clinical Pharmacology in Adult and Pediatric Inflammatory Bowel Disease.

PubMed

Hemperly, Amy; Sandborn, William J; Vande Casteele, Niels

2018-05-17

This review describes the clinical pharmacology of the major drugs used for the treatment of patients with inflammatory bowel disease (IBD). Pharmacokinetics, drug metabolism, mechanism of action, efficacy, and safety profile are discussed. Some small molecules were developed to act systemically (eg, ozanimod) or locally (eg, aminosalicylates) and thus have disparate pharmacokinetic properties. In addition, locally acting compounds have been optimized to mitigate systemic exposure-eg, budesonide, which undergoes extensive first-pass metabolism-thereby reducing systemic bioavailability and side effects. Other small molecules such as thiopurines are precursors of their active metabolites and differences in genotype or phenotype of metabolizing enzymes may affect efficacy and safety, requiring therapeutic drug monitoring (TDM). Monoclonal antibodies (MAs) are large molecules administered parenterally, and their pharmacokinetics may be influenced not only by the general immunoglobulin (Ig) G metabolism and recycling pathways but also by antigen properties such as antigen distribution and antigen concentration. In addition, antibody structure, host factors, concurrent medications, and immunogenicity may contribute to the substantial inter- and intrapatient variability in drug exposure and response observed for MAs. Current guidelines recommend reactive TDM of tumor necrosis factor antagonists at the time of loss of response. Evidence for proactive TDM and for the role of TDM for biologics with a different mechanism of action is emerging. Although small molecules offer potential benefits over biologics with oral administration and lack of immunogenicity, there may be risk for more systemic side effects due to off-target binding. Understanding drug metabolism, pharmacokinetic characteristics, and mechanism of action are important in selecting the right drug at the right time at the right dose for patients with IBD.10.1093/ibd/izy189_video1izy189.video15786062223001.

Phase division multiplexed EIT for enhanced temporal resolution.

PubMed

Dowrick, T; Holder, D

2018-03-29

The most commonly used EIT paradigm (time division multiplexing) limits the temporal resolution of impedance images due to the need to switch between injection electrodes. Advances have previously been made using frequency division multiplexing (FDM) to increase temporal resolution, but in cases where a fixed range of frequencies is available, such as imaging fast neural activity, an upper limit is placed on the total number of simultaneous injections. The use of phase division multiplexing (PDM) where multiple out of phase signals can be injected at each frequency is investigated to increase temporal resolution. TDM, FDM and PDM were compared in head tank experiments, to compare transfer impedance measurements and spatial resolution between the three techniques. A resistor phantom paradigm was established to investigate the imaging of one-off impedance changes, of magnitude 1% and with durations as low as 500 µs (similar to those seen in nerve bundles), using both PDM and TDM approaches. In head tank experiments, a strong correlation (r  >  0.85 and p  <  0.001) was present between the three sets of measured transfer impedances, and no statistically significant difference was found in reconstructed image quality. PDM was able to image impedance changes down to 500 µs in the phantom experiments, while the minimum duration imaged using TDM was 5 ms. PDM offers a possible solution to the imaging of fast moving impedance changes (such as in nerves), where the use of triggering or coherent averaging is not possible. The temporal resolution presents an order of magnitude improvement of the TDM approach, and the approach addresses the limited spatial resolution of FDM by increasing the number of simultaneous EIT injections.

A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: a real-world experience

PubMed Central

Vici, Patrizia; Pizzuti, Laura; Michelotti, Andrea; Sperduti, Isabella; Natoli, Clara; Mentuccia, Lucia; Lauro, Luigi Di; Sergi, Domenico; Marchetti, Paolo; Santini, Daniele; Magnolfi, Emanuela; Iezzi, Laura; Moscetti, Luca; Fabbri, Agnese; Cassano, Alessandra; Grassadonia, Antonino; Omarini, Claudia; Piacentini, Federico; Botticelli, Andrea; Bertolini, Ilaria; Scinto, Angelo Fedele; Zampa, Germano; Mauri, Maria; D’Onofrio, Loretta; Sini, Valentina; Barba, Maddalena; Maugeri-Saccà, Marcello; Rossi, Ernesto; Landucci, Elisabetta; Tomao, Silverio; Alberti, Antonio Maria; Giotta, Francesco; Ficorella, Corrado; Adamo, Vincenzo; Russo, Antonio; Lorusso, Vito; Cannita, Katia; Barni, Sandro; Laudadio, Lucio; Greco, Filippo; Garrone, Ornella; Giulia, Marina Della; Marolla, Paolo; Sanguineti, Giuseppe; Cocco, Barbara Di; Ciliberto, Gennaro; Maria, Ruggero De; Gamucci, Teresa

2017-01-01

We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab-pretreated (p=0.13), and 6 and 22 months in pertuzumab-naïve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-naïve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab-pretreated (p=0.05) and 6 and 17 months in pertuzumab-naïve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival benefit (p<0.0001), while overall survival was positively affected by lower ECOG PS (p<0.0001), absence of brain metastases (p 0.05), and clinical benefit (p<0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order. PMID:28915642

An expandable crosstalk reduction method for inline fiber Fabry-Pérot sensor array based on fiber Bragg gratings

NASA Astrophysics Data System (ADS)

Jiang, Peng; Ma, Lina; Hu, Zhengliang; Hu, Yongming

2016-07-01

The inline time division multiplexing (TDM) fiber Fabry-Pérot (FFP) sensor array based on fiber Bragg gratings (FBGs) is attractive for many applications. But the intrinsic multi-reflection (MR) induced crosstalk limits applications especially those needing high resolution. In this paper we proposed an expandable method for MR-induced crosstalk reduction. The method is based on complexing-exponent synthesis using the phase-generated carrier (PGC) scheme and the special common character of the impulse responses. The method could promote demodulation stability simultaneously with the reduction of MR-induced crosstalk. A polarization-maintaining 3-TDM experimental system with an FBG reflectivity of about 5 % was set up to validate the method. The experimental results showed that crosstalk reduction of 13 dB and 15 dB was achieved for sensor 2 and sensor 3 respectively when a signal was applied to the first sensor and crosstalk reduction of 8 dB was achieved for sensor 3 when a signal was applied to sensor 2. The demodulation stability of the applied signal was promoted as well. The standard deviations of the amplitude distributions of the demodulated signals were reduced from 0.0046 to 0.0021 for sensor 2 and from 0.0114 to 0.0044 for sensor 3. Because of the convenience of the linear operation of the complexing-exponent and according to the common character of the impulse response we found, the method can be effectively extended to the array with more TDM channels if the impulse response of the inline FFP sensor array with more TDM channels is derived. It offers potential to develop a low-crosstalk inline FFP sensor array using the PGC interrogation technique with relatively high reflectivity FBGs which can guarantee enough light power received by the photo-detector.

Trastuzumab uptake and its relation to efficacy in an animal model of HER2-positive breast cancer brain metastasis.

PubMed

Lewis Phillips, Gail D; Nishimura, Merry C; Lacap, Jennifer Arca; Kharbanda, Samir; Mai, Elaine; Tien, Janet; Malesky, Kimberly; Williams, Simon P; Marik, Jan; Phillips, Heidi S

2017-08-01

The extent to which efficacy of the HER2 antibody Trastuzumab in brain metastases is limited by access of antibody to brain lesions remains a question of significant clinical importance. We investigated the uptake and distribution of trastuzumab in brain and mammary fat pad grafts of HER2-positive breast cancer to evaluate the relationship of these parameters to the anti-tumor activity of trastuzumab and trastuzumab emtansine (T-DM1). Mouse transgenic breast tumor cells expressing human HER2 (Fo2-1282 or Fo5) were used to establish intracranial and orthotopic tumors. Tumor uptake and tissue distribution of systemically administered 89 Zr-trastuzumab or muMAb 4D5 (murine parent of trastuzumab) were measured by PET and ELISA. Efficacy of muMAb 4D5, the PI3K/mTOR inhibitor GNE-317, and T-DM1 was also assessed. 89 Zr-trastuzumab and muMAb 4D5 exhibited robust uptake into Fo2-1282 brain tumors, but not normal brains. Uptake into brain grafts was similar to mammary grafts. Despite this, muMAb 4D5 was less efficacious in brain grafts. Co-administration of muMAb 4D5 and GNE-317, a brain-penetrant PI3K/mTOR inhibitor, provided longer survival in mice with brain lesions than either agent alone. Moreover, T-DM1 increased survival in the Fo5 brain metastasis model. In models of HER2-positive breast cancer brain metastasis, trastuzumab efficacy does not appear to be limited by access to intracranial tumors. Anti-tumor activity improved with the addition of a brain-penetrant PI3K/mTOR inhibitor, suggesting that combining targeted therapies is a more effective strategy for treating HER2-positive breast cancer brain metastases. Survival was also extended in mice with Fo5 brain lesions treated with T-DM1.

A Highly Flexible and Efficient Passive Optical Network Employing Dynamic Wavelength Allocation

NASA Astrophysics Data System (ADS)

Hsueh, Yu-Li; Rogge, Matthew S.; Yamamoto, Shu; Kazovsky, Leonid G.

2005-01-01

A novel and high-performance passive optical network (PON), the SUCCESS-DWA PON, employs dynamic wavelength allocation to provide bandwidth sharing across multiple physical PONs. In the downstream, tunable lasers, an arrayed waveguide grating, and coarse/fine filtering combine to create a flexible new optical access solution. In the upstream, several distributed and centralized schemes are proposed and investigated. The network performance is compared to conventional TDM-PONs under different traffic models, including the self-similar traffic model and the transaction-oriented model. Broadcast support and deployment issues are addressed. The network's excellent scalability can bridge the gap between conventional TDM-PONs and WDM-PONs. The powerful architecture is a promising candidate for next generation optical access networks.

Distributed Weak Fiber Bragg Grating Vibration Sensing System Based on 3 × 3 Fiber Coupler

NASA Astrophysics Data System (ADS)

Li, Wei; Zhang, Jian

2018-06-01

A novel distributed weak fiber Bragg gratings (FBGs) vibration sensing system has been designed to overcome the disadvantages of the conventional methods for optical fiber sensing networking, which are: low signal intensity in the usually adopted time-division multiplexing (TDM) technology, insufficient quantity of multiplexed FBGs in the wavelength-division multiplexing (WDM) technology, and that the mixed WDM/TDM technology measures only the physical parameters of the FBG locations but cannot perform distributed measurement over the whole optical fiber. This novel system determines vibration events in the optical fiber line according to the intensity variation of the interference signals between the adjacent weak FBG reflected signals and locates the vibration points accurately using the TDM technology. It has been proven by tests that this system performs vibration signal detection and demodulation in a way more convenient than the conventional methods for the optical fiber sensing system. It also measures over the whole optical fiber, therefore, distributed measurement is fulfilled, and the system locating accuracy is up to 20 m, capable of detecting any signals of whose drive signals lower limit voltage is 0.2 V while the frequency range is 3 Hz‒1 000 Hz. The system has the great practical significance and application value for perimeter surveillance systems.

Promotional materials clearinghouse, year 5 final report 2001-2002

DOT National Transportation Integrated Search

2002-10-01

The Promotional Materials Clearinghouse is a participant-driven undertaking. All materials currently archived at the Clearinghouse were solicited from transit systems and transportation demand management (TDM) agencies nationwide with marketing manag...

The dimensions of crash risk : combination-unit vs. single-unit trucks vs. other vehicles

DOT National Transportation Integrated Search

2013-06-01

This report highlights four metropolitan planning organizations (MPOs) that embrace transportation demand management (TDM) and nonmotorized transportation in an ambitious, conscious, and holistic manner at both regional and local scales. These MPOs, ...

Getting the goods without the bads : freight transportation demand management strategies to reduce urban impacts.

DOT National Transportation Integrated Search

2013-09-01

This project identifies and evaluatesstrategies to reduce the social costs associated with goods movement in urban areas by managing : transportation demand. Information about various freight transportation demand management (TDM) strategies was gath...

Tuberculose pariétale compliquée d’embolie pulmonaire

PubMed Central

Bopaka, Regis Gothard; Bemba, Presley Lee Esthel; Janah, Hind; Okombi, Franck Hardain Okemba; Jabri, Hasna; Khattabi, Wiam El; Afif, Hicham

2017-01-01

La tuberculose est une maladie infectieuse qui reste fréquente dans les pays en développement. La localisation peut être pulmonaire ou extra-pulmonaire. Cette forme extra-pulmonaire pose un grand problème diagnostique. Nous rapportons le cas d'un patient présentant une embolie pulmonaire révélant une tuberculose pariétale. A travers cette observation, nous soulignons la nécessité de rechercher l'étiologie devant une embolie pulmonaire. PMID:28819528

Combining Acceleration Techniques for Low-Dose X-Ray Cone Beam Computed Tomography Image Reconstruction.

PubMed

Huang, Hsuan-Ming; Hsiao, Ing-Tsung

2017-01-01

Over the past decade, image quality in low-dose computed tomography has been greatly improved by various compressive sensing- (CS-) based reconstruction methods. However, these methods have some disadvantages including high computational cost and slow convergence rate. Many different speed-up techniques for CS-based reconstruction algorithms have been developed. The purpose of this paper is to propose a fast reconstruction framework that combines a CS-based reconstruction algorithm with several speed-up techniques. First, total difference minimization (TDM) was implemented using the soft-threshold filtering (STF). Second, we combined TDM-STF with the ordered subsets transmission (OSTR) algorithm for accelerating the convergence. To further speed up the convergence of the proposed method, we applied the power factor and the fast iterative shrinkage thresholding algorithm to OSTR and TDM-STF, respectively. Results obtained from simulation and phantom studies showed that many speed-up techniques could be combined to greatly improve the convergence speed of a CS-based reconstruction algorithm. More importantly, the increased computation time (≤10%) was minor as compared to the acceleration provided by the proposed method. In this paper, we have presented a CS-based reconstruction framework that combines several acceleration techniques. Both simulation and phantom studies provide evidence that the proposed method has the potential to satisfy the requirement of fast image reconstruction in practical CT.

Trans -cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis –induced inflammation and virulence

PubMed Central

Rao, Vivek; Gao, Feng; Chen, Bing; Jacobs, William R.; Glickman, Michael S.

2006-01-01

Recent studies have shown that fine structural modifications of Mycobacterium tuberculosis cell envelope lipids mediate host cell immune activation during infection. One such alteration in lipid structure is cis-cyclopropane modification of the mycolic acids on trehalose dimycolate (TDM) mediated by proximal cyclopropane synthase of α mycolates (pcaA), a proinflammatory lipid modification during early infection. Here we examine the pathogenetic role and immunomodulatory function of mycolic acid cyclopropane stereochemistry by characterizing an M. tuberculosis cyclopropane–mycolic acid synthase 2 (cmaA2) null mutant (ΔcmaA2) that lacks trans-cyclopropanation of mycolic acids. Although titers of WT and ΔcmaA2 organisms were identical during mouse infection, ΔcmaA2 bacteria were hypervirulent while inducing larger granulomas than WT M. tuberculosis. The hypervirulence of the ΔcmaA2 strain depended on host TNF-α and IFN-γ. Loss of trans-cyclopropanation enhanced M. tuberculosis–induced macrophage inflammatory responses, a phenotype that was transferable with petroleum ether extractable lipids. Finally, purified TDM lacking trans-cyclopropane rings was 5-fold more potent in stimulating macrophages. These results establish cmaA2-dependent trans-cyclopropanation of TDM as a suppressor of M. tuberculosis–induced inflammation and virulence. In addition, cyclopropane stereochemistries on mycolic acids interact directly with host cells to both positively and negatively influence host innate immune activation. PMID:16741578

Optical slotted circuit switched network: a bandwidth efficient alternative to wavelength-routed network

NASA Astrophysics Data System (ADS)

Li, Yan; Collier, Martin

2007-11-01

Wavelength-routed networks have received enormous attention due to the fact that they are relatively simple to implement and implicitly offer Quality of Service (QoS) guarantees. However, they suffer from a bandwidth inefficiency problem and require complex Routing and Wavelength Assignment (RWA). Most attempts to address the above issues exploit the joint use of WDM and TDM technologies. The resultant TDM-based wavelength-routed networks partition the wavelength bandwidth into fixed-length time slots organized as a fixed-length frame. Multiple connections can thus time-share a wavelength and the grooming of their traffic leads to better bandwidth utilization. The capability of switching in both wavelength and time domains in such networks also mitigates the RWA problem. However, TMD-based wavelength-routed networks work in synchronous mode and strict synchronization among all network nodes is required. Global synchronization for all-optical networks which operate at extremely high speed is technically challenging, and deploying an optical synchronizer for each wavelength involves considerable cost. An Optical Slotted Circuit Switching (OSCS) architecture is proposed in this paper. In an OSCS network, slotted circuits are created to better utilize the wavelength bandwidth than in classic wavelength-routed networks. The operation of the protocol is such as to avoid the need for global synchronization required by TDM-based wavelength-routed networks.

Health monitoring of unmanned aerial vehicle based on optical fiber sensor array

NASA Astrophysics Data System (ADS)

Luo, Yuxiang; Shen, Jingshi; Shao, Fei; Guo, Chunhui; Yang, Ning; Zhang, Jiande

2017-10-01

The unmanned aerial vehicle (UAV) in flight needs to face the complicated environment, especially to withstand harsh weather conditions, such as the temperature and pressure. Compared with conventional sensors, fiber Bragg grating (FBG) sensor has the advantages of small size, light weight, high reliability, high precision, anti-electromagnetic interference, long lift-span, moistureproof and good resistance to causticity. It's easy to be embedded in composite structural components of UAVs. In the paper, over 1000 FBG sensors distribute regularly on a wide range of UAVs body, combining wavelength division multiplexing (WDM), time division multiplexing (TDM) and multichannel parallel architecture. WDM has the advantage of high spatial resolution. TDM has the advantage of large capacity and wide range. It is worthful to constitute a sensor network by different technologies. For the signal demodulation of FBG sensor array, WDM works by means of wavelength scanning light sources and F-P etalon. TDM adopts the technology of optical time-domain reflectometry. In order to demodulate efficiently, the most proper sensor multiplex number with some reflectivity is given by the curves fitting. Due to the regular array arrangement of FBG sensors on the UAVs, we can acquire the health state of UAVs in the form of 3D visualization. It is helpful to master the information of health status rapidly and give a real-time health evaluation.

Inhibition of Megakaryocyte Differentiation by Antibody-Drug Conjugates (ADCs) is Mediated by Macropinocytosis: Implications for ADC-induced Thrombocytopenia.

PubMed

Zhao, Hui; Gulesserian, Sara; Ganesan, Sathish Kumar; Ou, Jimmy; Morrison, Karen; Zeng, Zhilan; Robles, Veronica; Snyder, Josh; Do, Lisa; Aviña, Hector; Karki, Sher; Stover, David R; Doñate, Fernando

2017-09-01

Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MK) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers. Effects of AGS-16C3F, T-DM1, and control ADCs on maturing megakaryocytes were evaluated in an in vitro system in which human hematopoietic stem cells (HSC) were differentiated into MKs. AGS-16C3F, like T-DM1, did not affect platelets directly, but inhibited MK differentiation by the activity of Cys-mcMMAF, its active metabolite. FcγRIIA did not appear to play an important role in ADC cytotoxicity to differentiating MKs. AGS-16C3F, cytotoxic to MKs, did not bind to FcγRIIA on MKs. Blocking the interaction of T-DM1 with FcγRIIA did not prevent the inhibition of MK differentiation and IgG1-mcMMAF was not as cytotoxic to MKs despite binding to FcγRIIA. Several lines of evidence suggest that internalization of AGS-16C3F into MKs is mediated by macropinocytosis. Macropinocytosis activity of differentiating HSCs correlated with cell sensitivity to AGS-16C3F. AGS-16C3F was colocalized with a macropinocytosis marker, dextran-Texas Red in differentiating MKs. Ethyl isopropyl amiloride (EIPA), a macropinocytosis inhibitor, blocked internalization of dextran-Texas Red and AGS-16C3F. These data support the notion that inhibition of MK differentiation via macropinocytosis-mediated internalization plays a role in ADC-induced thrombocytopenia. Mol Cancer Ther; 16(9); 1877-86. ©2017 AACR See related article by Zhao et al., p. 1866 . ©2017 American Association for Cancer Research.

Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States

PubMed Central

Adunlin, Georges; Ali, Askal A.; Zeichner, Simon B.; de Lima Lopes, Gilberto; Kohn, Christine G.; Montero, Alberto J.

2016-01-01

Purpose Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC). Patients and Methods We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) was captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results. Results The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third line therapy. Conclusion Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50% reduction in the total drug acquisition cost for it to be considered a cost-effective strategy. PMID:27654970

Role of TP53 in repair of N-(deoxyguanosin-8-yl)-4-aminobiphenyl adducts in human transitional cell carcinoma of the urinary bladder.

PubMed

Torino, J L; Burger, M S; Reznikoff, C A; Swaminathan, S

2001-01-01

The global genomic repair of DNA adducts was examined in human papillary transitional cell carcinoma (TCC) cell lines after exposure to N:-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), the proximate carcinogenic metabolite of the human bladder carcinogen 4-aminobiphenyl (ABP). (32)P-post-labeling analysis of TCC cultures exposed to N-OH-AABP revealed a major adduct, identified as the 3',5'-bisphosphate derivative of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP). The amount of adduct formation in TCC10 was dependent upon the dose and the duration of exposure and ranged between 1 and 5 adducts/10(7) nucleotides. To test if p53 regulates repair of the dG-C8-ABP adduct in genomic DNA, an isogeneic set of cell lines was obtained by infection of the TCC10 cultures with a retroviral construct expressing a trans-dominant mutant of p53, namely a Val-->Ala mutation at codon 143. The TDM143-TCC10 line expressing the mutant form of p53 was selected. The rate of repair of dG-C8-ABP was compared between TCC10 and TDM143-TCC10 cultures after treatment with 15 microM N-OH-AABP. The rate of disappearance of the adduct was monitored over a period of time after chemical treatment. (32)P-post-labeling analysis of dG-C8-ABP in parental TCC10 showed its rapid removal, the majority of adducts disappearing within 48 h. In contrast to TCC10, TDM143-TCC10 was relatively slower in removal of dG-C8-ABP. After 24 h DNA repair TDM143-TCC10 showed an approximately 3-fold greater amount of dG-C8-ABP compared with TCC10. These results imply that p53 plays a role in the repair of ABP adducts and that in p53 null cells the unrepaired DNA damage could cause accumulation of mutations, which might contribute to increased genomic instability and neoplastic progression.

Cardiotoxicity of novel HER2-targeted therapies.

PubMed

Sendur, Mehmet A N; Aksoy, Sercan; Altundag, Kadri

2013-08-01

Trastuzumab, an anti-HER2 humanized monoclonal antibody, is the standard treatment for both early and metastatic HER2-positive breast cancer. In addition to other chemotherapeutic agents, trastuzumab significantly improves response rate and survival in HER2-positive early and metastatic breast cancer. Although it is well known that trastuzumab therapy is closely associated with both symptomatic and asymptomatic cardiotoxicity, less is known about novel HER2-targeted therapies. The aim of this review is to discuss the cardiac safety data from recent studies of novel anti-HER2 drugs other than trastuzumab. Novel HER2-targeted therapies showed favorable results in HER2 positive metastatic breast cancer patients. Pubmed database, ASCO and San Antonio Breast Cancer Symposium Meeting abstracts were searched until January 2013 using the following search keywords; 'trastuzumab, trastuzumab cardiotoxicity, HER-2 targeted therapies, lapatinib, pertuzumab, trastuzumab emtansine, afatinib and neratinib'; papers which were considered relevant for the aim of this review were selected by the authors. Lapatinib, pertuzumab, T-DM1, neratinib and afatinib molecules are evaluated in the study. In a comprehensive analysis, 3689 lapatinib treated patients enrolled in 49 trials; asymptomatic cardiac events were reported in 53 patients (1.4%) and symptomatic grade III and IV systolic dysfunction was observed only in 7 patients (0.2%) treated with lapatinib. In phase I-III trials of pertuzumab, cardiac dysfunction was seen in 4.5-14.5% of patients with pertuzumab treatment and cardiac dysfunction was usually grade I and II. Cardiotoxicity of pertuzumab was usually reported with the trastuzumab combination and no additive cardiotoxicity was reported with addition of pertuzumab to trastuzumab. T-DM1 had a better safety profile compared to trastuzumab, no significant cardiotoxicity was observed with T-DM1 in heavily pre-treated patients. In the EMILIA study, only in 1.7% of patients in the T-DM

Nd isotopic characterization of metamorphic rocks in the Coast Mountains, Alaskan and Canadian Cordillera: Ancient crust bounded by juvenile terranes

NASA Astrophysics Data System (ADS)

Samson, Scott D.; Patchett, P. Jonathan; McClelland, William C.; Gehrels, George E.

1991-08-01

Nd isotopic data are reported for 52 samples from the crustal region between the Alexander-Wrangellia terrane and the Stikine terrane of the Alaskan and Canadian Cordillera. This region is composed of the Gravina belt, a Jurassic-Cretaceous assemblage of volcanic and clastic sedimentary rocks, the Taku terrane, a terrane of probable Early Permian to Late Triassic age, and four assemblages of metamorphic rocks that occur to the west of and within the Coast Mountains batholith. The Gravina belt has ɛNd(T) values that range from -1.1 to +8.3, similar to values of the underlying Alexander terrane, and consistent with the interpretation that it is a juvenile belt that formed in a back-arc or intra-arc basin within the Alexander terrane. Mid-Cretaceous plutons that were emplaced into the Gravina belt have ɛNd(T) values of +4.4 to +5.7 and were probably produced by mantle-derived melts that incorporated some Alexander terrane crust. The Taku terrane has ɛNd(0) values that range from -5.5 to +3.3, with corresponding depleted-mantle model (TDM) ages of 440 to 1430 Ma. A mid-Cretaceous pluton intruding the Taku terrane has an ɛNd(T) value of +5.1, a value indistinguishable from those determined for Cretaceous plutons intruding the Gravina belt. Metamorphic rocks east of and structurally overlying the Taku terrane are divided into the Tracy Arm assemblage, ɛNd(0)=-26 to 0, TDM=800-2450 Ma; the Endicott Arm assemblage, eNd(0)=-10 to -1.3, TDM=950-1500 Ma; the Port Houghton assemblage, ɛNd(0)=-9.4 to +1.1, TDM = 550-1500 Ma; and the Ruth assemblage, ɛNd(0) = -9.4 to +2.0, TDM=650-1300 Ma. These isotopic signatures indicate that a substantial component of each metamorphic assemblage was derived from Precambrian continental crust. The metamorphic rocks from these assemblages are lithologically very similar to rocks of the Yukon-Tanana (YTT) terrane of eastern Alaska and Yukon Territory and have such similar U-Pb detrital zircon ages and Nd isotopic compositions to YTT

The 30/20 Gigahertz transponder study. [wideband multichannel transponders for a communications satellite

NASA Technical Reports Server (NTRS)

1980-01-01

Design features and performance parameters are described for three types of wideband multiple channel satellite transponders for use in a 30/20 GHz communications satellite, which provides high data rate trunking service to ten ground station terminals. The three types of transponder are frequency division multiplex (FDM), time division multiplex (TDM), and a hybrid transponder using a combination of FDM and TDM techniques. The wideband multiple beam trunking concept, the traffic distribution between the trunking terminals, and system design constraints are discussed. The receiver front end design, the frequency conversion scheme, and the local oscillator design are described including the thermal interface between the transponders and the satellite. The three designs are compared with regard to performance, weight, power, cost and initial technology. Simplified block diagrams of the baseline transponder designs are included.

Time domain multiplexed spatial division multiplexing receiver.

PubMed

van Uden, Roy G H; Okonkwo, Chigo M; Chen, Haoshuo; de Waardt, Hugo; Koonen, Antonius M J

2014-05-19

A novel time domain multiplexed (TDM) spatial division multiplexing (SDM) receiver which allows for the reception of >1 dual polarization mode with a single coherent receiver, and corresponding 4-port oscilloscope, is experimentally demonstrated. Received by two coherent receivers and respective 4-port oscilloscopes, a 3 mode transmission of 28GBaud QPSK, 8, 16, and 32QAM over 41.7km of few-mode fiber demonstrates the performance of the TDM-SDM receiver with respect to back-to-back. In addition, by using carrier phase estimation employing one digital phase locked loop per output, the frequency offset between the transmitter laser and local oscillator is shown to perform similar to previous work which employs 3 coherent receivers and 4-port oscilloscopes which are dedicated to the reception of each the three modes.

The Space Station as a Construction Base for Large Space Structures

NASA Technical Reports Server (NTRS)

Gates, R. M.

1985-01-01

The feasibility of using the Space Station as a construction site for large space structures is examined. An overview is presented of the results of a program entitled Definition of Technology Development Missions (TDM's) for Early Space Stations - Large Space Structures. The definition of LSS technology development missions must be responsive to the needs of future space missions which require large space structures. Long range plans for space were assembled by reviewing Space System Technology Models (SSTM) and other published sources. Those missions which will use large space structures were reviewed to determine the objectives which must be demonstrated by technology development missions. The three TDM's defined during this study are: (1) a construction storage/hangar facility; (2) a passive microwave radiometer; and (3) a precision optical system.

Development of Kilo-Pixel Arrays of Transition-Edge Sensors for X-Ray Spectroscopy

NASA Technical Reports Server (NTRS)

Adams, J. S.; Bandler, S. R.; Busch, S. E.; Chervenak, J. A.; Chiao, M. P.; Eckart, M. E.; Ewin, A. J.; Finkbeiner, F. M.; Kelley, R. L.; Kelly, D. P.;

[Pharmacokinetic alterations in pregnancy and use of therapeutic drug monitoring].

PubMed

Panchaud, Alice; Weisskopf, Etienne; Winterfeld, Ursula; Baud, David; Guidi, Monia; Eap, Chin B; Csajka, Chantal; Widmer, Nicolas

2014-01-01

Following the thalidomide tragedy, pharmacological research in pregnant women focused primarily on drug safety for the unborn child and remains only limited regarding the efficacy and safety of treatment for the mother. Significant physiological changes during pregnancy may yet affect the pharmacokinetics of drugs and thus compromise its efficacy and/or safety. Therapeutic drug monitoring (TDM) would maximize the potential effectiveness of treatments, while minimizing the potential risk of toxicity for the mother and the fetus. At present, because of the lack of concentration-response relationship studies in pregnant women, TDM can rely only on individual assessment (based on an effective concentration before pregnancy) and remains reserved only to unexpected situations such as signs of toxicity or unexplained inefficiency. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Rhabdomyosarcome paratesticulaire (RMSP) multimétastatique : à propos d’un cas

PubMed Central

Bennani, Hassan; Ziouziou, Imad; El Ghanmi, Jihad; Karmouni, Tarik; El Khader, Khalid; Koutani, Abdellatif; Andaloussi, Ahmed Iben Attya

2014-01-01

Résumé Nous rapportons, dans le présent article, le cas clinique d’un RMSP découvert à un stade tardif chez un adolescent, dans le but de confirmer l’évolution fatale de cette pathologie au potentiel métastatique « affreux ». Nous discutons aussi les causes du retard diagnostique, l’implication du sous-type histologique comme facteur pronostique et la place de la chimiothérapie dans le traitement des formes évoluées de la maladie. PMID:25295143

Compression médullaire d'origine métastatique

PubMed Central

Bouhafa, Touria; Elmazghi, Abderrahman; Masbah, Ouafae; Hassouni, Khalid

2014-01-01

La compression médullaire d'origine métastatique est une complication neurologique fréquente du cancer. C'est une urgence diagnostique et thérapeutique qui nécessite une prise en charge rapide et efficace. L'imagerie par résonnance magnétique (IRM) constitue l'examen de choix pour l'exploration de l'ensemble de la moelle. La prise en charge thérapeutique doit être multidisciplinaire incluant la corticothérapie, la radiothérapie et la chirurgie. PMID:25829974

Long-term evaluation of individualized marketing programs for travel demand management

DOT National Transportation Integrated Search

2010-07-01

This research examines the use of individualized marketing as a transportation demand : management (TDM) strategy, using the City of Portlands SmartTrips program. This research : project has two specific aims: (1) to evaluate whether the benefits ...

Trastuzumab Emtansine for HER2-Positive Breast Cancer

Cancer.gov

An NCI Cancer Currents blog on results from the TH3RESA and EMILIA clinical trials showing trastuzumab emtansine (T-DM1) improved overall survival in patients with previously treated metastatic HER2-positive breast cancer.

Effects of operating practices on commercial driver alertness

DOT National Transportation Integrated Search

2011-08-01

This report presents the test plan for collecting and analyzing data dealing with travel demand management (TDM) activities for the Atlanta Congestion Reduction Demonstration (CRD) under the United States Department of Transportation (U.S. DOT) Urban...

Worksite trip reduction model and manual

DOT National Transportation Integrated Search

2004-04-01

According to Institute of Transportation Engineers, assessing the trip reduction claims from transportation demand management (TDM) programs is an issue for estimating future traffic volumes from trip generation data. To help assess those claims, a W...

Telecommunications and its future role in the public transportation arena

DOT National Transportation Integrated Search

2002-02-01

The objective of this report is to investigate current conditions in the application of telecommunications to TDM programs that support public transportation statewide. The report provides the results of a survey of transit agencies nationwide to asc...

Approche de prise en charge du trouble du spectre de l’autisme

PubMed Central

Lee, Patrick F.; Thomas, Roger E.; Lee, Patricia A.

2015-01-01

Résumé Objectif Se pencher sur les critères diagnostiques du trouble du spectre de l’autisme (TSA) comme les définit le Manuel diagnostique et statistique des troubles mentaux, cinquième édition (DSM-V), et concevoir une approche de prise en charge du TSA à l’aide du cadre CanMEDS–Médecine familiale (CanMEDS-MF). Sources d’information Le DSM-V, publié par l’American Psychiatric Association en mai 2013, énonce de nouveaux critères diagnostiques du TSA. Le cadre CanMEDS-MF du Collège des médecins de famille du Canada fournit un plan d’orientation pour la prise en charge complexe du TSA. Nous avons utilisé des données recueillies par le Centers for Disease Control and Prevention afin de déterminer la prévalence du TSA, ainsi que la revue systématique et méta-analyse détaillée effectuée par le National Institute for Health and Care Excellence du R.-U. pour ses lignes directrices sur le TSA dans le but d’évaluer les données probantes issues de plus de 100 interventions. Message principal Selon les données du Centers for Disease Control and Prevention, la prévalence du TSA se chiffrait à 1 sur 88 en 2008 aux États-Unis. La classification du TSA dans la quatrième édition du DSM incluait l’autisme, le syndrome d’Asperger, le trouble envahissant du développement et le trouble désintégratif de l’enfance. La dernière révision du DSM-V réunit tous ces troubles sous la mention TSA, avec différents niveaux de sévérité. La prise en charge du TSA est complexe; elle exige les efforts d’une équipe multidisciplinaire ainsi que des soins continus. Les rôles CanMEDS-MF fournissent un cadre de prise en charge. Conclusion Les médecins de famille sont au cœur de l’équipe de soins multidisciplinaire pour le TSA, et le cadre CanMEDS-MF tient lieu de plan détaillé pour guider la prise en charge d’un enfant atteint de TSA et aider la famille de cet enfant.

Simultaneous determination of nine β-lactam antibiotics in human plasma by an ultrafast hydrophilic-interaction chromatography-tandem mass spectrometry.

PubMed

Abdulla, Alan; Bahmany, Soma; Wijma, Rixt A; van der Nagel, Bart C H; Koch, Birgit C P

2017-08-15

Contemporary β-lactam antibiotic dosing is debatable in severely ill patients, since the occurrence of pathophysiological changes in critical illness can result in great inter-individual variability. Therapeutic drug monitoring (TDM) is a commonly used dosing strategy to optimize exposure and thereby minimize toxicity and maximize the efficacy. Currently, TDM of β-lactam antibiotics is rarely performed, due to poor availability in clinical practice. We describe an ultrafast Hydrophilic-Interaction Chromatography (HILIC) based UPLC-MS/MS method for the determination of amoxicillin, benzylpenicillin, cefotaxime, cefuroxime, ceftazidime, flucloxacillin, imipenem, meropenem and piperacillin in human plasma. This method involves simple sample preparation steps and was comprehensively validated according to standard FDA guidelines. For all analytes, mean accuracy and precision values were within the acceptance value. The lower and upper limits of quantification were found to be sufficient to cover the therapeutic range for all antibiotics. Finally, the method was successfully applied in a large pharmacokinetic study performed in the intensive care setting, and the feasibility of the analytical procedure was demonstrated in routine clinical practice. To the best of our knowledge, we report here the first HILIC-based UPLC-MS/MS assay for the determination of β-lactam antibiotics in human plasma. This simple, sensitive and ultrafast assay requires small-volume samples and can easily be implemented in clinical laboratories to promote the TDM of β-lactam antibiotics. Copyright © 2017 Elsevier B.V. All rights reserved.

Oral cyclosporine treatment in dogs: a review of the literature.

PubMed

Archer, T M; Boothe, D M; Langston, V C; Fellman, C L; Lunsford, K V; Mackin, A J

2014-01-01

Cyclosporine is an immunomodulatory drug used to treat an increasing spectrum of diseases in dogs. Cyclosporine is a calcineurin inhibitor, ultimately exerting its inhibitory effects on T-lymphocytes by decreasing production of cytokines, such as interleukin-2. Although, in the United States, oral cyclosporine is approved in dogs only for treatment of atopic dermatitis, there are many other indications for its use. Cyclosporine is available in 2 oral formulations: the original oil-based formulation and the more commonly used ultramicronized emulsion that facilitates oral absorption. Ultramicronized cyclosporine is available as an approved animal product, and human proprietary and generic preparations are also available. Bioavailability of the different formulations in dogs is likely to vary among the preparations. Cyclosporine is associated with a large number of drug interactions that can also influence blood cyclosporine concentrations. Therapeutic drug monitoring (TDM) can be used to assist in attaining consistent plasma cyclosporine concentrations despite the effects of varying bioavailability and drug interactions. TDM can facilitate therapeutic success by guiding dose adjustments on an individualized basis, and is recommended in cases that do not respond to initial oral dosing, or during treatment of severe, life-threatening diseases for which a trial-and-error approach to dose adjustment is too risky. Pharmacodynamic assays that evaluate individual patient immune responses to cyclosporine can be used to augment information provided by TDM. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Leveraging the trusted clinician: increasing retention in disease management through integrated program delivery.

PubMed

Frazee, Sharon Glave; Sherman, Bruce; Fabius, Raymond; Ryan, Pamela; Kirkpatrick, Patricia; Davis, Jeffery

2008-10-01

Disease management's (DM's) value largely depends on achieving and maintaining participation. Simply being enrolled in a program does not guarantee engaged participation by enrollees, a necessary factor to achieve the improved health outcomes and subsequent reduced health care costs that are the ultimate objective of DM. The objective of this study is to test the hypothesis that an integrated disease management (IDM) protocol (patent-pending), which combines telephonic-delivered disease management (TDM) with a worksite-based primary care center and pharmacy delivery, yields higher patient retention rates than traditional remote DM alone. An earlier study of the IDM protocol found that integrating a worksite-based primary care and pharmacy delivery system with traditional telephonic-based DM substantially increased contact, enrollment, and engagement rates compared to traditional stand-alone telephonic DM. This prospective cohort study tracks contact and enrollment rates for persons assigned to either IDM or traditional TDM protocols and compares participation rates at 6- and 12-month intervals as well as measures of continued retention in the DM program. The IDM protocol showed a significant improvement in participation persistence over traditional TDM. Integrating a worksite-based primary care and pharmacy delivery system led by "trusted clinicians at the workplace"trade mark with traditional telephonic-based DM not only increases contact and enrollment rates, but also results in higher patient engagement and retention. These improvements in participation are expected to result in improved outcomes for a larger proportion of the target population than traditional telephonic DM.

1999 status of the nation's highways, bridges and transit : conditions and performance : report to Congress : executive summary

DOT National Transportation Integrated Search

2011-06-01

This report presents the test plan for collecting and analyzing telecommuting/TDM data for the San Francisco Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The San Francisco UPA projects...

Selection and evaluation of travel demand management measures

DOT National Transportation Integrated Search

1997-01-01

Travel demand management (TDM) measures are designed to alter the attractiveness of competing travel modes to prompt individuals to carpool or use transit instead of driving alone. Determining the best set of measures for a given area and estimating ...

Evaluating effects of travel demand management in a medium-sized urban area : the study of I-40 Greensboro-Winston-Salem corridor

DOT National Transportation Integrated Search

2001-08-01

Travel demand management (TDM) is a set of procedures that have been shown to alleviate unlimited use of automobiles. Demand is managed by limiting highway capacity to meet demand to travel by car and providing incentives or disincentives to increase...

Development of a population pharmacokinetic model for carbamazepine based on sparse therapeutic monitoring data from pediatric patients with epilepsy.

PubMed

Carlsson, Kristin Cecilie; Hoem, Nils Ove; Glauser, Tracy; Vinks, Alexander A

2005-05-01

Population models can be important extensions of therapeutic drug monitoring (TDM), as they allow estimation of individual pharmacokinetic parameters based on a small number of measured drug concentrations. This study used a Bayesian approach to explore the utility of routinely collected and sparse TDM data (1 sample per patient) for carbamazepine (CBZ) monotherapy in developing a population pharmacokinetic (PPK) model for CBZ in pediatric patients that would allow prediction of CBZ concentrations for both immediate- and controlled-release formulations. Patient and TDM data were obtained from a pediatric neurology outpatient database. Data were analyzed using an iterative 2-stage Bayesian algorithm and a nonparametric adaptive grid algorithm. Models were compared by final log likelihood, mean error (ME) as a measure of bias, and root mean squared error (RMSE) as a measure of precision. Fifty-seven entries with data on CBZ monotherapy were identified from the database and used in the analysis (36 from males, 21 from females; mean [SD] age, 9.1 [4.4] years [range, 2-21 years]). Preliminary models estimating clearance (Cl) or the elimination rate constant (K(el)) gave good prediction of serum concentrations compared with measured serum concentrations, but estimates of Cl and K(el) were highly correlated with estimates of volume of distribution (V(d)). Different covariate models were then tested. The selected model had zero-order input and had age and body weight as covariates. Cl (L/h) was calculated as K(el) . V(d), where K(el) = [K(i) - (K(s) . age)] and V(d) = [V(i) + (V(s) . body weight)]. Median parameter estimates were V(i) (intercept) = 11.5 L (fixed); V(s) (slope) = 0.3957 L/kg (range, 0.01200-1.5730); K(i) (intercept) = 0.173 h(-1) (fixed); and K(s) (slope) = 0.004487 h(-1) . y(-1) (range, 0.0001800-0.02969). The fit was good for estimates of steady-state serum concentrations based on prior values (population median estimates) (R = 0.468; R(2) = 0.219) but

Therapeutic drug monitoring of boosted PIs in HIV-positive patients: undetectable plasma concentrations and risk of virological failure.

PubMed

Calcagno, A; Pagani, N; Ariaudo, A; Arduino, G; Carcieri, C; D'Avolio, A; Marinaro, L; Tettoni, M C; Trentini, L; Di Perri, G; Bonora, S

2017-06-01

Therapeutic drug monitoring (TDM) of antiretroviral drugs is performed in selected HIV-positive patients. The aim of this study was to estimate the prevalence of undetectable plasma concentrations of ritonavir and boosted PIs and to evaluate the association between those and the 48 week risk of virological failure. A TDM registry study and a retrospective follow-up study were conducted. Plasma concentrations were measured through validated methods. According to PI and ritonavir concentrations, patients were stratified as adherent, partially non-adherent or non-adherent. Virological outcome was evaluated 48 weeks afterwards. The TDM registry study included 2468 samples collected from 723 patients (68.1% male, median age 43.5 years). Eighty-seven samples (3.5%, 74 patients) and 68 samples (2.8%, 52 patients) were in the partially non-adherent and non-adherent groups, respectively; more patients on atazanavir/ritonavir (7.9%) versus darunavir/ritonavir (2% twice daily and 1.9% once daily) and lopinavir/ritonavir (1.5%; P  <   0.001) were observed in the partially non-adherent group. Two hundred and ninety patients were included in the follow-up study (64.1% male, median age 40 years). Patients in the adherent group had a higher chance of viral control [81.9% (167/204)] versus the partially non-adherent group and the non-adherent group [71.7% (33/46) and 53.1% (17/32), respectively; P  =   0.001]. Based on multivariate analysis, baseline HIV RNA >50 copies/mL ( P  <   0.001), genotypic susceptibility score ≤2 ( P  =   0.001), lower nadir CD4 cell count ( P  =   0.003) and not being in the adherent group ( P  =   0.029) were independent predictors of HIV RNA >50 copies/mL at 48 weeks. The measurement of PI and ritonavir plasma levels can uncover incomplete compliance with treatment; TDM may represent a useful tool for identifying patients in need of adherence-promoting interventions. © The Author 2017. Published by Oxford University

The Advent of WDM and the All-Optical Network: A Reality Check.

ERIC Educational Resources Information Center

Lutkowitz, Mark

1998-01-01

Discussion of the telecommunications industry focuses on WDM (wavelength division multiplexing) as a solution for dealing with capacity constraints. Highlights include fiber optic technology; cross-connecting and switching wavelengths; SONET (Synchronous Optical Network) and wavelength networking; and optical TDM (Time Division Multiplexing). (LRW)

Description and Simulation of a Fast Packet Switch Architecture for Communication Satellites

NASA Technical Reports Server (NTRS)

Quintana, Jorge A.; Lizanich, Paul J.

1995-01-01

The NASA Lewis Research Center has been developing the architecture for a multichannel communications signal processing satellite (MCSPS) as part of a flexible, low-cost meshed-VSAT (very small aperture terminal) network. The MCSPS architecture is based on a multifrequency, time-division-multiple-access (MF-TDMA) uplink and a time-division multiplex (TDM) downlink. There are eight uplink MF-TDMA beams, and eight downlink TDM beams, with eight downlink dwells per beam. The information-switching processor, which decodes, stores, and transmits each packet of user data to the appropriate downlink dwell onboard the satellite, has been fully described by using VHSIC (Very High Speed Integrated-Circuit) Hardware Description Language (VHDL). This VHDL code, which was developed in-house to simulate the information switching processor, showed that the architecture is both feasible and viable. This paper describes a shared-memory-per-beam architecture, its VHDL implementation, and the simulation efforts.

Analysis of prescription database extracted from standard textbooks of traditional Dai medicine.

PubMed

Zhang, Chuang; Chongsuvivatwong, Virasakdi; Keawpradub, Niwat; Lin, Yanfang

2012-08-29

Traditional Dai Medicine (TDM) is one of the four major ethnomedicine of China. In 2007 a group of experts produced a set of seven Dai medical textbooks on this subject. The first two were selected as the main data source to analyse well recognized prescriptions. To quantify patterns of prescriptions, common ingredients, indications and usages of TDM. A relational database linking the prescriptions, ingredients, herb names, indications, and usages was set up. Frequency of pattern of combination and common ingredients were tabulated. A total of 200 prescriptions and 402 herbs were compiled. Prescriptions based on "wind" disorders, a detoxification theory that most commonly deals with symptoms of digestive system diseases, accounted for over one third of all prescriptions. The major methods of preparations mostly used roots and whole herbs. The information extracted from the relational database may be useful for understanding symptomatic treatments. Antidote and detoxification theory deserves further research.

The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients.

PubMed

El-Najjar, Nahed; Jantsch, Jonathan; Gessner, André

2017-08-28

Cancer remains a leading cause of mortality and morbidity worldwide. In addition to organ failure, the most frequent reasons for admission of cancer patients to intensive care units (ICU) are: infections and sepsis. As critically ill, the complexity of the health situation of cancer patients renders the standard antimicrobial regimen more complex and even inadequate which results in increased mortality rates. This is due to pathophysiological changes in the volume of distribution, increased clearance, as well as to organ dysfunction. While in the former cases a decrease in drug efficacy is observed, the hallmark of the latter one is overdosing leading to increased toxicity at the expense of efficacy. Furthermore, an additional risk factor is the potential drug-drug interaction between antibiotics and antineoplastic agents. Therefore, therapeutic drug monitoring (TDM) is a necessity to improve the clinical outcome of antimicrobial therapy in cancer patients. To be applied in routine analysis the method used for TDM should be cheap, fast and highly accurate/sensitive. Furthermore, as ICU patients are treated with a cocktail of antibiotics the method has to cover the simultaneous analysis of antibiotics used as a first/second line of treatment. The aim of the current review is to briefly survey the pitfalls in the current antimicrobial therapy and the central role of TDM in dose adjustment and drug-drug interaction's evaluation. A major section is dedicated to summarize the currently published analytical methods and to shed light on the difficulties and potential problems that can be encountered during method development.

Impact of glucuronide interferences on therapeutic drug monitoring of posaconazole by tandem mass spectrometry.

PubMed

Krüger, Ralf; Vogeser, Michael; Burghardt, Stephan; Vogelsberger, Rita; Lackner, Karl J

2010-12-01

Posaconazole is a novel antifungal drug for oral application intended especially for therapy of invasive mycoses. Due to variable gastrointestinal absorption, adverse side effects, and suspected drug-drug interactions, therapeutic drug monitoring (TDM) of posaconazole is recommended. A fast ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification of posaconazole with a run-time <3 min was developed and compared to a LC-MS/MS method and HPLC method with fluorescence detection. During evaluation of UPLC-MS/MS, two earlier eluting peaks were observed in the MRM trace of posaconazole. This was only seen in patient samples, but not in spiked calibrator samples. Comparison with LC-MS/MS disclosed a significant bias with higher concentrations measured by LC-MS/MS, while UPLC-MS/MS showed excellent agreement with the commercially available HPLC method. In the LC-MS/MS procedure, comparably wide and left side shifted peaks were noticed. This could be ascribed to in-source fragmentation of conjugate metabolites during electrospray ionisation. Precursor and product ion scans confirmed the assumption that the additional compounds are posaconazole glucuronides. Reducing the cone voltage led to disappearance of the glucuronide peaks. Slight modification of the LC-MS/MS method enabled separation of the main interference, leading to significantly reduced deviation. These results highlight the necessity to reliably eliminate interference from labile drug metabolites for correct TDM results, either by sufficient separation or selective MS conditions. The presented UPLC-MS/MS method provides a reliable and fast assay for TDM of posaconazole.

US forest response to projected climate-related stress: a tolerance perspective.

PubMed

Liénard, Jean; Harrison, John; Strigul, Nikolay

2016-08-01

Although it is widely recognized that climate change will require a major spatial reorganization of forests, our ability to predict exactly how and where forest characteristics and distributions will change has been rather limited. Current efforts to predict future distribution of forested ecosystems as a function of climate include species distribution models (for fine-scale predictions) and potential vegetation climate envelope models (for coarse-grained, large-scale predictions). Here, we develop and apply an intermediate approach wherein we use stand-level tolerances of environmental stressors to understand forest distributions and vulnerabilities to anticipated climate change. In contrast to other existing models, this approach can be applied at a continental scale while maintaining a direct link to ecologically relevant, climate-related stressors. We first demonstrate that shade, drought, and waterlogging tolerances of forest stands are strongly correlated with climate and edaphic conditions in the conterminous United States. This discovery allows the development of a tolerance distribution model (TDM), a novel quantitative tool to assess landscape level impacts of climate change. We then focus on evaluating the implications of the drought TDM. Using an ensemble of 17 climate change models to drive this TDM, we estimate that 18% of US ecosystems are vulnerable to drought-related stress over the coming century. Vulnerable areas include mostly the Midwest United States and Northeast United States, as well as high-elevation areas of the Rocky Mountains. We also infer stress incurred by shifting climate should create an opening for the establishment of forest types not currently seen in the conterminous United States. © 2016 John Wiley & Sons Ltd.

Prospective validation of a novel IV busulfan fixed dosing for paediatric patients to improve therapeutic AUC targeting without drug monitoring.

PubMed

Vassal, G; Michel, G; Espérou, H; Gentet, J C; Valteau-Couanet, D; Doz, F; Mechinaud, F; Galambrun, C; Neven, B; Zouabi, H; Nguyen, L; Puozzo, C

2008-01-01

Oral busulfan clearance is age-dependent and children experience a wide variability in plasma exposure. BSA- or age-based dosing is used with therapeutic drug monitoring (TDM) to reduce this variability. A new intravenous (IV) dosing of busulfan (Bu) based on body weight, designed to improve AUC targeting without TDM and dose-adjustment, was prospectively evaluated. Bu was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for <9 kg; 1.2 mg/kg for 9 to <16 kg; 1.1 mg/kg for 16-23 kg; 0.95 mg/kg for >23-34 kg; 0.80 mg/kg for >34 kg. Bu treatment was followed by Cyclophosphamide or Melphalan prior to allogeneic or autologous transplantation in 55 children aged 0.3-17.2 years (median 5.6 years). No difference in AUC values was observed between weight strata (mean +/- SD 1248 +/- 205 micromol.min), whereas a significant difference in Bu clearance was demonstrated. This new dosing enabled to achieve a mean exposure comparable to that in adults. At dose 1, 91% of patients achieved the targeted AUC range (900-1500 micromol.min) while no patients were underexposed. At doses 9 and 13, over 75% of patients remained within that target whilst most of the others were slightly above. Successful engraftment was achieved in all patients. In conclusion, from infants to adults this new dosing enabled, without TDM and dose adjustment, to successfully target a therapeutic AUC window.

La tuberculose cutanée: observation de six cas confirmés au CHU Souro SANOU (CHUSS) de Bobo-Dioulasso (Burkina Faso)

PubMed Central

Andonaba, Jean Baptiste; Barro-Traoré, Fatou; Yaméogo, Téné; Diallo, Boukary; Korsaga-Somé, Nina; Traoré, Adama

2013-01-01

La localisation cutanée de la maladie tuberculeuse demeure une forme rare et représente seulement 2,1% des localisations. L'objet de cette étude est de rapporter le profil épidémiologique, anatomoclinique et évolutif des cas de tuberculose ganglio-cutanée diagnostiqués dans un CHU au Burkina Faso. La fréquence de la tuberculose cutanée est très faible au CHUSS. Six cas ont été diagnostiqués entre 2004 et 2010, soit une fréquence de un cas par an. La durée d’évolution des cas allait de deux jusqu’à dix ans avant leur diagnostic. Les lésions observées étaient: trois scrofulodermes, trois gommes, une tuberculose testiculaire associée à un mal de Pott, un cas de polyadénopathies et des cicatrices atropho-rétractiles dans la plupart des cas. Sur le plan anatomopathologique, des granulomes tuberculoïdes ont été mis en évidence dans tous les cas avec une forte réaction tuberculinique à l'IDR. Sous antituberculeux pendant six mois, l’évolution a été bonne dans tous les cas mais au prix de séquelles cutanées cicatricielles inesthétiques. Son ampleur reste peut-être encore méconnue. Le renforcement du plateau technique du CHU et une bonne collaboration interdisciplinaire contribuerait à un meilleur diagnostic et prise en charge de cette affection. PMID:24648863

Thrombocytose au cours d'un syndrome d'activation macrophagique compliquant un lupus érythémateux systémique

PubMed Central

Lekpa, Fernando Kemta; Ndongo, Souhaïbou; Fall, Seynabou; Pouye, Abdoulaye; Ka, Mamadou Mourtalla; Moreira-Diop, Thérèse

2014-01-01

Le syndrome d'activation macrophagique (SAM) est une complication du lupus érythémateux systémique (LES), due à l'activation et la prolifération incontrôlée des macrophages dans la moelle osseuse. La bycytopénie voire la pancytopénie est constante. Nous rapportons un cas atypique de SAM diagnostiqué au même moment qu'un LES chez une patiente noire de 17 ans. Le tableau initial associait une fièvre, un syndrome inflammatoire, une anémie, un taux normal de leucocytes et plus surprenant, une thrombocytose. PMID:25584123

Multi-Wavelength Mode-Locked Laser Arrays for WDM Applications

NASA Technical Reports Server (NTRS)

Davis, L.; Young, M.; Dougherty, D.; Keo, S.; Muller, R.; Maker, P.

1998-01-01

Multi-wavelength arrays of colliding pulse mode-locked (CPM) lasers have been demonstrated for wavelength division multiplexing (WDM) applications. The need for increased bandwidth is driving the development of both increased speed in time division multiplexing (TDM) and more channels in WDM for fiber optic communication systems.

Molecular Polygons Probe the Role of Intramolecular Strain in the Photophysics of π-Conjugated Chromophores.

PubMed

Wilhelm, Philipp; Vogelsang, Jan; Poluektov, Georgiy; Schönfelder, Nina; Keller, Tristan J; Jester, Stefan-Sven; Höger, Sigurd; Lupton, John M

2017-01-24

π-Conjugated segments, chromophores, are the electronically active units of polymer materials used in organic electronics. To elucidate the effect of the bending of these linear moieties on elementary electronic properties, such as luminescence color and radiative rate, we introduce a series of molecular polygons. The π-system in these molecules becomes so distorted in bichromophores (digons) that these absorb and emit light of arbitrary polarization: any part of the chain absorbs and emits radiation with equal probability. Bending leads to a cancellation of transition dipole moment (TDM), increasing excited-state lifetime. Simultaneously, fluorescence shifts to the red as radiative transitions require mixing of the excited state with vibrational modes. However, strain can become so large that excited-state localization on shorter units of the chain occurs, compensating TDM cancellation. The underlying correlations between shape and photophysics can only be resolved in single molecules. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes

NASA Astrophysics Data System (ADS)

Ranamukhaarachchi, Sahan A.; Padeste, Celestino; Dübner, Matthias; Häfeli, Urs O.; Stoeber, Boris; Cadarso, Victor J.

2016-07-01

Therapeutic drug monitoring (TDM) typically requires painful blood drawn from patients. We propose a painless and minimally-invasive alternative for TDM using hollow microneedles suitable to extract extremely small volumes (<1 nL) of interstitial fluid to measure drug concentrations. The inner lumen of a microneedle is functionalized to be used as a micro-reactor during sample collection to trap and bind target drug candidates during extraction, without requirements of sample transfer. An optofluidic device is integrated with this microneedle to rapidly quantify drug analytes with high sensitivity using a straightforward absorbance scheme. Vancomycin is currently detected by using volumes ranging between 50-100 μL with a limit of detection (LoD) of 1.35 μM. The proposed microneedle-optofluidic biosensor can detect vancomycin with a sample volume of 0.6 nL and a LoD of <100 nM, validating this painless point of care system with significant potential to reduce healthcare costs and patients suffering.

Spectroscopic and structural investigation for the ground and excited states of CaNa+ molecular ion

NASA Astrophysics Data System (ADS)

Jellali, Soulef; Habli, Héla; Mejrissi, Leila; Hamdi, Rafika; Oujia, Brahim; Xavier Gadéa, Florent

2018-04-01

In the current theoretical study, we investigated several electronic states correlated with the {Ca+Na+} and {Ca++Na} asymptotic limits of different symmetries (Σ+, Π, Δ). Our calculations were based on ab intio method using semi-empirical pseudo-potential theory of both cores Na+ and Ca2+ and Full Configuration Interaction (FCI). Hence, we computed the adiabatic potential energy curves (PECs) and vibrational levels of the ground state along with several higher states of (CaNa)+ molecular ion. From these curves, we extracted all related spectroscopic parameters (De, D0, Te, Re, Be, ωe and ωeχe). Dipolar properties of (CaNa)+ such as Permanent and Transition Dipole Moments (PDM, TDM) were determined and analyzed. Numerous Avoided Crossings (ACs) were detected in PECs and their reflections were clearly observed in PDM and TDM functions. The strong interactions could lead to significant charge or excitation transfer for atom-ion collisions in the diverse charge or excited states.

Dried blood spots analysis with mass spectrometry: Potentials and pitfalls in therapeutic drug monitoring.

PubMed

Antunes, Marina Venzon; Charão, Mariele Feiffer; Linden, Rafael

2016-09-01

Therapeutic drug monitoring (TDM) relays in the availability of specialized laboratory assays, usually available in reference centers that are not accessible to all patients. In this context, there is a growing interest in the use of dried blood spot (DBS) sampling, usually obtained from finger pricks, which allows simple and cost-effective logistics in many settings, particularly in Developing Countries. The use of DBS assays to estimate plasma concentrations is highly dependent on the hematocrit of the blood, as well as the particular characteristics of the measured analyte. DBS assays require specific validation assays, most of them are related to hematocrit effects. In the present manuscript, the application of mass spectrometric assays for determination of drugs for TDM purposes in the last ten years is reviewed, as well as the particular validation assays for new DBS methods. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Techniques for on-orbit cryogenic servicing

NASA Astrophysics Data System (ADS)

DeLee, C. H.; Barfknecht, P.; Breon, S.; Boyle, R.; DiPirro, M.; Francis, J.; Huynh, J.; Li, X.; McGuire, J.; Mustafi, S.; Tuttle, J.; Wegel, D.

2014-11-01

NASA (National Aeronautics and Space Administration) has a renewed interest in on-orbit cryogen storage and transfer to support its mission to explore near-earth objects such as asteroids and comets. The Cryogenic Propellant Storage and Transfer Technology Demonstration Mission (CPST-TDM), managed by the NASA Glenn Research Center (GRC) and scheduled for launch in 2018, will demonstrate numerous key technologies applicable to a cryopropellant fuel depot. As an adjunct to the CPST-TDM work, experiments at NASA Goddard Space Flight Center (GSFC) will support the development of techniques to manage and transfer cryogens on-orbit and expand these techniques as they may be applicable to servicing science missions using solid cryogens such as the Wide-field Infrared Survey Explorer (WISE). The results of several ground experiments are described, including autogenous pressurization used for transfer of liquid nitrogen and argon, characterization of the transfer and solidification of argon, and development of robotic tools for cryogen transfer.

Detecting and Quantifying Forest Change: The Potential of Existing C- and X-Band Radar Datasets.

PubMed

Tanase, Mihai A; Ismail, Ismail; Lowell, Kim; Karyanto, Oka; Santoro, Maurizio

2015-01-01

This paper evaluates the opportunity provided by global interferometric radar datasets for monitoring deforestation, degradation and forest regrowth in tropical and semi-arid environments. The paper describes an easy to implement method for detecting forest spatial changes and estimating their magnitude. The datasets were acquired within space-borne high spatial resolutions radar missions at near-global scales thus being significant for monitoring systems developed under the United Framework Convention on Climate Change (UNFCCC). The approach presented in this paper was tested in two areas located in Indonesia and Australia. Forest change estimation was based on differences between a reference dataset acquired in February 2000 by the Shuttle Radar Topography Mission (SRTM) and TanDEM-X mission (TDM) datasets acquired in 2011 and 2013. The synergy between SRTM and TDM datasets allowed not only identifying changes in forest extent but also estimating their magnitude with respect to the reference through variations in forest height.

Analysis of prescription database extracted from standard textbooks of traditional Dai medicine

PubMed Central

2012-01-01

Background Traditional Dai Medicine (TDM) is one of the four major ethnomedicine of China. In 2007 a group of experts produced a set of seven Dai medical textbooks on this subject. The first two were selected as the main data source to analyse well recognized prescriptions. Objective To quantify patterns of prescriptions, common ingredients, indications and usages of TDM. Methods A relational database linking the prescriptions, ingredients, herb names, indications, and usages was set up. Frequency of pattern of combination and common ingredients were tabulated. Results A total of 200 prescriptions and 402 herbs were compiled. Prescriptions based on "wind" disorders, a detoxification theory that most commonly deals with symptoms of digestive system diseases, accounted for over one third of all prescriptions. The major methods of preparations mostly used roots and whole herbs. Conclusion The information extracted from the relational database may be useful for understanding symptomatic treatments. Antidote and detoxification theory deserves further research. PMID:22931752

Cryogenic Propellant Storage and Transfer Technology Demonstration: Advancing Technologies for Future Mission Architectures Beyond Low Earth Orbit

NASA Technical Reports Server (NTRS)

Chojnacki, Kent T.; Crane, Deborah J.; Motil, Susan M.; Ginty, Carol A.; Tofil, Todd A.

2014-01-01

As part of U.S. National Space Policy, NASA is seeking an innovative path for human space exploration, which strengthens the capability to extend human and robotic presence throughout the solar system. NASA is laying the groundwork to enable humans to safely reach multiple potential destinations, including the Moon, asteroids, Lagrange points, and Mars and its environs. In support of this, NASA is embarking on the Technology Demonstration Mission Cryogenic Propellant Storage and Transfer (TDM CPST) Project to test and validate key cryogenic capabilities and technologies required for future exploration elements, opening up the architecture for large cryogenic propulsion stages and propellant depots. The TDM CPST will provide an on-orbit demonstration of the capability to store, transfer, and measure cryogenic propellants for a duration that enables long term human space exploration missions beyond low Earth orbit. This paper will present a summary of the cryogenic fluid management technology maturation effort, infusion of those technologies into flight hardware development, and a summary of the CPST preliminary design.

Etude des melanges co-continus d'acide polylactique et d'amidon thermoplastique (PLA/TPS)

NASA Astrophysics Data System (ADS)

Chavez Garcia, Maria Graciela

Les melanges co-continus sont des melanges polymeriques ou chaque composant se trouve dans une phase continue. Pour cette raison, les caracteristiques de chacun des composants se combinent et il en resulte un materiau avec une morphologie et des proprietes particulieres. L'acide polylactique (PLA) et l'amidon thermoplastique (TPS) sont des biopolymeres qui proviennent de ressources renouvelables et qui sont biodegradables. Dans ce projet, differents melanges de PLA et TPS a une haute concentration de TPS ont ete prepares dans une extrudeuse bi-vis afin de generer des structures co-continues. Grace a la technique de lixiviation selective, le TPS est enleve pour creer une structure poreuse de PLA qui a pu etre analysee au moyen de la microtomographie R-X et de la microscopie electronique a balayage MEB. L'analyse des images 2D et 3D confirme la presence de la structure co-continue dans les melanges dont la concentration en TPS. se situe entre 66% et 80%. L'effet de deux plastifiants, le glycerol seul et le melange de glycerol et de sorbitol, dans la formulation de TPS est etudie dans ce travail. De plus, nous avons evalue l'effet du PLA greffe a l'anhydride maleique (PLAg) en tant que compatibilisant. On a trouve que la phase de TPS obtenue avec le glycerol est plus grande. L'effet de recuit sur la taille de phases est aussi analyse. Grace aux memes techniques d'analyse, on a etudie l'effet du procede de moulage par injection sur la morphologie. On a constate que les pieces injectees presentent une microstructure heterogene et differente entre la surface et le centre de la piece. Pres de la surface, une peau plus riche en PLA est presente et les phases de TPS y sont allongees sous forme de lamelles. Plus au centre de la piece, une morphologie plus cellulaire est observee pour chaque phase continue. L'effet des formulations sur les proprietes mecaniques a aussi ete etudie. Les pieces injectees dont la concentration de TPS est plus grande presentent une moindre

Development and validation of a new method to simultaneously quantify triazoles in plasma spotted on dry sample spot devices and analysed by HPLC-MS.

PubMed

Baietto, Lorena; D'Avolio, Antonio; Marra, Cristina; Simiele, Marco; Cusato, Jessica; Pace, Simone; Ariaudo, Alessandra; De Rosa, Francesco Giuseppe; Di Perri, Giovanni

2012-11-01

Therapeutic drug monitoring (TDM) of triazoles is widely used in clinical practice to optimize therapy. TDM is limited by technical problems and cost considerations, such as sample storage and dry-ice shipping. We aimed to develop and validate a new method to analyse itraconazole, posaconazole and voriconazole in plasma spotted on dry sample spot devices (DSSDs) and to quantify them by an HPLC system. Extraction from DSSDs was done using n-hexane/ethyl acetate and ammonia solution. Samples were analysed using HPLC with mass spectrometry (HPLC-MS). Accuracy and precision were assayed by inter- and intra-day validation. The stability of triazoles in plasma spotted on DSSDs was investigated at room temperature for 1 month. The method was compared with a validated standard HPLC method for quantification of triazoles in human plasma. Mean inter- and intra-day accuracy and precision were <15% for all compounds. Triazoles were stable for 2 weeks at room temperature. The method was linear (r(2) > 0.999) in the range 0.031-8 mg/L for itraconazole and posaconazole, and 0.058-15 mg/L for voriconazole. High sensitivity was observed; limits of detection were 0.008, 0.004 and 0.007 mg/L for itraconazole, posaconazole and voriconazole, respectively. A high degree of correlation (r(2) > 0.94) was obtained between the DSSD method and the standard method of analysis. The method that we developed and validated to quantify triazoles in human plasma spotted on DSSDs is accurate and precise. It overcomes problems related to plasma sample storage and shipment, allowing TDM to be performed in a cheaper and safer manner.

Busulfan and metronidazole: an often forgotten but significant drug interaction.

PubMed

Gulbis, Alison M; Culotta, Kirk S; Jones, Roy B; Andersson, Borje S

2011-07-01

To report the case of a clinically significant drug interaction between intravenous busulfan and oral metronidazole observed through busulfan therapeutic drug monitoring (TDM). A 7-year-old boy with a history of myelodysplasia that progressed to acute myeloid leukemia received busulfan with therapeutic drug monitoring (TDM), clofarabine, and thiotepa as a pretransplant conditioning regimen for a cord blood transplant. The patient received metronidazole the day after a busulfan test dose of 0.5 mg/kg was administered. On the day of the first busulfan therapeutic dose, TDM was performed and the clearance of busulfan was significantly decreased by 46%. After 2 doses of busulfan therapy, the course area under the curve was exceeded, requiring discontinuation of busulfan. Metronidazole is not known to affect glutathione or the glutathione S-transferase A1 (GSTA1) enzyme system or cytochrome P450 (CYP) 3A4. Busulfan is a bifunctional alkylating agent widely used in pretransplant conditioning regimens in patients undergoing stem cell transplantation for hematologic malignancies. Busulfan metabolism is best described by hepatic conjugation to glutathione by GSTA1, although some CYP-dependent pathways have been described. Currently there is 1 publication describing the drug interaction between oral busulfan and oral metronidazole, in which concomitant use of metronidazole resulted in higher busulfan trough concentrations and higher risk of veno-occlusive disease. Our case represents a possible drug interaction based on the Horn Drug Interaction Probability Scale. Though the mechanistic basis for this interaction is unknown, the risks and benefits of using metronidazole during and in close proximity to busulfan should be carefully considered and therapeutic alternatives to metronidazole should be used when appropriate.

SYD985, a Novel Duocarmycin-Based HER2-Targeting Antibody-Drug Conjugate, Shows Antitumor Activity in Uterine Serous Carcinoma with HER2/Neu Expression.

PubMed

Black, Jonathan; Menderes, Gulden; Bellone, Stefania; Schwab, Carlton L; Bonazzoli, Elena; Ferrari, Francesca; Predolini, Federica; De Haydu, Christopher; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Wong, Serena; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Litkouhi, Babak; Schwartz, Peter E; Goedings, Peter; Beusker, Patrick H; van der Lee, Miranda M C; Timmers, C Marco; Dokter, Wim H A; Santin, Alessandro D

2016-08-01

Uterine serous carcinoma (USC) is an aggressive form of endometrial cancer. Up to 35% of USC may overexpress the HER2/neu oncogene at strong (i.e., 3+) levels by IHC while an additional 40% to 50% express HER2/neu at moderate (2+) or low (1+) levels. We investigated the efficacy of SYD985, (Synthon Biopharmaceuticals), a novel HER2-targeting antibody-drug conjugate (ADC) composed of the mAb trastuzumab linked to a highly potent DNA-alkylating agent (i.e., duocarmycin) in USC. We also compared the antitumor activity of SYD985 in head-to-head experiments to trastuzumab emtansine (T-DM1), a FDA-approved ADC, against multiple primary USC cell lines expressing different levels of HER2/neu in in vitro and in vivo experiments. Using antibody-dependent cellular cytotoxicity (ADCC), proliferation, viability, and bystander killing assays as well as propidium iodide-based flow cytometry assays and multiple in vivo USC mouse xenograft models, we demonstrate for the first time that SYD985 is a novel ADC with activity against USC with strong (3+) as well as low to moderate (i.e., 1+/2+) HER2/neu expression. SYD985 is 10- to 70-fold more potent than T-DM1 in comparative experiments and, unlike T-DM1, it is active against USC demonstrating moderate/low or heterogeneous HER2/neu expression. Clinical studies with SYD985 in patients harboring chemotherapy-resistant USC with low, moderate, and high HER2 expression are warranted. Mol Cancer Ther; 15(8); 1900-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Hybrid WDM/TDM-PON With Wavelength-Selection-Free Transmitters

NASA Astrophysics Data System (ADS)

Shin, Dong Jae; Jung, Dae Kwang; Shin, Hong Seok; Kwon, Jin Wook; Hwang, Seongtaek; Oh, Yunje; Shim, Changsup

2005-01-01

A hybrid wavelength-division-multiplexed/time-division-multiplexed passive optical network serving 128 subscribers with wavelength-selection-free transmitters is presented by cascading 1x16 arrayed-waveguide gratings (AWGs) and 1x8 splitters. The wavelength-selection-free transmitter is an uncooled Fabry-Pérot laser diode (FP-LD) wavelength-locked to an externally injected narrow-band amplified spontaneous emission (ASE). Bit-error rates better than 10^-9 over temperature ranging from 0 to 60 °C are achieved in all 16 wavelength channels using a single FP-LD with an ASE injection of about -15 and -2 dBm in 622-Mb/s upstream and 1.25-Gb/s downstream transmissions over a 10-km feeder fiber, respectively. It is also reported that the ASE injection does not exert penalty upon burst-mode operations of the FP-LDs in the upstream.

Zircon U-Pb geochronology, Sr-Nd-Hf isotopic composition and geological significance of the Late Triassic Baijiazhuang and Lvjing granitic plutons in West Qinling Orogen

NASA Astrophysics Data System (ADS)

Duan, Meng; Niu, Yaoling; Kong, Juanjuan; Sun, Pu; Hu, Yan; Zhang, Yu; Chen, Shuo; Li, Jiyong

2016-09-01

)CHUR(t) = 0.512638-0.1967 × (eλt - 1), TDM = 1/λ × ln{1 + [((143Nd/144Nd) - 0.51315) / ((147Sm/144Nd) - 0.21317)]}, λ Sm-Nd = 6.54 × 10- 12a- 1. (176Hf/177Hf)i = [(176Hf/177Hf) - (176Lu/177Hf) × (eλt - 1), εHf(t) = [(176Hf/177Hf) / (176Hf/177Hf)CHUR(t) - 1] × 104, TDM1 = 1/λ × ln[1 + ((176Hf/177Hf)Sample - (176Hf/177Hf)DM)/((176Lu/177Hf)Sample - (176Lu/177Hf)DM)], TDM2 = TDM1 - (TDM1 - t)((fCC - fSample) / (fCC - fDM)), fLu-Hf = (176Lu/177Hf)Sample / (176Lu/177Hf)CHUR-1, (176Lu/177Hf)CHUR = 0.0332, (176Hf/177Hf)CHUR, 0 = 0.282785, (176Lu/177Hf)DM = 0.0384, (176Hf/177Hf)DM = 0.28325, fCC, fSample, fDM are their own fLu-Hf, λ = 1.867 × 10- 11a- 1.

Cefepime plasma concentrations and clinical toxicity: a retrospective cohort study.

PubMed

Huwyler, T; Lenggenhager, L; Abbas, M; Ing Lorenzini, K; Hughes, S; Huttner, B; Karmime, A; Uçkay, I; von Dach, E; Lescuyer, P; Harbarth, S; Huttner, A

2017-07-01

Cefepime remains an important antibiotic for severe bacterial infections, yet some meta-analyses have shown elevated mortality among patients randomized to it. Therapeutic drug monitoring (TDM) of β-lactam antibiotics is increasing, but optimal plasma concentrations remain unknown. We examined clinical outcomes of patients undergoing cefepime TDM in an initial effort to define the drug's toxicity threshold. In this single-centre retrospective cohort study, we enrolled all adult hospitalized patients receiving cefepime and undergoing TDM from January 2013 through July 2016. The primary outcome was the incidence of clinical toxicity; a secondary outcome was clinical failure. Plasma samples were analysed via high-performance liquid chromatography with ultraviolet detection. A total of 161 cefepime concentrations were drawn from 93 patients. Roughly half (82/161, 51%) and one-third (49/161, 30%) were trough and steady-state levels from patients receiving intermittent and continuous infusions, respectively; median concentrations were 17.6 mg/L (IQR 9.7-35.2) and 29.2 mg/L (IQR 18.9-45.9). Ten patients (11%) experienced a neurologic event considered at least possibly related to cefepime; neurotoxicity was associated with poorer renal function (median creatinine clearance 54 (IQR 39-97) vs. 75 mL/min/1.73 2 (IQR 44-104)) and longer cefepime durations (mean 8.3 (SD±6.7) vs. 13.3 days (± 14.2), p = 0.071). Patients with trough levels >20 mg/L had a fivefold higher risk for neurologic events (OR 5.05, 95% CI 1.3-19.8). Neurotoxicity potentially related to cefepime occurred at plasma concentrations >35 mg/L. For those receiving intermittent infusions, trough concentrations >20 mg/L should be avoided until further information is available from prospective studies. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

HLA-DRB1 rheumatoid arthritis risk in African Americans at multiple levels: Hierarchical classification systems, amino acid positions and residues

PubMed Central

Reynolds, Richard J.; Ahmed, Altan F.; Danila, Maria I.; Hughes, Laura B.; Gregersen, Peter K.; Raychaudhuri, Soumya; Plenge, Robert M.; Bridges, S. Louis

2014-01-01

Objective To evaluate African American rheumatoid arthritis HLA-DRB1 genetic risk by three validated allele classification systems, and by amino acid position and residue. To compare the genetic risk between African American and European ancestries. Methods Four-digit HLA-DRB1 genotyping was performed on 561 autoantibody-positive African American cases and 776 African American controls. Association analysis was performed on Tezenas du Montcel (TdM); de Vries (DV); and Mattey classification system alleles and separately by amino acid position and individual residues. Results TdM S2 and S3P alleles were associated with RA (odds ratios (95% CI) 2.8 (2.0, 3.9) and 2.1 (1.7, 2.7), respectively). The DV (P-value=3.2 x 10−12) and Mattey (P-value=6.5 x 10−13) system alleles were both protective in African Americans. Amino acid position 11 (permutation P-value < 0.00001) accounted for nearly all variability explained by HLA-DRB1, although conditional analysis demonstrated that position 57 was also significant (0.01<= permutation P-val <=0.05). The valine and aspartic acid residues at position 11 conferred the highest risk for RA in African Americans. Conclusion With some exceptions, the genetic risk conferred by HLA-DRB1 in African Americans is similar to European ancestry at multiple levels: classification system (e.g., TdM), amino acid position (e.g. 11) and residue (Val 11). Unlike that reported from European ancestry, amino acid position 57 was associated with RA in African Americans, but positions 71 and 74 were not. Asp11 (OR = 1 in European ancestry) corresponds to the four digit classical allele, *09:01, also a risk allele for RA in Koreans. PMID:25524867

Antigen 85C Inhibition Restricts Mycobacterium tuberculosis Growth through Disruption of Cord Factor Biosynthesis

PubMed Central

Warrier, Thulasi; Tropis, Marielle; Werngren, Jim; Diehl, Anne; Gengenbacher, Martin; Schlegel, Brigitte; Schade, Markus; Oschkinat, Hartmut; Daffe, Mamadou; Hoffner, Sven; Eddine, Ali Nasser

2012-01-01

The antigen 85 (Ag85) protein family, consisting of Ag85A, -B, and -C, is vital for Mycobacterium tuberculosis due to its role in cell envelope biogenesis. The mycoloyl transferase activity of these proteins generates trehalose dimycolate (TDM), an envelope lipid essential for M. tuberculosis virulence, and cell wall arabinogalactan-linked mycolic acids. Inhibition of these enzymes through substrate analogs hinders growth of mycobacteria, but a link to mycolic acid synthesis has not been established. In this study, we characterized a novel inhibitor of Ag85C, 2-amino-6-propyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile (I3-AG85). I3-AG85 was isolated from a panel of four inhibitors that exhibited structure- and dose-dependent inhibition of M. tuberculosis division in broth culture. I3-AG85 also inhibited M. tuberculosis survival in infected primary macrophages. Importantly, it displayed an identical MIC against the drug-susceptible H37Rv reference strain and a panel of extensively drug-resistant/multidrug-resistant M. tuberculosis strains. Nuclear magnetic resonance analysis indicated binding of I3-AG85 to Ag85C, similar to its binding to the artificial substrate octylthioglucoside. Quantification of mycolic acid-linked lipids of the M. tuberculosis envelope showed a specific blockade of TDM synthesis. This was accompanied by accumulation of trehalose monomycolate, while the overall mycolic acid abundance remained unchanged. Inhibition of Ag85C activity also disrupted the integrity of the M. tuberculosis envelope. I3-AG85 inhibited the division of and reduced TDM synthesis in an M. tuberculosis strain deficient in Ag85C. Our results indicate that Ag85 proteins are promising targets for novel antimycobacterial drug design. PMID:22290959

An Improved LC-ESI-MS/MS Method to Quantify Pregabalin in Human Plasma and Dry Plasma Spot for Therapeutic Monitoring and Pharmacokinetic Applications.

PubMed

Dwivedi, Jaya; Namdev, Kuldeep K; Chilkoti, Deepak C; Verma, Surajpal; Sharma, Swapnil

2018-06-06

Therapeutic drug monitoring (TDM) of anti-epileptic drugs provides a valid clinical tool in optimization of overall therapy. However, TDM is challenging due to the high biological samples (plasma/blood) storage/shipment costs and the limited availability of laboratories providing TDM services. Sampling in the form of dry plasma spot (DPS) or dry blood spot (DBS) is a suitable alternative to overcome these issues. An improved, simple, rapid, and stability indicating method for quantification of pregabalin in human plasma and DPS has been developed and validated. Analyses were performed on liquid chromatography tandem mass spectrometer under positive ionization mode of electrospray interface. Pregabain-d4 was used as internal standard, and the chromatographic separations were performed on Poroshell 120 EC-C18 column using an isocratic mobile phase flow rate of 1 mL/min. Stability of pregabalin in DPS was evaluated under simulated real-time conditions. Extraction procedures from plasma and DPS samples were compared using statistical tests. The method was validated considering the FDA method validation guideline. The method was linear over the concentration range of 20-16000 ng/mL and 100-10000 ng/mL in plasma and DPS, respectively. DPS samples were found stable for only one week upon storage at room temperature and for at least four weeks at freezing temperature (-20 ± 5 °C). Method was applied for quantification of pregabalin in over 600 samples of a clinical study. Statistical analyses revealed that two extraction procedures in plasma and DPS samples showed statistically insignificant difference and can be used interchangeably without any bias. Proposed method involves simple and rapid steps of sample processing that do not require a pre- or post-column derivatization procedure. The method is suitable for routine pharmacokinetic analysis and therapeutic monitoring of pregabalin.

A simple, rapid and stability indicating validated method for quantification of lamotrigine in human plasma and dry plasma spot using LC-ESI-MS/MS: Application in clinical study.

PubMed

Namdev, Kuldeep Kumar; Dwivedi, Jaya; Chilkoti, Deepak Chandra; Sharma, Swapnil

2018-01-01

Lamotrigine (LTZ) is a phenyltriazine derivative which belongs to anti-epileptic drugs (AEDs) class and prescribed as mono- or adjunctive-therapy in treatment of epilepsy. Therapeutic drug monitoring (TDM) of AEDs provides a valid clinical tool in optimization of overall therapy. However, TDM is challenging due to the high biological samples (plasma/blood) storage/shipment costs and the limited availability of laboratories providing TDM services. Sampling in the form of dry plasma spot (DPS) or dry blood spot (DBS) are suitable alternative to overcome these issues. We developed and validated a new method for quantification of LTZ in human plasma and DPS. The extraction of LTZ from plasma and DPS was performed using liquid-liquid extraction with diethyl ether and an extraction solution composed of diethyl ether- methyl tert-butyl ether- acetone (50:30:20, v/v/v), respectively. Lamotrigine- 13C3, d3 was used as internal standard (ISTD) and the chromatographic separation was achieved on Hypurity Advance C18 column (150×4.6mm, 5μm). Quantitative estimation of LTZ and ISTD was performed on a liquid chromatography tandem mass spectrometer coupled with electrospray ionization interface operated under positive mode of ionization. Calibration curves were linear (r 2 >0.99) over the concentration range of 10-3020ng/mL for both plasma and DPS. Statistical analysis provides insignificant difference between LTZ concentration extracted from plasma and DPS samples. The method is found suitable for application in clinical study and in therapeutic monitoring of LTZ. To the best of our knowledge this is the first report which describing a validated stability indicating assay for quantification of LTZ in dry plasma spot. Copyright © 2017 Elsevier B.V. All rights reserved.

A SIEPON based transmitter sleep mode energy-efficient mechanism in EPON

NASA Astrophysics Data System (ADS)

Nikoukar, AliAkbar; Hwang, I.-Shyan; Wang, Chien-Jung; Ab-Rahman, Mohammad Syuhaimi; Liem, Andrew Tanny

2015-06-01

The main energy consumption in computer networks is the access networks. The passive optical network (PON) has the least energy consumption among access network technologies. In addition, the time division multiplexing (TDM) Ethernet PON (EPON) is one of the best candidates to improve energy consumption by time utilization. The optical network unit (ONU) can utilize the time and save the energy in the EPON by turning off its transmitter/receiver when there is no upstream/downstream traffic. The ITU-T and IEEE organizations are published standards for energy-saving in the TDM-PON. Although their standards provide the framework to accomplish the energy-saving, the algorithms/criteria to generate events to accommodate various operational policies, time to wake up, parameter values for timers are out of scope of the standards. Many studies have proposed schemes for energy-saving in TDM-PON to achieve maximum energy saving. Even so, these schemes increase the mean packet delay and consequently, reduce the quality of service (QoS). In this paper, first we take a look to the state of the art for PON energy-saving. Additionally, a mechanism based on SIEPON standard in EPON with new components in the ONUs and optical line terminal (OLT) is proposed to save the transmitter energy and guarantee QoS. The proposed mechanism follows the SIEPON standard, considers the QoS first, and then saves the energy as far as possible. The ONU sleep controller unit (OSC) and green dynamic bandwidth allocation (GDBA) are used to calculate the ONU transmitter sleep (Tx) duration and grant the proper time to the ONUs. Simulation results show that the proposed energy-saving mechanism not only promises the QoS performance in terms of mean packet delay, packet loss, throughput, and jitter, but also saves energy in different maximum cycle times.

Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care.

PubMed

Jager, N G L; Rosing, H; Schellens, J H M; Linn, S C; Beijnen, J H

2014-02-01

A sensitive and selective HPLC-MS/MS assay was used to analyze steady-state serum concentrations of tamoxifen, N-desmethyltamoxifen (E)-endoxifen, (Z)-endoxifen, N-desmethyl-4'-hydroxytamoxifen, 4-hydroxytamoxifen, and 4'-hydroxytamoxifen to support therapeutic drug monitoring (TDM) in patients treated with tamoxifen according to standard of care. When the (Z)-endoxifen serum concentration was below the predefined therapeutic threshold concentration of 5.9 ng/mL, the clinician was advised to increase the tamoxifen dose and to collect another serum sample. Paired serum samples from patients at one dose level at different time points during the tamoxifen treatment were used to assess the intra-patient variability. A total of 251 serum samples were analyzed, obtained from 205 patients. Of these patients, 197 used 20 mg tamoxifen per day and 8 patients used 10 mg/day. There was wide variability in tamoxifen and metabolite concentrations within the dosing groups. The threshold concentration for (Z)-endoxifen was reached in one patient (12 %) in the 10 mg group, in 153 patients (78 %) in the 20 mg group, and in 26 (96 %) of the patients who received a dose increase to 30 or 40 mg/day. Dose increase from 20 to 30 or 40 mg per day resulted in a significant increase in the mean serum concentrations of all analytes (p < 0.001). The mean intra-patient variability was between 10 and 20 % for all analytes. These results support the suitability of TDM for optimizing the tamoxifen treatment. It is shown that tamoxifen dose is related to (Z)-endoxifen exposure and increasing this dose leads to a higher serum concentration of tamoxifen and its metabolites. The low intra-patient variability suggests that only one serum sample is needed for TDM, making this a relatively noninvasive way to optimize the patient's treatment.

Surgical management of tumors invading the aorta and major arterial structures.

PubMed

Carpenter, Susanne G; Stone, William M; Bower, Thomas C; Fowl, Richard J; Money, Samuel R

2011-11-01

This study investigates surgical management of tumors arising from or involving the aorta and major arterial structures. A retrospective single institutional review was conducted of patients undergoing arterial resection for tumors involving the aorta or major arterial structures between January 1992 and May 2009 at a tertiary care center. Patients with tumors abutting arteries without necessitating resection and those involving only venous structures were excluded. Patients were analyzed in groups by vessel involvement: aorta, carotid, external/common iliac, internal iliac, superficial femoral, and miscellaneous. Sixty patients were identified and included for review. The iliac arteries were most often resected, and sarcomatous pathology was most common (37 patients, 62%). Twelve patients underwent aortic resection, with eight (67%) of these undergoing graft reconstruction, one (8%) graft patch, and two (17%) primary repair. None of the 17 patients undergoing internal iliac resection underwent reconstruction, whereas the majority of patients in all other groups underwent reconstruction. Thirty-day mortality (TDM) was 0% in all groups, except the aortic (2/12, 17% TDM), and internal iliac arteries (1/17, 6% TDM). Estimated blood loss varied widely and was not significantly different between vessel groups (p = 0.280). Overall, 44 of 60 (73%) patients had negative margins. Fourteen patients (23%) returned to the operating room, most for wound infection or dehiscence. Mean follow-up was 20.25 months (range: 0.5-122.0 months, SD: 23 months). Forty patients were followed up for more than 1 year. Thus, with an overall median follow-up of 12.25 months, overall survival was 60% with disease-free survival of 40%. Resection of tumors involving the aorta and major arterial structures provides a reasonable option for treatment, but with significant perioperative morbidity. In selected patients, this aggressive intervention should be considered. Copyright © 2011 Annals of

The Detector and Readout Systems of the Micro-X High Resolution Microcalorimeter X-Ray Imaging Rocket

NASA Astrophysics Data System (ADS)

Wikus, P.; Doriese, W. B.; Eckart, M. E.; Adams, J. S.; Bandler, S. R.; Brekosky, R. P.; Chervenak, J. A.; Ewin, A. J.; Figueroa-Feliciano, E.; Finkbeiner, F. M.; Galeazzi, M.; Hilton, G.; Irwin, K. D.; Kelley, R. L.; Kilbourne, C. A.; Leman, S. W.; McCammon, D.; Porter, F. S.; Reintsema, C. D.; Rutherford, J. M.; Trowbridge, S. N.

2009-12-01

The Micro-X sounding rocket experiment will deploy an imaging transition-edge-sensor (TES) microcalorimeter spectrometer to observe astrophysical sources in the 0.2-3.0 keV band. The instrument has been designed at a systems level, and the first items of flight hardware are presently being built. In the first flight, planned for January 2011, the spectrometer will observe a recently discovered Silicon knot in the Puppis-A supernova remnant. Here we describe the design of the Micro-X science instrument, focusing on the instrument's detector and detector assembly. The current design of the 2-dimensional spectrometer array contains 128 close-packed pixels with a pitch of 600 μm. The conically approximated Wolter-1 mirror will map each of these pixels to a 0.95 arcmin region on the sky; the field of view will be 11.4 arcmin. Targeted energy resolution of the TESs is about 2 eV over the full observing band. A SQUID time-division multiplexer (TDM) will read out the array. The detector time constants will be engineered to approximately 2 ms to match the TDM, which samples each pixel at 32.6 kHz, limited only by the telemetry system of the rocket. The detector array and two SQUID stages of the TDM readout system are accommodated in a lightweight Mg enclosure, which is mounted to the 50 mK stage of an adiabatic demagnetization refrigerator. A third SQUID amplification stage is located on the 1.6 K liquid He stage of the cryostat. An on-board 55-Fe source will fluoresce a Ca target, providing 3.69 and 4.01 keV calibration lines that will not interfere with the scientifically interesting energy band.

[Pharmacokinetics and pharmacodynamics of antibiotics in intensive care].

PubMed

Sörgel, F; Höhl, R; Glaser, R; Stelzer, C; Munz, M; Vormittag, M; Kinzig, M; Bulitta, J; Landersdorfer, C; Junger, A; Christ, M; Wilhelm, M; Holzgrabe, U

2017-02-01

Optimized dosage regimens of antibiotics have remained obscure since their introduction. During the last two decades pharmacokinetic(PK)-pharmacodynamic(PD) relationships, originally established in animal experiments, have been increasingly used in patients. The action of betalactams is believed to be governed by the time the plasma concentration is above the minimum inhibitory concentration (MIC). Aminoglycosides act as planned when the peak concentration is a multiple of the MIC and vancomycin seems to work best when the area under the plasma vs. time curve (AUC) to MIC has a certain ratio. Clinicians should be aware that these relationships can only be an indication in which direction dosing should go. Larger studies with sufficiently high numbers of patients and particularly severely sick patients are needed to prove the concepts. In times where all antibiotics can be measured with new technologies, the introduction of therapeutic drug monitoring (TDM) is suggested for ICUs (Intensive Care Unit). The idea of a central lab for TDM of antibiotics such as PEAK (Paul Ehrlich Antibiotika Konzentrationsmessung) is supported.

Therapeutic drug monitoring of flucytosine in serum using a SERS-active membrane system

NASA Astrophysics Data System (ADS)

Berger, Adam G.; White, Ian M.

2017-02-01

A need exists for near real-time therapeutic drug monitoring (TDM), in particular for antibiotics and antifungals in patient samples at the point-of-care. To truly fit the point-of-care need, techniques must be rapid and easy to use. Here we report a membrane system utilizing inkjet-fabricated surface enhanced Raman spectroscopy (SERS) sensors that allows sensitive and specific analysis despite the elimination of sophisticated chromatography equipment, expensive analytical instruments, and other systems relegated to the central lab. We utilize inkjet-fabricated paper SERS sensors as substrates for 5FC detection; the use of paper-based SERS substrates leverages the natural wicking ability and filtering properties of microporous membranes. We investigate the use of microporous membranes in the vertical flow assay to allow separation of the flucytosine from whole blood. The passive vertical flow assay serves as a valuable method for physical separation of target analytes from complex biological matrices. This work further establishes a platform for easy, sensitive, and specific TDM of 5FC from whole blood.

Green Propellant Infusion Mission Program Development and Technology Maturation

NASA Technical Reports Server (NTRS)

McLean, Christopher H.; Deininger, William D.; Joniatis, John; Aggarwal, Pravin K.; Spores, Ronald A.; Deans, Matthew; Yim, John T.; Bury, Kristen; Martinez, Jonathan; Cardiff, Eric H.;

On-board processing satellite network architecture and control study

NASA Technical Reports Server (NTRS)

Campanella, S. Joseph; Pontano, Benjamin A.; Chalmers, Harvey

1987-01-01

The market for telecommunications services needs to be segmented into user classes having similar transmission requirements and hence similar network architectures. Use of the following transmission architecture was considered: satellite switched TDMA; TDMA up, TDM down; scanning (hopping) beam TDMA; FDMA up, TDM down; satellite switched MF/TDMA; and switching Hub earth stations with double hop transmission. A candidate network architecture will be selected that: comprises multiple access subnetworks optimized for each user; interconnects the subnetworks by means of a baseband processor; and optimizes the marriage of interconnection and access techniques. An overall network control architecture will be provided that will serve the needs of the baseband and satellite switched RF interconnected subnetworks. The results of the studies shall be used to identify elements of network architecture and control that require the greatest degree of technology development to realize an operational system. This will be specified in terms of: requirements of the enabling technology; difference from the current available technology; and estimate of the development requirements needed to achieve an operational system. The results obtained for each of these tasks are presented.

The effect of triazole induced photosynthetic pigments and biochemical constituents of Zea mays L. (Maize) under drought stress

NASA Astrophysics Data System (ADS)

Rajasekar, Mahalingam; Rabert, Gabriel Amalan; Manivannan, Paramasivam

2016-06-01

In this investigation, pot culture experiment was carried out to estimate the ameliorating effect of triazole compounds, namely Triadimefon (TDM), Tebuconazole (TBZ), and Propiconazole (PCZ) on drought stress, photosynthetic pigments, and biochemical constituents of Zea mays L. (Maize). From 30 days after sowing (DAS), the plants were subjected to 4 days interval drought (DID) stress and drought with TDM at 15 mg l-1, TBZ at 10 mg l-1, and PCZ at 15 mg l-1. Irrigation at 1-day interval was kept as control. Irrigation performed on alternative day. The plant samples were collected on 40, 50, and 60 DAS and separated into root, stem, and leaf for estimating the photosynthetic pigments and biochemical constituents. Drought and drought with triazole compounds treatment increased the biochemical glycine betaine content, whereas the protein and the pigments contents chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid, and anthocyanin decreased when compared to control. The triazole treatment mitigated the adverse effects of drought stress by increasing the biochemical potentials and paved the way to overcome drought stress in corn plant.

Facility Effect Characterization Test of NASA's HERMeS Hall Thruster

NASA Technical Reports Server (NTRS)

Huang, Wensheng; Kamhawi, Hani; Haag, Thomas W.; Ortega, Alejandro Lopez; Mikellides, Ioannis G.

2016-01-01

A test to characterize the effect of varying background pressure on NASA's 12.5-kW Hall Effect Rocket with Magnetic Shielding had being completed. This thruster is the baseline propulsion system for the Solar Electric Propulsion Technology Demonstration Mission (SEP TDM). Potential differences in thruster performance and oscillation characteristics when in ground facilities versus on-orbit are considered a primary risk for the propulsion system of the Asteroid Redirect Robotic Mission, which is a candidate for SEP TDM. The first primary objective of this test was to demonstrate that the tools being developed to predict the zero-background-pressure behavior of the thruster can provide self-consistent results. The second primary objective of this test was to provide data for refining a physics-based model of the thruster plume that will be used in spacecraft interaction studies. Diagnostics deployed included a thrust stand, Faraday probe, Langmuir probe, retarding potential analyzer, Wien filter spectrometer, and high-speed camera. From the data, a physics-based plume model was refined. Comparisons of empirical data to modeling results are shown.

Measurements of multiple gas parameters in a pulsed-detonation combustor using time-division-multiplexed Fourier-domain mode-locked lasers.

PubMed

Caswell, Andrew W; Roy, Sukesh; An, Xinliang; Sanders, Scott T; Schauer, Frederick R; Gord, James R

2013-04-20

Hyperspectral absorption spectroscopy is being used to monitor gas temperature, velocity, pressure, and H(2)O mole fraction in a research-grade pulsed-detonation combustor (PDC) at the Air Force Research Laboratory. The hyperspectral source employed is termed the TDM 3-FDML because it consists of three time-division-multiplexed (TDM) Fourier-domain mode-locked (FDML) lasers. This optical-fiber-based source monitors sufficient spectral information in the H(2)O absorption spectrum near 1350 nm to permit measurements over the wide range of conditions encountered throughout the PDC cycle. Doppler velocimetry based on absorption features is accomplished using a counterpropagating beam approach that is designed to minimize common-mode flow noise. The PDC in this study is operated in two configurations: one in which the combustion tube exhausts directly to the ambient environment and another in which it feeds an automotive-style turbocharger to assess the performance of a detonation-driven turbine. Because the enthalpy flow [kilojoule/second] is important in assessing the performance of the PDC in various configurations, it is calculated from the measured gas properties.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elliott, T.B.; Madonna, G.S.; Ledney, G.D.

Increased susceptibility to bacterial infection, probably by translocation from the intestinal flora, can be a lethal complication for 2-3 weeks after exposure to ionizing radiation. Antibiotics alone do not provide adequate therapy for induced infections in neutropenic mice. Because some substances that are derived from bacterial cell walls activate macrophages and stimulate nonspecific resistance to infection, such agents might be used to prevent or treat postirradiation infections. In this study, a cell-wall glycolipid, trehalose dimycolate (TDM), was evaluated together with a third-generation cephalosporin, ceftriaxone, for their separate and combined effects on survival of B6D2F1 female mice that were exposed tomore » the sublethal dose of 7.0 Gy Co radiation and challenged s.c. with lethal doses of Klebsiella pneumoniae. A single injection of TDM inoculated i.p. 1 hr postirradiation increased 30-day survival to 80% after a lethal challenge by K. pneumoniae 4 days later. When the challenge dose of K. pneumoniae was increased to 5000 Ld 50/30 on Day 4, all mice died.« less

A truncated generalized singular value decomposition algorithm for moving force identification with ill-posed problems

NASA Astrophysics Data System (ADS)

Chen, Zhen; Chan, Tommy H. T.

2017-08-01

This paper proposes a new methodology for moving force identification (MFI) from the responses of bridge deck. Based on the existing time domain method (TDM), the MFI problem eventually becomes solving the linear algebraic equation in the form Ax = b . The vector b is usually contaminated by an unknown error e generating from measurement error, which often called the vector e as ''noise''. With the ill-posed problems that exist in the inverse problem, the identification force would be sensitive to the noise e . The proposed truncated generalized singular value decomposition method (TGSVD) aims at obtaining an acceptable solution and making the noise to be less sensitive to perturbations with the ill-posed problems. The illustrated results show that the TGSVD has many advantages such as higher precision, better adaptability and noise immunity compared with TDM. In addition, choosing a proper regularization matrix L and a truncation parameter k are very useful to improve the identification accuracy and to solve ill-posed problems when it is used to identify the moving force on bridge.

Integrated hollow microneedle-optofluidic biosensor for therapeutic drug monitoring in sub-nanoliter volumes

PubMed Central

Ranamukhaarachchi, Sahan A.; Padeste, Celestino; Dübner, Matthias; Häfeli, Urs O.; Stoeber, Boris; Cadarso, Victor J.

2016-01-01

Therapeutic drug monitoring (TDM) typically requires painful blood drawn from patients. We propose a painless and minimally-invasive alternative for TDM using hollow microneedles suitable to extract extremely small volumes (<1 nL) of interstitial fluid to measure drug concentrations. The inner lumen of a microneedle is functionalized to be used as a micro-reactor during sample collection to trap and bind target drug candidates during extraction, without requirements of sample transfer. An optofluidic device is integrated with this microneedle to rapidly quantify drug analytes with high sensitivity using a straightforward absorbance scheme. Vancomycin is currently detected by using volumes ranging between 50–100 μL with a limit of detection (LoD) of 1.35 μM. The proposed microneedle-optofluidic biosensor can detect vancomycin with a sample volume of 0.6 nL and a LoD of <100 nM, validating this painless point of care system with significant potential to reduce healthcare costs and patients suffering. PMID:27380889

Petrogenesis of the postcollisional Middle Devonian monzonitic to granitic magmatism of the Sierra de San Luis, Argentina

NASA Astrophysics Data System (ADS)

López de Luchi, Mónica G.; Siegesmund, Siegfried; Wemmer, Klaus; Nolte, Nicole

2017-09-01

Middle Devonian granitoids intruded the Eastern Sierras Pampeanas basement ca. 600 km east of the inferred proto-Pacific margin of Gondwana along which a ca. 390 Ma collisional event developed. In the Sierra de San Luis, voluminous Middle Devonian (393-382 Ma) batholiths are composed of I- to A-type hybrid Monzonite and Granite suites. Shoshonite and subordinated high-K series, stocks, synplutonic dikes and enclaves make up the Monzonite Suite; rocks are metaluminous alkali-calcic magnesian porphyritic or equigranular monzonite, quartz monzonite, monzodiorite and scarce monzogabbro. High-K and subordinated shoshonite series metaluminous to mildly peraluminous magnesian alkali-calcic to calc-alkalic porphyritic or equigranular quartz monzonite, granodiorite, monzogranite and equigranular leucomonzogranites make up the Granite Suite plutons and batholiths. Only a small group of highly evolved granites are ferroan. SiO2 (46-62%), Cr, Ni, V, Sc, LILE, LREE, Th, Zr and variable, Sr/Y, (La/Yb)N and (Tb/Yb)N, smooth Eu/Eu*, moderate Na2O (ca 3.5), and troughs at Nb and Ta for Monzonite Suite rocks suggest an subduction-related enriched lithospheric mantle source. Sm-Nd data (TDM 0.98-1.08 Ga, εNd(380 Ma) 0.66-1.47) and 87Sr/86Sri (0.703520-0.704203) are compatible with an enriched mantle source. The metaluminous porphyritic quartz monzonite-monzogranite and the mildly peraluminous equigranular biotite monzogranites of the Granite Suite are characterized by relatively moderate Al2O3, CaO, and 87Sr/86Sri, high LILE, Cr, variable Sr/Y, (La/Yb)N and Eu/Eu* and low Rb/Sr (< 1.2) suggest a mafic source. The porphyritic monzogranite (TDM 1.20-1.28 Ga, εNd(380Ma) - 3.02 to - 3.3, 87Sr/86Sri 0.706578-0.707027) and the biotite monzogranites (TDM 1.31 Ga, εNd(380Ma) - 3.3, 87Sr/86Sri 0.707782) would share a common source. The equigranular alkali-calcic leucomonzogranites are characterized by Rb/Sr > 1.5, ASI 1.05-1.18, and Ga/Al 2.6-3.9, εNd(380 Ma) - 3.74 to - 3.95 and (87Sr/86

Four-fold increase in users of time-wavelength division multiplexing (TWDM) passive optical network (PON) by delayed optical amplitude modulation (AM) upstream

NASA Astrophysics Data System (ADS)

Kachhatiya, Vivek; Prince, Shanthi

2016-12-01

In this paper, we have proposed and simulated optical time division multiplexed passive optical network (TDM-PON) using delayed optical amplitude modulation (AM). Eight upstream wavelengths are demonstrated to show optical time wavelength division multiplexed (TWDM) by combining optical network units (ONU) users data at the remote node (RN). Each ONU generates 2.5 Gb/s user data, and it is modulated using novel return to zero (RZ) delayed AM. Optical TDM aggregates 10 Gb/s data per wavelength from four 2.5 Gb/s upstream user data, which facilitates four different ONU data on the same wavelength as 10 Gb/s per upstream wavelength and, simplify the laser requirements (2.5 Gb/s) at each optical network unit (ONU) transmitter. Upstream optical TWDM-PON is investigated for eight wavelengths with wavelength spacing of 100 GHz. Novel optical TDM for upstream increased the number of the simultaneous user to fourfold from conventional TWDM-PON using delayed AM with a high-quality-factor of received signal. Despite performance degradation due to different fiber reach and dispersion compensation technique, Optical TWDM link shows significant improvement regarding receiver sensitivity when compared with common TWDM link. Hence, it offers optimistic thinking to show optical TDM at this phase as one of the future direction, where complex digital signal processing (DSP) and coherent optical communication are frequently demonstrated to serve the access network. Downstream side conventional TWDM eight wavelengths are multiplexed at the OLT and sent downstream to serve distributed tunable ONU receivers through an optical distribution network (ODN). Each downstream wavelengths are modulated at the peak rate of 10 Gb/s using non-return to zero external modulation (NRZ-EM). The proposed architecture is cost efficient and supports high data rates as well as ;pay as you grow; network for both service providers and the users perspectives. Users are classified into two categories viz home

Managing the TDM process : developing MPO institutional capacity - technical report.

DOT National Transportation Integrated Search

2015-04-01

Within Texas, the development of urban travel demand models (TDMs) is a cooperative process between the : Texas Department of Transportation and Metropolitan Planning Organizations (MPOs). Though TxDOT-Transportation Planning and Programming Division...

Cryogenic Propellant Storage and Transfer (CPST) Technology Demonstration Mission (TDM)

NASA Technical Reports Server (NTRS)

Chojnacki, Kent

2013-01-01

Objectives: 1) Store cryogenic propellants in a manner that maximizes their availability for use regardless of mission duration. 2) Efficiently transfer conditioned cryogenic propellant to an engine or tank situated in a microgravity environment. 3) Accurately monitor and gauge cryogenic propellants situated in a microgravity environment.

Les infestations par les poux de tête : une mise à jour clinique.

PubMed

Cummings, Carl; Finlay, Jane C; MacDonald, Noni E

2018-02-01

Les infestations par les poux de tête ( Pediculus humanus capitis ) ne constituent ni un risque sanitaire primaire ni un vecteur de maladie, mais représentent plutôt un problème de société au coût impor- tant. Pour diagnostiquer une infestation, il faut déceler un pou vivant. Même si les pyréthines et la perméthrine demeurent les traitements de première intention au Canada, la solution de myristate d'isopropyle et de ST-cyclométhicone et la diméticone peuvent être envisagées en deuxième intention après un échec thérapeutique démontré.

A Review of Communications Satellites and Related Spacecraft for Factors Influencing Mission Success. Volume 2

DTIC Science & Technology

1975-11-17

and control (subsystem) COMM., comm AEC Atomic Energy Commission comsat AFB Air Force Base COMSTAR ACE A-hr aerospace ground equipment ampere...array TDA Satellite Assembly Building TDAL Space and Missile Systems Organization (U.S. Air Force) TDM THIR satellite communications system TI...Satellite Control Facility (U.S. Air Force) TIROS selective chopper radiometer TLM, T/M surface composition mapping radiometer TOS TRUST

An Approximation for Computing Reduction in Bandwidth Requirements Using Intelligent Multiplexers

DTIC Science & Technology

1993-03-01

Naval Postgraduate School__ Sc. ALX)HRSS(City, State, andLPCode) 10 . SOURCE 01- FUNUINU NUMBERS Monterey, CA 93943 ELEGRMEN N RO. EC NO.ORUII EME T O... 10 IV. MODEL DEVELOPMENT ............................................................................ 13 A. THE ERLANG MODEL...channel. Also, the silent periods of a voice or data transmission go unused. For combined voice and data traffic, TDM averages only 10 -25% efficiency

The RACE (R&D in Advanced Communications Technologies for Europe) Program of the European Communities

DTIC Science & Technology

1988-08-17

asynchronous TDM for all channels; and hybrid solu- However, since technoeconomic considerations may im- tions, possibly involving dynamic rearranging. A...qualitative electronic switching are favored: CMOS, silicon bipolar, analysis , under the headings: timing of introduction, net- and gallium arsenide...or ring configurations. tem requirements. Project 1029. In this project an up-to-date analysis Microelectronic Components was made of the state of the

Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus

PubMed Central

Moreno-Indias, Isabel; Cardona, Fernando; Tinahones, Francisco J.; Queipo-Ortuño, María Isabel

2014-01-01

Obesity and its associated disorders are a major public health concern. Although obesity has been mainly related with perturbations of the balance between food intake and energy expenditure, other factors must nevertheless be considered. Recent insight suggests that an altered composition and diversity of gut microbiota could play an important role in the development of metabolic disorders. This review discusses research aimed at understanding the role of gut microbiota in the pathogenesis of obesity and type 2 diabetes mellitus (TDM2). The establishment of gut microbiota is dependent on the type of birth. With effect from this point, gut microbiota remain quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understand these changes is important to predict diseases and develop therapies. A new theory suggests that gut microbiota contribute to the regulation of energy homeostasis, provoking the development of an impairment in energy homeostasis and causing metabolic diseases, such as insulin resistance or TDM2. The metabolic endotoxemia, modifications in the secretion of incretins and butyrate production might explain the influence of the microbiota in these diseases. PMID:24808896

Target-mediated drug disposition model and its approximations for antibody-drug conjugates.

PubMed

Gibiansky, Leonid; Gibiansky, Ekaterina

2014-02-01

Antibody-drug conjugate (ADC) is a complex structure composed of an antibody linked to several molecules of a biologically active cytotoxic drug. The number of ADC compounds in clinical development now exceeds 30, with two of them already on the market. However, there is no rigorous mechanistic model that describes pharmacokinetic (PK) properties of these compounds. PK modeling of ADCs is even more complicated than that of other biologics as the model should describe distribution, binding, and elimination of antibodies with different toxin load, and also the deconjugation process and PK of the released toxin. This work extends the target-mediated drug disposition (TMDD) model to describe ADCs, derives the rapid binding (quasi-equilibrium), quasi-steady-state, and Michaelis-Menten approximations of the TMDD model as applied to ADCs, derives the TMDD model and its approximations for ADCs with load-independent properties, and discusses further simplifications of the system under various assumptions. The developed models are shown to describe data simulated from the available clinical population PK models of trastuzumab emtansine (T-DM1), one of the two currently approved ADCs. Identifiability of model parameters is also discussed and illustrated on the simulated T-DM1 examples.

A dual slope charge sampling analog front-end for a wireless neural recording system.

PubMed

Lee, Seung Bae; Lee, Byunghun; Gosselin, Benoit; Ghovanloo, Maysam

2014-01-01

This paper presents a novel dual slope charge sampling (DSCS) analog front-end (AFE) architecture, which amplifies neural signals by taking advantage of the charge sampling concept for analog signal conditioning, such as amplification and filtering. The presented DSCS-AFE achieves amplification, filtering, and sampling in a simultaneous fashion, while consuming very small amount of power. The output of the DSCS-AFE produces a pulse width modulated (PWM) signal that is proportional to the input voltage amplitude. A circular shift register (CSR) utilizes time division multiplexing (TDM) of the PWM pulses to create a pseudo-digital TDM-PWM signal that can feed a wireless transmitter. The 8-channel system-on-a-chip was fabricated in a 0.35-μm CMOS process, occupying 2.4 × 2.1 mm(2) and consuming 255 μW from a 1.8V supply. Measured input-referred noise for the entire system, including the FPGA in order to recover PWM signal is 6.50 μV(rms) in the 288 Hz~10 kHz range. For each channel, sampling rate is 31.25 kHz, and power consumption is 31.8 μW.

Adaptive upstream rate adjustment by RSOA-ONU depending on different injection power of seeding light in standard-reach and long-reach PON systems

NASA Astrophysics Data System (ADS)

Yeh, C. H.; Chow, C. W.; Shih, F. Y.; Pan, C. L.

2012-08-01

The wavelength division multiplexing-time division multiplexing (WDM-TDM) passive optical network (PON) using reflective semiconductor optical amplifier (RSOA)-based colorless optical networking units (ONUs) is considered as a promising candidate for the realization of fiber-to-the-home (FTTH). And this architecture is actively considered by Industrial Technology Research Institute (ITRI) for the realization of FTTH in Taiwan. However, different fiber distances and optical components would introduce different power budgets to different ONUs in the PON. Besides, due to the aging of optical transmitter (Tx), the power decay of the distributed optical carrier from the central office (CO) could also reduce the injection power into each ONU. The situation will be more severe in the long-reach (LR) PON, which is considered as an option for the future access. In this work, we investigate a WDM-TDM PON using RSOA-based ONU for upstream data rate adjustment depending on different continuous wave (CW) injection powers. Both standard-reach (25 km) and LR (100 km) transmissions are evaluated. Moreover, a detail analysis of the upstream signal bit-error rate (BER) performances at different injection powers, upstream data rates, PON split-ratios under stand-reach and long-reach is presented.

Scalloping minimization in deep Si etching on Unaxis DSE tools

NASA Astrophysics Data System (ADS)

Lai, Shouliang; Johnson, Dave J.; Westerman, Russ J.; Nolan, John J.; Purser, David; Devre, Mike

2003-01-01

Sidewall smoothness is often a critical requirement for many MEMS devices, such as microfludic devices, chemical, biological and optical transducers, while fast silicon etch rate is another. For such applications, the time division multiplex (TDM) etch processes, so-called "Bosch" processes are widely employed. However, in the conventional TDM processes, rough sidewalls result due to scallop formation. To date, the amplitude of the scalloping has been directly linked to the silicon etch rate. At Unaxis USA Inc., we have developed a proprietary fast gas switching technique that is effective for scalloping minimization in deep silicon etching processes. In this technique, process cycle times can be reduced from several seconds to as little as a fraction of second. Scallop amplitudes can be reduced with shorter process cycles. More importantly, as the scallop amplitude is progressively reduced, the silicon etch rate can be maintained relatively constant at high values. An optimized experiment has shown that at etch rate in excess of 7 μm/min, scallops with length of 116 nm and depth of 35 nm were obtained. The fast gas switching approach offers an ideal manufacturing solution for MEMS applications where extremely smooth sidewall and fast etch rate are crucial.

Impact of the gut microbiota on the development of obesity and type 2 diabetes mellitus.

PubMed

Moreno-Indias, Isabel; Cardona, Fernando; Tinahones, Francisco J; Queipo-Ortuño, María Isabel

2014-01-01

Obesity and its associated disorders are a major public health concern. Although obesity has been mainly related with perturbations of the balance between food intake and energy expenditure, other factors must nevertheless be considered. Recent insight suggests that an altered composition and diversity of gut microbiota could play an important role in the development of metabolic disorders. This review discusses research aimed at understanding the role of gut microbiota in the pathogenesis of obesity and type 2 diabetes mellitus (TDM2). The establishment of gut microbiota is dependent on the type of birth. With effect from this point, gut microbiota remain quite stable, although changes take place between birth and adulthood due to external influences, such as diet, disease and environment. Understand these changes is important to predict diseases and develop therapies. A new theory suggests that gut microbiota contribute to the regulation of energy homeostasis, provoking the development of an impairment in energy homeostasis and causing metabolic diseases, such as insulin resistance or TDM2. The metabolic endotoxemia, modifications in the secretion of incretins and butyrate production might explain the influence of the microbiota in these diseases.

A Dual Slope Charge Sampling Analog Front-End for a Wireless Neural Recording System

PubMed Central

Lee, Seung Bae; Lee, Byunghun; Gosselin, Benoit

2015-01-01

This paper presents a novel dual slope charge sampling (DSCS) analog front-end (AFE) architecture, which amplifies neural signals by taking advantage of the charge sampling concept for analog signal conditioning, such as amplification and filtering. The presented DSCS-AFE achieves amplification, filtering, and sampling in a simultaneous fashion, while consuming very small amount of power. The output of the DSCS-AFE produces a pulse width modulated (PWM) signal that is proportional to the input voltage amplitude. A circular shift register (CSR) utilizes time division multiplexing (TDM) of the PWM pulses to create a pseudo-digital TDM-PWM signal that can feed a wireless transmitter. The 8-channel system-on-a-chip was fabricated in a 0.35-µm CMOS process, occupying 2.4 × 2.1 mm2 and consuming 255 µW from a 1.8V supply. Measured input-referred noise for the entire system, including the FPGA in order to recover PWM signal is 6.50 µVrms in the 288 Hz~10 kHz range. For each channel, sampling rate is 31.25 kHz, and power consumption is 31.8 µW. PMID:25570655

Accurate Behavioral Simulator of All-Digital Time-Domain Smart Temperature Sensors by Using SIMULINK

PubMed Central

Chen, Chun-Chi; Chen, Chao-Lieh; Lin, You-Ting

2016-01-01

This study proposes a new behavioral simulator that uses SIMULINK for all-digital CMOS time-domain smart temperature sensors (TDSTSs) for performing rapid and accurate simulations. Inverter-based TDSTSs offer the benefits of low cost and simple structure for temperature-to-digital conversion and have been developed. Typically, electronic design automation tools, such as HSPICE, are used to simulate TDSTSs for performance evaluations. However, such tools require extremely long simulation time and complex procedures to analyze the results and generate figures. In this paper, we organize simple but accurate equations into a temperature-dependent model (TDM) by which the TDSTSs evaluate temperature behavior. Furthermore, temperature-sensing models of a single CMOS NOT gate were devised using HSPICE simulations. Using the TDM and these temperature-sensing models, a novel simulator in SIMULINK environment was developed to substantially accelerate the simulation and simplify the evaluation procedures. Experiments demonstrated that the simulation results of the proposed simulator have favorable agreement with those obtained from HSPICE simulations, showing that the proposed simulator functions successfully. This is the first behavioral simulator addressing the rapid simulation of TDSTSs. PMID:27509507

Portraying the Contribution of Individual Behaviors to Team Cohesion and Performance

NASA Technical Reports Server (NTRS)

Parke, Bonny; Orasanu, Judith

2012-01-01

Behaviors of individuals in teams both contribute to and are molded by team dynamics. How they do so has been the subject of much research. A method of portraying individuals' behaviors in teams, the Team Diagramming Method (TDM) is presented. Behaviors are rated by other team members on three important dimensions: positivity/negativity, dominant/submissive, and task-orientedness/expressiveness. A study of 5-person teams engaging in a 3-day moon simulation task demonstrated that measures of these perceived behaviors as well as the variances of these behaviors correlated with cohesion measures and performance. The method shows strengths and weaknesses of particular teams and, by comparison with high-performing teams, suggests interventions based on individual as well as team behaviors. The primary goal of this study was to determine the extent to which these team level variables, derived from all team members' rated behaviors, were associated with previous methods of measuring cohesion and with performance. A secondary goal was to determine the stability of TDM measures over time by comparing team level variables based on ratings early and later in the team s work together.

Architecture design and performance evaluation of multigranularity optical networks based on optical code division multiplexing

NASA Astrophysics Data System (ADS)

Huang, Shaowei; Baba, Ken-Ichi; Murata, Masayuki; Kitayama, Ken-Ichi

2006-12-01

In traditional lambda-based multigranularity optical networks, a lambda is always treated as the basic routing unit, resulting in low wavelength utilization. On the basis of optical code division multiplexing (OCDM) technology, a novel OCDM-based multigranularity optical cross-connect (MG-OXC) is proposed. Compared with the traditional lambda-based MG-OXC, its switching capability has been extended to support fiber switching, waveband switching, lambda switching, and OCDM switching. In a network composed of OCDM-based MG-OXCs, a single wavelength can be shared by distinct label switched paths (LSPs) called OCDM-LSPs, and OCDM-LSP switching can be implemented in the optical domain. To improve the network flexibility for an OCDM-LSP provisioning, two kinds of switches enabling hybrid optical code (OC)-wavelength conversion are designed. Simulation results indicate that a blocking probability reduction of 2 orders can be obtained by deploying only five OCs to a single wavelength. Furthermore, compared with time-division-multiplexing LSP (TDM-LSP), owing to the asynchronous accessibility and the OC conversion, OCDM-LSPs have been shown to permit a simpler switch architecture and achieve better blocking performance than TDM-LSPs.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabaeian, Mohammad, E-mail: sabaeian@scu.ac.ir; Shahzadeh, Mohammadreza

In this work, the effects of the shape and size on the intersubband electronic and optical properties of three-dimensional self-assembled pyramid-shaped InAs/GaAs quantum dots (QDs) were investigated in detail. More precisely, in-plane- and z-polarized transitions dipole moment (TDM), oscillator strength (OS), and absorption coefficients of P-to-S, WL-to-P, and WL-to-S transitions were studied as a function of the QD height. The P-to-S TDM showed to be strong and purely in-plane-polarized transition dominating two others. However, the TDMs and OSs of WL-to-P and WL-to-S transitions which are in-plane- and z-polarized transitions, respectively, showed a competition behavior for short and tall QDs. Themore » former dominates for short QDs, and the latter for tall QDs. The physical reasons behind these interesting phenomena were also explained using the probability of finding the carriers in the pyramid region attached to the WL. The theoretical results are in good agreement with experimental data reported for short QDs [Appl. Phys. Lett. 82, 630 (2003)].« less

Gravity deformation measurements of 70m reflector surfaces

NASA Technical Reports Server (NTRS)

Brenner, Michael; Imbriale, William A.; Britcliffe, Michael K.

2001-01-01

Two of NASA's Deep Space Network (DSN) 70-meter reflectors are measured using a Leica TDM-5000 theodolite. The main reflector surface was measured at five elevation angles so that a gravity deformation model could be derived that described the main reflector distortions over the entire range of elevation angles. The report describes the measurement equipment and accuracy and the results derived from the data.

A Heuristic Approach to the Theater Distribution Problem

DTIC Science & Technology

2014-03-27

outstanding guidance on this thesis research as well as the introduction to joint mobility modeling in OPER 674 which sparked my interest in this area of...32 xi List of Acronyms Acronym Definition AMP Analysis of Mobility Platform DARP Dial-A-Ride problem...tabu SMM Strategic Mobility Modeling TDD time definite delivery TDM Theater Distribution Model TDP Theater Distribution Problem TPFDD Time Phased Force

Relationship between self-reported adherence, antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection.

PubMed

Fabbiani, Massimiliano; Di Giambenedetto, Simona; Cingolani, Antonella; Fanti, Iuri; Colafigli, Manuela; Tamburrini, Enrica; Cauda, Roberto; Navarra, Pierluigi; De Luca, Andrea; Murri, Rita

2016-01-01

The aim of the study was to explore relationships between self-reported adherence, antiretroviral drug concentration measurement (TDM) and self-reported symptoms. We systematically administered to human immunodeficiency (HIV)-infected outpatients a questionnaire evaluating measures of self-reported adherence (missing doses during last week, deviations from the prescribed timing of therapy, self-initiated discontinuations for > 24 or 48 h, exhausting drugs and present sense of how patients are taking therapy) and a panel of referred symptoms (a symptom score was built summing self-reported scores for each listed symptom). We selected patients who completed the questionnaire and also had a TDM (mainly reflecting adherence in the past few days or weeks), thus comparing these two tools as measures of adherence. A total of 130 patients (64.6% males, median age 44 years, 76.2% with HIV RNA < 50 copies/ml, median CD4 540 cells/μl) were included. Mean self-reported adherence (on a 0-100 visual analogue scale) was 80% (standard deviation, 18.7). Drug concentration was subtherapeutic in 16 patients (12.3%), of which 7 (5.4%) had undetectable drug levels (< 0.05 mg/L). Of these last seven patients, five (71.4%) reported an adherence below 80%. In a multivariable analysis, females and patients with undetectable drug levels (mean change -18.43%, 95% confidence intervals (CIs) -31.83 to -5.03, p = 0.007) showed a lower self-reported adherence, while those with HIV RNA < 50 copies/ml showed a higher adherence. Lower self-reported adherence (odds ratio 0.62 per 10% increase, 95% CI = 0.43-0.89, p = 0.009) and longer time from last drug intake were independently related to the development of undetectable drug levels. We also found that a higher symptom score was associated with a lower self-reported adherence and with a higher proportion of undetectable drug levels. Self-reported adherence and TDM showed a correlation and seemed to be comparable tools for adherence estimation

High-intensity body weight training is comparable to combined training in changes in muscle mass, physical performance, inflammatory markers and metabolic health in postmenopausal women at high risk for type 2 diabetes mellitus: A randomized controlled clinical trial.

PubMed

Martins, Fernanda Maria; de Paula Souza, Aletéia; Nunes, Paulo Ricardo Prado; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Candido; Resende, Elisabete Aparecida Mantovani Rodrigues; de Oliveira, Erick Prado; Orsatti, Fábio Lera

2018-07-01

This study compared the effects of 12 weeks of high-intensity interval body weight training (HIBWT) with combined training (COMT; aerobic and resistance exercises on body composition, a 6-minute walk test (6MWT; physical performance), insulin resistance (IR) and inflammatory markers in postmenopausal women (PW) at high risk of type 2 diabetes mellitus (TDM2). In this randomized controlled clinical study, 16 PW at high risk of TDM2 were randomly allocated into two groups: HIBWT (n = 8) and COMT (n = 8). The HIBWT group performed a training protocol (length time ~28 min) consisting of ten sets of 60 s of high intensity exercise interspersed by a recovery period of 60 s of low intensity exercise. The COMT group performed a training protocol (length time ~60 min) consisting of a 30 min walk of moderate intensity following by five resistance exercises. All training sessions were performed in the university gym facility three days a week (no consecutive days) for 12 weeks. All outcomes (body composition, muscle function, and IR and inflammatory markers) were assessed at the baseline and at the end of the study. Both groups increased (P < 0.05) muscle mass index (MMI), 6MWT, and interleukin 1 receptor antagonist and decreased fasting glucose, glycated hemoglobin , Insulin, HOMA-IR, and monocyte chemoattractant protein-1 (trend, P = 0.056). HIBWT effects were indistinguishable (P > 0.05) from the effects of COMT. There was a significant (P < 0.05) interaction of time by the group in muscle strength, indicating that only the COMT increased the muscle strength. This study suggests that changes in HOMA, IL-1ra, 6MWT, and MMI with HITBW are similar when compared to COMT in PW at high risk of TDM2. The patients were part of a 12-week training study (ClinicalTrials.gov Identifier: NCT03200639). Copyright © 2018 Elsevier Inc. All rights reserved.

Potential impacts of climate change and adaptation strategies for sunflower in Pakistan.

PubMed

Awais, Muhammad; Wajid, Aftab; Saleem, Muhammad Farrukh; Nasim, Wajid; Ahmad, Ashfaq; Raza, Muhammad Aown Sammar; Bashir, Muhammad Usman; Mubeen, Muhammad; Hammad, Hafiz Mohkum; Habib Ur Rahman, Muhammad; Saeed, Umer; Arshad, Muhammad Naveed; Hussain, Jamshad

2018-05-01

Growth, development, and economic yield of agricultural crops rely on moisture, temperature, light, and carbon dioxide concentration. However, the amount of these parameters is varying with time due to climate change. Climate change is factual and ongoing so, first principle of agronomy should be to identify climate change potential impacts and adaptation measures to manage the susceptibilities of agricultural sector. Crop models have ability to predict the crop's yield under changing climatic conditions. We used OILCROP-SUN model to simulate the influence of elevated temperature and CO 2 on crop growth duration, maximum leaf area index (LAI), total dry matter (TDM), and achene yield of sunflower under semi-arid conditions of Pakistan (Faisalabad, Punjab). The model was calibrated and validated with the experimental data of 2012 and 2013, respectively. The simulation results showed that phenological events of sunflower were not changed at higher concentration of CO 2 (430 and 550 ppm). However LAI, achene yield, and TDM increased by 0.24, 2.41, and 4.67% at 430 ppm and by 0.48, 3.09, and 9.87% at 550 ppm, respectively. Increased temperature (1 and 2 °C) reduced the sunflower duration to remain green that finally led to less LAI, achene yield, and TDM as compared to present conditions. However, the drastic effects of increased temperature on sunflower were reduced to some extent at 550 ppm CO 2 concentration. Evaluation of different adaptation options revealed that 21 days earlier (as compared to current sowing date) planting of sunflower crop with increased plant population (83,333 plants ha -1 ) could reduce the yield losses due to climate change. Flowering is the most critical stage of sunflower to water scarcity. We recommended skipping second irrigation or 10% (337.5 mm) less irrigation water application to conserve moisture under possible water scarce conditions of 2025 and 2050.

Therapeutic drug monitoring and the conservative management of chronic tuberculous empyema: case report and review of the literature.

PubMed

Long, Richard; Barrie, James; Peloquin, Charles A

2015-08-12

Chronic tuberculous empyema (CTE) is a rare and unusual, low grade and protracted, infection of the pleural space resulting in marked thickening, even calcification of the visceral and parietal pleura. Historically its management has been extraordinarily challenging. Differential penetration of anti-TB drugs into the pleural space has resulted in acquired drug resistance and surgery to remove the empyema or close a complicating bronchopleural fistula (BPF) has been technically difficult or unacceptably hazardous. On the basis of limited experience, the combination of tube thoracostomy or catheter drainage and high-end dosing of anti-TB drugs has been recommended as an initial approach to these lesions. Herein we report the first well documented case of closure of a BPF and cure of a CTE using this approach. The chances of a favorable outcome are improved, we suggest, by using therapeutic drug monitoring (TDM) to guide high-end drug dosing. An 84 year old male immigrant to Canada from Croatia was diagnosed with a CTE after he developed a BPF. The diagnosis was made 62 years after what was, in retrospect, an episode of tuberculous pleurisy. He was treated with computed tomography-guided catheter drainage and TDM-guided high-end dosed anti-TB drugs (serum and pleural fluid drug concentrations) over a 10 month period. Sustained closure of the BPF and mycobacteriologic cure of the CTE was achieved. Drug concentrations in the present case and all other reported cases are summarized and interpreted. When serum concentrations of the anti-TB drugs isoniazid, pyrazinamide and ethambutol at the high end of the normal range are achieved, pleural fluid concentrations at the low end of the normal range may be anticipated in CTE. Though highly protein bound drugs such as rifampin and moxifloxacin appear to penetrate CTEs less well, their free concentrations in the pleural space may be proportionately higher on account of lower protein concentrations. Interventional radiology and

Development and pilot‐testing of a Decision Aid for use among Chinese women facing breast cancer surgery

PubMed Central

Au, Angel H.Y.; Lam, Wendy W.T.; Chan, Miranda C.M.; Or, Amy Y.M.; Kwong, Ava; Suen, Dacita; Wong, Annie L.; Juraskova, Ilona; Wong, Teresa W.T.; Fielding, Richard

2011-01-01

Abstract Background  Women choosing breast cancer surgery encounter treatment decision‐making (TDM) difficulties, which can cause psychological distress. Decision Aids (DAs) may facilitate TDM, but there are no DAs designed for Chinese populations. We developed a DA for Chinese women newly diagnosed with breast cancer, for use during the initial surgical consultation. Aims  Conduct a pilot study to assess the DA acceptability and utility among Chinese women diagnosed with breast cancer. Methods  Women preferred the DA in booklet format. A booklet was developed and revised and evaluated in two consecutive pilot studies (P1 and P2). On concluding their initial diagnostic consultation, 95 and 38 Chinese women newly diagnosed with breast cancer received the draft and revised draft DA booklet, respectively. Four‐day post‐consultation, women had questionnaires read out to them and to which they responded assessing attitudes towards the DA and their understanding of treatment options. Results  The original DA was read/partially read by 66/22% (n = 84) of women, whilst the revised version was read/partially read by 74/16% (n = 35), including subliterate women (χ2 = 0.76, P = 0.679). Knowledge scores varied with the extent the booklet was read (P1: F = 12.68, d.f. 2, P < 0.001; P2: F = 3.744, d.f. 2, P = 0.034). The revised, shorter version was graphically rich and resulted in improved perceived utility, [except for the ‘treatment options’ (χ2 = 5.50, P = 0.019) and ‘TDM guidance’ (χ2 = 8.19, P = 0.004) sections] without increasing anxiety (F = 0.689, P = 0.408; F = 3.45, P = 0.073). Conclusion  The DA was perceived as acceptable and useful for most women. The DA effectiveness is currently being evaluated using a randomized controlled trial. PMID:21223468

Microbiological quality and somatic cell count in bulk milk of dromedary camels (Camelus dromedarius): descriptive statistics, correlations, and factors of variation.

PubMed

Nagy, P; Faye, B; Marko, O; Thomas, S; Wernery, U; Juhasz, J

2013-09-01

The objectives of the present study were to monitor the microbiological quality and somatic cell count (SCC) of bulk tank milk at the world's first large-scale camel dairy farm for a 2-yr period, to compare the results of 2 methods for the enumeration of SCC, to evaluate correlation among milk quality indicators, and to determine the effect of specific factors (year, season, stage of lactation, and level of production) on milk quality indicators. The study was conducted from January 2008 to January 2010. Total viable count (TVC), coliform count (CC), California Mastitis Test (CMT) score, and SCC were determined from daily bulk milk samples. Somatic cell count was measured by using a direct microscopic method and with an automatic cell counter. In addition, production parameters [total daily milk production (TDM, kg), number of milking camels (NMC), average milk per camel (AMC, kg)] and stage of lactation (average postpartum days, PPD) were recorded for each test day. A strong correlation (r=0.33) was found between the 2 methods for SCC enumeration; however, values derived using the microscopic method were higher. The geometric means of SCC and TVC were 394×10(3) cells/mL and 5,157 cfu/mL during the observation period, respectively. Somatic cell count was >500×10(3) cells/mL on 14.6% (106/725) and TVC was >10×10(3) cfu/mL on 4.0% (30/742) of the test days. Both milk quality indicators had a distinct seasonal pattern. For log SCC, the mean was lowest in summer and highest in autumn. The seasonal pattern of log TVC was slightly different, with the lowest values being recorded during the spring. The monthly mean TVC pattern showed a clear difference between years. Coliform count was <10 cfu/mL in most of the samples (709/742, 95.6%). A positive correlation was found between log SCC and log TVC (r=0.32), between log SCC and CMT score (r=0.26), and between log TVC and CC in yr 1 (r=0.30). All production parameters and stage of lactation showed strong seasonal

Tracing Nile sediment sources by Sr and Nd isotope signatures (Uganda, Ethiopia, Sudan)

NASA Astrophysics Data System (ADS)

Padoan, Marta; Garzanti, Eduardo; Harlavan, Yehudit; Villa, Igor Maria

2011-06-01

Strontium and neodymium isotopes, measured on diverse mud and sand fractions of sediment in transit along all major Nile branches, identify detritus sourced from Precambrian basements, Mesozoic strata, and Tertiary volcanic rocks exposed along the shoulders of the East African rift and in Ethiopian highlands. Sr and Nd isotopic ratios reflect the weighted average of detrital components generated in different catchments, allowing us to discriminate provenance, calculate sediment budgets, and investigate grain-size and hydraulic-sorting effects. 87Sr/ 86Sr and 143Nd/ 144Nd range, respectively, from as high as 0.722 and as low as 0.5108 for sediment derived from Archean gneisses in northern Uganda, to 0.705 and 0.5127 for sediment derived from Neoproterozoic Ethiopian and Eritrean basements. 87Sr/ 86Sr and 143Nd/ 144Nd, ranging 0.705-0.709 and 0.5124-0.5130 for Blue Nile tributaries, are 0.704-0.705 and 0.5127-0.5128 for largely volcaniclastic sediments of River Tekeze-Atbara, and 0.705-0.706 and 0.5126-0.5127 for main Nile sediments upstream Lake Nasser. Model mantle derivation ages ( tDM), oldest in Uganda where sediment is principally derived from the Congo Craton (3.4-3.0 Ga for Victoria and Albert Nile), progressively decrease northward across the Saharan Metacraton, from 2.6 Ga (Bahr el Jebel in South Sudan), to 2.4-2.2 Ga (Bahr ez Zeraf across the Sudd), and finally 1.6-1.3 Ga (White Nile upstream Khartoum). Instead, tDM ages of Sobat mud increase from 0.9 to 1.5 Ga across the Machar marshes. TDM ages are younger for sediments shed by Ethiopian (1.2-0.7 Ga) and Eritrean basements (1.5-1.2 Ga), and youngest for sediments shed from Ethiopian flood basalts (0.3-0.2 Ga). Integrated geochemical, mineralogical, and settling-equivalence analyses suggest influence on the Nd isotopic signal by volcanic lithic grains and titanite rather than by LREE-rich monazite or allanite. Because contributions by ultradense minerals is subordinate, intrasample variability of Sr and

Turnaround Operations Analysis for OTV. Volume 3: Technology Development Plan

NASA Technical Reports Server (NTRS)

1988-01-01

An integrated technology development plan for the technologies required to process both GBOTVs and SBOTVs are described. The plan includes definition of the tests and experiments to be accomplished on the ground, in a Space Shuttle Sortie Mission, on an Expendable Launch Vehicle, or at the Space Station as a Technology Development Mission (TDM). The plan reflects and accommodates current and projected research and technology programs where appropriate.

The Generic Data Capture Facility

NASA Technical Reports Server (NTRS)

Connell, Edward B.; Barnes, William P.; Stallings, William H.

1987-01-01

The Generic Data Capture Facility, which can provide data capture support for a variety of different types of spacecraft while enabling operations costs to be carefully controlled, is discussed. The data capture functions, data protection, isolation of users from data acquisition problems, data reconstruction, and quality and accounting are addressed. The TDM and packet data formats utilized by the system are described, and the development of generic facilities is considered.

Bridging the Capability Gap for Battle Command On-the-Move

DTIC Science & Technology

2005-06-01

FDM) and synchronous Time Division Multiplexing (TDM) network components. This advantage will become further realized once mobile satellite modem... synchronize the initial network timing . Once a NM receives this beacon, it reports the measured receive signal strength back to the NC using the NM’s...in certain areas of the world. Due to M4’s synchronous network connections, link engineering to manage required distributed network timing is often

Automated Air Information Production System - Phase II.

DTIC Science & Technology

1980-10-01

Alphanumeric CRT terminals, 2 Gandalf Data Inc. Model LDS 250/3 56 Kbps synchronous short haul modems , 2 General Data Comm Industries TDM-1205 time...supplied encrypt/decrypt devices which would interface to the communications multiplexers supplied by Synectics. Synectics also supplied short haul modems ...During the development effort and throughput of the T&E period the high speed ( 56K bps) link would intermittently go out of synchronization. The problem

Simultaneous determination of gabapentin, pregabalin, vigabatrin, and topiramate in plasma by HPLC with fluorescence detection.

PubMed

Martinc, Boštjan; Roškar, Robert; Grabnar, Iztok; Vovk, Tomaž

2014-07-01

Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) has been recognized as a useful tool in management of epilepsy. We developed a simple analytical method for simultaneous determination of four second generation AEDs, including gabapentin (GBP), pregabalin (PGB), vigabatrin (VGB), and topiramate (TOP). Analytes were extracted from human plasma using universal solid phase extraction, derivatized with 4-chloro-7-nitrobenzofurazan (NBD-Cl) and analyzed by HPLC with fluorescence detection. Using mass spectrometry we confirmed that NBD-Cl reacts with sulfamate group of TOP similarly as with amine group of the other three analytes. The method is linear (r(2)>0.998) across investigated analytical ranges (0.375-30.0μg/mL for GBP, PGB, and VGB; 0.50-20.0μg/mL for TOP). Intraday and interday precision do not exceed 9.40%. The accuracy is from 95.6% to 106%. The recovery is higher than 80.6%, and the lower limit of quantification is at least 0.5μg/mL. The method is selective and robust. For TOP determination the method was compared to a previously published method and the results obtained by the two methods were in good agreement. The developed method is suitable for routine TDM. Copyright © 2014 Elsevier B.V. All rights reserved.

Do Asian renal transplant patients need another mycophenolate mofetil dose compared with Caucasian or African American patients?

PubMed

Li, Pengmei; Shuker, Nauras; Hesselink, Dennis A; van Schaik, Ron H N; Zhang, Xianglin; van Gelder, Teun

2014-10-01

Mycophenolate mofetil (MMF) is used to prevent acute rejection following solid organ transplantation in transplant centers all over the world. Patients from different ethnic backgrounds are treated with this drug, for which therapeutic drug monitoring (TDM) has not become the standard of practice in most centers. Whether or not some ethnic groups require a different MMF dose has been a topic of debate in recent years. In this review, it is shown that Asian patients, compared with Caucasian patients, with a comparable MMF dose reach higher mycophenolic acid (MPA) exposure. Also clinical experience points toward more adverse events in case of treatment with 1 g MMF bid in Asian patients, and therefore, for this ethnic group, a lower maintenance dose seems justified. In contrast, African American patients reach similar drug concentrations as Caucasians patients receiving the same MMF dose, but due to immunological reasons, they require a higher MMF dose to reach comparable acute rejection incidences. When TDM is performed, clinicians can correct the dose and compensate for interethnic differences in drug exposure. Otherwise, it is important to choose the right dose. This optimal dose is 20-46% lower in Asian transplant recipients than in Caucasian or African American patients. © 2014 Steunstichting ESOT.

Rational design of adjuvants targeting the C-type lectin Mincle.

PubMed

Decout, Alexiane; Silva-Gomes, Sandro; Drocourt, Daniel; Barbe, Sophie; André, Isabelle; Cueto, Francisco J; Lioux, Thierry; Sancho, David; Pérouzel, Eric; Vercellone, Alain; Prandi, Jacques; Gilleron, Martine; Tiraby, Gérard; Nigou, Jérôme

2017-03-07

The advances in subunit vaccines development have intensified the search for potent adjuvants, particularly adjuvants inducing cell-mediated immune responses. Identification of the C-type lectin Mincle as one of the receptors underlying the remarkable immunogenicity of the mycobacterial cell wall, via recognition of trehalose-6,6'-dimycolate (TDM), has opened avenues for the rational design of such molecules. Using a combination of chemical synthesis, biological evaluation, molecular dynamics simulations, and protein mutagenesis, we gained insight into the molecular bases of glycolipid recognition by Mincle. Unexpectedly, the fine structure of the fatty acids was found to play a key role in the binding of a glycolipid to the carbohydrate recognition domain of the lectin. Glucose and mannose esterified at O -6 by a synthetic α-ramified 32-carbon fatty acid showed agonist activity similar to that of TDM, despite their much simpler structure. Moreover, they were seen to stimulate proinflammatory cytokine production in primary human and murine cells in a Mincle-dependent fashion. Finally, they were found to induce strong Th1 and Th17 immune responses in vivo in immunization experiments in mice and conferred protection in a murine model of Mycobacterium tuberculosis infection. Here we describe the rational development of new molecules with powerful adjuvant properties.

An audit of therapeutic drug monitoring of anticonvulsants.

PubMed Central

Sharpe, P. C.; Morrow, J.; Trimble, E. R.

1995-01-01

An audit of therapeutic drug monitoring (TDM) of anticonvulsants was performed to assess both its use and misuse in the management of patients with epilepsy. Over a four week period all samples received for phenytoin, carbamazepine, sodium valproate and phenobarbitone assays were included in the audit. The aims were to establish the source of the specimens, the reasons for the requests and to ascertain what action, if any, would be taken when the result of the assay was provided. A total of 163 separate assays were performed over the four week period (43 phenytoin, 74 carbamazepine, 41 valproate, 5 phenobarbitone). Only 18.7% of all requests originated from the adult neurology department. The vast majority of tests had been ordered by junior medical staff (only 10% by consultants) and approximately 50% were 'routine' with no satisfactory clinical reason for the request offered. There was a tendency to manipulate prescribed doses on the basis of drug levels alone without taking the clinical picture into consideration. These results demonstrate a general ignorance, especially amongst junior medical staff, of the value of TDM of anticonvulsants, and reinforce the need for both an educative and interpretive service to be provided by the Chemical Pathology Department. PMID:8533181

The quality and scope of information provided by medical laboratories to patients before laboratory testing: Survey of the Working Group for Patient Preparation of the Croatian Society of Medical Biochemistry and Laboratory Medicine.

PubMed

Nikolac, Nora; Simundic, Ana-Maria; Kackov, Sanja; Serdar, Tihana; Dorotic, Adrijana; Fumic, Ksenija; Gudasic-Vrdoljak, Jelena; Klenkar, Kornelija; Sambunjak, Jadranka; Vidranski, Valentina

2015-10-23

The aim of this work was to evaluate to what extent the scope and content of information provided to patients is standardized across medical biochemistry laboratories in Croatia. Two on-line self-report surveys were sent out: Survey A regarding attitudes on importance of patient preparation and Survey B on the contents of patient preparation instructions. 13/118 laboratories (11%) do not provide written instructions to patients on how to prepare for laboratory testing, and 36 (40%) do not include information about water intake in their instructions. Only half of laboratories provide instructions for prostate-specific antigen (53.8%), female sex hormones (53.7%) and therapeutic drug monitoring (TDM) (52.5%). Inadequate information about fasting status (55.0%) and 24 hour urine collection (77.9%) were frequent errors with high severity and were associated with the greatest potential to cause patient harm. Laboratory professionals in Croatia have a positive attitude towards the importance of patient preparation for laboratory testing. However, the information for laboratory testing is not standardized and frequently lacks guidance for tests related to TDM, coagulation and endocrinology. This study highlights the need for standardized, updated and evidence-based recommendations for patient preparation in order to minimize the risk for patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Multiplex Liquid Chromatography-Tandem Mass Spectrometry Assay for Simultaneous Therapeutic Drug Monitoring of Ribavirin, Boceprevir, and Telaprevir

PubMed Central

Aouri, Manel; Moradpour, Darius; Cavassini, Matthias; Mercier, Thomas; Buclin, Thierry; Csajka, Chantal; Telenti, Amalio; Rauch, Andri

2013-01-01

New directly acting antivirals (DAAs) that inhibit hepatitis C virus (HCV) replication are increasingly used for the treatment of chronic hepatitis C. A marked pharmacokinetic variability and a high potential for drug-drug interactions between DAAs and numerous drug classes have been identified. In addition, ribavirin (RBV), commonly associated with hemolytic anemia, often requires dose adjustment, advocating for therapeutic drug monitoring (TDM) in patients under combined antiviral therapy. However, an assay for the simultaneous analysis of RBV and DAAs constitutes an analytical challenge because of the large differences in polarity among these drugs, ranging from hydrophilic (RBV) to highly lipophilic (telaprevir [TVR]). Moreover, TVR is characterized by erratic behavior on standard octadecyl-based reversed-phase column chromatography and must be separated from VRT-127394, its inactive C-21 epimer metabolite. We have developed a convenient assay employing simple plasma protein precipitation, followed by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of levels of RBV, boceprevir, and TVR, as well as its metabolite VRT-127394, in plasma. This new, simple, rapid, and robust HPLC-MS/MS assay offers an efficient method of real-time TDM aimed at maximizing efficacy while minimizing the toxicity of antiviral therapy. PMID:23629707

Diagnostic moléculaire du complexe Mycobacterium tuberculosis résistant à l'isoniazide et à la rifampicine au Burkina Faso

PubMed Central

Désire, Ilboudo; Cyrille, Bisseye; Florencia, Djigma; Souba, Diande; Albert, Yonli; Valerie, Bazie Jean Telesphore; Rebecca, Compaore; Charlemagne, Gnoula; Tamboura, Djibril; Rémy, Moret; Virginio, Pietra; Simplice, Karou Damintoti; Martial, Ouedraogo; Jacques, Simpore

2015-01-01

Introduction Cette étude a eu pour objectifs de diagnostiquer la tuberculose pulmonaire par l'examen microscopique et par la PCR des crachats et de déterminer les bases moléculaires de la résistance à la rifampicine et à l'isoniazide. Méthodes Le diagnostic du Complexe Mycobacterium Tuberculosis (CMTB) a été effectué par microscopie après coloration au Ziehl Nielsen et par PCR en temps réel en utilisant le kit d'identification du complexe MTB (Sacace Biotechnologie, Italie). Les résistances à la Rifampicine et à l'Isoniazide ont été étudiées par la technique de la PCR en utilisant le kit MTB résistance 8 (Sacace, Biotechnologie). Résultats Sur les 59 patients diagnostiqués pour la tuberculose pulmonaire, 59,3% étaient positifs en microscopie optique et 44,1% étaient positifs par PCR en Temps réel. Les résistances à la rifampicine (rpoB) et à l'isoniazide (katG et inhA) ont été observées chez 9 patients. La résistance à la rifampicine était due aux mutations (Asp516Val, Ser531Trp, Leu533Pro) et celle à l'isoniazide par les substitutions Ser315Thr du gène katG et C209T du gène inhA. Les multi résistances à la rifampicine et à l'isoniazide ont été observées dans 55,5% des échantillons et concernaient les associations: ropBAsp513Val + inhAC209T et rpoBLeu533Pro + katGSer315Thr. Conclusion La PCR en temps réel qui permet l'identification des allèles mutants rpoB, katG et inhA de M. tuberculosis est un outil de diagnostic épidémiologique de grande importance car elle permet de déterminer le niveau de résistance à la rifampicine et à l'isoniazide. PMID:26491516

Tuberculose cutanée à Bamako, Mali

PubMed Central

Dicko, Adama; Faye, Ousmane; Fofana, Youssouf; Soumoutera, Moussa; Berthé, Siritio; Touré, Saidou; Traoré, Bekaye; Guindo, Binta; Tall, Koureissi; Keita, Alimata; Kéita, Lassine; Coulibaly, Karim; Keita, Somita

2017-01-01

Introduction La tuberculose est la mycobactériose la plus fréquente en Afrique subsaharienne. La localisation cutanée est rare et sous diagnostiquée à cause de son polymorphisme clinique et la faiblesse du plateau technique. Le but de cette étude était de décrire les aspects épidémiologiques, cliniques, histopathologiques de la tuberculose cutanée à Bamako (Mali). Méthodes De janvier 1991 à décembre 2008 nous avons réalisé une étude transversale descriptive. L’étude s’est déroulée dans le service de Dermatologie du Centre National d’Appui à la lutte contre la Maladie et le service de Pneumo-phtisiologie au l’hôpital du Point G. Ont été inclus dans l’étude les cas de tuberculose confirmés par l’histologie et ou la biologie. Résultats Sur 4269 dossiers, 61 cas de tuberculose cutanée étaient recensées (1,43%). Les hommes représentaient 59% des cas (36 malades) et les femmes 41 % soit (25 cas); soit un sex-ratio de 1,44. L’âge des malades variait de 3 mois à 61 ans pour une moyenne de 27,56 ± 36 ans. La durée d’évolution était en moyenne de 10,9 ± 10 mois. Les formes cliniques recensées étaient le scrofuloderme (41 cas), la forme ulcéreuse (13 cas), la forme verruqueuse (4 cas), et le lupus tuberculeux (3 cas). La tuberculose était associée au VIH dans 7 cas, à la lèpre dans 3 cas. Conclusion La tuberculose cutanée est sous diagnostiquée au Mali. Des efforts sont nécessaires pour améliorer l’accessibilité et le plateau technique des services spécialisés, pour mener une étude approfondie interdisciplinaire sur cette pathologie. PMID:28819523

Tumeurs Stromales Gastro-Intestinales «GIST»: état des lieux et actualités à travers notre expérience portant sur 54 cas et une Revue de littérature

PubMed Central

Taoufiq, Nezha; Naim, Asmaa; Bouchbika, Zineb; Benchekroune, Nadia; Jouhadi, Hassan; Sahraoui, Souha; Benider, Abdelatif

2017-01-01

Les Tumeurs Stromales Gastro-intestinales « GIST » sont une forme très rare de cancers du tube digestif appartenant à la famille des sarcomes. Le but de ce travail est d'établir le profil épidémiologique et évolutif ainsi que les difficultés diagnostique et thérapeutique de cette pathologie maligne prise en charge dans un pays en développement. Une Etude rétrospective étalée sur 8 ans de Janvier 2002 à Mars 2010, a été mené au Service de Radiothérapie et d'Oncologie du CHU de Casablanca (Maroc) ayant colligée 54 cas de tumeurs stromales gastro-intestinales. L'âge moyen de nos patients était de 55 ans. Le délai moyen d'évolution était de 11 mois (0-72 mois). La biopsie a permis de confirmer le diagnostic dans 14 cas et la chirurgie dans 40 cas. La principale forme histologique était fusiforme (92,6%). Les GIST dans notre série avaient une taille tumorale moyenne de 12,5 cm avec un C-Kit positif dans 52 cas. Le risque évolutif a pu être établi dans 47 cas dont 39 avaient un risque élevé. La chirurgie était le principal traitement des patients de notre sérieAprès un recul moyen de 31 mois, la moitié des patients évaluables de notre série (n=19) est en rémission complète maintenue, le tiers (n=13) est décédé alors que le quart (n=8) présente une récidive locale et /ou métastatique. Quoique les recommandations soient éditées pour la prise en charge de ces tumeurs, ces dernières soulèvent encore de nombreux problèmes aussi bien diagnostiques que thérapeutiques dans notre contexte. PMID:28904693

Leucémie aigue érythroblastique: à propos de sept observations

PubMed Central

Tlamçani, Imane; Benjelloun, Salma; Yahyaoui, Ghita; Amrani, Moncef Hassani

2014-01-01

La leucémie aigue érythroblastique (LAM-M6) est une entité rare, représente 3 à 4% de l'ensemble des leucémies aigues. Il en existe deux types: l’érythroleucémie et la leucémie érythroïde pure. Elle se manifeste le plus souvent par des signes de cytopénie et d'infiltration des tissus extra-hématopoïétiques, elle est plus fréquente chez les adultes que chez les enfants et est de mauvais pronostic. Le but de notre travail est de mettre en évidence les particularités épidémiologiques, diagnostiques et évolutives de cette pathologie rare au sein du CHU HASSAN II de Fès. Nous rapportons le cas de sept patients diagnostiqués leucémie aigue érythroblastique LAM-M6 au laboratoire d'hématologie du CHU Hassan II de Fès entre Janvier 2009 et Aout 2013. Le diagnostic de leucémie aigue érythroblastique a été retenu sur un examen cytologique du frottis sanguin et du médullogramme ainsi que l'examen immunophénotypique. Il s'agit de deux adultes et cinq enfants, la plupart ont présenté une altération de l’état général, des signes de cytopénie et un syndrome tumoral. L’étude cytologique du frottis sanguin et du médullogramme ainsi que les résultats de l'immunophénotypage ont conduit au diagnostic de l’érythroleucémie chez six de nos patients et de leucémie érythroïde pure chez un seul patient. L’évolution a été différente pour ces patients. Le pronostic est grave d'où l'intérêt d'un diagnostic rapide et d'une prise en charge adéquate. PMID:26113895

Problématique de la prise en charge des cancers du sein au Sénégal: une approche transversale

PubMed Central

Gueye, Serigne Modou Kane; Gueye, Mamour; Coulbary, Sophie Aminata; Diouf, Alassane; Moreau, Jean Charles

2016-01-01

L’heure où les thérapeutiques innovantes se multiplient dans le cancer du sein, des pays moins nantis comme le Sénégal accusent encore un retard considérable dans la prise en charge globale de ce type de cancer. Au Sénégal, même si la prise en charge des cancers du sein avancés est actuellement bien codifiée, les résultats en terme de survie et de morbidités sont encore médiocres vu les retards diagnostiques et les traitements mutilants, parfois onéreux et mal tolérés, devenus nécessaires. Pour ces cancers avancés, les défis qui restent à relever résident dans l’érection de centres de soins palliatifs et le développement de la pluridisciplinarité pour améliorer la qualité de vie et l’accompagnement des malades. En revanche, pour les cancers infracliniques ou potentiellement guérissables, les défis restent immenses car il s’agira de les dépister, de bien les localiser et les diagnostiquer aussitôt (biopsie écho guidée ou stéréotaxique) mais également de les opérer de façon précise et entière (repérage – exérèse in sano et radiographie de pièce opératoire) tout en limitant les complications comme celles du curage classique (biopsie du ganglion sentinelle). Il s’agit là autant d’objectifs auxquels nos structures de santé ne sont pas toujours préparées. Cette mise au point est une analyse situationnelle sur les écueils contextuels qui grèvent encore la prise en charge globale des cancers du sein au Sénégal. PMID:28154696

The Islamic State Battle Plan: Press Release Natural Language Processing

DTIC Science & Technology

2016-06-01

Processing, text mining , corpus, generalized linear model, cascade, R Shiny, leaflet, data visualization 15. NUMBER OF PAGES 83 16. PRICE CODE...Terrorism and Responses to Terrorism TDM Term Document Matrix TF Term Frequency TF-IDF Term Frequency-Inverse Document Frequency tm text mining (R...package=leaflet. Feinerer I, Hornik K (2015) Text Mining Package “tm,” Version 0.6-2. (Jul 3) https://cran.r-project.org/web/packages/tm/tm.pdf

Thirty-Four Megabit Four-Channel Multiplexer

DTIC Science & Technology

1985-10-01

person or conveying any rights or permis- sion to manufacture , use, or sell any patented invention thai ma> in any way be related thereto. WARNING...System (DCS) in Europe. The system is evolving from frequency division multiplex ( FDM ) to time division multiplex (TDM) equipment. The bulk of the...channel multi- plexer permits expansion by providing the spare MBS and 2.048~Mb/s data channels, and will do so with no additional cost

Une spondylodiscite tuberculeuse chez une transplantée rénale compliquée d’une mycose systémique

PubMed Central

Haddiya, Intissar; El Housni, Siham; El Harraqui, Ryme; Rhou, Hakima; Benamar, Loubna; Eziatouni, Fatima; Ouzeddoun, Naima; Bayahia, Rabia

2014-01-01

En transplantation, les complications infectieuses sont fréquentes et de diagnostic souvent délicat. Elles peuvent coexister chez le transplanté rénal rendant leur diagnostic encore plus difficile. Le but de ce cas clinique est de discuter les difficultés diagnostiques et de surveillance de deux types de pathologies assez fréquentes chez le transplanté rénal, qui sont la tuberculose et la mycose, à travers l’observation clinique d’une patiente de 24 ans transplantée rénale qui présente une spondylodiscite tuberculeuse et qui développe secondairement une septicémie à Candida non albicans à point de départ urinaire dont le seul point d’appel est la fièvre post opératoire. PMID:25667684

Hémothorax spontané révélant une vascularite de Wegener chez une femme enceinte

PubMed Central

Serhane, Hind; Yassine, Msougar; Amro, Lamyae

2016-01-01

L’hémothorax spontané demeure une pathologie rare. Ses étiologies sont multiples mais restent parfois inconnues. Chez certains patients, la thoracotomie peut être le seul recours pour déterminer son origine. Les vascularites n’ont pas été rapporté comme cause habituelle des hémothorax spontanés. La grossesse ne semble pas avoir d’effet causal, ni aggravant des hémothorax spontanés, ni des vascularites. Nous rapportons une observation assez particulière d’une jeune patiente, présentant au cours de sa grossesse un hémothorax spontané secondaire à une vasularite de type Wegener, diagnostiquée par la biopsie pleurale faite au cours d’une thoracotomie exploratrice et confirmée par le dosage des ANCA. PMID:28154726

Faux anévrisme artériel traumatique intracrânien

PubMed Central

Laaguili, Jawad; El Asri, Abad Cherif; Gazzaz, Miloud; El Hassani, Moulay Rachid; El Mostarchid, Brahim

2015-01-01

Nous rapportons un cas d'anévrysme post-traumatique de l'artère carotide interne chez un enfant de 11 ans, ayant présenté une ophtalmoplégie droite. Un faux anévrisme de la carotide interne droite a été diagnostiqué par angiographie cérébrale. Le malade a bénéficié d'un traitement endovasculaire et l’évolution fut favorable. Malgré leur rareté, le diagnostic des anévrysmes post traumatiques devrait être évoqué chez tout traumatisé crânien en cas d'aggravation clinique secondaire, afin de réaliser une exploration angiographique avant d'envisager un traitement radical soit chirurgical soit par voie endovasculaire. PMID:26113901

Mantle contribution and tectonic transition in the Aqishan-Yamansu Belt, Eastern Tianshan, NW China: Insights from geochronology and geochemistry of Early Carboniferous to Early Permian felsic intrusions

NASA Astrophysics Data System (ADS)

Du, Long; Long, Xiaoping; Yuan, Chao; Zhang, Yunying; Huang, Zongying; Wang, Xinyu; Yang, Yueheng

2018-04-01

Late Paleozoic is a key period for the accretion and collision of the southern Central Asian Orogenic Belt (CAOB). Here, we present new zircon U-Pb ages, whole-rock geochemistry and Sr-Nd isotopic compositions for four Late Paleozoic felsic plutons in Eastern Tianshan (or Tienshan in some literatures) in order to constrain the tectonic evolution of the southern CAOB. The granodioritic pluton and its dioritic enclaves were synchronously formed in the Early Carboniferous (336 ± 3 Ma and 335 ± 2 Ma, respectively). These rocks are depleted in Nb, Ta and Ti, and enriched in Rb, Ba, Th and U related to the primitive mantle, which show typical features of arc rocks. They both have similar Sr-Nd isotopic ratios to those granitic rocks from the eastern Central Tianshan Block and have the latest Mesoproterozoic two stage Nd model ages (TDM2) (1111-1195 Ma for the granodioritic pluton and 1104-1108 Ma for the enclaves, respectively), indicating that their source magmas may have been derived from the Mesoproterozoic crust. The albitophyric pluton was also emplaced in the Early Carboniferous (333 ± 3 Ma). Rocks of this pluton have similar εNd(t) values (-0.69 to -0.37) and TDM2 ages (1135-1161 Ma) to those of the granodioritic rocks, suggest similar crustal source for both types of rocks. In contrast, the K-feldspar granitic and monzonitic plutons were emplaced in the Early Permian (292 ± 3 Ma and 281 ± 2 Ma, respectively). Samples of the K-feldspar granitic pluton have high K2O + Na2O, FeO/MgO, Ga/Al, HFSE (e.g., Zr and Hf) and low CaO, Sr and Ba, exhibiting characteristics of A2-type granites, which probably emplaced in a post-collisional extension environment. They have higher εNd(t) values (+2.77 to +3.27) and more juvenile TDM2 ages (799-841 Ma) than the Early Carboniferous plutons, suggesting that they were derived from relatively younger crustal sources. The monzonitic granites are metaluminous to weakly peraluminous with A/CNK ranging from 0.93 to 1.05, and have

[Therapeutic Drug Monitoring of Valproic Acid in Children: A Prospective Study of The Effect of The Compliance and The Economic Level on the Trough Plasmatic Concentrations and Epileptic Seizures].

PubMed

Charfi, Rim; Lakhal, Mohamed; Klouz, Anis; Trabelsi, Sameh; Salouage, Issam

2015-01-01

Valproic acid (VA) is a widely used antiepileptic drug. Because of its pharmacokinetic variability and the influence of intrinsic and extrinsic factors such as the treatment compliance, VA therapeutic drug monitoring (TDM) is recommended in children. The aim of this study is to evaluate the effect of treatment compliance and the economic level on VA tough plasmatic concentration (TPC) and epileptic rhythm in children. A one-year prospective study (August 2008-August 2009) concerning children (age≤5 years) regularly treated by VA who had a VA TDM. So, 276 plasmatic samples from 238 children were collected. The children were divided in two groups as following: the group 1 (G1) presenting a good compliance and a reliable questioning and the group 2 (G2) presenting a bad compliance and a non reliable questioning. We evaluated the interindividual variability by correlating the TPC to the dose. Then, we divided the hole group in function of their economic levels (low-medium-high). Sex ratio male/female was 1.3. Median age was 5 years+/-3,9. The mean TPC was 62 µg/mL [0.12-131 µg/mL]. VA TPC were in the therapeutic range (TR) in 62%. Adverse drug reactions were noted in 4.2% of the children. G1 represented 70% of the children and G2, 30%. The TPC were in the TR in 67% of G1 and 51% of G2 (p=0.02). There was a significant difference between the TPC in G1 and G2 (p=0.02).There was no significative difference in the TPC in function of the economic levels. There was no correlation between TPC and the administered doses. The epileptic seizures were more spaced in children with therapeutic TPC than those with TPC in the TR (p=0.002) and in G1 than in G2 (p=0.03). Compliance should be appropriate in order to optimize the TDM rule. A good compliance and a therapeutic TPC allow a better control of epileptic seizures. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Vancomycin-induced acute kidney injury in elderly Chinese patients: a single-centre cross-sectional study.

PubMed

Pan, Kun-Ming; Wu, Yi; Chen, Can; Chen, Zhang-Zhang; Xu, Jian-An; Cao, Lei; Xu, Qing; Wu, Wei; Dai, Pei-Fang; Li, Xiao-Yu; Lv, Qian-Zhou

2018-04-01

The objective of the present study was to investigate the current situation concerning, and risk factors for, vancomycin (VAN)-induced acute kidney injury (VI-AKI) in elderly Chinese patients, to assess outcomes and risk factors in patients who have developed VI-AKI, in order to provide suggestions for improving the prevention and treatment of this condition in these patients. We retrospectively identified elderly older inpatients who had received four or more doses of VAN treatment. We compared patients with VI-AKI with those who received VAN treatment and had not developed AKI (NO-AKI). We defined VI-AKI as developing AKI during VAN therapy or within 3 days after withdrawal of VAN. A total of 647 out of 862 elderly inpatients were included in the study. Among those excluded, in 89.3% of cases (192/215) this was because of lack of data on serum creatinine (SCr). Among included patients, 32.5% (210/647) of patients received therapeutic drug monitoring (TDM) during VAN therapy. In 66.9% of cases (424/634), there was insufficient TDM, and in 3.9% (25/634) this was appropriate. A total of 102 patients had confirmed VI-AKI, with an incidence of 15.8% (102/647). Multiple logistic regression analysis revealed that hyperuricaemia [odds ratio (OR) = 3.045; P = 0.000)], mechanical ventilation (OR = 1.906; P = 0.022) and concomitant vasopressor therapy (OR = 1.919; P = 0.027) were independent risk factors for VI-AKI; higher serum albumin (OR = 0.885; P = 0.000) was determined to be an independent protective factor for VI-AKI. For the elderly Chinese patients treated with VAN, there was insufficient monitoring of SCr, too little use of VAN TDM, and lower rate of patients whose VAN though serum concentrations were not obtained at the correct time. We recommend that hospital managers increase investment in clinical pharmacists, to strengthen professional management. Patients with concomitant hyperuricaemia and on mechanical ventilation and vasopressor therapy should be paid

Target concentration intervention: beyond Y2K

PubMed Central

Holford, Nicholas H G

1999-01-01

Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions. PMID:10383553

Target concentration intervention: beyond Y2K.

PubMed

Holford, N H

2001-01-01

Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions.

Target concentration intervention: beyond Y2K

PubMed Central

Holford, Nicholas H G

2001-01-01

Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions. PMID:11564053

JPRS Report Telecommunications.

DTIC Science & Technology

1988-02-17

was talking about censorship of television from Macau. Cen- sorship by jamming the signal. TdM, the Macau TV sta- tion, is well-advanced with a...Macau imbroglio presents a case in miniature of the sort of cross-border prob- lems we can look forward to when satellite television takes off in... censorship barriers as easily and as cheaply as short-wave radio once did. And just as governments the world over have recognised the futility of

Demonstration of Time Domain Multiplexed Readout for Magnetically Coupled Calorimeters

NASA Technical Reports Server (NTRS)

Porst, J.-P.; Adams, J. S.; Balvin, M.; Bandler, S.; Beyer, J.; Busch, S. E.; Drung, D.; Seidel, G. M.; Smith, S. J.; Stevenson, T. R.

2012-01-01

Magnetically coupled calorimeters (MCC) have extremely high potential for x-ray applications due to the inherent high energy resolution capability and being non-dissipative. Although very high energy-resolution has been demonstrated, until now there has been no demonstration of multiplexed read-out. We report on the first realization of a time domain multiplexed (TDM) read-out. While this has many similarities with TDM of transition-edge-sensors (TES), for MGGs the energy resolution is limited by the SQUID read-out noise and requires the well established scheme to be altered in order to minimize degradation due to noise aliasing effects. In cur approach, each pixel is read out by a single first stage SQUID (SQ1) that is operated in open loop. The outputs of the SQ1 s are low-pass filtered with an array of low cross-talk inductors, then fed into a single-stage SQUID TD multiplexer. The multiplexer is addressed from room temperature and read out through a single amplifier channel. We present results achieved with a new detector platform. Noise performance is presented and compared to expectations. We have demonstrated multiplexed X-ray spectroscopy at 5.9keV with delta_FWHM=10eV. In an optimized setup, we show it is possible to multiplex 32 detectors without significantly degrading the Intrinsic detector resolution.

MoNET: media over net gateway processor for next-generation network

NASA Astrophysics Data System (ADS)

Elabd, Hammam; Sundar, Rangarajan; Dedes, John

2001-12-01

MoNETTM (Media over Net) SX000 product family is designed using a scalable voice, video and packet-processing platform to address applications with channel densities from few voice channels to four OC3 per card. This platform is developed for bridging public circuit-switched network to the next generation packet telephony and data network. The platform consists of a DSP farm, RISC processors and interface modules. DSP farm is required to execute voice compression, image compression and line echo cancellation algorithms for large number of voice, video, fax, and modem or data channels. RISC CPUs are used for performing various packetizations based on RTP, UDP/IP and ATM encapsulations. In addition, RISC CPUs also participate in the DSP farm load management and communication with the host and other MoP devices. The MoNETTM S1000 communications device is designed for voice processing and for bridging TDM to ATM and IP packet networks. The S1000 consists of the DSP farm based on Carmel DSP core and 32-bit RISC CPU, along with Ethernet, Utopia, PCI, and TDM interfaces. In this paper, we will describe the VoIP infrastructure, building blocks of the S500, S1000 and S3000 devices, algorithms executed on these device and associated channel densities, detailed DSP architecture, memory architecture, data flow and scheduling.

Test Data Monitor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bosas, Joseph

The National Security Campus (NSC) collects a large amount of test data used The National Security Campus (NSC) collects a large amount of test data used to accept high value and high rigor product. The data has been used historically to support root cause analysis when anomalies are detected in down-stream processes. The opportunity to use the data for predictive failure analysis however, had never been exploited. The primary goal of the Test Data Monitor (TDM) software is to provide automated capabilities to analyze data in near-real-time and report trends that foreshadow actual product failures. To date, the aerospace industrymore » as a whole is challenged at utilizing collected data to the degree that modern technology allows. As a result of the innovation behind TDM, Honeywell is able to monitor millions of data points through a multitude of SPC algorithms continuously and autonomously so that our personnel resources can more efficiently and accurately direct their attention to suspect processes or features. TDM’s capabilities have been recognized by our U.S. Department of Energy National Nuclear Security Administration (NNSA) sponsor for potential use at other sites within the NNSA. This activity supports multiple initiatives including expectations of the NNSA and broader corporate goals that center around data-based quality controls on production.« less

Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages in vitro and adjuvant activity in vivo.

PubMed

Huber, Alexandra; Kallerup, Rie S; Korsholm, Karen S; Franzyk, Henrik; Lepenies, Bernd; Christensen, Dennis; Foged, Camilla; Lang, Roland

2016-08-01

The T-cell adjuvanticity of mycobacterial cord factor trehalose 6,6'-dimycolate (TDM) is well established. The identification of the C-type lectin Mincle on innate immune cells as the receptor for TDM and its synthetic analogue trehalose 6,6'-dibehenate (TDB) has raised interest in development of synthetic Mincle ligands as novel adjuvants. Trehalose mono- (TMXs) and diesters (TDXs) with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), and myristate (M)] were tested. Upon stimulation of murine macrophages, G-CSF secretion and NO production were strongly augmented by all TDXs tested, in a wide concentration range. In contrast, the TMXs triggered macrophage activation only at high concentrations. Macrophage activation by all TDXs required Mincle, but was independent of MyD88. The superior capacity of TDXs for activating macrophages was paralleled by direct binding of TDXs, but not of TMXs, to a Mincle-Fc fusion protein. Insertion of a short polyethylene glycol between the sugar and acyl chain in TDS reduced Mincle-binding and macrophage activation. Immunization of mice with cationic liposomes containing the analogues demonstrated the superior adjuvant activity of trehalose diesters. Overall, immune activation in vitro and in vivo by trehalose esters of simple fatty acids requires two acyl chains of length and involves Mincle. © The Author(s) 2016.

Electro-optic architecture (EOA) for sensors and actuators in aircraft propulsion systems

NASA Technical Reports Server (NTRS)

Glomb, W. L., Jr.

1989-01-01

Results of a study to design an optimal architecture for electro-optical sensing and control in advanced aircraft and space systems are described. The propulsion full authority digital Electronic Engine Control (EEC) was the focus for the study. The recommended architecture is an on-engine EEC which contains electro-optic interface circuits for fiber-optic sensors on the engine. Size and weight are reduced by multiplexing arrays of functionally similar sensors on a pair of optical fibers to common electro-optical interfaces. The architecture contains common, multiplex interfaces to seven sensor groups: (1) self luminous sensors; (2) high temperatures; (3) low temperatures; (4) speeds and flows; (5) vibration; (6) pressures; and (7) mechanical positions. Nine distinct fiber-optic sensor types were found to provide these sensing functions: (1) continuous wave (CW) intensity modulators; (2) time division multiplexing (TDM) digital optic codeplates; (3) time division multiplexing (TDM) analog self-referenced sensors; (4) wavelength division multiplexing (WDM) digital optic code plates; (5) wavelength division multiplexing (WDM) analog self-referenced intensity modulators; (6) analog optical spectral shifters; (7) self-luminous bodies; (8) coherent optical interferometers; and (9) remote electrical sensors. The report includes the results of a trade study including engine sensor requirements, environment, the basic sensor types, and relevant evaluation criteria. These figures of merit for the candidate interface types were calculated from the data supplied by leading manufacturers of fiber-optic sensors.

Therapeutic drug monitoring of isoniazid and rifampicin during anti-tuberculosis treatment in Auckland, New Zealand.

PubMed

Maze, M J; Paynter, J; Chiu, W; Hu, R; Nisbet, M; Lewis, C

2016-07-01

There is uncertainty as to the optimal therapeutic concentrations of anti-tuberculosis drugs to achieve cure. To characterise the use of therapeutic drug monitoring (TDM), and identify risk factors and outcomes for those with concentrations below the drug interval. Patients treated for tuberculosis (TB) who had rifampicin (RMP) or isoniazid (INH) concentrations measured between 1 January 2005 and 31 December 2012 were studied retrospectively. Matched concentrations and drug dosing time were assessed according to contemporary regional drug intervals (RMP > 6 μmol/l, INH > 7.5 μmol/l) and current international recommendations (RMP > 10 μmol/l, INH > 22 μmol/l). Outcomes were assessed using World Health Organization criteria. Of 865 patients, 121 had concentrations of either or both medications. RMP concentrations were within the regional drug intervals in 106/114 (93%) and INH in 91/100 (91%). Concentrations were within international drug intervals for RMP in 76/114 (67%) and INH in 53/100 (53%). Low weight-based dose was the only statistically significant risk factor for concentrations below the drug interval. Of the 35 patients with low concentrations, 21 were cured, 9 completed treatment and 5 transferred out. There were no relapses during follow-up (mean 66.5 months). There were no clinically useful characteristics to guide use of TDM. Many patients had concentrations below international therapeutic intervals, but were successfully treated.

Crosstalk analyse of DFB fiber laser hydrophone array based on time division multiplexing

NASA Astrophysics Data System (ADS)

Li, Yu; Huang, Junbin; Gu, Hongcan; Tang, Bo; Wu, Jing

2014-12-01

In this paper, the crosstalk of a time division multiplexed (TDM) system of distributed feedback (DFB) fiber laser (FL)hydrophones based on optical switch using Phase Generated Carrier (PGC) method was quantitatively analyzed. After mathematical deduction, the relationship among crosstalk, multiplexing scale and extinction ratio of optical switch was given. The simulation results show that to realize a TDM system of DFB fiber laser hydrophones with crosstalk lower than -40dB, the average extinction ratio should be higher than 24.78dB for a 4- channel system, while higher than 28.45dB for an 8- channel system. Two experiments to analyze the array crosstalk to a certain channel in an 8- channel array were conducted in this paper. Firstly, by testing the powers of leak laser to a certain channel from others, the array crosstalk to this channel was obtained according to the equation mathematically deduced in this paper. The result shows the array crosstalk to a certain channel of the 8-channel array was -7.6dB. An experiment of underwater acoustic detection was carried out finally to get the real array crosstalk to this certain channel, and the experimental result shows that the array crosstalk to this channel is -8.8dB, which is close to the calculated result.

A Hybrid OFDM-TDM Architecture with Decentralized Dynamic Bandwidth Allocation for PONs

PubMed Central

Cevik, Taner

2013-01-01

One of the major challenges of passive optical networks is to achieve a fair arbitration mechanism that will prevent possible collisions from occurring at the upstream channel when multiple users attempt to access the common fiber at the same time. Therefore, in this study we mainly focus on fair bandwidth allocation among users, and present a hybrid Orthogonal Frequency Division Multiplexed/Time Division Multiplexed architecture with a dynamic bandwidth allocation scheme that provides satisfying service qualities to the users depending on their varying bandwidth requirements. Unnecessary delays in centralized schemes occurring during bandwidth assignment stage are eliminated by utilizing a decentralized approach. Instead of sending bandwidth demands to the optical line terminal (OLT) which is the only competent authority, each optical network unit (ONU) runs the same bandwidth demand determination algorithm. ONUs inform each other via signaling channel about the status of their queues. This information is fed to the bandwidth determination algorithm which is run by each ONU in a distributed manner. Furthermore, Light Load Penalty, which is a phenomenon in optical communications, is mitigated by limiting the amount of bandwidth that an ONU can demand. PMID:24194684

Effect of ferroelastic domain pattern changes on the EPR spectra in TDM

NASA Astrophysics Data System (ADS)

Zapart, W.; Zapart, M. B.

2011-09-01

This article presents polarized light microscopy studies of the ferroelastic domain structure and the analysis of electron paramagnetic resonance spectra of Cr3+ admixture ions in trigonal double molybdates. The correlation has been found between abnormal EPR lineshape and domain structure in ferroelastic phases of these crystals.

San Francisco urban partnership agreement, national evaluation : telecommuting/TDM data test plan.

DOT National Transportation Integrated Search

2002-04-01

The Standards Requirements Document (SRD) collects information from the other National ITS Architecture program documents and reorganizes it in a manner intended to support the development of critical ITS standards. The key results in the SRD a...

L'atteinte vésicale au cours de la neurofibromatose de Von Recklinghausen

PubMed Central

Benazzouz, Mohamed Hicham; Hajjad, Tilila; Essatara, Younes; El Sayegh, Hachem; Iken, Ali; Benslimane, Lounis; Nouini, Yassine

2014-01-01

La neurofibromatose de type 1 ou maladie de Von Recklinghausen est une maladie génétique autosomique dominante en rapport avec des mutations dans le gène suppresseur de tumeur NF1. L'atteinte uro-génitale au cours de cette maladie est rare et moins de 80 cas ont été rapportés à ce jour dans la littérature mondiale. Les auteurs rapportent un nouveau cas d'atteinte vésicale découverte fortuitement au cours du suivi d'une patiente atteinte de la maladie de Von Recklinghausen. A travers cette observation et une revue de la littérature les auteurs discutent également les difficultés diagnostiques, thérapeutiques ainsi que les modalités de suivi dans cette maladie. PMID:25328590

Une masse palpébrale révélant une fistule carotidocaverneuse

PubMed Central

Oulali, Noureddine; Moufid, Fayçal; Khoulali, Mohammed; Sekhsoukh, Rachid; Housni, Brahim; Ghailan, Mohamed Rachid

2012-01-01

Les auteurs rapportent une observation particulière, chez un homme de 48 ans ayant dans ces antécédents un traumatisme crânio-faciale grave il y'a dix ans, qui présente depuis huit mois une masse palpébrale droite, avec une discrète exophtalmie et hémorragie sous conjonctivale, l'angio IRM a permis de confirmer le diagnostique d'une fistule carotidocaverneuse à haut débit, qui est responsable de cette symptomatologie. L'objectif de cet article est de mettre la lumière sur cette pathologie rare, en insistant sur les particularités cliniques de présentation d'une part, et sur le plan thérapeutique d'autre part, en exposant l'intérêt de la radiologie interventionnelle. PMID:23330040

Néphrocalcinose compliquant une miliaire tuberculeuse chez un nourrisson

PubMed Central

El Maghraoui, Jaouad; Souilmi, Fatima Zahrae; Hbibi, Mohamed; Houssaini, Tarik Sqalli; Hida, Mustapha

2015-01-01

La néphrocalcinose se définit par la présence anormale dans le parenchyme rénal de dépôts calciques pouvant résulter de différentes affections. Nous rapportons le cas d'un nourrisson de 7 mois chez qui nous avons diagnostiqué une hypercalcémie compliquée par une néphrocalcinose secondaire à une tuberculose miliaire aggravée par l'intoxication à la vitamine D améliorée sous hyperhydratation, furosémide et glucocorticoïdes. A travers ce travail, nous insistons sur l'intérêt de la recherche d'une hypercalcémie devant toute infection tuberculeuse, de la prise en charge rapide et adaptée sans oublié d'interrompre la supplémentation en vitamine D. PMID:26309458

Fiber Optic Geophysics Sensor Array

NASA Astrophysics Data System (ADS)

Grochowski, Lucjan

1989-01-01

The distributed optical sensor arrays are analysed in view of specific needs of 3-D seismic explorations methods. There are compared advantages and disadventages of arrays supported by the sensors which are modulated in intensity and phase. In these systems all-fiber optic structures and their compabilities with digital geophysic formats are discussed. It was shown that the arrays based on TDM systems with the intensity modulated sensors are economically and technically the best matched for geophysic systems supported by a large number of the sensors.

Microlaser-based compact optical neuro-processors (Invited Paper)

NASA Astrophysics Data System (ADS)

Paek, Eung Gi; Chan, Winston K.; Zah, Chung-En; Cheung, Kwok-wai; Curtis, L.; Chang-Hasnain, Constance J.

1992-10-01

This paper reviews the recent progress in the development of holographic neural networks using surface-emitting laser diode arrays (SELDAs). Since the previous work on ultrafast holographic memory readout system and a robust incoherent correlator, progress has been made in several areas: the use of an array of monolithic `neurons' to reconstruct holographic memories; two-dimensional (2-D) wavelength-division multiplexing (WDM) for image transmission through a single-mode fiber; and finally, an associative memory using time- division multiplexing (TDM). Experimental demonstrations on these are presented.

Multi-carrier mobile TDMA system with active array antenna

NASA Technical Reports Server (NTRS)

Suzuki, Ryutaro; Matsumoto, Yasushi; Hamamoto, Naokazu

1990-01-01

A multi-carrier time division multiple access (TDMA) is proposed for the future mobile satellite communications systems that include a multi-satellite system. This TDMA system employs the active array antenna in which the digital beam forming technique is adopted to control the antenna beam direction. The antenna beam forming is carried out at the base band frequency by using the digital signal processing technique. The time division duplex technique is applied for the TDM/TDMA burst format, in order not to overlap transmit and receive timing.

Kystes de l'ovaire: score échographique de malignité

PubMed Central

Dimassi, Kaouther; Bettaieb, Hajeur; Derbel, Mohammed; Triki, Amel; Gara, Mohammed Faouzi

2014-01-01

Les kystes de l'ovaire constituent l'un des motifs les plus fréquents de consultation en gynécologie. L’étape diagnostique repose principalement sur l’échographie. Nous proposons dans ce travail un score échographique reproductible prédictif de malignité. Nous évaluons la fiabilité de ce score après confrontations des données échographiques et histologiques. Il s'agit d'une étude rétrospective réalisée sur une période de 3 ans. Nous avons élaboré un score basé sur les signes échographiques décrits dans la littérature comme prédictifs de malignité et avons classé les examens échographiques préopératoires selon leurs scores respectifs. Les données échographiques étaient comparées aux résultats histologiques et un seuil prédictif de malignité a été déterminé pour le score adopté. 150 patientes ont été colligées. Les deux signes échographiques les plus prédictifs de malignité étaient: les végétations endo-kystiques, avec une Valeur Prédictive Positive (VPP) à 86,67% et une Valeur Prédictive Négative (VPN) à 100%, et le caractère vascularisé au Doppler couleur avec une VPP à 72,52% et une VPN à 100%. Le seuil retenu pour le score proposé était de 6 avec une spécificité de 100%, une sensibilité de 100%, une VPP de 100% et une VPN de 100%. L’échographie joue un rôle décisif dans la conduite à tenir devant une masse ovarienne. Seul un faisceau d'arguments permet d’évoquer la malignité lors de l'examen échographique. L'utilisation de scores basés sur des signes simples, reproductibles augmente la valeur diagnostique de l’échographie en matière de malignité. PMID:25419341

Voriconazole pharmacokinetic variability in cystic fibrosis lung transplant patients.

PubMed

Berge, M; Guillemain, R; Boussaud, V; Pham, M-H; Chevalier, P; Batisse, A; Amrein, C; Dannaoui, E; Loriot, M-A; Lillo-Le Louet, A; Billaud, E M

2009-06-01

Aspergillosis is a high-risk complication in cystic fibrosis (CF) lung transplant patients. Azole antifungal drugs inhibit CYP3A4, resulting in significant metabolic drug-drug interactions. Voriconazole (VRZ) was marketed without therapeutic drug monitoring (TDM) recommendations, consistent with favorable pharmacokinetics, but regular determinations of plasma VRZ concentration were introduced in our center to manage interactions with calcineurin inhibitors and to document the achievement of therapeutic levels. VRZ TDM data analysis for trough concentration (C0) and peak concentration (C2) was carried out, using validated liquid chromatography assay with ultraviolet detection, for 35 CF lung transplant patients (mean age 25 years, mean weight 47 kg, balanced sex ratio) since 2003. Therapeutic range (C0: 1.5 +/- 0.5 - C2 : 4.0 +/- 1.0 mg/L) was expressed relative to pivotal pharmacokinetic trial data. The duration of VRZ treatment ranged from 9 days to 22 months. The recommended standard dose of VRZ (200 mg twice a day, following the loading dose) resulted in significant plasma concentrations (>0.5 mg/L) in 20% of CF lung transplant patients. Therapeutic concentrations were obtained using higher doses (average 570 +/- 160 mg/day, +43%, P<0.01). Despite adaptation, C0 remained <0.5 mg/L (11%), even when the drug was administered intravenously, highlighting the variability of VRZ pharmacokinetics, possibly enhanced by CYP2C19 polymorphism. The risk of inefficacy during periods of underdosage was overcome by treatment with antifungal drug combinations (caspofungin, n=10). The therapeutic index was limited by neurologic effects (14%) and hepatic abnormalities (30%). VRZ concentrations correlated significantly (P<0.01) with aspartate aminotransferase levels but not with bilirubin levels. VRZ acted as a metabolic inhibitor of tacrolimus (C0 to dose ratio 5.8 +/- 2.6, n=31/VRZ versus 1.7 +/- 0.9 alone, P<0.001). Large changes in azole concentration affected the magnitude of

Provenance and sedimentary environments of the Proterozoic São Roque Group, SE-Brazil: Contributions from petrography, geochemistry and Sm-Nd isotopic systematics of metasedimentary rocks

NASA Astrophysics Data System (ADS)

Henrique-Pinto, R.; Janasi, V. A.; Tassinari, C. C. G.; Carvalho, B. B.; Cioffi, C. R.; Stríkis, N. M.

2015-11-01

The Proterozoic metasedimentary sequences exposed in the São Roque Domain (Apiaí Terrane, Ribeira Belt, southeast Brazil) consist of metasandstones and meta-felspathic wackes with some volcanic layers of within-plate geochemical signature (Boturuna Formation), a passive margin turbidite sequence of metawackes and metamudstones (Piragibu Formation), and volcano-sedimentary sequences with MORB-like basalts (Serra do Itaberaba Group; Pirapora do Bom Jesus Formation). A combination of zircon provenance studies in metasandstones, whole-rock geochemistry and Sm-Nd isotopic systematics in metamudstones was used to understand the provenance and tectonic significance of these sequences, and their implications to the evolution of the Precambrian crust in the region. Whole-rock geochemistry of metamudstones, dominantly from the Piragibu Formation, points to largely granitic sources (as indicated for instance by LREE-rich moderately fractionated REE patterns and subtle negative Eu anomalies) with some mafic contribution (responding for higher contents of Fe2O3, MgO, V, and Cr) and were subject to moderate weathering (CIA - 51 to 85). Sm-Nd isotope data show three main peaks of Nd TDM ages at ca. 1.9, 2.1 and 2.4 Ga; the younger ages define an upper limit for the deposition of the unit, and reflect greater contributions from sources younger than the >2.1 Ga basement. The coincident age peaks of Nd TDM and U-Pb detrital zircons at 2.1-2.2 Ga and 2.4-2.5 Ga, combined with the possible presence of a small amount of zircons derived from mafic (gabbroid) sources with the same ages, as indicated by a parallel LA-ICPMS U-Pb dating study in metapsammites, are suggestive that these were major periods of crustal growth in the sources involving not only crust recycling but also some juvenile addition. A derivation from similar older Proterozoic sources deposited in a passive margin basin is consistent with the main sedimentary sequences in the São Roque Domain being broadly coeval and

Human urinary bladder epithelial cells lacking wild-type p53 function are deficient in the repair of 4-aminobiphenyl-DNA adducts in genomic DNA.

PubMed

Swaminathan, Santhanam; Torino, Jennifer L; Burger, Melissa S

2002-01-29

The effect of the tumor suppressor gene TP53 on repair of genomic DNA damage was examined in human urinary bladder transitional cell carcinoma (TCC) cell lines. Utilizing TCC10 containing wild-type p53 (wt-p53) as the parental line, an isogenic set of cell lines was derived by retroviral infection that expressed a transdominant mutant p53 (Arg --> His at codon 273, TDM273-TCC10), or the human papilloma virus 16-E6 oncoprotein (E6-TCC10). 32P-postlabeling analyses were performed on DNA from TCC cultures obtained after treatment with N-hydroxy-4-aminobiphenyl (N-OH-ABP), N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and N-acetoxy-4-acetylaminobiphenyl (N-OAc-AABP). The major adduct was identified as N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP) with all three chemicals. The amount of adducts in urothelial DNA ranged between 0.1 and 20 per 10(6) nucleotides, N-OAc-AABP yielding the highest levels, followed by N-OH-ABP and N-OH-AABP. To determine, if the functional status of p53 affects the rate of repair of dG-C8-ABP in genomic DNA, TCC10 and the TDM273-TCC10 and E6-TCC10 isotypes were exposed to N-OH-AABP for 12h and the DNA damage was allowed to repair up to 24h. The adduct levels were quantified and compared between the TCC10 isotypes. The amounts of dG-C8-ABP that remained in genomic DNA from E6-TCC10 and TDM273-TCC10 were approximately two-fold higher, as compared to the parental TCC10. At the dose used for DNA repair studies, N-OH-AABP or N-OAc-AABP did not induce apoptosis in TCC10. However, N-OAc-AABP at high doses (>5 microM) induced apoptosis, as evidenced by DNA fragmentation analyses. Furthermore, N-OAc-AABP-mediated apoptosis was independent of the functional status of wt-p53, since both E6-TCC10 and the parental TCC10 exhibited DNA fragmentation following treatment. These results suggest that p53 might modulate the repair of DNA adducts generated from the human bladder carcinogen ABP in its target human uroepithelial cells. This implies that in p53

Practical Considerations for Optimizing Position Sensitivity in Arrays of Position-sensitive TES's

NASA Technical Reports Server (NTRS)

Smith, Stephen J.; Bandler, Simon R.; Figueroa-Feliciano, Encetali; Iyomoto, Naoko; Kelley, Richard L.; Kilbourne, Caroline A.; Porder, Frederick S.; Sadleir, John E.

2007-01-01

We are developing Position-Sensitive Transitions-Edge Sensors (PoST's) for future X-ray astronomy missions such as NASA's Constellation-X. The PoST consists of one or more Transitions Edge Sensors (TES's) thermally connected to a large X-ray absorber, which through heat diffusion, gives rise to position dependence. The development of PoST's is motivated by the desire to achieve the largest the focal-plan coverage with the fewest number of readout channels. In order to develop a practical array, consisting of an inner pixellated core with an outer array of large absorber PoST's, we must be able to simultaneously read out all (-1800) channels in the array. This is achievable using time division multiplexing (TDM), but does set stringent slew rate requirements on the array. Typically, we must damp the pulses to reduce the slew rate of the input signal to the TDM. This is achieved by applying a low-pass analog filter with large inductance to the signal. This attenuates the high frequency components of the signal, essential for position discrimination in PoST's, relative to the white noise of the readout chain and degrades the position sensitivity. Using numerically simulated data, we investigate the position sensing ability of typical PoST designs under such high inductance conditions. We investigate signal-processing techniques for optimal determination of the event position and discuss the practical considerations for real-time implementation.

The Río de la Plata Craton: a review of units, boundaries, ages and isotopic signature

NASA Astrophysics Data System (ADS)

Oyhantçabal, Pedro; Siegesmund, Siegfried; Wemmer, Klaus

2011-04-01

A review of the lithostratigraphic units in the Río de la Plata Craton and of new and previously published geochronological, isotopic and geophysical data is presented. Sm-Nd TDM model ages between 2.6 and 2.2 Ga characterize the Piedra Alta Terrane of this craton. Crystallization ages between 2.2 and 2.1 Ga for the metamorphic protoliths and 2.1-2.0 Ga for the post-orogenic granitoids indicate juvenile crust, followed by a short period of crustal recycling. Cratonization of this terrane occurred during the late Paleoproterozoic. Younger overprinting is not observed, suggesting it had a thick and strong lithosphere in the Neoproterozoic. A similar scenario is indicated for the Tandilia Belt of Argentina. Sm-Nd TDM model ages for the Nico Pérez Terrane show two main events of crustal growth (3.0-2.6 and 2.3-1.6 Ga). The crystallization ages on zircon ranges between 3.1 and 0.57 Ga, which is evidence for long-lived crustal reworking. The age for cratonization is still uncertain. In the Taquarembó Block, which is considered the prolongation of the Nico Pérez Terrane in southern Brazil, a similar scenario can be observed. These differences together with contrasting geophysical signatures support the redefinition of the Río de la Plata Craton comprising only the Piedra Alta Terrane and the Tandilia Belt. The Sarandí del Yí Shear Zone is regarded as the eastern margin of this Craton.

Pharmacological considerations for azole antifungal drug management in cystic fibrosis lung transplant patients.

PubMed

Billaud, Eliane M; Guillemain, Romain; Berge, Maud; Amrein, Catherine; Lefeuvre, Sandrine; Louët, Agnès Lillo-Le; Boussaud, Véronique; Chevalier, Patrick

2010-11-01

This paper aims to present our experience in the pharmacological approach of the management of azole antifungal drugs in cystic fibrosis lung transplant patients. Cystic fibrosis (CF) lung transplantation is associated with multi-factorial care management, because of immunosuppressive requirements, risk of infections, frequency of gastro-oesophageal reflux disease, hepatic alterations and CF pharmacokinetics (PK) specificities that result in important PK variability. CF is associated with frequent colonization of the airways by filamentous fungi, especially by Aspergillus species. Today the antifungal therapeutic arsenal offers several possibilities for long-term oral therapy including azole drugs (itraconazole, voriconazole and posaconazole). Therefore, nephrotoxic amphotericin B should be avoided. The liver is important in the pharmacological profile of azole drugs, due to metabolic elimination, hepatotoxicity and PK drug-drug interaction (DDI) involving CYP3A4 metabolic inhibition. Targets for such DDI are numerous, but immunosuppressive drugs are of major concern, justifying combined therapeutic drug monitoring (TDM) of both azoles (inhibitors) and immunosuppressants (targets) on an individualized patient basis to adjust the coprescription quantitatively. The risk of long under-dosed periods, frequently addressed in this population, could justify, on a PK basis, the need for combination with an exclusive parenteral antifungal while waiting for azole relevant drug level. High PK variability, the risk of low exposure, therapeutic issues and DDI management in this complex underlying disease justify close monitoring with systematic combined TDM of azole and immunosuppressants, in case of coprescription.

Overview of systematic reviews of therapeutic ranges: methodologies and recommendations for practice.

PubMed

Cooney, Lewis; Loke, Yoon K; Golder, Su; Kirkham, Jamie; Jorgensen, Andrea; Sinha, Ian; Hawcutt, Daniel

2017-06-02

Many medicines are dosed to achieve a particular therapeutic range, and monitored using therapeutic drug monitoring (TDM). The evidence base for a therapeutic range can be evaluated using systematic reviews, to ensure it continues to reflect current indications, doses, routes and formulations, as well as updated adverse effect data. There is no consensus on the optimal methodology for systematic reviews of therapeutic ranges. An overview of systematic reviews of therapeutic ranges was undertaken. The following databases were used: Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts and Reviews of Effects (DARE) and MEDLINE. The published methodologies used when systematically reviewing the therapeutic range of a drug were analyzed. Step by step recommendations to optimize such systematic reviews are proposed. Ten systematic reviews that investigated the correlation between serum concentrations and clinical outcomes encompassing a variety of medicines and indications were assessed. There were significant variations in the methodologies used (including the search terms used, data extraction methods, assessment of bias, and statistical analyses undertaken). Therapeutic ranges should be population and indication specific and based on clinically relevant outcomes. Recommendations for future systematic reviews based on these findings have been developed. Evidence based therapeutic ranges have the potential to improve TDM practice. Current systematic reviews investigating therapeutic ranges have highly variable methodologies and there is no consensus of best practice when undertaking systematic reviews in this field. These recommendations meet a need not addressed by standard protocols.

Development, validation and clinical application of an online-SPE-LC-HRMS/MS for simultaneous quantification of phenobarbital, phenytoin, carbamazepine, and its active metabolite carbamazepine 10,11-epoxide.

PubMed

Qu, Lihua; Fan, Yuanjie; Wang, Wenjun; Ma, Kai; Yin, Zheng

2016-09-01

A simple and efficient bioanalytical method for simultaneous determination of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ), and its active metabolite carbamazepine 10,11-epoxide (CBZE) in human plasma using online solid phase extraction (SPE)-liquid chromatography (LC) coupled with high resolution mass spectrum (HRMS) under targeted MS/MS (t-MS(2)) analysis mode has been developed. The procedure integrated an automated sample clean-up of human plasma by Oasis®HLB SPE cartridge, a separation by ZORBAX SB-C18 analysis column, and a quantification by Q-Exactive Hybrid Quadrupole-Orbitrap. The total running time was 13min. The lower limit of quantification (LLOQ) of PB, PHT, CBZ, and CBZE were 0.008, 0.008, 0.0016 and 0.0016μgmL(-1) respectively and the linearities were in the range of 0.008-2.500, 0.008-2.500, 0.0016-0.500 and 0.0016-0.500μgmL(-1) respectively. The mean recovery was between 91.82% and 108.27% and the matrix effect was between 93.29% and 102.09%. The relative standard deviations of interday and intraday were less than 6.41%. The method has been successfully applied in therapeutic drug monitoring (TDM) of four Chinese epilepsy patients. This fully automated, simple, sensitive and reliable online-SPE-LC-HRMS/MS method serves well for TDM of PB, PHT, CBZ and CBZE at clinics for either single or combination treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Mid-Tertiary (25-21 Ma) lamprophyres in NW Mexico derived from subduction-modified subcontinental lithospheric mantle in an extensional backarc environment following steepening of the Benioff zone

NASA Astrophysics Data System (ADS)

Orozco-Garza, Alberto; Dostal, Jaroslav; Keppie, J. Duncan; Paz-Moreno, Francisco A.

2013-04-01

The mid-Tertiary lamprophyre dike swarm (~ 8 km × 2.5 km in size) from Hermosillo (Sonora, NW Mexico) has calc-alkaline characteristics and includes NNW-striking, amphibole-phyric spessartite (~ 85% of the swarm) and NNE-striking, phlogopite-phyric kersantite. The 40Ar/39Ar geochronology of amphibole and phlogopite gives overlapping plateau ages ranging from 25 to 21 Ma. Although all the lamprophyres are enriched in incompatible elements and display negative Nb-Ta and Ti anomalies on the primitive mantle-normalized plots, kersantite has higher K/Na, La/Yb, P, Ti and incompatible trace elements (e.g., Zr) compared to spessartite. The lamprophyres have radiogenic Sr and Nd isotopic signatures (87Sr/86Sr ~ 0.7057-0.7065 and ɛNd ~- 1 to - 2.3) suggesting derivation from the subcontinental lithospheric mantle that was previously modified by subduction-related fluids. This mantle is similar to that beneath the southern Grenvillian orogen, which has younger TDM ages than the 1.6-1.7 Ga TDM ages of the Caborca block. The lamprophyric magmas were generated at various mantle depths at the southwestern edge of North America. Intrusion of the lamprophyres was synchronous with extension that produced normal faults and core complexes with WSW-vergence. Extension occurred immediately following steepening of the Benioff zone, during which the magmatic arc migrated from east to west of Hermosillo, and the lamprophyres were intruded just behind the contemporaneous arc.

An Inductively-Powered Wireless Neural Recording System with a Charge Sampling Analog Front-End

PubMed Central

Lee, Seung Bae; Lee, Byunghun; Kiani, Mehdi; Mahmoudi, Babak; Gross, Robert; Ghovanloo, Maysam

2015-01-01

An inductively-powered wireless integrated neural recording system (WINeR-7) is presented for wireless and battery less neural recording from freely-behaving animal subjects inside a wirelessly-powered standard homecage. The WINeR-7 system employs a novel wide-swing dual slope charge sampling (DSCS) analog front-end (AFE) architecture, which performs amplification, filtering, sampling, and analog-to-time conversion (ATC) with minimal interference and small amount of power. The output of the DSCS-AFE produces a pseudo-digital pulse width modulated (PWM) signal. A circular shift register (CSR) time division multiplexes (TDM) the PWM pulses to create a TDM-PWM signal, which is fed into an on-chip 915 MHz transmitter (Tx). The AFE and Tx are supplied at 1.8 V and 4.2 V, respectively, by a power management block, which includes a high efficiency active rectifier and automatic resonance tuning (ART), operating at 13.56 MHz. The 8-ch system-on-a-chip (SoC) was fabricated in a 0.35-μm CMOS process, occupying 5.0 × 2.5 mm2 and consumed 51.4 mW. For each channel, the sampling rate is 21.48 kHz and the power consumption is 19.3 μW. In vivo experiments were conducted on freely behaving rats in an energized homecage by continuously delivering 51.4 mW to the WINeR-7 system in a closed-loop fashion and recording local field potentials (LFP). PMID:27069422

An Inductively-Powered Wireless Neural Recording System with a Charge Sampling Analog Front-End.

PubMed

Lee, Seung Bae; Lee, Byunghun; Kiani, Mehdi; Mahmoudi, Babak; Gross, Robert; Ghovanloo, Maysam

2016-01-15

An inductively-powered wireless integrated neural recording system (WINeR-7) is presented for wireless and battery less neural recording from freely-behaving animal subjects inside a wirelessly-powered standard homecage. The WINeR-7 system employs a novel wide-swing dual slope charge sampling (DSCS) analog front-end (AFE) architecture, which performs amplification, filtering, sampling, and analog-to-time conversion (ATC) with minimal interference and small amount of power. The output of the DSCS-AFE produces a pseudo-digital pulse width modulated (PWM) signal. A circular shift register (CSR) time division multiplexes (TDM) the PWM pulses to create a TDM-PWM signal, which is fed into an on-chip 915 MHz transmitter (Tx). The AFE and Tx are supplied at 1.8 V and 4.2 V, respectively, by a power management block, which includes a high efficiency active rectifier and automatic resonance tuning (ART), operating at 13.56 MHz. The 8-ch system-on-a-chip (SoC) was fabricated in a 0.35-μm CMOS process, occupying 5.0 × 2.5 mm 2 and consumed 51.4 mW. For each channel, the sampling rate is 21.48 kHz and the power consumption is 19.3 μW. In vivo experiments were conducted on freely behaving rats in an energized homecage by continuously delivering 51.4 mW to the WINeR-7 system in a closed-loop fashion and recording local field potentials (LFP).

High capacity fiber optic sensor networks using hybrid multiplexing techniques and their applications

NASA Astrophysics Data System (ADS)

Sun, Qizhen; Li, Xiaolei; Zhang, Manliang; Liu, Qi; Liu, Hai; Liu, Deming

2013-12-01

Fiber optic sensor network is the development trend of fiber senor technologies and industries. In this paper, I will discuss recent research progress on high capacity fiber sensor networks with hybrid multiplexing techniques and their applications in the fields of security monitoring, environment monitoring, Smart eHome, etc. Firstly, I will present the architecture of hybrid multiplexing sensor passive optical network (HSPON), and the key technologies for integrated access and intelligent management of massive fiber sensor units. Two typical hybrid WDM/TDM fiber sensor networks for perimeter intrusion monitor and cultural relics security are introduced. Secondly, we propose the concept of "Microstructure－Optical X Domin Refecltor (M-OXDR)" for fiber sensor network expansion. By fabricating smart micro-structures with the ability of multidimensional encoded and low insertion loss along the fiber, the fiber sensor network of simple structure and huge capacity more than one thousand could be achieved. Assisted by the WDM/TDM and WDM/FDM decoding methods respectively, we built the verification systems for long-haul and real-time temperature sensing. Finally, I will show the high capacity and flexible fiber sensor network with IPv6 protocol based hybrid fiber/wireless access. By developing the fiber optic sensor with embedded IPv6 protocol conversion module and IPv6 router, huge amounts of fiber optic sensor nodes can be uniquely addressed. Meanwhile, various sensing information could be integrated and accessed to the Next Generation Internet.

Transferability of antibody pairs from ELISA to fiber optic surface plasmon resonance for infliximab detection

NASA Astrophysics Data System (ADS)

Van Stappen, Thomas; Lu, Jiadi; Bloemen, Maarten; Geukens, Nick; Spasic, Dragana; Delport, Filip; Verbiest, Thierry; Lammertyn, Jeroen; Gils, Ann

2015-03-01

Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine up-regulated in inflammatory bowel disease, rheumatoid arthritis and psoriasis. The introduction of anti-TNF drugs such as infliximab has revolutionized the treatment of these diseases. Recently, therapeutic drug monitoring (TDM) of infliximab has been introduced in clinical decision making to increase cost-efficiency. Nowadays, TDM is performed using radio-immunoassays, homogeneous mobility shift assays or ELISA. Unfortunately, these assays do not allow for in situ treatment optimization, because of the required sample transportation to centralized laboratories and the subsequent assay execution time. In this perspective, we evaluated the potential of fiber optic-surface plasmon resonance (FO-SPR). To achieve this goal, a panel of 55 monoclonal anti-infliximab antibodies (MA-IFX) was developed and characterized in-house, leading to the identification of nine different clusters. Based on this high diversity, 22 antibody pairs were selected and tested for their reactivity towards IFX, using one MA-IFX as capture and one MA-IFX for detection, in a sandwich type ELISA and FO-SPR. This study showed that the reactivity towards IFX of each antibody pair in ELISA is highly similar to its reactivity on FO-SPR, indicating that antibody pairs are easily transferable between both platforms. Given the fact that FO-SPR shows the potential for miniaturization and fast assay time, it can be considered a highly promising platform for on-site infliximab monitoring.

Development of Increasingly Autonomous Traffic Data Manager Using Pilot Relevancy and Ranking Data

NASA Technical Reports Server (NTRS)

Le Vie, Lisa R.; Houston, Vincent E.

2017-01-01

NASA's Safe Autonomous Systems Operations (SASO) project goal is to define and safely enable all future airspace operations by justifiable and optimal autonomy for advanced air, ground, and connected capabilities. This work showcases how Increasingly Autonomous Systems (IAS) could create operational transformations beneficial to the enhancement of civil aviation safety and efficiency. One such IAS under development is the Traffic Data Manager (TDM). This concept is a prototype 'intelligent party-line' system that would declutter and parse out non-relevant air traffic, displaying only relevant air traffic to the aircrew in a digital data communications (Data Comm) environment. As an initial step, over 22,000 data points were gathered from 31 Airline Transport Pilots to train the machine learning algorithms designed to mimic human experts and expertise. The test collection used an analog of the Navigation Display. Pilots were asked to rate the relevancy of the displayed traffic using an interactive tablet application. Pilots were also asked to rank the order of importance of the information given, to better weight the variables within the algorithm. They were also asked if the information given was enough data, and more importantly the "right" data to best inform the algorithm. The paper will describe the findings and their impact to the further development of the algorithm for TDM and, in general, address the issue of how can we train supervised machine learning algorithms, critical to increasingly autonomous systems, with the knowledge and expertise of expert human pilots.

Recent Advances in Antibody-Drug Conjugates for Breast Cancer Treatment.

PubMed

Deng, Shanshan; Lin, Zongtao; Li, Wei

2017-01-01

Breast cancer is the most common cancer in women, with roughly half a million deaths per year worldwide. Among various approaches for breast cancer treatment, chemotherapy is predominantly used for patients at stages II-IV, and monoclonal antibody (mAb) therapy is used for patients with human epidermal growth factor receptor 2 (HER2) overexpression. Integrating the tumor specificity provided by unique mAbs and cytotoxicity of small molecule drugs, antibody-drug conjugates (ADCs) are a series of smart chemotherapeutics that have recently shown great promise in treating a number of cancer types. ADCs are designed to selectively attack and kill cancer cells with minimal toxicity to normal tissues. Ado-Trastuzumab emtansine (T-DM1) was the first and only ADC approved by the US Food and Drug Administration for HER2-positive breast cancer. Following the success of T-DM1, many novel ADCs have been developed, and their anticancer efficacies are currently undergoing preclinical or clinical investigation. The development of ADCs is a rapidly progressing field, and this review aims to summarize the most recent advances in ADCs targeting breast cancer over the past five years (2011-2016). The review highlights compositions and mechanisms of action of these newly developed ADCs and discusses current challenges and future directions of developing new ADCs for improved treatment of breast cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

La tuberculose sternale: à propos de 2 cas

PubMed Central

Ouarssani, Aziz; Atoini, Fouad; Ait Lhou, Fatima; Idrissi Rguibi, Mustapha

2012-01-01

La tuberculose ostéoarticulaire touche surtout le rachis. L’atteinte sternale est rare, elle représente moins de 1% des ostéomyélites tuberculeuses. L’abcès froid compliqué par une fracture pathologique constitue le mode de révélation le plus fréquent. Le traitement chirurgical assure l’évacuation des abcès et permet le diagnostique histologique et bactériologique. On rapporte deux cas de tuberculose sternale âgés respectivement de 45 ans et de 10ans, colligés au service de pneumologie, l’examen histologique et bactériologique ont permis d’affirmer le diagnostic de tuberculose, et le traitement antibacillaire a permis une évolution favorable .A la lumière de ces observations, les auteurs proposent de faire une mise au point sur l’ostéite sternale tuberculeuse. PMID:22514767

Intérêt de l’algorithme rocuronium - sugammadex dans la laryngoscopie directe en suspension

PubMed Central

El jaouhari, Sidi Driss; Meziane, Mohamed; Ahtil, Redouane; Bensghir, Mustapha; Haimeur, Charki

2017-01-01

La laryngoscopie directe en suspension est un geste chirurgical diagnostique et/ou thérapeutique des lésions endo-laryngées. Sa gestion anesthésique est compliquée. Différentes techniques anesthésiques peuvent être proposées. Malgré les contraintes, les curares gardent tout leur intérêt. L’association rocuronium et sugammadex est envisageable, elle permet une inversion rapide du bloc neuromusculaire profond et par conséquent une réduction de la morbidité postopératoire. Nous rapportons un cas d’une laryngoscopie directe en suspension réalisée sous anesthésie générale dont l’utilisation de l’association rocuronium-sugammadex a permis une facilité du geste chirurgicale, une sécurité pour le patient et un confort pour l’anesthésiste. PMID:28690746

Ultrahigh-speed clock recovery with optical phase lock loop based on four-wave-mixing in a semiconductor optical amplifier

NASA Astrophysics Data System (ADS)

Kim, Dong Hwan; Kim, Sang Hyuck; Jo, Jae Cheol; Choi, Sang Sam

2000-08-01

A new phase lock loop (PLL) is proposed and demonstrated for clock recovery from 40 Gbps time-division-multiplexed (TDM) optical signal using simple optical phase lock loop circuit. The proposed clock recovery scheme improves the jitter effect in PLL circuit from the clock pulse laser of harmonically-mode locked fiber laser. The cross-correlation component between the optical signal and an optical clock pulse train is detected as a four-wave-mixing (FWM) signal generated in SOA. The lock-in frequency range of the clock recovery is found to be within 10 KHz.

High-speed clock recovery with phase-locked-loop-based on LiNbO3 modulators

NASA Astrophysics Data System (ADS)

Zhu, Guanghao; Chen, Hongmin; Wang, Qiang; Dutta, Niloy K.

2003-08-01

In this paper, we present a scheme for recovering 10 GHz clock from 40 Gb/s and 80 Gb/s time division multiplexed (TDM) return to zero (RZ) data stream. The proposed clock recovery is successfully demonstrated using an electrical phase locked loop (PLL). The jitter of the recovered clock is estimated to be around 50 fs. The key part in the proposed clock recovery circuit is a LiNbO3 Mach-Zehnder modulator which is shown to be highly effective in optical to electrical down conversion.

Information Switching Processor (ISP) contention analysis and control

NASA Technical Reports Server (NTRS)

Shyy, D.; Inukai, T.

1993-01-01

Future satellite communications, as a viable means of communications and an alternative to terrestrial networks, demand flexibility and low end-user cost. On-board switching/processing satellites potentially provide these features, allowing flexible interconnection among multiple spot beams, direct to the user communications services using very small aperture terminals (VSAT's), independent uplink and downlink access/transmission system designs optimized to user's traffic requirements, efficient TDM downlink transmission, and better link performance. A flexible switching system on the satellite in conjunction with low-cost user terminals will likely benefit future satellite network users.

Impact of transportation demand management (TDM) elements on managed lanes toll prices : [summary].

DOT National Transportation Integrated Search

2015-04-01

The 95 Express in Miami, Florida, is a set of dynamically tolled, managed lanes on I-95. : Single occupant vehicles must pay a toll to use 95 Express, but registered carpools, vanpools, : motorcycles, inherently low emission vehicles (ILEV; generally...

Atlanta congestion reduction demonstration. National evaluation : travel demand management (TDM) data test plan.

DOT National Transportation Integrated Search

2001-01-01

Internet-based Advanced Traveler Information Services (ATIS) provide the urban traveler with estimated travel times based on current roadway congestion. Survey research indicates that the vast majority of current ATIS users are satisfied consumers wh...

Developing a technique that predicts the impacts of TDM on a transportation system.

DOT National Transportation Integrated Search

2010-02-01

Given declining resources, pressing problems, and environmental constraints, state departments of transportation (DOTs) are increasingly motivated to manage peak demand of vehicle trips as a way to mitigate congestion and improve overall performance ...

Torsion d'annexe en cours de grossesse: à propos d'un cas à l'Hôpital Central de Yaoundé, Cameroun

PubMed Central

Fouedjio, Jeanne Hortence; Fouogue, Jovanny Tsuala; Fouelifack, Florent Ymele; Nangue, Charlette; Sando, Zacharie; Enow Mbu, Robinson

2014-01-01

Les kystes ovariens sont dans la majorité des cas asymptomatiques et peuvent être de découverte fortuite lors d'une échographie. Ils ne deviennent symptomatiques que lorsque survient une complication. Nous présentons un cas de torsion d'annexe gauche diagnostiqué à 8 semaines et 4 jours de grossesse. Nous avons réalisé une annexectomie Suivie de l'administration de progestérone retard à la dose 500 mg par jour. L'évolution a été marquée par la survenue d'un avortement au cinquième jour post opératoire. L'analyse anatomopathologique de la masse chirurgicale a conclu à une apoplexie ovarienne. L'ablation chirurgicale du corps jaune au premier trimestre de la grossesse pose le problème du maintien de celle - ci et devrait être présente à l'esprit des praticiens avant toute chirurgie pelvienne pendant cette période. PMID:24932350

Le pronostic statural après une pseudo-puberté précoce par déficit en 11ß hydroxylase chez une fille de 7 ans: à propos d'un cas avec revue de la literature

PubMed Central

Latrech, Hanane; Gaouzi, Ahmed

2015-01-01

L'hyperplasie congénitale des surrénales par déficit en 11ß hydroxylase se voit dans 5 à 10% des cas et est diagnostiquée, habituellement, devant des signes de virilisation d'un nouveau né ou d'un fœtus 46 XX et plus tard devant une HTA avec une hypokaliémie. Le pronostic de taille chez ces patients est très souvent compromis. Nous rapportons le cas d'un déficit en 11ß hydroxylase chez une enfant âgée de 7 ans révélé par une pseudo- puberté précoce traitée par hydrocortisone. La survenue d'une puberté précoce centrale complique encore plus la situation par la mise en jeu du pronostic de taille finale et nécessitant une prise en charge thérapeutique particulière. PMID:26113905

Predictors of affect following treatment decision-making for prostate cancer: conversations, cognitive processing, and coping.

PubMed

Christie, Kysa M; Meyerowitz, Beth E; Giedzinska-Simons, Antoinette; Gross, Mitchell; Agus, David B

2009-05-01

Research suggests that cancer patients who are more involved in treatment decision-making (TDM) report better quality of life following treatment. This study examines the association and possible mechanisms between prostate cancer patient's discussions about TDM and affect following treatment. We predicted that the length of time patients spent discussing treatment options with social networks and physicians prior to treatment would predict emotional adjustment after treatment. We further predicted that cognitive processing, coping, and patient understanding of treatment options would mediate this association. Fifty-seven patients completed questionnaires prior to treatment and at 1 and 6 months following treatment completion. Findings from the present study suggest that discussing treatment options with others, prior to beginning treatment for prostate cancer, significantly contributed to improvements in affect 1 and 6 months following treatment. Residualized regression analyses indicated that discussing treatment options with patient's social networks predicted a decrease in negative affect 1 and 6 months following treatment, while discussions with physicians predicted an increase in positive affect 1 month following treatment. Patients who spent more time discussing treatment options with family and friends also reported greater pre-treatment social support and emotional expression. Mediation analyses indicated that these coping strategies facilitated cognitive processing (as measured by a decrease in intrusive thoughts) and that cognitive processing predicted improvement in affect. Greater time spent talking with family and friends about treatment options may provide opportunities for patients to cope with their cancer diagnosis and facilitate cognitive processing, which may improve patient distress over time. Copyright (c) 2008 John Wiley & Sons Ltd.

Carbon Back Sputter Modeling for Hall Thruster Testing

NASA Technical Reports Server (NTRS)

Gilland, James H.; Williams, George J.; Burt, Jonathan M.; Yim, John Tamin

2016-01-01

Lifetime requirements for electric propulsion devices, including Hall Effect thrusters, are continually increasing, driven in part by NASA's inclusion of this technology in it's exploration architecture. NASA will demonstrate high-power electric propulsion system on the Solar Electric Propulsion Technology Demonstration Mission (SEP TDM). The Asteroid Redirect Robotic mission is one candidate SEP TDM, which is projected to require tens of thousands of thruster life. As thruster life is increased, for example through the use of improved magnetic field designs, the relative influence of facility effects increases. One such effect is the sputtering and redeposition, or back sputter, of facility materials by the high energy thruster plumes. In support of wear testing for the Hall Effect Rocket with Magnetic Shielding (HERMeS) project, the back sputter from a Hall effect thruster plume has been modeled for the NASA Glenn Research Center's Vacuum Facility 5. The predicted wear at a near-worst case condition of 600 V, 12.5 kW was found to be on the order of 1 micron/kh in a fully carbon-lined chamber. A more detailed numerical Monte Carlo code was also modified to estimate back sputter for a detailed facility and pumping configuration. This code demonstrated similar back sputter rate distributions, but is not yet accurately modeling the magnitudes. The modeling has been benchmarked to recent HERMeS wear testing, using multiple microbalance measurements. These recent measurements have yielded values on the order of 1.5 - 2 micron/kh at 600 V and 12.5 kW.

Milrinone therapeutic drug monitoring in a pediatric population: Development and validation of a quantitative liquid chromatography-tandem mass spectrometry method.

PubMed

Raizman, Joshua E; Taylor, Katherine; Parshuram, Christopher; Colantonio, David A

2017-05-01

Milrinone is a potent selective phosphodiesterase type III inhibitor which stimulates myocardial function and improves myocardial relaxation. Although therapeutic monitoring is crucial to maintain therapeutic outcome, little data is available. A proof-of-principle study has been initiated in our institution to evaluate the clinical impact of optimizing milrinone dosing through therapeutic drug monitoring (TDM) in children following cardiac surgery. We developed a robust LC-MS/MS method to quantify milrinone in serum from pediatric patients in real-time. A liquid-liquid extraction procedure was used to prepare samples for analysis prior to measurement by LC-MS/MS. Performance characteristics, such as linearity, limit of quantitation (LOQ) and precision, were assessed. Patient samples were acquired post-surgery and analyzed to determine the concentration-time profile of the drug as well as to track turn-around-times. Within day precision was <8.3% across 3 levels of QC. Between-day precision was <12%. The method was linear from 50 to 800μg/l; the lower limit of quantification was 22μg/l. Comparison with another LC-MS/MS method showed good agreement. Using this simplified method, turnaround times within 3-6h were achievable, and patient drug profiles demonstrated that some milrinone levels were either sub-therapeutic or in the toxic range, highlighting the importance for milrinone TDM. This simplified and quick method proved to be analytically robust and able to provide therapeutic monitoring of milrinone in real-time in patients post-cardiac surgery. Copyright © 2017. Published by Elsevier B.V.

Ultra high performance liquid chromatography-tandem mass spectrometry vs. commercial immunoassay for determination of vancomycin plasma concentration in children. Possible implications for everyday clinical practice.

PubMed

Barco, Sebastiano; Castagnola, Elio; Gennai, Iulian; Barbagallo, Laura; Loy, Anna; Tripodi, Gino; Cangemi, Giuliana

2016-10-01

Vancomycin therapeutic drug monitoring (TDM) is necessary for effective and safetherapy. The aim of the this paper was to develop a specific and robust ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for vancomycin quantification starting from low plasma volumes to be applied for the routine TDM in children. Samples from children receiving intravenous vancomycin were analysed using a TSQ Quantum Access MAX Triple Quadrupole system coupled with an Accela 1250 UHPLC system after a rapid protein precipitation. Gradient separation chromatography was carried out using a Hypersil GOLD aQ C18 column (50 × 2.1 mm, particle size 1.9 μm). Method performance was validated following international guidelines. UHPLC-MS/MS allowed a rapid and specific quantification of vancomycin over the range 0.1-128 μg/mL from 50 μL of plasma with high reproducibility and accuracy in the absence of matrix effect. The comparison with the commercial immunoassay performed on 138 samples demonstrated the presence of a proportional bias. The concentrations of vancomycin measured with immunoassay were found to be 4.5% (95% CI: 1.3-7.7) higher than those determined with UHPLC-MS/MS. Importantly, a clinical discordance was found in about 10% of samples analysed. This new UHPLC-MS/MS method is accurate and specific for the measurement of vancomycin starting from small (50 μL) plasma volumes. The use of UHPLC-MS/MS is recommended to prevent a misclassification of therapeutic or toxic vancomycin levels in paediatrics.

Therapeutic drug monitoring of infliximab: performance evaluation of three commercial ELISA kits.

PubMed

Schmitz, Ellen M H; van de Kerkhof, Daan; Hamann, Dörte; van Dongen, Joost L J; Kuijper, Philip H M; Brunsveld, Luc; Scharnhorst, Volkher; Broeren, Maarten A C

2016-07-01

Therapeutic drug monitoring (TDM) of infliximab (IFX, Remicade®) can aid to optimize therapy efficacy. Many assays are available for this purpose. However, a reference standard is lacking. Therefore, we evaluated the analytical performance, agreement and clinically relevant differences of three commercially available IFX ELISA kits on an automated processing system. The kits of Theradiag (Lisa Tracker Infliximab), Progenika (Promonitor IFX) and apDia (Infliximab ELISA) were implemented on an automated processing system. Imprecision was determined by triplicate measurements of patient samples on five days. Agreement was evaluated by analysis of 30 patient samples and four spiked samples by the selected ELISA kits and the in-house IFX ELISA of Sanquin Diagnostics (Amsterdam, The Netherlands). Therapeutic consequences were evaluated by dividing patients into four treatment groups using cut-off levels of 1, 3 and 7 μg/mL and determining assay concordance. Within-run and between-run imprecision were acceptable (≤12% and ≤17%, respectively) within the quantification range of the selected ELISA kits. The apDia assay had the best precision and agreement to target values. Statistically significant differences were found between all assays except between Sanquin Diagnostics and the Lisa Tracker assay. The Promonitor assay measured the lowest IFX concentrations, the apDia assay the highest. When patients were classified in four treatment categories, 70% concordance was achieved. Although all assays are suitable for TDM, significant differences were observed in both imprecision and agreement. Therapeutic consequences were acceptable when patients were divided in treatment categories, but this could be improved by assay standardization.

Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate.

PubMed

Marcoux, Julien; Champion, Thierry; Colas, Olivier; Wagner-Rousset, Elsa; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

2015-08-01

Antibody-drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM-MS) for the characterization of trastuzumab emtansine (T-DM1, Kadcyla(®)). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and combines the anti-HER2 antibody trastuzumab (Herceptin(®)), with the cytotoxic microtubule-inhibiting maytansine derivative, DM1. We show that native MS combined with high-resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM-MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T-DM1. © 2015 The Protein Society.

Impact of Roux-en-Y Gastric Bypass Surgery on Pharmacokinetics of Administered Drugs: Implications and Perspectives.

PubMed

Srinivas, Nuggehally R

Obesity epidemic has grown out of proportion with increased heath cost because of comorbidity associated with obesity. Due to mediocre benefit from pharmacological interventions, bariatric surgery popularly known as Roux-en-Y gastric bypass (RYGB) surgery has been increasingly practiced. Although RYGB significantly reduces body mass index, it also alters the local gut environment leading to significant changes in the drug absorption and bioavailability. The focus of the review is to present and critically evaluate case studies pertaining to pharmacokinetic data gathered till date on subjects after RYGB. A large portion of the reviewed examples showed reduced area under the concentration versus time curve [area under curve (AUC)] of drugs after RYGB (44%), whereas equal number of investigations showed increased (26%) or unaltered AUC (26%) after RYGB. There was one instance (4%), where the AUC was highly variable and individual subject dependent. Examination of drugs that showed reduced bioavailability suggested that a complex interplay of various factors such as solubility, permeability, metabolic enzymes, and transporters may have contributed for the observed effect. The increased bioavailability seemed to be related to permeability enhancement and generally in drug classes that have reduced metabolism. Based on the review, there is a significant risk of therapy failure for certain drugs because of subtherapeutic plasma levels. The need to readjust doses immediately after RYGB may be considered based on the therapeutic drug monitoring (TDM) findings. It seems prudent to initiate TDM for certain disease areas or drug classes until stable doses are established after RYGB through the appropriate pharmacokinetic and/or pharmacodynamics surrogate, as appropriate.

Definition of technology development missions for early space stations: Large space structures

NASA Technical Reports Server (NTRS)

Gates, R. M.; Reid, G.

1984-01-01

The objectives studied are the definition of the tested role of an early Space Station for the construction of large space structures. This is accomplished by defining the LSS technology development missions (TDMs) identified in phase 1. Design and operations trade studies are used to identify the best structural concepts and procedures for each TDMs. Details of the TDM designs are then developed along with their operational requirements. Space Station resources required for each mission, both human and physical, are identified. The costs and development schedules for the TDMs provide an indication of the programs needed to develop these missions.

A reconfigurable multicarrier demodulator architecture

NASA Technical Reports Server (NTRS)

Kwatra, S. C.; Jamali, M. M.

1991-01-01

An architecture based on parallel and pipline design approaches has been developed for the Frequency Division Multiple Access/Time Domain Multiplexed (FDMA/TDM) conversion system. The architecture has two main modules namely the transmultiplexer and the demodulator. The transmultiplexer has two pipelined modules. These are the shared multiplexed polyphase filter and the Fast Fourier Transform (FFT). The demodulator consists of carrier, clock, and data recovery modules which are interactive. Progress on the design of the MultiCarrier Demodulator (MCD) using commercially available chips and Application Specific Integrated Circuits (ASIC) and simulation studies using Viewlogic software will be presented at the conference.

Large Deployable Reflector (LDR) system concept and technology definition study. Analysis of space station requirements for LDR

NASA Technical Reports Server (NTRS)

Agnew, Donald L.; Vinkey, Victor F.; Runge, Fritz C.

1989-01-01

A study was conducted to determine how the Large Deployable Reflector (LDR) might benefit from the use of the space station for assembly, checkout, deployment, servicing, refurbishment, and technology development. Requirements that must be met by the space station to supply benefits for a selected scenario are summarized. Quantitative and qualitative data are supplied. Space station requirements for LDR which may be utilized by other missions are identified. A technology development mission for LDR is outlined and requirements summarized. A preliminary experiment plan is included. Space Station Data Base SAA 0020 and TDM 2411 are updated.

Demonstration and field trial of a resilient hybrid NG-PON test-bed

NASA Astrophysics Data System (ADS)

Prat, Josep; Polo, Victor; Schrenk, Bernhard; Lazaro, Jose A.; Bonada, Francesc; Lopez, Eduardo T.; Omella, Mireia; Saliou, Fabienne; Le, Quang T.; Chanclou, Philippe; Leino, Dmitri; Soila, Risto; Spirou, Spiros; Costa, Liliana; Teixeira, Antonio; Tosi-Beleffi, Giorgio M.; Klonidis, Dimitrios; Tomkos, Ioannis

2014-10-01

A multi-layer next generation PON prototype has been built and tested, to show the feasibility of extended hybrid DWDM/TDM-XGPON FTTH networks with resilient optically-integrated ring-trees architecture, supporting broadband multimedia services. It constitutes a transparent common platform for the coexistence of multiple operators sharing the optical infrastructure of the central metro ring, passively combining the access and the metropolitan network sections. It features 32 wavelength connections at 10 Gbps, up to 1000 users distributed in 16 independent resilient sub-PONs over 100 km. This paper summarizes the network operation, demonstration and field trial results.

Performance Characterization of the Air Force Transformational Satellite 12 kW Hall Thruster

NASA Technical Reports Server (NTRS)

Kamhawi, Hani; Haag, Thomas W.; Smith, Timothy; Herman, Daniel; Huang, Wensheng; Shastry, Rohit; Peterson, Peter; Mathers, Alex

2013-01-01

The STMD GCD ISP project is tasked with developing, maturing, and testing enabling human exploration propulsion requirements and potential designs for advanced high-energy, in-space propulsion systems to support deep-space human exploration and reduce travel time between Earth's orbit and future destinations for human activity. High-power Hall propulsion systems have been identified as enabling technologies and have been the focus of the activities at NASA Glenn-In-house effort to evaluate performance and interrogate operation of NASA designed and manufactured Hall thrusters. Evaluate existing high TRL EP devices that may be suitable for implementation in SEP TDM.

Rapid multispectral cw multiplexing technique for photon migration measurements

NASA Astrophysics Data System (ADS)

Siegel, Andrew M.; Boas, David A.

2001-06-01

A discussion of photon migration will introduce both some fundamental limitations and practical concerns which directly affect the design and construction of DOT instrumentation. The utility of four different multiplexing schemes will be discussed and then contrasted in light of these concerns. The relative merits of each scheme will be used to determine which measurements they are best suited for, given some of the realistic technical, legal, and practical issues common to the medical research community. Within this context, the unique advantages offered by a variant of time-division multiplexing; Pulse-TDM, will be introduced and explained.

Large Deployable Reflector (LDR) system concept and technology definition study. Analysis of space station requirements for LDR

NASA Astrophysics Data System (ADS)

Agnew, Donald L.; Vinkey, Victor F.; Runge, Fritz C.

1989-04-01

A study was conducted to determine how the Large Deployable Reflector (LDR) might benefit from the use of the space station for assembly, checkout, deployment, servicing, refurbishment, and technology development. Requirements that must be met by the space station to supply benefits for a selected scenario are summarized. Quantitative and qualitative data are supplied. Space station requirements for LDR which may be utilized by other missions are identified. A technology development mission for LDR is outlined and requirements summarized. A preliminary experiment plan is included. Space Station Data Base SAA 0020 and TDM 2411 are updated.

Definition of technology development missions for early Space Station satellite servicing. Volume 2: Technical

NASA Technical Reports Server (NTRS)

Cable, D. A.; Diewald, C. A.; Hills, T. C.; Parmentier, T. J.; Spencer, R. A.; Stone, G. E.

1984-01-01

Volume 2 contains the Technical Report of the approach and results of the Phase 2 study. The phase 2 servicing study was initiated in June 1983, and is being reported in this document. The scope of the contract was to: (1) define in detail five selected technology development missions (TDM); (2) conduct a design requirement analysis to refine definitions of satellite servicing requirements at the space station; and (3) develop a technology plan that would identify and schedule prerequisite precursor technology development, associated. STS flight experiments and space station experiments needed to provide onorbit validation of the evolving technology.

La tuberculose abdominale pseudo-tumorale

PubMed Central

El Barni, Rachid; Lahkim, Mohamed; Achour, Abdessamad

2012-01-01

Introduction L’objectif de ce travail est de rapporter cinq cas de tuberculose abdominale pseudo-tumorale afin d’en souligner les aspects diagnostiques et thérapeutiques. Cinq observations sont colligées dans le service de chirurgie générale de l’hôpital militaire Avicenne de Marrakech au cours de l’année 2007. Les aspects cliniques sont disparates. Ainsi, les auteurs ont noté un syndrome péritonéal dans un cas, une masse épigastrique dans un cas, une lésion suspect du sigmoïde dans un cas, une masse de la fosse iliaque droite dans un cas et une altération de l’état général avec fièvre dans le dernier cas. Un seul patient avaient bénéficié d’une biopsie scano-guidée et les quatre patients restants avaient été opérés. Une masse du méso côlon était notée dans le premier cas. Dans le second cas, l’aspect de la masse épigastrique et son siège avaient orienté vers une tumeur du grand omentum. Une localisation tuberculeuse péritonéale et sigmoïdienne avait été trouvée dans le troisième cas. Le diagnostic d’une tumeur du côlon droit était hautement suspect chez le patient séropositif qui avait présenté une péritonite post-opératoire et décédé à J + 3 dans un tableau de choc septique. Le siège et l’aspect nécrotique des lésions trouvées à la tomodensitométrie chez la seule patiente de l’étude avaient fait discuter en premier un lymphome. Même en l’absence d’antécédents de tuberculose pulmonaire, le diagnostic tuberculose abdominale pseudo-tumorale doit être évoqué surtout dans un pays d’endémie comme le notre et le recours à une laparotomie est justifié chaque fois que persiste un doute diagnostique ou en cas de complication. PMID:23330023

Comparison of the docetaxel concentration in human plasma measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS) and a nanoparticle immunoassay and clinical applications of that assay.

PubMed

Geng, Chunmei; Li, Pingli; Chen, Xuwang; Yuan, Guiyan; Guo, Nan; Liu, Huanjun; Zhang, Rui; Guo, Ruichen

2017-05-23

To determine the feasibility of using a nanoparticle immunoassay for clinical therapeutic drug monitoring (TDM) of docetaxel concentrations, a sensitive and simple method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established to measure the docetaxel concentration in human plasma and the results of LC-MS/MS and the immunoassay were compared. Docetaxel and paclitaxel (the internal standard, or IS) in human plasma were extracted through protein precipitation, separated on a Diamonsil C18 column (150 mm × 4.6 mm, 5 μm), ionized with positive ions, and detected with LC-MS/MS in multi-reaction monitoring (MRM) mode. Plasma samples from 248 cancer patients were assayed with LC-MS/MS and a nanoparticle immunoassay. Data from the samples were analyzed with the statistical software SPSS and the software MedCalc. Results indicated that the calibration curve of the validated method of LC-MS/MS was linear over the range of 10-2,000 ng/mL, with an lowest limit of quantitation (LLOQ) of 10 ng/mL, and the intra- and inter- day precision and accuracy were both < ± 15%. Comparison of the two methods indicated that results of the LC-MS/MS were closely related to those of the nanoparticle immunoassay, with a correlation coefficient (R) of 0.965 and acceptable 95% confidence intervals (CI) of ‒ 231.7-331.1 ng/mL. Overall, the established method of LC-MC/MS and the nanoparticle immunoassay were both suitable for measurement of the docetaxel concentration in human plasma, and the immunoassay was far more cost-effective and better at clinical TDM of docetaxel in clinical practice.

Therapeutic drug monitoring of beta-lactam antibiotics - Influence of sample stability on the analysis of piperacillin, meropenem, ceftazidime and flucloxacillin by HPLC-UV.

PubMed

Pinder, Nadine; Brenner, Thorsten; Swoboda, Stefanie; Weigand, Markus A; Hoppe-Tichy, Torsten

2017-09-05

Therapeutic drug monitoring (TDM) is a useful tool to optimize antibiotic therapy. Increasing interest in alternative dosing strategies of beta-lactam antibiotics, e.g. continuous or prolonged infusion, require a feasible analytical method for quantification of these antimicrobial agents. However, pre-analytical issues including sample handling and stability are to be considered to provide valuable analytical results. For the simultaneous determination of piperacillin, meropenem, ceftazidime and flucloxacillin, a high performance liquid chromatography (HPLC) method including protein precipitation was established utilizing ertapenem as internal standard. Long-term stability of stock solutions and plasma samples were monitored. Furthermore, whole blood stability of the analytes in heparinized blood tubes was investigated comparing storage under ambient conditions and 2-8°C. A calibration range of 5-200μg/ml (piperacillin, ceftazidime, flucloxacillin) and 2-200μg/ml (meropenem) was linear with r 2 >0.999, precision and inaccuracy were <9% and <11%, respectively. The successfully validated HPLC assay was applied to clinical samples and stability investigations. At -80°C, plasma samples were stable for 9 months (piperacillin, meropenem) or 13 months (ceftazidime, flucloxacillin). Concentrations of the four beta-lactam antibiotics in whole blood tubes were found to remain within specifications for 8h when stored at 2-8°C but not at room temperature. The presented method is a rapid and simple option for routine TDM of piperacillin, meropenem, ceftazidime and flucloxacillin. Whereas long-term storage of beta-lactam samples at -80°C is possible for at least 9 months, whole blood tubes are recommended to be kept refrigerated until analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Open-Label Randomized Trial of Titrated Disease Management for Patients with Hypertension: Study Design and Baseline Sample Characteristics

PubMed Central

Jackson, George L.; Weinberger, Morris; Kirshner, Miriam A.; Stechuchak, Karen M.; Melnyk, Stephanie D.; Bosworth, Hayden B.; Coffman, Cynthia J.; Neelon, Brian; Van Houtven, Courtney; Gentry, Pamela W.; Morris, Isis J.; Rose, Cynthia M.; Taylor, Jennifer P.; May, Carrie L.; Han, Byungjoo; Wainwright, Christi; Alkon, Aviel; Powell, Lesa; Edelman, David

2016-01-01

Despite the availability of efficacious treatments, only half of patients with hypertension achieve adequate blood pressure (BP) control. This paper describes the protocol and baseline subject characteristics of a 2-arm, 18-month randomized clinical trial of titrated disease management (TDM) for patients with pharmaceutically-treated hypertension for whom systolic blood pressure (SBP) is not controlled (≥140mmHg for non-diabetic or ≥130mmHg for diabetic patients). The trial is being conducted among patients of four clinic locations associated with a Veterans Affairs Medical Center. An intervention arm has a TDM strategy in which patients' hypertension control at baseline, 6, and 12 months determines the resource intensity of disease management. Intensity levels include: a low-intensity strategy utilizing a licensed practical nurse to provide bi-monthly, non-tailored behavioral support calls to patients whose SBP comes under control; medium-intensity strategy utilizing a registered nurse to provide monthly tailored behavioral support telephone calls plus home BP monitoring; and high-intensity strategy utilizing a pharmacist to provide monthly tailored behavioral support telephone calls, home BP monitoring, and pharmacist-directed medication management. Control arm patients receive the low-intensity strategy regardless of BP control. The primary outcome is SBP. There are 385 randomized (192 intervention; 193 control) veterans that are predominately older (mean age 63.5 years) men (92.5%). 61.8% are African American, and the mean baseline SBP for all subjects is 143.6mmHg. This trial will determine if a disease management program that is titrated by matching the intensity of resources to patients' BP control leads to superior outcomes compared to a low-intensity management strategy. PMID:27417982

Cryogenian (˜830 Ma) mafic magmatism and metamorphism in the northern Madurai Block, southern India: A magmatic link between Sri Lanka and Madagascar?

NASA Astrophysics Data System (ADS)

Teale, William; Collins, Alan S.; Foden, John; Payne, Justin L.; Plavsa, Diana; Chetty, T. R. K.; Santosh, M.; Fanning, Mark

2011-08-01

The northern Madurai Block, southern India, lies directly south of, and partly deformed by, the Palghat-Cauvery Shear Zone System (PCSS) - a potential suture of the Neoproterozoic Mozambique Ocean. The Kadavur gabbro-anorthosite complex lies south of the PCSS, in the northern Madurai Block, and crystallized at 829 ± 14 Ma (LA-ICPMS zircon data) in a supra-subduction zone setting. The complex contains zircon ɛHf(t) values of -12.5 to -8.6 that represent Palaeoproterozoic T(DM) model ages (2.3-2.5 Ga). These broadly agree with a whole rock neodymium T(DM) model age of 2287 Ma. Oxygen isotope δ 18O ratios range from 5.82‰ and 6.74‰. The parental magma for the gabbro-anorthosites are interpreted to be derived from a juvenile Neoproterozoic mantle contaminated by Mesoarchaean igneous infra-crustal sources. The gabbro-anorthosites intrude quartzites with dominantly Palaeoproterozoic detrital zircons that contain Neoarchaean and Mesoarchaean hafnium model ages. These quartzite zircons contain metamorphic rims that yield an age of 843 ± 23 Ma demonstrating the autochthonous nature of the gabbro-anorthosite complex. Later felsic magmatism is recorded by the 766 ± 8 Ma crystallisation age of the protolith of a felsic gneiss. Cryogenian magmatism in the Madurai Block is interpreted to form part of an extensive arc magmatic province within the southern East African Orogen that can be traced from central Madagascar, through southern India to the Wanni Complex of Sri Lanka. This province is interpreted to have formed above a south/west dipping subduction system as the Mozambique Ocean was subducted under the Neoproterozoic continent Azania.

Open-label randomized trial of titrated disease management for patients with hypertension: Study design and baseline sample characteristics.

PubMed

Jackson, George L; Weinberger, Morris; Kirshner, Miriam A; Stechuchak, Karen M; Melnyk, Stephanie D; Bosworth, Hayden B; Coffman, Cynthia J; Neelon, Brian; Van Houtven, Courtney; Gentry, Pamela W; Morris, Isis J; Rose, Cynthia M; Taylor, Jennifer P; May, Carrie L; Han, Byungjoo; Wainwright, Christi; Alkon, Aviel; Powell, Lesa; Edelman, David

2016-09-01

Despite the availability of efficacious treatments, only half of patients with hypertension achieve adequate blood pressure (BP) control. This paper describes the protocol and baseline subject characteristics of a 2-arm, 18-month randomized clinical trial of titrated disease management (TDM) for patients with pharmaceutically-treated hypertension for whom systolic blood pressure (SBP) is not controlled (≥140mmHg for non-diabetic or ≥130mmHg for diabetic patients). The trial is being conducted among patients of four clinic locations associated with a Veterans Affairs Medical Center. An intervention arm has a TDM strategy in which patients' hypertension control at baseline, 6, and 12months determines the resource intensity of disease management. Intensity levels include: a low-intensity strategy utilizing a licensed practical nurse to provide bi-monthly, non-tailored behavioral support calls to patients whose SBP comes under control; medium-intensity strategy utilizing a registered nurse to provide monthly tailored behavioral support telephone calls plus home BP monitoring; and high-intensity strategy utilizing a pharmacist to provide monthly tailored behavioral support telephone calls, home BP monitoring, and pharmacist-directed medication management. Control arm patients receive the low-intensity strategy regardless of BP control. The primary outcome is SBP. There are 385 randomized (192 intervention; 193 control) veterans that are predominately older (mean age 63.5years) men (92.5%). 61.8% are African American, and the mean baseline SBP for all subjects is 143.6mmHg. This trial will determine if a disease management program that is titrated by matching the intensity of resources to patients' BP control leads to superior outcomes compared to a low-intensity management strategy. Published by Elsevier Inc.

Physician, Patient and Contextual Factors Affecting Treatment Decisions in Older Adults with Cancer: A Literature Review

PubMed Central

Tariman, J. D.; Berry, D. L.; Cochrane, B.; Doorenbos, A.; Schepp, K.

2010-01-01

Purpose/Objectives To review physician, patient, and contextual factors that affect treatment decision-making in older adults diagnosed with cancer and relate these factors to theoretical models of decision-making. Data Sources PubMed (1966-April 2010), PsycINFO (1967-April 2010) and CINAHL (1982-April 2010) databases were searched to access relevant medical, psychological and nursing literature. Data Synthesis Physician factors in treatment decisions include physician personal beliefs and values, expertise, practice type, perception of lowered life expectancy, medical factors, power, and communication style. Patient factors include personal beliefs and values, ethnicity, decisional control preferences, previous health-related experience, perception of the decision-making process, and personal factors. Contextual factors include availability of caregiver, lack of insurance, poor financial status, and geographical barrier. The interplay of physician, patient, and contextual factors are not well understood. Existing models of decision-making are not sufficient to explicate TDM process in older adults diagnosed with cancer. Conclusions Clinical studies in older adult patient population using a longitudinal and prospective design are needed to examine real-time interplay of patient, physician, and contextual factors and to better understand how these divergent factors influenced actual treatment decisions. Implications for Nursing Oncology nurses can advocate for a patient’s autonomy during TDM by coaching them to seek evidence-based discussion of various treatment options, benefits and risks assessments, and truthful discussion of the probability of success for each treatment option from their physicians. Oncology nurses must promote an informed treatment decisions that are consistent with a patient’s personal preference and values within the limits of the patient’s personal contexts. PMID:22201670

GPIM AF-M315E Propulsion System

NASA Technical Reports Server (NTRS)

Spores, Ronald A.; Masse, Robert; Kimbrel, Scott; McLean, Chris

2014-01-01

The NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) Technology Demonstration Mission (TDM) will demonstrate an operational AF-M315E green propellant propulsion system. Aerojet-Rocketdyne is responsible for the development of the propulsion system payload. This paper statuses the propulsion system module development, including thruster design and system design; Initial test results for the 1N engineering model thruster are presented. The culmination of this program will be high-performance, green AF-M315E propulsion system technology at TRL 7+, with components demonstrated to TRL 9, ready for direct infusion to a wide range of applications for the space user community.

The Galileo Orbiter - Command and telemetry subsystems on their way to Jupiter

NASA Astrophysics Data System (ADS)

Erickson, James K.

1990-09-01

An overview is given of the Galileo command and telemetry subsystems, which exemplify the rigid time-synchronized systems required by TDM (time division multiplexing). The spacecraft clock is examined, along with some of the rationale for the development of the clock structure and timing to give a sense of the design imperatives for rigidly synchronized systems. Additional subjects include the structure of the science and engineering frames, emphasizing the subcommutated structure of the engineering frame and its relationship to the spacecraft clock; ground processing for and basic uses of the telemetry; the various message types used to transmit commands to the spacecraft; and the generation processes for the command message types.

Automated Performance Monitoring and Assessment for DCS Digital Systems

DTIC Science & Technology

1980-07-01

in an automated technical con-. trol environnrunt. j UNCLASSIFIED SECURITY CLASSIFICATION OF I , PAGE(Wh n O tD . E e d) ACKNOWLEDGEMENT This program...5-2 Second Level MUX TD -1193 Alarms 5-3 5-3 First Level MUX TD -1192 Alarms 5-4 5.-4 Submultiplexer TDM-1251 Alarms 5-5 5 RF Distribution System...i 0 (0: I- O)’dU 04i (0) 0 0a 04 U) (04 04r 04 r- (O 0) 0) 41 ~ 0) 0H (z (0 0) Q) 4J a r- ) -4’ iHQ ) w .41 Q) > 4-4 !O ~ -4 ) > 114 > 44 >4 UU O4 u

A Note About HARP's State Trimming Method

NASA Technical Reports Server (NTRS)

Butler, Ricky W.; Hayhurst, Kelly J.; Johnson, Sally C.

1998-01-01

This short note provides some additional insight into how the HARP program works. In some cases, it is possible for HARP to tdm away too many states and obtain an optimistic result. The HARP Version 7.0 manual warns the user that 'Unlike the ALL model, the SAME model can automatically drop failure modes for certain system models. The user is cautioned to insure that no important failure modes are dropped; otherwise, a non-conservative result can be given.' This note provides an example of where this occurs and a pointer to further documentation that gives a means of bounding the error associated with trimming these states.

Que nous apprennent les petits frères et sœurs sur les signes précoces d’autisme?1

PubMed Central

Rogers, Sally J.

2010-01-01

L’objectif de cette revue est de présenter une synthèse des réponses que l’on peut actuellement apporter à la question de savoir quelles sont les premières caractéristiques comportementales qui prédisent le développement de l’autisme. L’article se centre sur 5 points : la présence de Troubles du Spectre Autistique (TSA) dans des groupes de frères et sœurs puînés d’enfants déjà diagnostiqués, les patterns et caractéristiques du développement moteur, les patterns et caractéristiques du développement social et émotionnel, les patterns et caractéristiques de la communication intentionnelle verbale et non verbale, et les patterns qui marquent le début de comportements pathognomoniques de TSA. La discussion porte sur les aspects inattendus des résultats et les pistes de recherche nouvelles qu’ils peuvent engendrer. PMID:20890377

Prospective Evaluation of a Model-Based Dosing Regimen for Amikacin in Preterm and Term Neonates in Clinical Practice

PubMed Central

De Cock, R. F. W.; Allegaert, K.; Vanhaesebrouck, S.; Danhof, M.; Knibbe, C. A. J.

2015-01-01

Based on a previously derived population pharmacokinetic model, a novel neonatal amikacin dosing regimen was developed. The aim of the current study was to prospectively evaluate this dosing regimen. First, early (before and after second dose) therapeutic drug monitoring (TDM) observations were evaluated for achieving target trough (<3 mg/liter) and peak (>24 mg/liter) levels. Second, all observed TDM concentrations were compared with model-predicted concentrations, whereby the results of a normalized prediction distribution error (NPDE) were considered. Subsequently, Monte Carlo simulations were performed. Finally, remaining causes limiting amikacin predictability (i.e., prescription errors and disease characteristics of outliers) were explored. In 579 neonates (median birth body weight, 2,285 [range, 420 to 4,850] g; postnatal age 2 days [range, 1 to 30 days]; gestational age, 34 weeks [range, 24 to 41 weeks]), 90.5% of the observed early peak levels reached 24 mg/liter, and 60.2% of the trough levels were <3 mg/liter (93.4% ≤5 mg/liter). Observations were accurately predicted by the model without bias, which was confirmed by the NPDE. Monte Carlo simulations showed that peak concentrations of >24 mg/liter were reached at steady state in almost all patients. Trough values of <3 mg/liter at steady state were documented in 78% to 100% and 45% to 96% of simulated cases with and without ibuprofen coadministration, respectively; suboptimal trough levels were found in patients with postnatal age <14 days and current weight of >2,000 g. Prospective evaluation of a model-based neonatal amikacin dosing regimen resulted in optimized peak and trough concentrations in almost all patients. Slightly adapted dosing for patient subgroups with suboptimal trough levels was proposed. This model-based approach improves neonatal dosing individualization. PMID:26248375

Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO).

PubMed

Mellinghoff, Sibylle C; Panse, Jens; Alakel, Nael; Behre, Gerhard; Buchheidt, Dieter; Christopeit, Maximilian; Hasenkamp, Justin; Kiehl, Michael; Koldehoff, Michael; Krause, Stefan W; Lehners, Nicola; von Lilienfeld-Toal, Marie; Löhnert, Annika Y; Maschmeyer, Georg; Teschner, Daniel; Ullmann, Andrew J; Penack, Olaf; Ruhnke, Markus; Mayer, Karin; Ostermann, Helmut; Wolf, Hans-H; Cornely, Oliver A

2018-02-01

Immunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods. Since the last edition of antifungal prophylaxis recommendations of the German Society for Haematology and Medical Oncology in 2014, seven clinical trials regarding antifungal prophylaxis in patients with haematological malignancies have been published, comprising 1227 patients. This update assesses the impact of this additional evidence and effective revisions. Our key recommendations are the following: prophylaxis should be performed with posaconazole delayed release tablets during remission induction chemotherapy for AML and MDS (AI). Posaconazole iv can be used when the oral route is contraindicated or not feasible. Intravenous liposomal amphotericin B did not significantly decrease IFI rates in acute lymphoblastic leukaemia (ALL) patients during induction chemotherapy, and there is poor evidence to recommend it for prophylaxis in these patients (CI). Despite substantial risk of IFI, we cannot provide a stronger recommendation for these patients. There is poor evidence regarding voriconazole prophylaxis in patients with neutropenia (CII). Therapeutic drug monitoring TDM should be performed within 2 to 5 days of initiating voriconazole prophylaxis and should be repeated in case of suspicious adverse events or of dose changes of interacting drugs (BIItu). General TDM during posaconazole prophylaxis is not recommended (CIItu), but may be helpful in

Using pharmacokinetic modelling to improve prescribing practices of intravenous aminophylline in childhood asthma exacerbations.

PubMed

Cooney, Lewis; McBride, Antonia; Lilley, Andrew; Sinha, Ian; Johnson, Trevor N; Hawcutt, Daniel B

2017-04-01

To evaluate physiologically based pharmacokinetic modelling (PBPK) software in paediatric asthma patients using intravenous aminophylline. Prospective clinical audit of children receiving iv aminophylline (July 2014 to June 2016), and in-silico modelling using Simcyp software. Thirty-eight admissions (25 children) were included. Children with aminophylline levels ≥10 mg/l had equivalent clinical outcomes compared to those <10 mg/L, and adverse effects occurred in 57%. Therapeutic drug monitoring (TDM) data correlated well with PBPK model. PBPK modelling of a 5 mg/kg iv loading dose (≤18yr) shows a mean C max of 8.99 mg/L (5th-95th centiles 5.5-13.7 mg/L), with 70.3% of subjects <10 mg/L, 29.4% achieving 10-20 mg/L, and 0.1% > 20 mg/L. For an aminophylline infusion (0-12 y) of 1.0  mg/kg/h, the mean steady state infusion concentration was 16.4 mg/L, (5th-95th centiles 5.3-32 mg/L), with 26.8% having a serum concentration >20 mg/L. For 12-18yr receiving 0.5  mg/kg/h infusion, the mean steady state infusion concentration was 9.37 mg/L (5th-95th centiles 3.4-18 mg/L), with 59.8% having a serum concentration <10 mg/L. PBPK software modelling correlates well with clinical data. Current aminophylline iv loading dosage recommendations achieve levels <10 mg/l in 70% of children. Routine TDM may need altering as low risk of toxicity (>20 mg/l). Copyright © 2017 Elsevier Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morita, Daisuke; Miyamoto, Ayumi; Hattori, Yuki

Highlights: •Glucose monomycolate (GMM) is a marker glycolipid for active tuberculosis. •Tissue responses to GMM involved up-regulation of Th1-attracting chemokines. •Th1-skewed local responses were mounted at the GMM-injected tissue. -- Abstract: Trehalose 6,6′-dimycolate (TDM) is a major glycolipid of the cell wall of mycobacteria with remarkable adjuvant functions. To avoid detection by the host innate immune system, invading mycobacteria down-regulate the expression of TDM by utilizing host-derived glucose as a competitive substrate for their mycolyltransferases; however, this enzymatic reaction results in the concomitant biosynthesis of glucose monomycolate (GMM) which is recognized by the acquired immune system. GMM-specific, CD1-restricted T cellmore » responses have been detected in the peripheral blood of infected human subjects and monkeys as well as in secondary lymphoid organs of small animals, such as guinea pigs and human CD1-transgenic mice. Nevertheless, it remains to be determined how tissues respond at the site where GMM is produced. Here we found that rhesus macaques vaccinated with Mycobacterium bovis bacillus Calmette–Guerin mounted a chemokine response in GMM-challenged skin that was favorable for recruiting T helper (Th)1 T cells. Indeed, the expression of interferon-γ, but not Th2 or Th17 cytokines, was prominent in the GMM-injected tissue. The GMM-elicited tissue response was also associated with the expression of monocyte/macrophage-attracting CC chemokines, such as CCL2, CCL4 and CCL8. Furthermore, the skin response to GMM involved the up-regulated expression of granulysin and perforin. Given that GMM is produced primarily by pathogenic mycobacteria proliferating within the host, the Th1-skewed tissue response to GMM may function efficiently at the site of infection.« less

Geochronology and geochemistry of late Paleozoic-early Mesozoic igneous rocks of the Erguna Massif, NE China: Implications for the early evolution of the Mongol-Okhotsk tectonic regime

NASA Astrophysics Data System (ADS)

Li, Yu; Xu, Wen-Liang; Wang, Feng; Tang, Jie; Zhao, Shuo; Guo, Peng

2017-08-01

We undertook geochemical and geochronological studies on late Paleozoic-early Mesozoic igneous rocks from the Erguna Massif with the aim of constraining the early evolution of the Mongol-Okhotsk tectonic regime. Zircon crystals from nine representative samples are euhedral-subhedral, display oscillatory growth zoning, and have Th/U values of 0.14-6.48, indicating a magmatic origin. U-Pb dating of zircon using SIMS and LA-ICP-MS indicates that these igneous rocks formed during the Late Devonian (∼365 Ma), late Carboniferous (∼303 Ma), late Permian (∼256 Ma), and Early-Middle Triassic (246-238 Ma). The Late Devonian rhyolites, together with coeval A-type granites, formed in an extensional environment related to the northwestwards subduction of the Heihe-Nenjiang oceanic plate. Their positive εHf(t) values (+8.4 to +14.4) and Hf two-stage model ages (TDM2 = 444-827 Ma) indicate they were derived from a newly accreted continental crustal source. The late Carboniferous granodiorites are geochemically similar to adakites, and their εHf(t) values (+10.4 to +12.3) and Hf two-stage model ages (TDM2 = 500-607 Ma) suggest they were sourced from thickened juvenile lower crustal material, this thickening may be related to the amalgamation of the Erguna-Xing'an and Songnen-Zhangguangcai Range massifs. Rocks of the late Permian to Middle Triassic suite comprise high-K calc-alkaline monzonites, quartz monzonites, granodiorites, and monzogranites. These rocks are relatively enriched in light rare earth elements and large ion lithophile elements, and depleted in heavy rare earth elements and high field strength elements. They were emplaced, together with coeval porphyry-type ore deposits, along an active continental margin where the Mongol-Okhotsk oceanic plate was subducting beneath the Erguna Massif.

Geochemical and Nd-Sr-Pb isotope characteristics of synorogenic lower crust-derived granodiorites (Central Damara orogen, Namibia)

NASA Astrophysics Data System (ADS)

Simon, I.; Jung, S.; Romer, R. L.; Garbe-Schönberg, D.; Berndt, J.

2017-03-01

The 547 ± 7 Ma old Achas intrusion (Damara orogen, Namibia) includes magnesian, metaluminous to slightly peraluminous, calcic to calc-alkalic granodiorites and ferroan, metaluminous to slightly peraluminous, calc-alkalic to alkali-calcic leucogranites. For the granodiorites, major and trace element variations show weak if any evidence for fractional crystallization whereas some leucogranites are highly fractionated. Both, granodiorites and leucogranites are isotopically evolved (granodiorites: εNdinit: - 12.4 to - 20.5; TDM: 2.4-1.9; leucogranites: εNdinit: - 12.1 to - 20.6, TDM: 2.5-2.0), show similar Pb isotopic compositions, and may be derived from late Archean to Paleoproterozoic crustal source rocks. Comparison with melting experiments and simple partial melting modeling indicate that the granodiorites may be derived by extensive melting (> 40%) at 900-950 °C under water-undersaturated conditions (< 5 wt.% H2O) of felsic gneisses. Al-Ti and zircon saturation thermometry of the most primitive granodiorite sample yielded temperatures of ca. 930 °C and ca. 800 °C. In contrast to other lower crust-derived granodiorites and granites of the Central Damara orogen, the composition of the magma source is considered the first-order cause of the compositional diversity of the Achas granite. Second-order processes such as fractional crystallization at least for the granodiorites were minor and evidence for coupled assimilation-fractional crystallization processes is lacking. The most likely petrogenetic model involves high temperature partial melting of a Paleoproterozoic felsic source in the lower crust ca. 10-20 Ma before the first peak of regional high-temperature metamorphism. Underplating of the lower crust by magmas derived from the lithospheric mantle may have provided the heat for melting of the basement to produce anhydrous granodioritic melts.

Mantle evolution in the Variscides of SW England: Geochemical and isotopic constraints from mafic rocks

NASA Astrophysics Data System (ADS)

Dupuis, Nicolle E.; Murphy, J. Brendan; Braid, James A.; Shail, Robin K.; Nance, R. Damian

2016-06-01

The geology of SW England has long been interpreted to reflect Variscan collisional processes associated with the closure of the Rhenohercynian Ocean and the formation of Pangea. The Cornish peninsula is composed largely of Early Devonian to Late Carboniferous volcanosedimentary successions that were deposited in pre- and syn-collisional basins and were subsequently metamorphosed and deformed during the Variscan orogeny. Voluminous Early Permian granitic magmatism (Cornubian Batholith) is broadly coeval with the emplacement of ca. 280-295 Ma lamprophyric dykes and flows. Although these lamprophyres are well mapped and documented, the processes responsible for their genesis and their relationship with regional Variscan tectonic events are less understood. Pre- to syn-collisional basalts have intra-continental alkalic affinities, and have REE profiles consistent with derivation from the spinel-garnet lherzolite boundary. εNd values for the basalts range from + 0.37 to + 5.2 and TDM ages from 595 Ma to 705 Ma. The lamprophyres are extremely enriched in light rare earth elements, large iron lithophile elements, and are depleted in heavy rare earth elements, suggesting a deep, garnet lherzolite source that was previously metasomatised. They display εNd values ranging from - 1.4 to + 1.4, initial Sr values of ca. 0.706, and TDM ages from 671 Ma to 1031 Ma, suggesting that metasomatism occurred in the Neoproterozoic. Lamprophyres and coeval granite batholiths of similar chemistry to those in Cornwall occur in other regions of the Variscan orogen, including Iberia and Bohemia. By using new geochemical and isotopic data to constrain the evolution of the mantle beneath SW England and the processes associated with the formation of these post-collisional rocks, we may be able to gain a more complete understanding of mantle processes during the waning stages of supercontinent formation.

Multi-channel photon counting DOT system based on digital lock-in detection technique

NASA Astrophysics Data System (ADS)

Wang, Tingting; Zhao, Huijuan; Wang, Zhichao; Hou, Shaohua; Gao, Feng

2011-02-01

Relying on deeper penetration of light in the tissue, Diffuse Optical Tomography (DOT) achieves organ-level tomography diagnosis, which can provide information on anatomical and physiological features. DOT has been widely used in imaging of breast, neonatal cerebral oxygen status and blood oxygen kinetics observed by its non-invasive, security and other advantages. Continuous wave DOT image reconstruction algorithms need the measurement of the surface distribution of the output photon flow inspired by more than one driving source, which means that source coding is necessary. The most currently used source coding in DOT is time-division multiplexing (TDM) technology, which utilizes the optical switch to switch light into optical fiber of different locations. However, in case of large amounts of the source locations or using the multi-wavelength, the measurement time with TDM and the measurement interval between different locations within the same measurement period will therefore become too long to capture the dynamic changes in real-time. In this paper, a frequency division multiplexing source coding technology is developed, which uses light sources modulated by sine waves with different frequencies incident to the imaging chamber simultaneously. Signal corresponding to an individual source is obtained from the mixed output light using digital phase-locked detection technology at the detection end. A digital lock-in detection circuit for photon counting measurement system is implemented on a FPGA development platform. A dual-channel DOT photon counting experimental system is preliminary established, including the two continuous lasers, photon counting detectors, digital lock-in detection control circuit, and codes to control the hardware and display the results. A series of experimental measurements are taken to validate the feasibility of the system. This method developed in this paper greatly accelerates the DOT system measurement, and can also obtain the

Treatment of advanced HER2-positive breast cancer: 2018 and beyond.

PubMed

Pondé, Noam; Brandão, Mariana; El-Hachem, Georges; Werbrouck, Emilie; Piccart, Martine

2018-05-02

In the 1980s the importance of HER2 signalling to the aberrant behaviour of a subset of breast cancer cells was recognized for the first time and, consequently, a hitherto unknown subtype of breast cancer - HER2-positive (HER2+) breast cancer was identified. The development of the anti-HER2 class of drugs, first with trastuzumab, followed closely by lapatinib, pertuzumab, and T-DM1, has improved outcomes dramatically. Nevertheless, metastatic HER2+ breast cancer remains an incurable disease and new therapeutic options are needed. Additionally, the rapid changes in treatment standards 5 years ago have left unanswered numerous questions, including the "real-life" benefit of pertuzumab and T-DM1, since both the CLEOPATRA and EMILIA trials were conducted in populations that no longer exist in practice and, moreover, on the role of endocrine therapy in HER2+ disease. Furthermore, despite significant research efforts, including translational efforts and new imaging techniques, no predictive biomarkers have been clinically validated and therefore a more refined approach to treatment tailoring remains beyond our reach. Finally, a better understanding of resistance to currently existing anti-HER2 agents and of the role played by the microenvironment (e.g. immune system) and of interconnected signalling pathways (e.g. PI3K-mTOR-AKT) is at the core of clinical trials exploring new drugs and new regimens. These include the combination of anti-HER2 agents and anti-PD-1/PDL-1, PI3K inhibitors and CDK 4/6 inhibitors, as well as a host of new panHER inhibitors, drug antibody conjugates and anti-HER antibodies, which may, in coming years further push the boundaries of what we can do for our patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, Sean E., E-mail: semcguir@mdanderson.org; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas; Lee, Andrew K.

2013-01-01

Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specificmore » mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.« less

Improving the cost effectiveness of financial incentives in managing travel demand management (TDM) : [technical summary].

DOT National Transportation Integrated Search

2013-10-01

During the last two decades, financial incentives : have become common in efforts to reduce : demand on roadways by motivating commuters to : use alternative modes of transportation. Despite : common use, limited effort has been made to : understand ...

Demonstration of hybrid orbital angular momentum multiplexing and time-division multiplexing passive optical network.

PubMed

Wang, Andong; Zhu, Long; Liu, Jun; Du, Cheng; Mo, Qi; Wang, Jian

2015-11-16

Mode-division multiplexing passive optical network (MDM-PON) is a promising scheme for next-generation access networks to further increase fiber transmission capacity. In this paper, we demonstrate the proof-of-concept experiment of hybrid mode-division multiplexing (MDM) and time-division multiplexing (TDM) PON architecture by exploiting orbital angular momentum (OAM) modes. Bidirectional transmissions with 2.5-Gbaud 4-level pulse amplitude modulation (PAM-4) downstream and 2-Gbaud on-off keying (OOK) upstream are demonstrated in the experiment. The observed optical signal-to-noise ratio (OSNR) penalties for downstream and upstream transmissions at a bit-error rate (BER) of 2 × 10(-3) are less than 2.0 dB and 3.0 dB, respectively.

Macintosh II based space Telemetry and Command (MacTac) system

NASA Technical Reports Server (NTRS)

Dominy, Carol T.; Chesney, James R.; Collins, Aaron S.; Kay, W. K.

1991-01-01

The general architecture and the principal functions of the Macintosh II based Telemetry and Command system, presently under development, are described, with attention given to custom telemetry cards, input/output interfaces, and the icon driven user interface. The MacTac is a low-cost, transportable, easy to use, compact system designed to meet the requirements specified by the Consultative Committeee for Space Data Systems while remaining flexible enough to support a wide variety of other user specific telemetry processing requirements, such as TDM data. In addition, the MacTac can accept or generate forward data (such as spacecraft commands), calculate and append a Polynomial Check Code, and output these data to NASCOM to provide full Telemetry and Command capability.

Aborder la syllogomanie en médecine familiale

PubMed Central

Frank, Christopher; Misiaszek, Brian

2012-01-01

Résumé Objectif Examiner comment se présente la syllogomanie et suggérer aux médecins de famille des approches et des ressources pour sa prise en charge. Source des données On a fait une recension dans PubMed de 2001 à mai 2011. Le mot-clé MeSH hoarding a été utilisé pour identifier la recherche à ce sujet et passer en revue les articles portant sur les aspects neuropsychologiques de l’accumulation pathologique, son diagnostic et son traitement. Message principal La syllogomanie ou accumulation pathologique est souvent un problème peu évident en médecine familiale. Les patients qui ont une syllogomanie se présentent souvent à cause d’un événement sentinelle comme une chute ou un incendie à leur domicile. Quoique la syllogomanie soit traditionnellement associée à un trouble obsessionnel-compulsif, le plus souvent, les patients ont une maladie systémique secondaire associée à un comportement syllogomaniaque ou ont une syllogomanie en l’absence de caractéristiques compulsives considérables. On s’attend à ce que la syllogomanie soit incluse dans la 5e édition du Manuel diagnostique et statistique des troubles mentaux. Si possible, il vaut mieux prendre en charge la syllogomanie selon une approche multidisciplinaire. Un nombre grandissant de centres offrent des programmes pour améliorer les symptômes ou réduire les dangers. Il a été démontré que la prise en charge pharmacologique a une certaine utilité pour traiter les causes secondaires. Chez les personnes plus âgées, des problèmes comme la démence, la dépression et la toxicomanie sont souvent associés à un comportement d’accumulation pathologique. Il faudrait essayer de maintenir les patients à domicile dans la mesure du possible, mais l’évaluation de la capacité devrait guider l’approche à adopter. Conclusion L’accumulation pathologique est plus fréquente que ne le pensent les médecins de famille. Si on identifie une syllogomanie, il faudrait

Profil épidémiologique et clinique de la tuberculose dans la zone de santé de Lubumbashi (RD Congo)

PubMed Central

Ngama, Christian Kakisingi; Muteya, Michel Manika; Lukusha, Yves Isango Idi; Kapend, Serge Matanda; Tshamba, Henri Mundongo; Makinko, Paul Ilunga; Mulumba, Claude Mwamba; Kalala, Liévin Kapend a

2014-01-01

Introduction L'objectif de notre travail était de déterminer la distribution sociodémographique des patients tuberculeux, les types de tuberculose en fonction de la localisation de la maladie et déterminer l'issue thérapeutique des patients en fonction de différentes localisations. Méthodes C'est une étude descriptive transversale des patients diagnostiqués et traités pour tuberculose du 1er Janvier 2010 au 30 Juin 2011 dans la zone de santé de Lubumbashi. Une de 11 zones de santé du District de Lubumbashi dans la province du Katanga(RD Congo). Ont été inclus tous les patients tuberculeux de nationalité congolaise consultés dans la zone de santé pendant la période d’étude. L’âge, le sexe, la commune de résidence, le tableau clinique à la première consultation et les résultats des examens de laboratoire des crachats par la coloration Ziehl-Neelsen ont été les paramètres d'analyse. Résultats Nous avons enregistré 708 patients tuberculeux soit une prévalence de 0.5%. Le sexe masculin représentait 58.78% contre 41.25% de sexe féminin avec un sexe ratio de 1.42 en faveur du sexe masculin. La moyenne d’âge était de 33±;15 ans. La majorité des patients soit 54.79 appartiennent à la tranche d’âge entre 21 et 40 ans. La tuberculose extra pulmonaire a représenté 51.8% contre 50.2% de tuberculose pulmonaire dont 31.9% à bacilloscopie positive. Le décès a intéressé les patients bacillifères puis qu'il y a 5 fois plus de décès liés à une tuberculose pulmonaire à microscopie positive qu'aux autres formes de tuberculose (OR (IC 95%): 5.27 (2.92-9.59, p = 0.00). La majorité des patients résidaient les communes Lubumbashi (41.7%) et Kampemba (23.2%). Conclusion La tuberculose extrapulmonaire (pleurale) a été plus rencontrée que la tuberculose pulmonaire et c'est cette dernière forme de tuberculose qui a entrainé beaucoup plus de décès. Ce qui nécessite une amélioration du système de santé de prise en charge des

150 kW Class Solar Electric Propulsion Spacecraft Power Architecture Model

NASA Technical Reports Server (NTRS)

Csank, Jeffrey T.; Aulisio, Michael V.; Loop, Benjamin

2017-01-01

The National Aeronautics and Space Administration (NASA) Solar Electric Propulsion Technology Demonstration Mission (SEP TDM), in conjunction with PC Krause and Associates, has created a Simulink-based power architecture model for a 50 kilo-Watt (kW) solar electric propulsion system. NASA has extended this model to investigate 150 kW solar electric propulsion systems. Increasing the power capability to 150 kW is an intermediate step to the anticipated power requirements for Mars and other deep space applications. The high-power solar electric propulsion capability has been identified as a critical part of NASA’s future beyond-low-Earth-orbit for human-crewed exploration missions. This paper presents four versions of a 150 kW architecture, simulation results, and a discussion of their merits.

Fibre Optic Mechanical Sensors For Aerospace Applications

NASA Astrophysics Data System (ADS)

Batchellor, C. R.; Dakin, J. P.; Pearce, D. A. J.

1989-04-01

A fiber optic multisensor methane detection system matched to topology and environment of a coal mine is reported. The system involves time domain multiplexed (TDM) methane sensors based on selective absorption of source radiation by atomic or molecular species in the gas sensing heads. A two-wavelength ratiometric approach allows simple self referencing, cancels out errors arising from other contaminants, and improves the measurement contrast. The laboratory system consists of a high radiance LED source, multimode fiber, optical sensing head, optical bandpass filters, and involves synchronous detection with low noise photodiodes and a lock-in amplifier. Detection sensitivity upon spectral resolution of the optical filters has also been investigated and described. The system performance was evaluated and the results are presented.

Self-Referenced Fiber Optic System For Remote Methane Detection

NASA Astrophysics Data System (ADS)

Zientkiewicz, Jacek K.

1989-10-01

The paper discusses a fiber optic multisensor methane detection system matched to topology and environment of the underground mine. The system involves time domain multiplexed (TDM) methane sensors based on selective absorption of source radiation by atomic/molecular species in the gas sensing heads. A two-wavelength ratiometric approach allows simple self-referencing, cancels out errors arising from other contaminants, and improves the measurement contrast. The laboratory system consists of a high radiance LED source, multimode fiber, optical sensing head, optical bandpass filters, and involves synchronous detection with low noise photodiodes and a lock-in amplifier. Detection sensitivity versus spectral resolution of the optical filters has also been investigated and described. The system performance was evaluated and the results are presented.

On board processing for future satellite communications systems: Comparison of FDM, TDM and hybrid accessing schemes

NASA Technical Reports Server (NTRS)

Berk, G.; Jean, P. N.; Rotholz, E.

1982-01-01

Several satellite uplink and downlink accessing schemes for customer premises service are compared. Four conceptual system designs are presented: satellite-routed frequency division multiple access (FDMA), satellite-switched time division multiple access (TDMA), processor-routed TDMA, and frequency-routed TDMA, operating in the 30/20 GHz band. The designs are compared on the basis of estimated satellite weight, system capacity, power consumption, and cost. The systems are analyzed for fixed multibeam coverage of the continental United States. Analysis shows that the system capacity is limited by the available satellite resources and by the terminal size and cost.

Acides gras oméga-3 et dyslexie

PubMed Central

Zelcer, Michal; Goldman, Ran D.

2015-01-01

Résumé Question À la lumière de la hausse du nombre d’enfants d’âge scolaire ayant reçu un diagnostic de dyslexie, quel est le rôle des suppléments d’acides gras oméga-3 dans la prise en charge de cette affection? Réponse La dyslexie est le trouble d’apprentissage le plus répandu et elle est connue pour ses causes multifactorielles. De récentes données probantes pointent vers une corrélation entre le métabolisme défectueux des acides gras polyinsaturés et les troubles de neurodéveloppement, tels que la dyslexie. Bien que l’administration de suppléments d’acides gras oméga-3 aux enfants dyslexiques ait fait l’objet d’études, les données probantes sont limitées. Les critères diagnostiques homogènes de dyslexie, les mesures objectives de carence en acides gras et la surveillance étroite de l’apport alimentaire ne sont que quelques-uns des facteurs pouvant améliorer la qualité de la recherche dans ce domaine.

[Efficacy of therapeutic monitoring of cyclosporine through C2 and AUC(0-4) during the first 24 months following kidney transplantation].

PubMed

Vavić, Neven; Ignjatović, Ljiljana; Drasković, Biljana; Hrvacević, Rajko; Kovacević, Zoran; Paunić, Zoran

2008-02-01

Cyclosporine (CyA) therapeutic drug monitoring (TDM) through the measurement of drug concentration in blood two hours after the administration (C2), and/or according to the calculated value of the area under the concentration-time curve during the first four hours following administration (AUC(0-4)) shows favourable correlation with clinical manifestations in patients with kidney transplantation (Tx). The aim of this study was to analyze clinical efficiency and usability of TDM CyA through C2 and AUC(0-4) in the group of our kidney transplanted patients during the first 24 months following Tx. The study included 50 patients who had undergone kidney Tx using living donors at the Clinic of Nephrology Military Medical Academy, from 1996 to 2003. The first group (group C2) consisted of 25 patients in whom CyA dose was adjusted according to the target C2 and AUC(0-4) (calculated by the regression formula based on C1, C2 and C3), while the second group (group CO) consisted of 25 "historical" patients in whom the dose of this drug was adjusted according to CO. On the 6th day the average daily dose of CyA in the group C2 was 10.1 +/- 0.8 mg/kg, while in the group CO it was 7.6 +/- 1.6 (p < 0.05). One month following the Tx, daily drug doses were quite similar in the two observed groups (6.2 mg/kg in CO and 6.6 mg/kg in group C2, p = NS). In the group C2, target C2/AUC(0-4) (C2 1700 ng/ml, AUC(0-4) 4400 ng h/ml) on the sixth day was achieved in 36.3%, and on day 14 in 76% of the patients. The target AUC(0-4), in relation with C2, in each observed time interval was reached in the higher number of patients. Maximum CyA concentrations in the group C2 were registered 2 hours following the administration (C2), when compared with the concentrations registered after the first and the third hour (C1 and C3). In relation with C1 and C3, C2 concentration correlated most favorably with AUC(0-4), both on the 6th (r = 0.85) and on the 9th day (r = 0.87). During the first three months

Long-term prognosis in patients with type 1 and 2 diabetes mellitus after coronary artery bypass grafting.

PubMed

Holzmann, Martin J; Rathsman, Björn; Eliasson, Björn; Kuhl, Jeanette; Svensson, Ann-Marie; Nyström, Thomas; Sartipy, Ulrik

2015-04-28

Patients with diabetes mellitus (DM) have an increased risk of adverse outcomes after coronary artery bypass grafting (CABG). Previous studies have reported prognosis in relation to treatment with or without insulin, and not to the type of diabetes. This study investigated long-term survival in patients with type 1 DM (T1DM) and type 2 DM (T2DM) following CABG. We included all patients from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register who underwent primary isolated CABG in Sweden during 2003 through 2013. We identified patients with T1DM or T2DM in the Swedish National Diabetes Register. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause mortality in patients with T1DM or T2DM. In total, 39,235 patients were included, of whom 725 (1.8%) had T1DM and 8,208 (21%) had T2DM. Patients with TDM1 were younger (59 vs. 67 years), had reduced kidney function (31% vs. 24%), and had peripheral vascular disease (21% vs. 11%) more often than patients with TDM2 or no diabetes. During a mean follow-up of 5.9±3.2 years (230,085 person-years), 6,765 (17%) patients died. Among patients with T1DM, 152 (21%) died, and among patients with T2DM, 1,549 (19%) died. Adjusted hazard ratio (95% confidence interval) for death in patients with T1DM and T2DM, compared with patients without diabetes, were 2.04 (1.72 to 2.42), and 1.11 (1.05 to 1.18), respectively. Patients with T1DM had more than double the long-term risk of death after CABG compared with patients without diabetes. The long-term risk of death in patients with T2DM was only slightly increased. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Inter- and Intraindividual Variation of Methylphenidate Concentrations in Serum and Saliva of Patients with Attention-Deficit/Hyperactivity Disorder.

PubMed

Preiskorn, Joshua; Studer, Sophie; Rauh, Reinhold; Lukačin, Richard; Geffert, Christoph; Fleischhaker, Christian; Clement, Hans-Willi; Schulz, Eberhard; Biscaldi, Monica

2018-05-03

BackgroundTherapeutic drug monitoring (TDM) is becoming increasingly important in psychiatric therapy; especially in children. However, for several reasons, it cannot yet be implemented as a daily routine in clinical or outpatient settings. To evaluate new, non-invasive procedures; blood and saliva (oral fluid) samples were collected from patients with attention-deficit/hyperactivity disorder (ADHD) who were also being administered methylphenidate (MPH). The study's main purposes were to correlate MPH concentrations in serum and saliva between subjects; and to analyze intraindividual variation of serum concentration.MethodsThirty-six ADHD patients (27 children and 9 adults) on methylphenidate medication were included for drug analysis. MPH and its major metabolite ritalinic acid (RA) were quantified using LC-MS/MS measurements. The following correlations were investigated: 1) between drug concentrations in serum and saliva, and 2) between pH value and saliva to serum concentration ratio. Furthermore, the mean intraindividual MPH-concentration fluctuation in saliva under constant frame conditions was analyzed.ResultsAfter quantification, MPH concentrations were approximately 5 times higher in the saliva than in the serum, while the concentrations of RA were much lower in saliva. We found significant correlations between concentrations of MPH in serum and saliva (r=0.51, p<0.05). Saliva MPH measures, compared to serum, were pH-dependent(r=-0.56, p<0.01). Daily coefficient of variance of saliva concentration in children taking constant medication was 27.3% (11%-42 %), while the coefficient of variance for the ratio of saliva to serum was 122% (2%-2060%).ConclusionsOur data indicates that the interindividual variation in saliva to serum concentrations is rather high, while the intraindividual variation is fairly low, as already shown in the literature for repeated citalopram serum measurements. Saliva may well serve as an alternative matrix for TDM of MPH in ADHD

A source-depleted Early Jurassic granitic pluton from South China: Implication to the Mesozoic juvenile accretion of the South China crust

NASA Astrophysics Data System (ADS)

Zhou, Zuo-Min; Ma, Chang-Qian; Wang, Lian-Xun; Chen, Shu-Guang; Xie, Cai-Fu; Li, Yong; Liu, Wei

2018-02-01

Source-depleted granites were rarely reported in South China. Hereby we identified such a granitic pluton, the Tiandong pluton, at Northeastern Guangdong province in Southeastern (SE) China. Whole-rock Sr-Nd and zircon Hf isotopes of the Tiandong granites both revealed obviously depleted source signatures, with initial isotopic values of initial 87Sr/86Sr = 0.7032-0.7040, εNd(t) = 1.1-1.5, and εHf(t) = 6-13, respectively. Zircon U-Pb dating implied the granite was intruded in Early Jurassic (188 Ma). The dominant minerals of the Tiandong granite consist of K-feldspar, plagioclase, quartz and biotite, with accessory mineral assemblage of apatite + zircon + magnetite. Based on the mineralogy and the depleted isotopic signature, the granites chemically show I-type affinity such as low Zr + Nb + Ce + Y (131.6 to 212.2), 104 × Ga/Al (2.12-2.27), A/CNK values < 1.1 (0.97-1.03), corundum molecule < 1 (0-0.55) and extremely low P2O5 contents (0.05 wt%). The one-stage and two-stage depleted mantle Nd model ages (TDM = 0.89 to 0.84 Ga, T2DM = 0.88 to 0.85 Ga) are consistent. TDM(Hf) values of 0.31-0.63 Ga are also indistinguishable from T2DM(Hf) values of 0.35-0.75 Ga. The Nd and Hf isotopic compositions confirm that the Tiandong granites are juvenile crustal accretion but decoupled Nd-Hf isotopic systems. The juvenile crust is likely to originate from a mixed source of the primary asthenospheric mantle and the subordinate EMII. Combined with early studies of adjacent rocks, we propose that the early Jurassic ( 200-175 Ma) magmatism as evidenced by the Tiandong granites might be driven by upwelling of asthenosphere and subsequent underplating of mafic melts in an intra-plate extensional setting as a response to far-field stress during early stage subduction of the paleo-pacific plate.

Model-based clinical dose optimization for phenobarbital in neonates: An illustration of the importance of data sharing and external validation.

PubMed

Völler, Swantje; Flint, Robert B; Stolk, Leo M; Degraeuwe, Pieter L J; Simons, Sinno H P; Pokorna, Paula; Burger, David M; de Groot, Ronald; Tibboel, Dick; Knibbe, Catherijne A J

2017-11-15

Particularly in the pediatric clinical pharmacology field, data-sharing offers the possibility of making the most of all available data. In this study, we utilize previously collected therapeutic drug monitoring (TDM) data of term and preterm newborns to develop a population pharmacokinetic model for phenobarbital. We externally validate the model using prospective phenobarbital data from an ongoing pharmacokinetic study in preterm neonates. TDM data from 53 neonates (gestational age (GA): 37 (24-42) weeks, bodyweight: 2.7 (0.45-4.5) kg; postnatal age (PNA): 4.5 (0-22) days) contained information on dosage histories, concentration and covariate data (including birth weight, actual weight, post-natal age (PNA), postmenstrual age, GA, sex, liver and kidney function, APGAR-score). Model development was carried out using NONMEM ® 7.3. After assessment of model fit, the model was validated using data of 17 neonates included in the DINO (Drug dosage Improvement in NeOnates)-study. Modelling of 229 plasma concentrations, ranging from 3.2 to 75.2mg/L, resulted in a one compartment model for phenobarbital. Clearance (CL) and volume (V d ) for a child with a birthweight of 2.6kg at PNA day 4.5 was 0.0091L/h (9%) and 2.38L (5%), respectively. Birthweight and PNA were the best predictors for CL maturation, increasing CL by 36.7% per kg birthweight and 5.3% per postnatal day of living, respectively. The best predictor for the increase in V d was actual bodyweight (0.31L/kg). External validation showed that the model can adequately predict the pharmacokinetics in a prospective study. Data-sharing can help to successfully develop and validate population pharmacokinetic models in neonates. From the results it seems that both PNA and bodyweight are required to guide dosing of phenobarbital in term and preterm neonates. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Neoarchean crustal growth and Paleoproterozoic reworking in the Borborema Province, NE Brazil: Insights from geochemical and isotopic data of TTG and metagranitic rocks of the Alto Moxotó Terrane

NASA Astrophysics Data System (ADS)

Montefalco de Lira Santos, Lauro Cézar; Dantas, Elton Luiz; Cawood, Peter A.; José dos Santos, Edilton; Fuck, Reinhardt A.

2017-11-01

Pre-Brasiliano rocks in the Borborema Province (NE Brazil) are concentrated in basement blocks, such as the Alto Moxotó Terrane. Petrographic, geochemical, and U-Pb and Sm-Nd isotopic data from two basement metagranitic suites within the terrane provide evidence for Neoarchean (2.6 Ga) and Paleoproterozoic (2.1 Ga) subduction-related events. The Riacho das Lajes Suite is made of medium to coarse-grained hornblende and biotite-bearing metatonalites and metamonzogranites. Whole-rock geochemical data indicate that these rocks represent calcic, magnesian and meta-to peraluminous magmas, and have unequivocal affinities with high-Al low-REE tonalite-trondhjemite-granodiorites (TTG). Zircon U-Pb data from two samples of this suite indicate that they were emplaced at 2.6 Ga, which is the first discovered Archean crust in the central portion of the province. The suite has Neoarchean depleted mantle model ages (TDM) and slightly negative to positive εNd(t), indicating slight crustal contamination. The overall geochemical and isotopic data indicate a Neoarchean intraoceanic setting for genesis of the Riacho das Lajes magma via melting of basaltic oceanic crust submitted to high-pressure eclogite facies conditions. On the other hand, the Floresta Suite comprise metaigneous rocks, which are mostly tonalitic and granodioritic in composition. Geochemical data indicate that this suite shares similarities with calcic to calc-alkalic magmas with magnesian and metaluminous to slightly peraluminous characteristics. Other geochemical features include anomolous Ni, V and Cr contents, as well as high large-ion litophile elements (LILE) values. The suite yields U-Pb zircon ages of approximately 2.1 Ga, Archean to Paleoproterozoic TDM ages, and negative to positive εNd(t) values, suggesting both new crust formation and reworking of Archean crust, in addition to mantle metasomatism, reflecting mixed sources. The most likely tectonic setting for the Floresta Suite magmas involved crustal

Detrital zircon U-Pb geochronology and whole-rock Nd-isotope constraints on sediment provenance in the Neoproterozoic Sergipano orogen, Brazil: From early passive margins to late foreland basins

NASA Astrophysics Data System (ADS)

Oliveira, E. P.; McNaughton, N. J.; Windley, B. F.; Carvalho, M. J.; Nascimento, R. S.

2015-11-01

SHRIMP U-Pb detrital zircon geochronology and depleted-mantle Nd-model ages of clastic rocks were combined to understand the sediment provenance in the Neoproterozoic Sergipano Belt. The Sergipano is the main orogenic belt between the Borborema province and the São Francisco Craton, eastern South America; it is divisible into several lithostratigraphic domains from North to South: Canindé, Poço Redondo-Marancó, Macururé, Vaza Barris, and Estância. Nd model ages (TDM) and detrital zircon U-Pb SHRIMP geochronology indicate that the protoliths of clastic metasedimentary rocks from the Marancó and Macururé domains were mostly derived from eroded late Mesoproterozoic to early Neoproterozoic rocks (1000-900 Ma), whereas detritus of similar rocks from the Canindé domain came from a younger source (ca. 700 Ma and 1000 Ma). Samples from the Vaza Barris domain show the greatest scatter of both TDM and zircon ages amongst all domains, but with important contributions from Proterozoic sources (690-1050 Ma and ca. 2100 Ma) and less from Archaean sources. The Estância domain samples have zircon population peaks at 570 Ma, 600 Ma, and 920-980 Ma, with a few older grains; one diamictite contains only ca. 2150 Ma zircon grains. Our preliminary results support a model in which sediments of the Marancó and Macururé domains were deposited on a continental margin of the ancient Borborema plate before its collision with the São Francisco Craton; the Canindé domain is likely to be an aborted Neoproterozoic rift assemblage within the southern part of the Borborema plate (Pernambuco-Alagoas massif). The basal units of the Vaza Barris and Estância domains have clast sources from the São Francisco Craton and are best interpreted as passive margin sediments. However, the uppermost units of the Estância and Vaza Barris domains come from foreland basins formed during collision of Borborema plate with the São Francisco Craton.

Therapeutic drug monitoring of quetiapine in adolescents with psychotic disorders.

PubMed

Gerlach, M; Hünnerkopf, R; Rothenhöfer, S; Libal, G; Burger, R; Clement, H-W; Fegert, J M; Wewetzer, Ch; Mehler-Wex, C

2007-03-01

There are developmental and age-dependent differences in the pharmacokinetics and the pharmacodynamics of drugs in children and adolescents. Therefore, there is a need to carry out standardised studies to find out therapeutic ranges of plasma/serum concentrations in psychopharmacotherapy of children and adolescents. The aim of this prospective study was to examine the relationship between quetiapine serum concentration, treatment response, and side effects in a clinical setting to elucidate the age-specific therapeutic range of quetiapine in adolescents. Over a period of two years, therapeutic drug monitoring (TDM) was routinely performed in 21 adolescents (mean age was 15.9+/-1.5 years, 57% male) with psychotic disorders according to the guidelines of the AGNP TDM expert group. The psychopathology was assessed by using the Clinical Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS). Side effects were assessed by using the Dose Record and Treatment Emergent Symptom Scale (DOTES). Trough quetiapine concentrations were determined under steady state conditions after multiple-dose regimes (median 600 mg/day; range 100-800 mg/day). There was a marked variability of the serum concentrations, ranging from 19-877 ng/ml. 40.8% of the determined values were below and 24.5% above the therapeutic range (70-170 ng/ml) recommended for adults. None of the patients had severe side effects. We found a weak correlation between dose and serum concentration of quetiapine and no relationship between serum concentration and treatment response. There are several limitations of this study, and our results should therefore be interpreted with caution. Notwithstanding, differences in the ontogenesis of pharmacokinetics and pharmacodynamics may be the reason for the difference in the relationship between blood concentrations and therapeutic response to psychopharmaca in children, adolescents and adults. Further studies using larger samples, baseline assessment of

Levofloxacin dosing regimen in severely morbidly obese patients (BMI ≥40 kg/m(2)) should be guided by creatinine clearance estimates based on ideal body weight and optimized by therapeutic drug monitoring.

PubMed

Pai, Manjunath P; Cojutti, Piergiorgio; Pea, Federico

2014-08-01

Levofloxacin is a commonly prescribed antimicrobial where recommendations exist to reduce doses for renal impairment but not to increase doses for augmented renal function. Morbidly obese patients are increasing in prevalence, and represent a population that can have augmented renal function requiring higher-than-standard doses. The current investigation was performed to characterize the pharmacokinetics (PK) and evaluate the influence of alternate body size descriptors and renal function as predictors of levofloxacin clearance (CL) and the area under the curve over 24 h (AUC24). A database of patients undergoing levofloxacin therapeutic drug monitoring (TDM) were queried to identify patients ≥18 years of age with a body mass index ≥40 kg/m(2). A maximum a posteriori probability Bayesian approach using a two-compartment linear PK model was used to estimate individual PK parameters and AUC24. A total of 394 concentration-time data points (peaks and trough) from 68 patients between 98 and 250 kg were evaluated. The median (5th, 95th percentile) daily dose and AUC24 was 1,000 (250, 1,500) mg and 90.7 (44.4, 228) mg·h/L, respectively. Levofloxacin CL was significantly (p < 0.05) related to height but not weight. As a result, levofloxacin CL was best related (R (2) = 0.57) to creatinine CL (CLcr) estimated by the Cockcroft-Gault (CG) equation and ideal body weight (IBW) because IBW is a height transformation. An empiric four-category daily-dose regimen (500, 750, 1,000, 1,250 mg) stratified by CLcr (CG-IBW) is expected to have >90 % probability of achieving an AUC24 of 50-150 mg·h/L in morbidly obese patients. Subsequent application of TDM and integration with pathogen-specific information could then be applied to tailor the levofloxacin regimen. The proposed approach serves as a relevant alternative to the current fixed-dosing paradigm of levofloxacin in the morbidly obese.

Sound component duration of healthy human pharyngoesophageal swallowing: a gender comparison study.

PubMed

Morinière, Sylvain; Beutter, Patrice; Boiron, Michèle

2006-07-01

Cervical auscultation is a noninvasive technique for studying swallowing that was first used in the 1960s. The aim of our study was to use the numeric acoustic recording technique for analyzing swallowing sound signals in healthy subjects while they ingested a defined volume and consistency of a specific substance. Twenty males and ten females were included in the study and given 10 ml of a barium suspension to swallow. A microphone was placed on the skin overlying the lateral border of the trachea, directly under the inferior border of the cricoid, and connected to a computer. For each sound recording, the total duration of the sound (td), the number (n) of sound components (SC), the duration of each SC (c1, c2, c3,...), and the intervals (i1, i2,...) between the SCs were measured. For all the recordings, the mean durations of acoustic parameters (TDm, C1m, C2m, C3m, I1m, I2m) were calculated and compared by using Student's t test. In the 20 male subjects, the mean acoustic parameters were calculated (MTDm, MC1m, MC2m, MC3m, MI1m, MI2m) and compared with the mean acoustic parameters (FTDm, FC1m, FC2m, FC3m, FI1m, FI2m) in the ten females by using a Wilcoxon nonparametric statistical test. We were able to interpret 80% of the recordings. The TDm was 710 +/- 28 ms. Three main SCs were detected: C1m = 100 +/- 56, C2m = 150 +/- 90, C3m = 80 +/- 54 ms; I1m = 100 +/- 66, I2m = 190 +/- 120 ms. No significant difference in these parameters was observed with respect to gender. This study enabled us to decompose the swallowing sounds into three main SCs and to quantify their normal durations. These results should prove useful for the assessment of sound variations in pathologic conditions.

Exogenous application of plant growth regulators (PGRs) induces chilling tolerance in short-duration hybrid maize.

PubMed

Waqas, Muhammad Ahmed; Khan, Imran; Akhter, Muhammad Javaid; Noor, Mehmood Ali; Ashraf, Umair

2017-04-01

Chilling stress hampers the optimal performance of maize under field conditions precipitously by inducing oxidative stress. To confer the damaging effects of chilling stress, the present study aimed to investigate the effects of some natural and synthetic plant growth regulators, i.e., salicylic acid (SA), thiourea (TU), sorghum water extract (SWE), and moringa leaf extract (MLE) on chilling stress tolerance in autumn maize hybrid. Foliar application of growth regulators at low concentrations was carried out at six leaf (V6) and tasseling stages. An increase in crop growth rate (CGR), leaf area index (LAI), leaf area duration (LAD), plant height (PH), grain yield (GY), and total dry matter accumulation (TDM) was observed in exogenously applied plants as compared to control. In addition, improved physio-biochemical, phenological, and grain nutritional quality attributes were noticed in foliar-treated maize plots as compared to non-treated ones. SA-treated plants reduced 20% electrolyte leakage in cell membrane against control. MLE and SA were proved best in improving total phenolic, relative water (19-23%), and chlorophyll contents among other applications. A similar trend was found for photosynthetic and transpiration rates, whereas MLE and SWE were found better in improving CGR, LAI, LAD, TDM, PH, GY, grains per cob, 1000 grain weight, and biological yield among all treatments including control. TU and MLE have significantly reduced the duration in phenological events of crop at the reproductive stage. MLE, TU, and SA also improved the grain protein, oil, and starch contents as compared to control. Enhanced crop water productivity was also observed in MLE-treated plants. Economic analysis suggested that MLE and SA applications were more economical in inducing chilling stress tolerance under field conditions. Although eliciting behavior of all growth regulators improved morpho-physiological attributes against suboptimal temperature stress conditions, MLE and SA

Provenance and tectonic setting of siliciclastic rocks associated with the Neoproterozoic Dahongliutan BIF: Implications for the Precambrian crustal evolution of the Western Kunlun orogenic belt, NW China

NASA Astrophysics Data System (ADS)

Hu, Jun; Wang, He; Wang, Min

2017-10-01

The Late Neoproterozoic Dahongliutan BIF is associated with siliciclastic rocks in the Tianshuihai terrane of the Western Kunlun orogenic belt (WKO), NW China. The sedimentary rocks have various weathering indices (e.g., CIA = 57-87, PIA = 61-96 and Th/U = 4.85-12.45), indicative of varying degrees of weathering in the source area. The rocks have trace element ratios, such as Th/Sc = 0.60-1.21 and Co/Th = 0.29-1.67, and light rare earth element (LREE) enriched chondrite-normalized REE patterns, suggesting that they were mainly sourced from intermediate and felsic rocks. Available U-Pb ages of detrital zircon from these rocks reveal that the detrital sources may have been igneous and metamorphic rocks from the WKO and the Tarim Block. Our study suggests that the Dahongliutan BIF and hosting siliciclastic rocks may have deposited in a setting transitional from a passive to active continental margin, probably related to the Late Neoproterozoic-Early Cambrian seafloor spreading and subduction of the Proto-Tethys Ocean. U-Pb dating of 163 detrital zircons defines five major age populations at 2561-2329 Ma, 2076-1644 Ma, 1164-899 Ma, 869-722 Ma and 696-593 Ma. These age groups broadly correspond to the major stages of supercontinent assembly and breakup events widely accepted for Columbia, Rodinia and Gondwana. Some zircons have TDM2 model ages of 3.9-1.8 Ga and negative εHf(t) values, suggesting that the Archean to Paleoproterozoic (as old as Eoarchean) crustal materials were episodically reworked and incorporated into the late magmatic process in the WKO. Some Neoproterozoic zircons have TDM2 model ages of 1.47-1.07 Ga and 1.81-1.53 Ga and positive εHf(t) values, indicating juvenile crustal growth during the Mesoproterozoic. Our new results, combined with published data, imply that both the Tianshuihai terrane in the WKO and the Tarim Block share the same Precambrian tectonic evolution history.

Productivity responses of desert vegetation to precipitation patterns across a rainfall gradient.

PubMed

Li, Fang; Zhao, Wenzhi; Liu, Hu

2015-03-01

The influences of previous-year precipitation and episodic rainfall events on dryland plants and communities are poorly quantified in the temperate desert region of Northwest China. To evaluate the thresholds and lags in the response of aboveground net primary productivity (ANPP) to variability in rainfall pulses and seasonal precipitation along the precipitation-productivity gradient in three desert ecosystems with different precipitation regimes, we collected precipitation data from 2000 to 2012 in Shandan (SD), Linze (LZ) and Jiuquan (JQ) in northwestern China. Further, we extracted the corresponding MODIS Normalized Difference Vegetation Index (NDVI, a proxy for ANPP) datasets at 250 m spatial resolution. We then evaluated different desert ecosystems responses using statistical analysis, and a threshold-delay model (TDM). TDM is an integrative framework for analysis of plant growth, precipitation thresholds, and plant functional type strategies that capture the nonlinear nature of plant responses to rainfall pulses. Our results showed that: (1) the growing season NDVIINT (INT stands for time-integrated) was largely correlated with the warm season (spring/summer) at our mildly-arid desert ecosystem (SD). The arid ecosystem (LZ) exhibited a different response, and the growing season NDVIINT depended highly on the previous year's fall/winter precipitation and ANPP. At the extremely arid site (JQ), the variability of growing season NDVIINT was equally correlated with the cool- and warm-season precipitation; (2) some parameters of threshold-delay differed among the three sites: while the response of NDVI to rainfall pulses began at about 5 mm for all the sites, the maximum thresholds in SD, LZ, and JQ were about 55, 35 and 30 mm respectively, increasing with an increase in mean annual precipitation. By and large, more previous year's fall/winter precipitation, and large rainfall events, significantly enhanced the growth of desert vegetation, and desert ecosystems

Development and validation of an analytical method using UPLC-MS/MS to quantify everolimus in dried blood spots in the oncology setting.

PubMed

Knapen, Lotte M; Beer, Yvo de; Brüggemann, Roger J M; Stolk, Leo M; Vries, Frank de; Tjan-Heijnen, Vivianne C G; Erp, Nielka P van; Croes, Sander

2018-02-05

While the therapeutic drug monitoring (TDM) of everolimus has been routinely performed for over 10 years in solid organ transplantation medicine, in order to optimize the balance between effectiveness and toxicity, it is yet uncommon in the treatment of malignancies. The aim of this study was to develop and validate a bioanalytical method to quantify everolimus in dried blood spots (DBS) to facilitate TDM for the oncology outpatient setting. The hematocrit effect of everolimus was investigated. An 7.5mm disk from the central part of the DBS was punched, followed by the extraction of everolimus from the DBS by methanol/acetonitrile (80/20%) spiked with deuterium-labelled everolimus as internal standard. Subsequently, everolimus was separated and analyzed using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The UPLC-MS/MS method was validated according to the European Medicine Agency (EMA) guideline. Everolimus concentrations could be quantified over the range of 3-75μg/L. The intra- and inter-assay precision and accuracy of the method were shown to be acceptable (coefficient of variation ≤10.7% and relative error ≤4.4%, respectively). The matrix effects appeared to be influenced by the hematocrit effect. The hematocrit effect was tested in a range of 0.20-0.50L/L, at which hematocrit accuracy and precision were satisfactory at values ≥0.25L/L. However, at 0.20L/L hematocrit in combination with high everolimus concentrations of 20 and 40μg/L, the precision was adequate (≤7.4%), but the accuracy was >15% of the nominal concentration. Everolimus was stable in DBS for at least 80days at 2-8°C. Given these results, the everolimus DBS method has been successfully developed and validated. Special attention is necessary for cancer patients with both a 0.20L/L hematocrit in combination with everolimus concentrations ≥20μg/L. A clinical validation for the use of everolimus DBS in cancer patients is currently being undertaken

The relation between treatment outcome and efavirenz, atazanavir or lopinavir exposure in the NORTHIV trial of treatment-naïve HIV-1 infected patients.

PubMed

Josephson, Filip; Andersson, Maria C H; Flamholc, Leo; Gisslén, Magnus; Hagberg, Lars; Ormaasen, Vidar; Sönnerborg, Anders; Vesterbacka, Jan; Böttiger, Ylva

2010-04-01

The relation between treatment outcome and trough plasma concentrations of efavirenz (EFV), atazanavir (ATV) and lopinavir (LPV) was studied in a pharmacokinetic/pharmacodynamic substudy of the NORTHIV trial-a randomised phase IV efficacy trial comparing antiretroviral-naïve human immunodeficiency virus-1-infected patients treated with (1) EFV + 2 nucleoside reverse transcriptase inhibitors (2NRTI) once daily, (2) ritonavir-boosted ATV + 2NRTI once daily or (3) ritonavir-boosted LPV + 2NRTI twice daily. The findings were related to the generally cited minimum effective concentration levels for the respective drugs (EFV 1,000 ng/ml, ATV 150 ng/ml, LPV 1,000 ng/ml). The relation between atazanavir-induced hyperbilirubinemia and virological efficacy was also studied. Drug concentrations were sampled at weeks 4 and 48 and optionally at week 12 and analysed by high-performance liquid chromatography with UV detector. When necessary, trough values were imputed by assuming the reported average half-lives for the respective drugs. Outcomes up to week 48 are reported. No relation between plasma concentrations of EFV, ATV or LPV and virological failure, treatment withdrawal due to adverse effects or antiviral potency (viral load decline from baseline to week 4) was demonstrated. Very few samples were below the suggested minimum efficacy cut-offs, and their predictive value for treatment failure could not be validated. There was a trend toward an increased risk of virological failure in patients on ATV who had an average increase of serum bilirubin from baseline of <25 micromol/l. The great majority of treatment-naïve and adherent patients on standard doses of EFV, ritonavir-boosted ATV and ritonavir-boosted LPV have drug concentrations above that considered to deliver the maximum effect for the respective drug. The results do not support the use of routine therapeutic drug monitoring (TDM) for efficacy optimisation in treatment-naïve patients on these drugs, although TDM

Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis

PubMed Central

Gerona, Roy; Wen, Anita; Chin, Aaron T.; Koss, Catherine A.; Bacchetti, Peter; Metcalfe, John; Gandhi, Monica

2016-01-01

Background Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV. Methods A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay’s suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested. Results Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10–25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05–50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range. Conclusions An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to

Early Paleozoic dioritic and granitic plutons in the Eastern Tianshan Orogenic Belt, NW China: Constraints on the initiation of a magmatic arc in the southern Central Asian Orogenic Belt

NASA Astrophysics Data System (ADS)

Du, Long; Long, Xiaoping; Yuan, Chao; Zhang, Yunying; Huang, Zongying; Sun, Min; Zhao, Guochun; Xiao, Wenjiao

2018-03-01

Early Paleozoic dioritic and granitic plutons in the Eastern Tianshan Orogenic Belt (ETOB) have been studied in order to constraint the initiation of a magmatic arc formed in this region. Zircon U-Pb dating indicates that two dioritic plutons in the northern ETOB were generated in the Late Ordovician (452 ± 4 Ma) and the Early Silurian (442 ± 3 Ma), respectively. Diorites from the two plutons are characterized by enrichments in large ion lithophile elements (LILE) and highly incompatible elements, with depletions in high field strength elements (HSFE) displaying typical geochemical features of a subduction-related origin. They have positive εNd(t) values (+5.08-+6.58), relatively young Nd model ages (TDM = 0.71-1.08 Ga), with Ta/Yb (0.05-0.09) and Nb/Ta ratios (12.06-15.19) similar to those of depleted mantle, suggesting a juvenile mantle origin. Their high Ba/La (13.3-35.9), low Th/Yb (0.72-2.02), and relatively low Ce/Th (4.57-14.7) and Ba/Th (47.8-235) ratios indicate that these diorites were probably produced by partial melting of a depleted mantle wedge metasomatized by both subducted sediment-derived melts and slab-derived aqueous fluids. Zircon U-Pb dating of a granitic pluton in the northern ETOB yielded a Late Ordovician intrusion age of 447 ± 5 Ma. Granites from this pluton show calc-alkaline compositions with geochemical characteristics of I-type granites. They also show positive εNd(t) values (+6.49-+6.95) and young Nd model ages (TDM = 0.69-0.87 Ga), indicating that the granites were most likely derived from juvenile lower crust. Our new dating results on the dioritic and granitic plutons suggest that arc-type magmatism in the northern ETOB began prior to or at the Late Ordovician (452-442 Ma). In addition, north-dipping subduction of the Kangguertage oceanic lithosphere may account for the arc-type magmatism and the geodynamic process of the ETOB in the Early Paleozoic.

Simultaneous determination of fluoxetine and norfluoxetine in dried blood spots using high-performance liquid chromatography-tandem mass spectrometry.

PubMed

da Silva, Anne Caroline Cezimbra; Raasch, Juliana Raquel; Vargas, Tainara Gomes; Peteffi, Giovana Piva; Hahn, Roberta Zilles; Antunes, Marina Venzon; Perassolo, Magda Susana; Linden, Rafael

2018-02-01

Therapeutic drug monitoring (TDM) of the widely prescribed antidepressant fluoxetine (FLU) is recommended in certain situations, such as occurrence of toxicity, inadequate response or suspect of poor adherence. Dried blood spot (DBS) sampling is an increasingly studied alternative for TDM, particularly for outpatients, due to its ease of collection and inherent stability. The aim of this study was to develop and validate an LC-MS/MS assay for the simultaneous quantification of FLU and norfluoxetine (NFLU) in DBS. The assay is based on a liquid extraction of single DBS with 8mm of diameter, using FLU-D6 as the internal standard, followed by reversed phase separation in an Accucore® C18 column (100×2.1mm, 2.6μm). Mobile phase was composed of water and acetonitrile (gradient from 80:20 to 50:50, v/v), both containing formic acid 0.1%. The assay was validated and applied to 30 patients under FLU pharmacotherapy. The assay was linear in the range 10-750ngmL -1 . Precision assays presented CV% of 3.13-9.61 and 3.54-7.99 for FLU and NFLU, respectively, and accuracy in the range of 97.98-110.44% and 100.25-105.8%. FLU and NFLU were stable at 25 and 45°C for 7days. The assay was evaluated in 30 patients under FLU treatment. Concentrations of both compounds were higher in DBS than in plasma, and the use of the multiplying factors 0.71 and 0.68 for FLU and NFLU, respectively, allowed acceptable estimation of plasma concentrations, with median prediction bias of -0.55 to 0.55% and mean differences of 0.4 to 2.2ngmL -1 . The presented data support the clinical use of DBS for therapeutic drug monitoring of FLU. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

All-Optical Fibre Networks For Coal Mines

NASA Astrophysics Data System (ADS)

Zientkiewicz, Jacek K.

1987-09-01

A topic of the paper is fiber-optic integrated network (FOIN) suited to the most hostile environments existing in coal mines. The use of optical fibres for transmission of mine instrumentation data offers the prospects of improved safety and immunity to electromagnetic interference (EMI). The feasibility of optically powered sensors has opened up new opportunities for research into optical signal processing architectures. This article discusses a new fibre-optic sensor network involving a time domain multiplexing(TDM)scheme and optical signal processing techniques. The pros and cons of different FOIN topologies with respect to coal mine applications are considered. The emphasis has been placed on a recently developed all-optical fibre network using spread spectrum code division multiple access (COMA) techniques. The all-optical networks have applications in explosive environments where electrical isolation is required.

Proposal for implementation of CCSDS standards for use with spacecraft engineering/housekeeping data

NASA Technical Reports Server (NTRS)

Welch, Dave

1994-01-01

Many of today's low earth orbiting spacecraft are using the Consultative Committee for Space Data Systems (CCSDS) protocol for better optimization of down link RF bandwidth and onboard storage space. However, most of the associated housekeeping data has continued to be generated and down linked in a synchronous, Time Division Multiplexed (TDM) fashion. There are many economies that the CCSDS protocol will allow to better utilize the available bandwidth and storage space in order to optimize the housekeeping data for use in operational trending and analysis work. By only outputting what is currently important or of interest, finer resolution of critical items can be obtained. This can be accomplished by better utilizing the normally allocated housekeeping data down link and storage areas rather than taking space reserved for science.

Space station experiment definition: Long-term cryogenic fluid storage

NASA Technical Reports Server (NTRS)

Jetley, R. L.; Scarlotti, R. D.

1987-01-01

The conceptual design of a space station Technology Development Mission (TDM) experiment to demonstrate and evaluate cryogenic fluid storage and transfer technologies is presented. The experiment will be deployed on the initial operational capability (IOC) space station for a four-year duration. It is modular in design, consisting of three phases to test the following technologies: passive thermal technologies (phase 1), fluid transfer (phase 2), and active refrigeration (phase 3). Use of existing hardware was a primary consideration throughout the design effort. A conceptual design of the experiment was completed, including configuration sketches, system schematics, equipment specifications, and space station resources and interface requirements. These requirements were entered into the NASA Space Station Mission Data Base. A program plan was developed defining a twelve-year development and flight plan. Program cost estimates are given.

Proposal for implementation of CCSDS standards for use with spacecraft engineering/housekeeping data

NASA Astrophysics Data System (ADS)

Welch, Dave

1994-11-01

Many of today's low earth orbiting spacecraft are using the Consultative Committee for Space Data Systems (CCSDS) protocol for better optimization of down link RF bandwidth and onboard storage space. However, most of the associated housekeeping data has continued to be generated and down linked in a synchronous, Time Division Multiplexed (TDM) fashion. There are many economies that the CCSDS protocol will allow to better utilize the available bandwidth and storage space in order to optimize the housekeeping data for use in operational trending and analysis work. By only outputting what is currently important or of interest, finer resolution of critical items can be obtained. This can be accomplished by better utilizing the normally allocated housekeeping data down link and storage areas rather than taking space reserved for science.

Definition of technology development missions for early Space Station satellite servicing. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1984-01-01

The Executive Summary volume 1, includes an overview of both phases of the Definition of Technology Development Missions for Early Space Station Satellite Servicing. The primary purpose of Phase 1 of the Marshall Space Flight Center (MSFC) Satellite Servicing Phase 1 study was to establish requirements for demonstrating the capability of performing satellite servicing activities on a permanently manned Space Station in the early 1990s. The scope of Phase 1 included TDM definition, outlining of servicing objectives, derivation of initial Space Station servicing support requirements, and generation of the associated programmatic schedules and cost. The purpose of phase 2 of the satellite servicing study was to expand and refine the overall understanding of how best to use the manned space station as a test bed for demonstration of satellite servicing capabilities.

Enterprise virtual private network (VPN) with dense wavelength division multiplexing (DWDM) design

NASA Astrophysics Data System (ADS)

Carranza, Aparicio

An innovative computer simulation and modeling tool for metropolitan area optical data communication networks is presented. These models address the unique requirements of Virtual Private Networks for enterprise data centers, which may comprise a mixture of protocols including ESCON, FICON, Fibre Channel, Sysplex protocols (ETR, CLO, ISC); and other links interconnected over dark fiber using Dense Wavelength Division Multiplexing (DWDM). Our models have the capability of designing a network with minimal inputs; to compute optical link budgets; suggest alternative configurations; and also optimize the design based on user-defined performance metrics. The models make use of Time Division Multiplexing (TDM) wherever possible for lower data rate traffics. Simulation results for several configurations are presented and they have been validated by means of experiments conducted on the IBM enterprise network testbed in Poughkeepsie, N.Y.

Full-band TDM-OPDMA for OBI-reduced simultaneous multiple access in a single-wavelength optical access network.

PubMed

Jung, Sun-Young; Kim, Chang-Hun; Han, Sang-Kook

2018-05-14

Simultaneous multiple access (MA) within a single wavelength can increase the data rate and split ratio in a passive optical network while optical beat interference (OBI) becomes serious in the uplink. Previous techniques to reduce OBI were limited by their complexity and lack of extendibility; as well, bandwidth allocation among MA signals is needed for single photo diode (PD) detection. We proposed and experimentally demonstrated full-band optical pulse division multiplexing-based MA (OPDMA) in an optical access network, which can effectively reduce OBI with extendibility and fully utilize frequency resources of optical modulator without bandwidth allocation in a single-wavelength MA.

Pseudotumeur cardiaque révélant une maladie de Behçet

PubMed Central

Nya, Fouad; Abdou, Abdessamad; Bamous, Mehdi; Moutakiallah, Younes; Atmani, Noureddine; Seghrouchni, Aniss; Houssa, Mahdi Ait; Boulahya, Abdellatif

2017-01-01

La thrombose intracardiaque est une complication rare de la maladie de Behçet (MB), qui peut se présenter comme une tumeur intracardiaque. Sa découverte précède, dans la moitié des cas, le diagnostic de MB. La mortalité élevée peut être en rapport avec des complications post-chirurgicales et/ou une atteinte associée des artères pulmonaires. Nous rapportons l’observation d’un jeune patient de 29 ans, aux antécédents d’aphtose bipolaire, qui a bénéficie d’une intervention chirurgicale après la découverte d’une tumeur de l’atrium et du ventricule droits. Il s’agissait d’un thrombus à l’examen anatomopathologique et dans les suites opératoires nous avons diagnostiqué une MB. L’évolution a été favorable sous traitement médical associant une corticothérapie, de la colchicine et des antivitamines K (AVK). La découverte d’une masse intracardiaque chez un sujet jeune doit faire évoquer le diagnostic de thrombus cardiaque et de maladie de Behçet, même en l’absence de facteur ethnique ou géographique prédisposant. PMID:28533874

Infection respiratoire aigüe et statut nutritionnel chez les enfants de 0-5 ans: cas des cliniques universitaires de Lubumbashi, République Démocratique du Congo

PubMed Central

Ngombe, Léon Kabamba; Mbombo-Ditunga; Kameya, Nduwa; Malingo, Aimé Abasiko; Kayomb, Nathalie Kaj; ea Ngolomba, Jean Ngolomba; Nday, David Kakez; Numbi, Luboya

2014-01-01

Les auteurs rapportent les données d'une étude rétrospective de 153 dossiers d'enfants hospitalisés dans le service de pédiatrie des Cliniques Universitaires de Lubumbashi/RD Congo pour IRA. En ce qui nous concerne, les IRA chez les enfants de moins de 5 ans représentent 26,11% de l'effectif, dont 17,75% âgés de moins d'un an. Le sexe masculin est légèrement prédominant (85 contre 68) et près de 70% des enfants ont un statut nutritionnel précaire. La répartition mensuelle connaît des pics en mars et octobre. Les diagnostiques notifiés sont: rhinite(16,3%),Amygdalite(5,9%),Otite Moyenne Aigue(0,7%),Laryngite (3,3%), Rhinopharyngite (39,2%), Pharyngite (6,5%), Bronchite (7,2%), Bronchopneumonie (5,9%), Pneumonie(2,6%) et Bronchiolite (12,4%).Tous les cas ont bien évolués sous traitement. Le but de ce travail est de déterminer la fréquence des IRA et le statut nutritionnel des enfants ayant été admis dans le service des pédiatries aux C.U.L. PMID:25995789

Carcinome neuroendocrine thymique: à propos d’un cas et revue de la littérature

PubMed Central

Ramahandrisoa, Andriatsihoarana Voahary Nasandratriniavo; Hasiniatsy, Nomeharisoa Rodrigue Emile; Refeno, Valéry; Vololonantenaina, Clairette Raharisolo; Rakotoarisoa, Andriamihaja Jean Claude; Rakotovao, Hanitrala Jean Louis; Rafaramino, Florine

2017-01-01

Les tumeurs neuroendocrines thymiques (TNET) sont rares, de pronostic mal connu. L'objectif est de rapporter un cas de TNET et discuter la difficulté diagnostique et thérapeutique en milieu à faibles ressources. Un homme de 60 ans présentait une douleur thoracique, une toux grasse et un amaigrissement récent. Le scanner thoracique révélait une masse tissulaire médiastinale antérieure. L'histologie définitive obtenue quatre mois après la biopsie par médiastinotomie antérieure montrait une TNET bien différenciée, avec marquage intense à la chromogranine et à la synaptophysine. La recherche d'autres tumeurs neuroendocrines et le bilan d'extension étaient négatifs. La tumeur était inextirpable d'emblée et la radiothérapie indisponible. Le patient a reçu deux lignes de chimiothérapie première. Avec un recul de 16 mois, le patient était asymptomatique, mais en progression tumorale. Le diagnostic de TNET peut être retardé quand l'examen immunohistochimique n'est pas réalisé en routine. La chimiothérapie apporte une amélioration des symptômes en situation palliative. PMID:28451004

Advances in Systemic Therapy for Metastatic or Advanced Gastric Cancer.

PubMed

Shitara, Kohei; Ohtsu, Atsushi

2016-10-01

In recent years, various new agents have been investigated for the treatment of advanced gastric cancer (AGC). The anti-HER2 antibody trastuzumab has been shown to prolong the overall survival of patients with HER2-positive AGC and has become a standard treatment. However, lapatinib, or ado-trastuzumab emtansine (T-DM1), did not show survival benefit in AGC, although it has shown remarkable efficacy for HER2-positive breast cancer. The efficacy of the anti-vascular endothelial growth factor receptor monoclonal antibody ramucirumab for pretreated gastric cancer is a milestone for antiangiogenic therapy for AGC. Early clinical trials of TAS-118, TAS-102, and STAT3 inhibitors; IMAB362 (anti-Claudin 18.2); and immune checkpoint inhibitors are all encouraging. These findings warrant further evaluation in larger clinical trials. Copyright © 2016 by the National Comprehensive Cancer Network.

Update on the Medical Management of Crohn's Disease.

PubMed

Deepak, Parakkal; Bruining, David H

2015-11-01

The medical management of Crohn's disease is a rapidly evolving field with expanding therapeutic drug options and treatment strategies. In addition to corticosteroids, immunomodulators, and anti-tumor necrosis (anti-TNF) agents, a new anti-adhesion medication (vedolizumab) has been approved. Individualized patient-based dosing of immunomodulators and biologic agents is now possible with therapeutic drug monitoring (TDM). There is a changing paradigm in treatment goals to achieve deeper remission identified by composite clinical and endoscopic endpoints. More aggressive treatment strategies in the postoperative setting have been proposed due to emerging data on medication efficacy in this setting. Management algorithms that stratify CD patients into risk groups to balance treatment benefit against adverse events and costs are being developed to translate research into clinical practice. This review provides an update on these new developments for practicing gastroenterologists.

Une localisation exceptionnelle de la tuberculose vertébrale Mal de Pott sous-occipital

PubMed Central

Yahyaoui, Sana; Majdoub, Senda; Zaghouani, Houneida; Fradj, Hosni Ben; Bakir, Dejla; Bouajina, Elyes; Kraiem, Chakib

2013-01-01

Le mal de Pott est la forme la plus commune de la tuberculose osseuse touchant essentiellement le rachis dorso-lombaire. La localisation sous-occipitale reste exceptionnelle. Le diagnostic de cette entité est le plus souvent tardif ce qui expose à des complications graves. Les radiographies standard ne sont parlantes qu’à un stade tardif de la maladie, d'où l'intérêt de l'imagerie moderne notamment la tomodensitométrie (TDM) et l'imagerie par résonance magnétique (IRM) qui permettent un diagnostic précoce. Nous rapportons un nouveau cas de tuberculose sous-occipitale. Le diagnostic était posé sur l'imagerie en coupe et confirmé histologiquement à la biopsie transorale. Sont rappelés les aspects en imagerie de cette localisation particulière du mal de Pott. PMID:23819005

Quantification of greenhouse gas (GHG) emissions from wastewater treatment plants using a ground-based remote sensing approach

NASA Astrophysics Data System (ADS)

Delre, Antonio; Mønster, Jacob; Scheutz, Charlotte

2016-04-01

The direct release of nitrous oxide (N2O) and methane (CH4) from wastewater treatment plants (WWTP) is important because it contributes to the global greenhouse gases (GHGs) release and strongly effects the WWTP carbon footprint. Biological nitrogen removal technologies could increase the direct emission of N2O (IPCC, 2006), while CH4 losses are of environmental, economic and safety concern. Currently, reporting of N2O and CH4 emissions from WWTPs are performed mainly using methods suggested by IPCC which are not site specific (IPCC, 2006). The dynamic tracer dispersion method (TDM), a ground based remote sensing approach implemented at DTU Environment, was demonstrated to be a novel and successful tool for full-scale CH4 and N2O quantification from WWTPs. The method combines a controlled release of tracer gas from the facility with concentration measurements downwind of the plant (Mønster et al., 2014; Yoshida et al., 2014). TDM in general is based on the assumption that a tracer gas released at an emission source, in this case a WWTP, disperses into the atmosphere in the same way as the GHG emitted from process units. Since the ratio of their concentrations remains constant along their atmospheric dispersion, the GHG emission rate can be calculated using the following expression when the tracer gas release rate is known: EGHG=Qtr*(CGHG/Ctr)*(MWGHG/MWtr) EGHG is the GHG emission in mass per time, Qtr is the tracer release in mass per time, CGHG and Ctr are the concentrations measured downwind in parts per billion subtracted of their background values and integrated over the whole plume, and MWGHG and MWtr are the molar weights of GHG and tracer gas respectively (Mønster et al. 2014). In this study, acetylene (C2H2) was used as tracer. Downwind plume concentrations were measured driving along transects with two cavity ring down spectrometers (Yoshida et al., 2014). TDM was successfully applied in different seasons at several Scandinavian WWTPs characterized by

Experimental demonstration of wavelength domain rogue-free ONU based on wavelength-pairing for TDM/WDM optical access networks.

PubMed

Lee, Jie Hyun; Park, Heuk; Kang, Sae-Kyoung; Lee, Joon Ki; Chung, Hwan Seok

2015-11-30

In this study, we propose and experimentally demonstrate a wavelength domain rogue-free ONU based on wavelength-pairing of downstream and upstream signals for time/wavelength division-multiplexed optical access networks. The wavelength-pairing tunable filter is aligned to the upstream wavelength channel by aligning it to one of the downstream wavelength channels. Wavelength-pairing is implemented with a compact and cyclic Si-AWG integrated with a Ge-PD. The pairing filter covered four 100 GHz-spaced wavelength channels. The feasibility of the wavelength domain rogue-free operation is investigated by emulating malfunction of the misaligned laser. The wavelength-pairing tunable filter based on the Si-AWG blocks the upstream signal in the non-assigned wavelength channel before data collision with other ONUs.

Age and composition of the UHP garnet peridotites in the Dabie orogenic belt (central China) record complex crust-mantle interaction in continental margin

NASA Astrophysics Data System (ADS)

Zhao, Y.; Zheng, J.; Wang, B.

2017-12-01

The Dabie-Sulu UHP belt was created by the collision between the North and South China cratons in Middle Triassic time (240-225 Ma). There are lots of garnet-bearing ultramafic body occurs as a lens in the belt. Age and composition of the Maowu garnet peridotites in the Dabie orogenic belt are reported. The garnet harzburgites are main moderately refractory (Mg#Ol=92) and minor fertile (Mg#Ol=88) with high Ni (2344-2603 ppm) and low Al2O3 (0.35-0.54 wt.%), CaO (0.76-2.19 wt.%) and TiO2 (˜0.01 wt.%). Zircons in the harzburgites mainly document metamorphism at 230 ± 2 Ma, 275 ± 5 Ma, 357 ± 4 Ma, and complex minor populations of ages including: 1.8 Ga, 1.3 Ga, and Neoproterozic-early Paleozoic ages (901-420 Ma). The early Meszosic and late Paleozoic zircons have similar trace-element patterns and ranges in ɛHf(t) (+0.6 to +3.4), Th/U ratio (0.2-0.7) and Hf depleted-mantle model ages (TDM ) mainly cluster in the interval 1.2-0.9 Ga. In contrast, the Paleo-Mesoproterozoic zircons have negative ɛHf(t) (-24.9 to -2.7) and oldest Hf TDM = 3.4Ga. Zircons of Neoproterozic-early Paleozoic have a wide range of Hf depleted-mantle model ages (2.4-0.7Ga) and ɛHf(t) (-15.3 to +9.5). Above of the all, we suggest that the Maowu garnet harzburgites are interpreted as a fragment of the metasomatized ancient lithospheric mantle beneath the southern margin of the North China Craton. They experienced the Proterozoic thermal event (1.9-1.8Ga), which is coeval with the assembly of the supercontinent Columbia. And then 1.3Ga mantle metasomatism with asthenospheric materials resulted in the final breakup of the Columbia supercontinent. Neoproterozic-early Paleozoic (901-420 Ma), deep parts of the south margin of the craton were metasomatized during the assembly and breakup of the Rodinia supercontinent. Then, the southern margin of the craton occurred oceanic crust subduction ( 357 Ma), subsequent continental deep subduction and final continent-continent collision in Triassic.

Geochronology and geochemistry of early Paleozoic igneous rocks of the Lesser Xing'an Range, NE China: Implications for the tectonic evolution of the eastern Central Asian Orogenic Belt

NASA Astrophysics Data System (ADS)

Wang, Zhi-wei; Xu, Wen-liang; Pei, Fu-ping; Wang, Feng; Guo, Peng

2016-09-01

This paper presents new zircon U-Pb, Hf isotope, and whole-rock major and trace element data for early Paleozoic igneous rocks of the Lesser Xing'an Range, NE China, in order to constrain the early Paleozoic tectonic evolution of the eastern Central Asian Orogenic Belt (CAOB). Zircon U-Pb dating indicates that early Paleozoic magmatic events within the northern Songnen-Zhangguangcai Range Massif (SZM) can be subdivided into four stages: Middle Cambrian ( 505 Ma), Late Cambrian ( 490 Ma), Early-Middle Ordovician ( 470 Ma), and Late Ordovician (460-450 Ma). The Middle Cambrian monzogranites are K-rich, weakly to strongly peraluminous, and characterized by pronounced heavy rare earth element (HREE) depletions, high Sr/Y ratios, low Y concentrations, low primary zircon εHf(t) values (- 6.79 to - 1.09), and ancient two-stage model (TDM2) ages (1901-1534 Ma). These results indicate derivation from partial melting of thickened ancient crustal materials that formed during the amalgamation of the northern SZM and the northern Jiamusi Massif (JM). The Late Cambrian monzonite, quartz monzonite, and monzogranite units are chemically similar to A-type granites, and contain zircons with εHf(t) values of - 2.59 to + 1.78 and TDM2 ages of 1625-1348 Ma. We infer that these rocks formed from primary magmas generated by partial melting of Mesoproterozoic accreted lower crustal materials in a post-collisional extensional environment. The Early-Middle Ordovician quartz monzodiorite, quartz monzonite, monzogranite, and rhyolite units are calc-alkaline, relatively enriched in light REEs (LREEs) and large ion lithophile elements (LILEs; e.g., Rb, Th, and U), depleted in HREEs and high field strength elements (HFSEs; e.g., Nb, Ta, and Ti), and contain zircons with εHf(t) values of - 7.33 to + 4.98, indicative of formation in an active continental margin setting. The Late Ordovician alkali-feldspar granite and rhyolite units have A-type granite affinities that suggest they formed in an

Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer.

PubMed

Hashimoto, Masaki; Tanaka, Fumihiro; Yoneda, Kazue; Takuwa, Teruhisa; Matsumoto, Seiji; Okumura, Yoshitomo; Kondo, Nobuyuki; Tsujimura, Tohru; Nakano, Takashi; Hasegawa, Seiki

2018-01-01

In non-small cell lung cancer (NSCLC), circulating tumor cells (CTC) are shed and circulate to the peripheral blood through the pulmonary vein. Previously, CTC count in pulmonary venous blood (pvCTC) was shown to significantly increase after surgical manipulation. Therefore, we assessed the correlation between the changes in the pvCTC count (ΔpvCTC) and clinical outcomes. Consecutive patients with peripheral-type, NSCLC, who underwent lobectomy or bi-lobectomy through open thoracotomy, were enrolled prospectively. Before and after lobectomy, 2.5 mL of blood was drawn from the associated lobar pulmonary vein (PV), and was served for the quantitative evaluation of CTC using the CellSearch ® system. The cut-off point of ΔpvCTC was determined according to clinical outcomes and ΔpvCTC using receiver operation characteristic (ROC) curve. Then the correlation between ΔpvCTC and clinical outcomes was evaluated by Kaplan-Meier analyses and log-rank test. In addition, the correlation between ΔpvCTC and perioperative variables was assessed. A total of 30 patients were enrolled, tumor recurrence occurred in 11 patients over a median follow-up of 64.4 months. Of these, 7 patients had distant metastasis and 4 had local recurrence. The median ΔpvCTC was 49 cells/2.5 mL, and pvCTC-count was increased during surgical manipulation in 24 patients (80%). We divided patients into two groups based on ΔpvCTC with the cut-off value as 119 cells/2.5 mL according to ROC curve. Significant shorter time to distant metastasis (TDM) (P=0.0123) was observed in high ΔpvCTC group (ΔpvCTC ≥119 cells/2.5 mL) than low ΔpvCTC group (ΔpvCTC <119 cells/ 2.5mL). Neither disease-free survival (DFS) nor overall survival (OS) was significantly correlated with ΔpvCTC. Increasing pvCTC count during surgical manipulation was significantly correlated with postoperative distant metastasis in completely resected NSCLC patients. Significant shorter TDM was observed in patient with high ΔpvCTC group.

Flexible and evolutionary optical access networks

NASA Astrophysics Data System (ADS)

Hsueh, Yu-Li

Passive optical networks (PONs) are promising solutions that will open the first-mile bottleneck. Current PONs employ time division multiplexing (TDM) to share bandwidth among users, leading to low cost but limited capacity. In the future, wavelength division multiplexing (WDM) technologies will be deployed to achieve high performance. This dissertation describes several advanced technologies to enhance PON systems. A spectral shaping line coding scheme is developed to allow a simple and cost-effective overlay of high data-rate services in existing PONs, leaving field-deployed fibers and existing services untouched. Spectral shapes of coded signals can be manipulated to adapt to different systems. For a specific tolerable interference level, the optimal line code can be found which maximizes the data throughput. Experiments are conducted to demonstrate and compare several optimized line codes. A novel PON employing dynamic wavelength allocation to provide bandwidth sharing across multiple physical PONs is designed and experimentally demonstrated. Tunable lasers, arrayed waveguide gratings, and coarse/fine filtering combine to create a flexible optical access solution. The network's excellent scalability can bridge the gap between conventional TDM PONs and WDM PONs. Scheduling algorithms with quality of service support are also investigated. Simulation results show that the proposed architecture exhibits significant performance gain over conventional PON systems. Streaming video transmission is demonstrated on the prototype experimental testbed. The powerful architecture is a promising candidate for next-generation optical access networks. A new CDR circuit for receiving the bursty traffic in PONs is designed and analyzed. It detects data transition edges upon arrival of the data burst and quickly selects the best clock phase by a control logic circuit. Then, an analog delay-locked loop (DLL) keeps track of data transitions and removes phase errors throughout the

Quantification of 21 antihypertensive drugs in serum using UHPLC-MS/MS.

PubMed

Gundersen, Per Ole M; Helland, Arne; Spigset, Olav; Hegstad, Solfrid

2018-04-28

Poor drug adherence in hypertensive patients can lead to treatment failure and increased cardiovascular morbidity, as well as increased costs to society. An analytical method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MSMS) was developed and validated for use in routine therapeutic drug monitoring (TDM). The method includes 21 antihypertensive drugs or active metabolites from the groups beta blockers (n=5), calcium antagonists (n=5), angiotensin II receptor antagonists (n=4), angiotensin converting enzyme (ACE) inhibitors (n=3) and diuretics (n = 3), in addition to one α1-selective alpha blocker. A 200 µL serum sample was handled automatically using a pipetting robot. Protein precipitation was performed with 600 µL of 1% formic acid in acetonitrile (v:v) and phospholipid removal was carried out using a Waters OSTRO™ 96-well plate. After evaporation and reconstitution the eluent was injected thrice with different inlet and mass spectrometric methods to cover the different physico-chemical properties of the drugs and the variations in therapeutic concentration ranges between drugs. Acquity UPLC BEH C18 (2.1x50mm, 1.7 µm) column equipped with a corresponding pre-column was used for chromatographic separation. For every analyte an isotopically labelled analogue served as internal standard, except for lisinopril where enalaprilat-d5 was used. Accuracies were in the range of -13.7 to 13.2% and intra-day and inter-day precisions in the range of 1.1 to 10.5%. The linearity within the calibration ranges expressed as coefficient of determination was higher than 0.995 for all compounds. Matrix effects and recovery efficiencies were within acceptable limits. The limits of quantitation varied from 0.02 to 10.7 µg/L. The stability of the drugs in serum at different conditions was tested. Diltiazem was not stable at 4-8 °C with up to 23.5 % loss after six days. Degradation of atenolol, irbesartan, bendroflumethiazide

Analysis of single-nucleotide polymorphisms (SNPs) in human CYP3A4 and CYP3A5 genes: potential implications for the metabolism of HIV drugs

PubMed Central

2014-01-01

Background Drug metabolism via the cytochrome P450 (CYP450) system has emerged as an important determinant in the occurrence of several drug interactions (adverse drug reactions, reduced pharmacological effect, drug toxicities). In particular, CYP3A4 and CYP3A5 (interacting with more than 60% of licensed drugs) exhibit the most individual variations of gene expression, mostly caused by single nucleotide polymorphisms (SNPs) within the regulatory region of the CYP3A4 and CYP3A5 genes which might affect the level of enzyme production. In this study, we sought to improve the performance of sensitive screening for CYP3A polymorphism detection in twenty HIV-1 infected patients undergoing lopinavir/ritonavir (LPV/r) monotherapy. Methods The study was performed by an effective, easy and inexpensive home-made Polymerase Chain Reaction Direct Sequencing approach for analyzing CYP3A4 and CYP3A5 genes which can detect both reported and unreported genetic variants potentially associated with altered or decreased functions of CYP3A4 and CYP3A5 proteins. Proportions and tests of association were used. Results Among the genetic variants considered, CYP3A4*1B (expression of altered function) was only found in 3 patients (15%) and CYP3A5*3 (expression of splicing defect) in 3 other patients (15%). CYP3A5*3 did not appear to be associated with decreased efficacy of LPV/r in any patient, since none of the patients carrying this variant showed virological rebound during LPV/r treatment or low levels of TDM. In contrast, low-level virological rebound was observed in one patient and a low TDM level was found in another; both were carrying CYP3A4*1B. Conclusions Our method exhibited an overall efficiency of 100% (DNA amplification and sequencing in our group of patients). This may contribute to producing innovative results for better understanding the inter-genotypic variability in gene coding for CYP3A, and investigating SNPs as biological markers of individual response to drugs

An adiabatic spectroscopic investigation of the CsRb system in ground and numerous excited states

NASA Astrophysics Data System (ADS)

Souissi, Hanen; Jellali, Soulef; Maha, Chaieb; Habli, Héla; Oujia, Brahim; Gadéa, Florent Xavier

2017-10-01

Via ab-initio approximations, we investigate the electronic and structural features of the CsRb molecule. Adiabatic potential energy curves of 261,3Σ+, 181,3Π and 61,3Δ electronic states with their derived spectroscopic constants as well as vibrational levels spacing have been carried out and well explained. Our approach is founded on an Effective Core Potential (ECP) describing the valence electrons of the system. Using a large Gaussian basis set, the full valence Configuration Interaction can be applied easily on the two-effective valence electrons of the CsRb system. Furthermore, a detailed analysis of the electric dipolar properties has been made through the investigation of both permanent and transition dipole moments (PDM and TDM). It is significant that the ionic character connected with electron transfer that is linked to Cs+ Rb- state has been clearly illustrated in the adiabatic permanent dipole moment.

All-optical virtual private network and ONUs communication in optical OFDM-based PON system.

PubMed

Zhang, Chongfu; Huang, Jian; Chen, Chen; Qiu, Kun

2011-11-21

We propose and demonstrate a novel scheme, which enables all-optical virtual private network (VPN) and all-optical optical network units (ONUs) inter-communications in optical orthogonal frequency-division multiplexing-based passive optical network (OFDM-PON) system using the subcarrier bands allocation for the first time (to our knowledge). We consider the intra-VPN and inter-VPN communications which correspond to two different cases: VPN communication among ONUs in one group and in different groups. The proposed scheme can provide the enhanced security and a more flexible configuration for VPN users compared to the VPN in WDM-PON or TDM-PON systems. The all-optical VPN and inter-ONU communications at 10-Gbit/s with 16 quadrature amplitude modulation (16 QAM) for the proposed optical OFDM-PON system are demonstrated. These results verify that the proposed scheme is feasible. © 2011 Optical Society of America

Hierarchical automated clustering of cloud point set by ellipsoidal skeleton: application to organ geometric modeling from CT-scan images

NASA Astrophysics Data System (ADS)

Banegas, Frederic; Michelucci, Dominique; Roelens, Marc; Jaeger, Marc

1999-05-01

We present a robust method for automatically constructing an ellipsoidal skeleton (e-skeleton) from a set of 3D points taken from NMR or TDM images. To ensure steadiness and accuracy, all points of the objects are taken into account, including the inner ones, which is different from the existing techniques. This skeleton will be essentially useful for object characterization, for comparisons between various measurements and as a basis for deformable models. It also provides good initial guess for surface reconstruction algorithms. On output of the entire process, we obtain an analytical description of the chosen entity, semantically zoomable (local features only or reconstructed surfaces), with any level of detail (LOD) by discretization step control in voxel or polygon format. This capability allows us to handle objects at interactive frame rates once the e-skeleton is computed. Each e-skeleton is stored as a multiscale CSG implicit tree.

Arthrite septique à Proteus mirabilis

PubMed Central

Sbiti, Mohammed; Bouhamidi, Bahia; Louzi, Lhoussaine

2017-01-01

L'arthrite septique aigue est une pathologie peu fréquente mais grevée d'un pronostic lourd en termes de mortalité et morbidité. Nous rapportons un cas d'arthrite septique à Proteus mirabilis survenue de façon spontanée chez un patient de 61 ansprésentant un diabète compliqué,associée à des hémoculturespositives et des cultures positives du liquide articulaire. L'évolution était favorable grâce au diagnostic précoce et à l'institution d'une antibiothérapie adéquate. L'arthrite septique à Proteus Mirabilis est rare, ce qui nous a incité à revoir dans la littérature des séries d'arthrites à pyogènes incluant Proteus mirabilis portant sur les facteurs de risque, la pathogénie, le traitement et l'évolution de ces pathologies. Le diagnostic est avant tout microbiologique, la ponction articulaire précoce est réalisée avant toute antibiothérapie, l'examen direct, la culture et l'antibiogramme qui va guider le choix d'une antibiothérapie. L'arthrite septique est une urgence diagnostique et thérapeutique, la prise en charge précoce de cette pathologie permet une guérison sans séquelles. PMID:28674590

[Backstage of a massive open online course (MOOC) on cancer diagnosis].

PubMed

Gardair, Charlotte; Bousquet, Guilhem; Lehmann-Che, Jacqueline; de Bazelaire, Cédric; de Cremoux, Patricia; Tran Van Nhieu, Jeanne; Sockeel, Marie; Battistella, Maxime; Calvani, Julien; Gervais, Jocelyne; Pottier, Yohann; Prévaut, Laurent; Sekri, Karima; Bertheau, Philippe

2016-10-01

Massive open online course (or MOOC) is a new online and open access teaching approach aimed at unlimited participation and providing interactions among students and teaching staff. These academic courses, often still free, lead to the delivery of a certificate of attendance and could soon also deliver a diploma. The MOOC "Stratégies diagnostiques des cancers" will be hosted in autumn 2016 on the platform "France Université Numérique" and will have two levels of learners: students in the field of health and biology and the general public. This MOOC will also be integrated into the teaching program of medical students of Paris Diderot University and Paris 13 University. The educational objective of this MOOC is to convey to all participants an overview of the diagnostic steps of cancers and of the various medical specialties involved in this diagnosis. The second week of the MOOC, entitled "tumor samples, macroscopic and microscopic analysis", presents the pathology specialty with the technical treatment of tissue or cell samples and the basic elements of the tissue section analysis to get a diagnosis of benign or malignant tumor. After this MOOC, it is planned to assess the impact of this new modality of teaching the pathology specialty or pathology, especially by the general public. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Le carcinome neuro-endocrine cutané primitif: à propos d'un nouveau cas et revue de la littérature

PubMed Central

Boukind, Samira; Elatiqi, Oumkeltoum; Dlimi, Meriem; Elamrani, Driss; Benchamkha, Yassine; Ettalbi, Saloua

2015-01-01

Le carcinome neuro- endocrine cutané primitif (CNEC) est une tumeur cutanée rare et agressive du sujet âgé, favorisée par le soleil et l'immunodépression. Elle est caractérisée par une évolution agressive avec un fort taux de récidive, une évolution ganglionnaire régionale et un risque de métastases à distance. Nous rapportons un cas de cette tumeur chez un patient âgé de 67 ans sous forme d'un placard nodulaire hémorragique mesurant 16 /14 cm. Le patient a bénéficié d'une exérèse chirurgicale large avec couverture de la perte de substance par un lambeau musculo-cutané du muscle grand dorsal, un curage ganglionnaire axillaire et une radiothérapie adjuvante. Après un recul de 2 ans et 2 mois, le patient est toujours vivant sans métastase ni récidive. La littérature étant pauvre, la prise en charge diagnostique et thérapeutique est controversée et donc hétérogène. Globalement le pronostic est mauvais, et certains paramètres corrélés au pronostic sont précisés. PMID:26185585

L’actinomycose thoracique multiple chez l’immunocompétent

PubMed Central

Msougar, Yassine; Fenane, Hicham; Maidi, Mehdi; Benosman, Abdellatif

2013-01-01

L′actinomycose est une affection bactérienne granulomateuse, suppurative, étendue et chronique provoquée par la bactérie anaérobique gram positif Actinomyces israelii. La localisation thoracique est rare, elle peut simuler une pathologie néoplasique ou une tuberculose. Il s’agit d’un patient de 54ans sans antécédents pathologiques, qui s’est présenté avec deux tuméfactions pariétales basithoarciques droites, l’une antérieure et l’autre postérieure s’accompagnant d’une altération de l’état général. L’examen clinique ainsi que le bilan radiologique ont montré deux masses de la paroi thoracique et une atteinte parenchymateuse basale droite. L’examen anatomopathologique de la biopsie de la masse antérieure a montré des foyers d’actinomycose permettant d’établir le diagnostic d’actinomycose thoraco-pulmonaire. Un bilan immunologique s’est révélé normal. Le patient est alors mis sous traitement antibiotique à base d’amoxicilline protégée avec bonne évolution clinique et radiologique. Le but de cette observation est de rappeler les aspects radio-clinique, histologiques, thérapeutiques et évolutifs ainsi que les difficultés diagnostiques de cette affection. PMID:24672630

Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations

PubMed Central

Choi, Rihwa; Jeong, Byeong-Ho

2017-01-01

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response. PMID:28028995

A Millimeter-Wave Digital Link for Wireless MRI

PubMed Central

Aggarwal, Kamal; Joshi, Kiran R.; Rajavi, Yashar; Taghivand, Mazhareddin; Pauly, John M.; Poon, Ada S. Y.; Scott, Greig

2017-01-01

A millimeter (mm) wave radio is presented in this work to support wireless MRI data transmission. High path loss and availability of wide bandwidth make mm-waves an ideal candidate for short range, high data rata communication required for wireless MRI. The proposed system uses a custom designed integrated chip (IC) mm-wave radio with 60 GHz as radio frequency carrier. In this work, we assess performance in a 1.5 T MRI field, with the addition of optical links between the console room and magnet. The system uses ON-OFF keying (OOK) modulation for data transmission and supports data rates from 200 Mb/s to 2.5 Gb/s for distances up-to 65 cm. The presence of highly directional, linearly polarized, on-chip dipole antennas on the mm-wave radio along with the time division multiplexing (TDM) circuitry allows multiple wireless links to be created simultaneously with minimal inter-channel interference. This leads to a highly scalable solution for wireless MRI. PMID:27810803

Connection anonymity analysis in coded-WDM PONs

NASA Astrophysics Data System (ADS)

Sue, Chuan-Ching

2008-04-01

A coded wavelength division multiplexing passive optical network (WDM PON) is presented for fiber to the home (FTTH) systems to protect against eavesdropping. The proposed scheme applies spectral amplitude coding (SAC) with a unipolar maximal-length sequence (M-sequence) code matrix to generate a specific signature address (coding) and to retrieve its matching address codeword (decoding) by exploiting the cyclic properties inherent in array waveguide grating (AWG) routers. In addition to ensuring the confidentiality of user data, the proposed coded-WDM scheme is also a suitable candidate for the physical layer with connection anonymity. Under the assumption that the eavesdropper applies a photo-detection strategy, it is shown that the coded WDM PON outperforms the conventional TDM PON and WDM PON schemes in terms of a higher degree of connection anonymity. Additionally, the proposed scheme allows the system operator to partition the optical network units (ONUs) into appropriate groups so as to achieve a better degree of anonymity.

A Single Chip VLSI Implementation of a QPSK/SQPSK Demodulator for a VSAT Receiver Station

NASA Technical Reports Server (NTRS)

Kwatra, S. C.; King, Brent

1995-01-01

This thesis presents a VLSI implementation of a QPSK/SQPSK demodulator. It is designed to be employed in a VSAT earth station that utilizes the FDMA/TDM link. A single chip architecture is used to enable this chip to be easily employed in the VSAT system. This demodulator contains lowpass filters, integrate and dump units, unique word detectors, a timing recovery unit, a phase recovery unit and a down conversion unit. The design stages start with a functional representation of the system by using the C programming language. Then it progresses into a register based representation using the VHDL language. The layout components are designed based on these VHDL models and simulated. Component generators are developed for the adder, multiplier, read-only memory and serial access memory in order to shorten the design time. These sub-components are then block routed to form the main components of the system. The main components are block routed to form the final demodulator.

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

PubMed

Adams, Stephen R; Yang, Howard C; Savariar, Elamprakash N; Aguilera, Joe; Crisp, Jessica L; Jones, Karra A; Whitney, Michael A; Lippman, Scott M; Cohen, Ezra E W; Tsien, Roger Y; Advani, Sunil J

2016-10-04

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery.

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize

PubMed Central

Adams, Stephen R.; Yang, Howard C.; Savariar, Elamprakash N.; Aguilera, Joe; Crisp, Jessica L.; Jones, Karra A.; Whitney, Michael A.; Lippman, Scott M.; Cohen, Ezra E. W.; Tsien, Roger Y.; Advani, Sunil J.

2016-01-01

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery. PMID:27698471

Evolutionary Telemetry and Command Processor (TCP) architecture

NASA Technical Reports Server (NTRS)

Schneider, John R.

1992-01-01

A low cost, modular, high performance, and compact Telemetry and Command Processor (TCP) is being built as the foundation of command and data handling subsystems for the next generation of satellites. The TCP product line will support command and telemetry requirements for small to large spacecraft and from low to high rate data transmission. It is compatible with the latest TDRSS, STDN and SGLS transponders and provides CCSDS protocol communications in addition to standard TDM formats. Its high performance computer provides computing resources for hosted flight software. Layered and modular software provides common services using standardized interfaces to applications thereby enhancing software re-use, transportability, and interoperability. The TCP architecture is based on existing standards, distributed networking, distributed and open system computing, and packet technology. The first TCP application is planned for the 94 SDIO SPAS 3 mission. The architecture enhances rapid tailoring of functions thereby reducing costs and schedules developed for individual spacecraft missions.

A Millimeter-Wave Digital Link for Wireless MRI.

PubMed

Aggarwal, Kamal; Joshi, Kiran R; Rajavi, Yashar; Taghivand, Mazhareddin; Pauly, John M; Poon, Ada S Y; Scott, Greig

2017-02-01

A millimeter (mm) wave radio is presented in this work to support wireless MRI data transmission. High path loss and availability of wide bandwidth make mm-waves an ideal candidate for short range, high data rata communication required for wireless MRI. The proposed system uses a custom designed integrated chip (IC) mm-wave radio with 60 GHz as radio frequency carrier. In this work, we assess performance in a 1.5 T MRI field, with the addition of optical links between the console room and magnet. The system uses ON-OFF keying (OOK) modulation for data transmission and supports data rates from 200 Mb/s to 2.5 Gb/s for distances up-to 65 cm. The presence of highly directional, linearly polarized, on-chip dipole antennas on the mm-wave radio along with the time division multiplexing (TDM) circuitry allows multiple wireless links to be created simultaneously with minimal inter-channel interference. This leads to a highly scalable solution for wireless MRI.

Atlanta Centennial Olympic Games and Paralympic Games event study, 1996. Final report, July 1996--August 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amodei, R.; Bard, E.; Brong, B.

1998-11-01

The Atlanta metropolitan region was the location of one of the most ambitious Intelligent Transportation Systems (ITS) deployments in the United States. This deployment included several individual projects--a Central Transportation Management Center (TMC), six Traffic Control Centers (TCCs), one Transit Information Center (TIC), The Travel Information Showcase (TIS), and the extension of the Metropolitan Atlanta Rapid Transit Authority (MARTA) Rail network and the new high-occupancy vehicle (HOV) lanes on I-85 and I-75. The 1996 Atlanta Centennial Olympic Games and Paralympic Games created a focus for these projects. All of these systems were to be brought on-line in time for themore » Olympic Games. This report presents the findings of the 1996 Olympic and Paralympic Games Events Study--a compilation of findings of system performance, the benefits realized, and the lessons learned during their operations over the event period. The study assessed the performance of the various Travel Demand Management (TDM) plans employed for Olympic Games traffic management.« less

Insulinome de haut grade découvert après 5 ans d’hypoglycémies graves

PubMed Central

Anoun, Nadia; Hasnaoui, Hamza; Hassani, Firdaous Ameziane; Idrissi, Mehdi Bourakkadi; Ousadden, Abdelmalek; Ouahabi, Hanan El; Taleb, Khalid Ait

2017-01-01

Les tumeurs endocrines fonctionnelles du pancréas sont des lésions rares, parmi lesquelles les insulinomes sont les plus fréquents. La majorité des patients atteints d'insulinome ont entre 30 et 60 ans et 59% d'entre eux sont des femmes. La plupart des insulinomes sont sporadiques, alors que 10% sont développés chez des patients atteints de NEM. Le diagnostic repose sur la clinique et sur le bilan biologique. Le bilan d'imagerie préopératoire (Echo-endoscopie, TDM, IRM) est essentiel localisant la tumeur dans plus de 80% des cas. Le traitement de référence est l'exérèse chirurgicale de la tumeur. Nous rapportons ici un cas d'insulinome de haut grade développé sur la face antérieure de la queue du pancréas chez une patiente de 50 ans. PMID:28979651

3.3 Ga SHRIMP U-Pb zircon age of a felsic metavolcanic rock from the Mundo Novo greenstone belt in the São Francisco craton, Bahia (NE Brazil)

NASA Astrophysics Data System (ADS)

Peucat, J. J.; Mascarenhas, J. F.; Barbosa, J. S. F.; de Souza, S. L.; Marinho, M. M.; Fanning, C. M.; Leite, C. M. M.

2002-07-01

Felsic metavolcanics associated with supracrustal rocks provide U-Pb zircon and Sm-Nd TDM ages of approximately 3.3 Ga, which establish an Archean age of the Mundo Novo greenstone belt. A granodioritic gneiss from the Mairi complex, located on the eastern boundary of the Mundo Novo greenstone belt, exhibits a zircon evaporation minimum age of 3.04 Ga and a Nd model age of 3.2 Ga. These results constrain the occurrence of at least three major geological units in this area: the Archean Mundo Novo greenstone belt, the Archean Mairi gneisses, and the adjoining Paleoproterozoic (<2.1 Ga) Jacobina sedimentary basin. The Jacobina basin follows the same trend as the Archean structure, extending southward to the Contendas-Mirante belt, in which a similar Archean-Paleoproterozoic association appears. We postulate that during the Paleoproterozoic in the eastern margin of the Gavião block, these Archean greenstone belts constituted a zone of weakness along which a late-stage orogenic sedimentary basin developed.

Urine phenobarbital drug screening: potential use for compliance assessment in neonates.

PubMed

Guillet, Ronnie; Kwon, Jennifer M; Chen, Sixaio; McDermott, Michael P

2012-02-01

This study was done to determine if urine phenobarbital measurements provide a reliable indicator of presence of the drug in neonates. Urine was collected from neonates treated with phenobarbital for clinical indications within 4 to 6 hours of clinically indicated collection of serum phenobarbital levels. Urine samples were also collected from control neonates not treated with phenobarbital. One aliquot was assayed fresh, another frozen at -30°C and assayed 1 to 3 months later. Phenobarbital was assayed using the ONLINE TDM Roche/Hitachi automated clinical chemistry analyzer. Serum and urine concentrations were compared as were fresh and frozen urine measurements. Serum phenobarbital ranged from 5.6 to 52.7 μg/mL. Matched urine samples were 56.6 ± 12.5% of the serum level. Frozen samples were 98.3 ± 8.0% of the fresh samples. Urine phenobarbital concentrations, either fresh or frozen, can be used in neonates as a noninvasive estimate of drug levels.

[The therapeutic drug monitoring network server of tacrolimus for Chinese renal transplant patients].

PubMed

Deng, Chen-Hui; Zhang, Guan-Min; Bi, Shan-Shan; Zhou, Tian-Yan; Lu, Wei

2011-07-01

This study is to develop a therapeutic drug monitoring (TDM) network server of tacrolimus for Chinese renal transplant patients, which can facilitate doctor to manage patients' information and provide three levels of predictions. Database management system MySQL was employed to build and manage the database of patients and doctors' information, and hypertext mark-up language (HTML) and Java server pages (JSP) technology were employed to construct network server for database management. Based on the population pharmacokinetic model of tacrolimus for Chinese renal transplant patients, above program languages were used to construct the population prediction and subpopulation prediction modules. Based on Bayesian principle and maximization of the posterior probability function, an objective function was established, and minimized by an optimization algorithm to estimate patient's individual pharmacokinetic parameters. It is proved that the network server has the basic functions for database management and three levels of prediction to aid doctor to optimize the regimen of tacrolimus for Chinese renal transplant patients.

[Study on high accuracy detection of multi-component gas in oil-immerse power transformer].

PubMed

Fan, Jie; Chen, Xiao; Huang, Qi-Feng; Zhou, Yu; Chen, Gang

2013-12-01

In order to solve the problem of low accuracy and mutual interference in multi-component gas detection, a kind of multi-component gas detection network with high accuracy was designed. A semiconductor laser with narrow bandwidth was utilized as light source and a novel long-path gas cell was also used in this system. By taking the single sine signal to modulate the spectrum of laser and using space division multiplexing (SDM) and time division multiplexing (TDM) technique, the detection of multi-component gas was achieved. The experiments indicate that the linearity relevance coefficient is 0. 99 and the measurement relative error is less than 4%. The system dynamic response time is less than 15 s, by filling a volume of multi-component gas into the gas cell gradually. The system has advantages of high accuracy and quick response, which can be used in the fault gas on-line monitoring for power transformers in real time.

Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations.

PubMed

Choi, Rihwa; Jeong, Byeong Ho; Koh, Won Jung; Lee, Soo Youn

2017-03-01

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.

Simultaneous generation of 40, 80 and 120 GHz optical millimeter-wave from one Mach-Zehnder modulator and demonstration of millimeter-wave transmission and down-conversion

NASA Astrophysics Data System (ADS)

Zhou, Wen; Qin, Chaoyi

2017-09-01

We demonstrate multi-frequency QPSK millimeter-wave (mm-wave) vector signal generation enabled by MZM-based optical carrier suppression (OCS) modulation and in-phase/quadrature (I/Q) modulation. We numerically simulate the generation of 40-, 80- and 120-GHz vector signal. Here, the three different signals carry the same QPSK modulation information. We also experimentally realize 11Gbaud/s QPSK vector signal transmission over 20 km fiber, and the generation of the vector signals at 40-GHz, 80-GHz and 120-GHz. The experimental results show that the bit-error-rate (BER) for all the three different signals can reach the forward-error-correction (FEC) threshold of 3.8×10-3. The advantage of the proposed system is that provide high-speed, high-bandwidth and high-capacity seamless access of TDM and wireless network. These features indicate the important application prospect in wireless access networks for WiMax, Wi-Fi and 5G/LTE.

MHD simulation of the Bastille day event

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linker, Jon, E-mail: linkerj@predsci.com; Torok, Tibor; Downs, Cooper

2016-03-25

We describe a time-dependent, thermodynamic, three-dimensional MHD simulation of the July 14, 2000 coronal mass ejection (CME) and flare. The simulation starts with a background corona developed using an MDI-derived magnetic map for the boundary condition. Flux ropes using the modified Titov-Demoulin (TDm) model are used to energize the pre-event active region, which is then destabilized by photospheric flows that cancel flux near the polarity inversion line. More than 10{sup 33} ergs are impulsively released in the simulated eruption, driving a CME at 1500 km/s, close to the observed speed of 1700km/s. The post-flare emission in the simulation is morphologically similarmore » to the observed post-flare loops. The resulting flux rope that propagates to 1 AU is similar in character to the flux rope observed at 1 AU, but the simulated ICME center passes 15° north of Earth.« less

Advanced mobile satellite communications system using Ka and MM-wave bands in Japan's R and D satellite project

NASA Technical Reports Server (NTRS)

Isobe, Shunkichi; Ohmori, Shingo; Hamamoto, Naokazu; Yamamoto, Minoru

1991-01-01

Communications Research Laboratory (CRL) studied an advanced mobile satellite communications system using Ka and millimeter-wave bands in the R&D Satellite project. The project started in 1990 and the satellite will be launched in 1997. On-board multi-beam interconnecting is one of basic functions to realize one-hop connection among Very Small Aperture Terminals (VSATs), mobile, and hand-held terminals in future mobile satellite communications system. An Intermediate Frequency (IF) filter bank and regenerative transponder are suitable for this function. The transponder configuration of an advanced mobile communications mission of the R&D Satellite for experiment is shown. High power transmitters of Ka and millimeter-wave bands, a 3x3 IF filter band and Single Channel Per Carrier/Time Division Multiplexing (SCPC/TDM) regenerative MODEMS, which will be boarded on the R&D Satellite, are being developed for the purpose of studying the feasibility of advanced mobile communications system.

Extensive hydrothermal activity revealed by multi-tracer survey in the Wallis and Futuna region (SW Pacific)

NASA Astrophysics Data System (ADS)

Konn, C.; Fourré, E.; Jean-Baptiste, P.; Donval, J. P.; Guyader, V.; Birot, D.; Alix, A. S.; Gaillot, A.; Perez, F.; Dapoigny, A.; Pelleter, E.; Resing, J. A.; Charlou, J. L.; Fouquet, Y.

2016-10-01

The study area is close to the Wallis and Futuna Islands in the French EEZ. It exists on the western boundary of the fastest tectonic area in the world at the junction of the Lau and North-Fiji basins. At this place, the unstable back-arc accommodates the plate motion in three ways: (i) the north Fiji transform fault, (ii) numerous unstable spreading ridges, and (iii) large areas of recent volcanic activity. This instability creates bountiful opportunity for hydrothermal discharge to occur. Based on geochemical (CH4, TDM, 3He) and geophysical (nephelometry) tracer surveys: (1) no hydrothermal activity could be found on the Futuna Spreading Centre (FSC) which sets the western limit of hydrothermal activity; (2) four distinct hydrothermal active areas were identified: Kulo Lasi Caldera, Amanaki Volcano, Fatu Kapa and Tasi Tulo areas; (3) extensive and diverse hydrothermal manifestations were observed and especially a 2D distribution of the sources. At Kulo Lasi, our data and especially tracer ratios (CH4/3He 50×106 and CH4/TDM 4.5) reveal a transient CH4 input, with elevated levels of CH4 measured in 2010, that had vanished in 2011, most likely caused by an eruptive magmatic event. By contrast at Amanaki, vertical tracer profiles and tracer ratios point to typical seawater/basalt interactions. Fatu Kapa is characterised by a substantial spatial variability of the hydrothermal water column anomalies, most likely due to widespread focused and diffuse hydrothermal discharge in the area. In the Tasi Tulo zone, the hydrothermal signal is characterised by a total lack of turbidity, although other tracer anomalies are in the same range as in nearby Fatu Kapa. The background data set revealed the presence of a Mn and 3He chronic plume due to the extensive and cumulative venting over the entire area. To that respect, we believe that the joined domain composed of our active area and the nearby active area discovered in the East by Lupton et al. (2012) highly contribute to the

Apport de la tomodensitométrie dans le diagnostic de la tuberculose vertébrale à propos de 496 cas à Abidjan

PubMed Central

Gbané-Koné, Mariam; Ouattara, Baly; Diomandé, Mohamed; Sessou, Viva; Kaboré, Fulgence; Djoko, Kouadio Flore; Traoré, Moriba; Eti, Edmond; Kouakou, N'zué Marcel

2015-01-01

Introduction Le mal de Pott est la forme la plus fréquente des tuberculoses ostéo articulaires, le diagnostic de certitude reste difficile. L'imagerie tient une place indéniable dans le diagnostic. L'objectif de cette étude était de déterminer la prévalence de la tuberculose vertébrale et l'apport de la TDM dans le diagnostic. Méthodes Nous avons mené une étude rétrospective sur dossiers de tuberculose vertébrale dans le service de Rhumatologie du CHU de Cocody de Janvier 2006 à Décembre 2013. N'ont pas été inclus dans l’étude, tous les dossiers ne comportant pas d'imagerie. Resultats La prévalence hospitalière de la tuberculose vertébrale était de 10,95%, elle représentait 90,2% de la tuberculose ostéoarticulaire. Elle concernait les 2 sexes, l’âge moyen était de 43,27 ans (4-88ans). L'atteinte dorsolombaire était la localisation la plus fréquente (95,13%). L'atteinte du rachis cervical était rare. La spondylodiscite était fréquente (92,14%). La spondylite (6%) et l'atteinte de l'arc postérieur (0,86%) étaient rares. La spondylodiscite était unique le plus souvent (70,05%), les formes multiétagées ont été notées dans 28,65% des cas, les atteintes mutifocales ont été notées dans14, 63% des cas. Les localisations inhabituelles étaient: atteinte sous occipitale (n=3), atteinte concomitante des 3 segments rachidiens (n=3), atteinte du sacrum (n=1), abcès isolés du psoas (n=4). La prévalence des abcès était de 85,91%, celle des épidurites était de 80,17%. La ponction scannoguidée des abcès a été réalisée dans 20 cas, la recherche de BAAR était positive dans 15 cas. Il existait une tuberculose viscérale évolutive dans 20% des cas. Conclusion La TDM est indéniable dans le diagnostic positif et lésionnel de la tuberculose vertébrale. Le retard au diagnostic explique l’étendue des lésions. PMID:26113932

Carboniferous-Permian tectonic transition envisaged in two magmatic episodes at the Kuruer Cu-Au deposit, Western Tianshan (NW China)

NASA Astrophysics Data System (ADS)

Yu, Jie; Li, Nuo; Qi, Nan; Guo, Jian-Ping; Chen, Yan-Jing

2018-03-01

The Western Tianshan in NW China is one of the most important gold provinces in the Central Asian Orogenic Belt (CAOB). The recently discovered Kuruer Cu-Au deposit has been interpreted to represent a transition from high-sulfidation epithermal to porphyry mineralization system. In this study, we present new LA-ICP-MS zircon U-Pb ages for the many magmatic rock types at Kuruer, including the Dahalajunshan Formation andesitic tuff (333.2 ± 1.6 Ma), diorite porphyry (269.7 ± 2.0 Ma), slightly-altered (264.4 ± 2.6 Ma) and intensively-altered (270.5 ± 2.5 Ma) albite porphyry. These ages reveal two distinct magmatic episodes: The Early Carboniferous Dahalajunshan Formation (wall rocks) andesitic tuff samples contain narrow ranges of SiO2 (60.29-61.28 wt.%), TiO2 (0.96-0.98 wt.%), Al2O3 (16.55-16.57 wt.%) and Fe2O3T (5.36-5.57 wt.%). The tuff is characterized by LREE enrichment and HFSE depletion, as well as LREE/HREE enrichment ((La/Yb)N = 8.31-8.76) and negative Eu anomalies (δEu = 0.64-0.76). Zircon εHf (t) values are 5.4-8.2, and two-stage Hf model ages (TDM2) are 821-1016 Ma, indicating partial melting of a moderately depleted mantle wedge with Precambrian continental crustal input. The ore-forming Middle Permian diorite porphyry and (quartz) albite porphyry have variable major oxide compositions (e.g., SiO2 = 53.09-53.12 wt.% for the diorite porphyry, 70.84-78.03 wt.% for the albite porphyry, and 74.07-75.03 wt.% for the quartz albite porphyry) but similar chondrite-normalized REE and primitive mantle-normalized multi-element patterns. These porphyries display LREE enrichment and HFSE depletion, as well as elevated LREE/HREE enrichment and negative Eu anomalies. The positive zircon εHf(t) values (11.7-15.9 for the diorite porphyry, 8.9-14.9 for the albite porphyry) and young two-stage Hf model ages (TDM2) (282-542 Ma for the diorite porphyry, 337-717 Ma for the albite porphyry) indicate a major juvenile continental crustal involvement. We propose that the

U-Pb and Lu-Hf zircon geochronology of the Cañadón Asfalto Basin, Chubut, Argentina: Implications for the magmatic evolution in central Patagonia

NASA Astrophysics Data System (ADS)

Hauser, N.; Cabaleri, N. G.; Gallego, O. F.; Monferran, M. D.; Silva Nieto, D.; Armella, C.; Matteini, M.; Aparicio González, P. A.; Pimentel, M. M.; Volkheimer, W.; Reimold, W. U.

2017-10-01

The Cañadón Asfalto basin, central Chubut, Argentina, comprises a volcano-sedimentary sequence related to the opening of the Atlantic Ocean during Mesozoic times. The Lonco Trapial, Cañadón Asfalto and Cañadón Calcáreo formations are the main units related to the evolution of this basin. The Las Chacritas and Puesto Almada members are distinguished in the Cañadón Asfalto Formation. LA-HR-ICP-MS U-Pb and Lu-Hf data on zircon were obtained on these units. The Lonco Trapial Formation gave a weighted average age of 172.3 ± 1.8 Ma. A pyroclastic level from the Las Chacritas Member gave a weighted average age of 168.2 ± 2.2 Ma. Two U-Pb concordant ages of 160.3 ± 1.7 Ma on a laminated tuffite and 158.3 ± 1.3 Ma on a pyroclastic level were obtained for the Puesto Almada Member. Two maximum depositional ages constrain the sedimentary provenance areas for the basin: 1) A sample from the Sierra de la Manea range, where a controversial unit related either to the Cañadón Asfalto or to the Cañadón Calcáreo formation occurs, gave an age of 176.6 ± 1.0 Ma. Two younger zircon crystals indicate that this unit may be related to the Cañadón Calcáreo Formation. 2) A sandstone with cross-stratification from the Puesto Almada Member gave a maximum depositional age of 173.6 ± 6.4 Ma. In terms of U-Pb and Lu-Hf isotopes, two magmatic events are identified in central Patagonia: the Mamil Choique magmatic event characterized by negative εHf values around -5.0 and representing recycling during Permian times of Mesoproterozoic crust (TDM of ∼1.5 Ga), and the Cañadón Asfalto magmatic event with negative (-8.2) to positive (+4) εHf values and Meso- to Neoproterozoic TDM between 1.5 and 0.8 Ga. The younger event is characterized by three main cycles: C1 related to the Lonco Trapial magmatism, C2 to the Las Chacritas volcanism, and C3 to the Puesto Almada volcanism. These cycles are related with Marifil, Chon Aike and El Quemado formations volcanics events of

1.88 Ga São Gabriel AMCG association in the southernmost Uatumã-Anauá Domain: Petrological implications for post-collisional A-type magmatism in the Amazonian Craton

NASA Astrophysics Data System (ADS)

Valério, Cristóvão da Silva; Macambira, Moacir José Buenano; Souza, Valmir da Silva; Dantas, Elton Luiz; Nardi, Lauro Valentim Stoll

2018-02-01

In the southernmost Uatumã-Anauá Domain, central Amazonian craton (Brazil), crop out 1.98 Ga basement inliers represented by (meta)leucosyenogranites and amphibolites (Igarapé Canoas Suite), 1.90-1.89 Ga high-K calc-alkaline granitoids (Água Branca Suite), a 1.88-1.87 Ga alkali-calcic A-type volcano-plutonic system (Iricoumé-Mapuera), Tonian SiO2-satured alkaline granitoids, 1.45-1.25 Ga orthoderived metamorphic rocks (Jauaperi Complex) and Orosirian-Upper Triassic mafic intrusions. New data on petrography, multielementar geochemistry, in situ zircon U-Pb ages and Nd and Hf isotopes of alkali-calcic A-type granites (São Gabriel Granite, Mapuera Suite) and related rocks are indicative of a 1.89-1.87 Ga volcano-plutonic system integrated to the São Gabriel AMCG association. Its magmatic evolution was controlled by the fractional crystallization combined with magma mixing and cumulation processes. Nd isotope values (εNdt values = - 3.71 to + 0.51 and Nd TDM model age = 2.44 to 2.12 Ga) and U-Pb inherited zircon crystals (2115 ± 22 Ma; 2206 ± 21 Ma; 2377 ± 17 Ma, 2385 ± 17 Ma) of the São Gabriel system indicate a large participation of Siderian-Rhyacian crust (granite-greenstones and granulites) and small contribution of Rhyacian mantelic magma. εHft values (+ 5.2 to - 5.8) and Hf TDM ages (3.27-2.14 Ga) also point to contribution of Paleoarchean-Rhyacian crustal melts and small participation of Siderian-Rhyacian mantle melts. Residual melts from the lower crust have been mixed with basaltic melts generated by partial melting of the subcontinental lithospheric mantle (peridotite) in a post-collisional setting at 1.89-1.87 Ga. The mafic melts of such a mixture could have been originated through partial melting of residual ocean plate fragments (eclogites) which ascended onto a residual mantle wedge (hornblende peridotite) and melted it, resulting in modified basaltic magma which, by underplating, led heat to the anatexis of the lower continental crust