Dynamic Bandwidth Allocation with Effective Utilization of Polling Interval over WDM/TDM PON

NASA Astrophysics Data System (ADS)

Ni, Cuiping; Gan, Chaoqin; Gao, Ziyue

2014-12-01

WDM/TDM (wavelength-division multiplexing/time-division multiplexing) PON (passive optical network) appears to be an attractive solution for the next generation optical access networks. Dynamic bandwidth allocation (DBA) plays a crucial role in efficiently and fairly allocating the bandwidth among all users in WDM/TDM PON. In this paper, two dynamic bandwidth allocation schemes (DBA1 and DBA2) are proposed to eliminate the idle time of polling cycles (i.e. polling interval), improve bandwidth utilization and make full use of bandwidth resources. The two DBA schemes adjust the time slot of sending request information and make fair scheduling among users to achieve the effective utilization of polling interval in WDM/TDM PON. The simulation and theoretical analyses verify that the proposed schemes outperform the conventional DBA scheme. We also make comparisons between the two schemes in terms of bandwidth utilization and average packet delay to further demonstrate the effectiveness of the scheme of DBA2.

Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

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

Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com; Flagella, Kelly; Beyer, Joseph

2013-12-01

Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeysmore » and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and

A novel survivable architecture for hybrid WDM/TDM passive optical networks

NASA Astrophysics Data System (ADS)

Qiu, Yang; Chan, Chun-Kit

2014-02-01

A novel tree-ring survivable architecture, which consists of an organization of a wavelength-division-multiplexing (WDM) tree from optical line terminal (OLT) to remote nodes (RNs) and a time division multiplexing (TDM) ring in each RN, is proposed for hybrid WDM/TDM passive optical networks. By utilizing the cyclic property of arrayed waveguide gratings (AWGs) and the single-ring topology among a group of optical network units (ONUs) in the remote node, not only the feeder and distribution fibers, but also any fiber failures in the RN rings are protected simultaneously. Five-Gbit/s transmissions under both normal working and protection modes were experimentally demonstrated and a traffic restoration time was successfully measured.

Direct Digital Demultiplexing of Analog TDM Signals for Cable Reduction in Ultrasound Imaging Catheters

PubMed Central

Carpenter, Thomas M.; Rashid, M. Wasequr; Ghovanloo, Maysam; Cowell, David M. J.; Freear, Steven; Degertekin, F. Levent

2016-01-01

In real-time catheter based 3D ultrasound imaging applications, gathering data from the transducer arrays is difficult as there is a restriction on cable count due to the diameter of the catheter. Although area and power hungry multiplexing circuits integrated at the catheter tip are used in some applications, these are unsuitable for use in small sized catheters for applications like intracardiac imaging. Furthermore, the length requirement for catheters and limited power available to on-chip cable drivers leads to limited signal strength at the receiver end. In this paper an alternative approach using Analog Time Division Multiplexing (TDM) is presented which addresses the cable restrictions of ultrasound catheters. A novel digital demultiplexing technique is also described which allows for a reduction in the number of analog signal processing stages required. The TDM and digital demultiplexing schemes are demonstrated for an intracardiac imaging system that would operate in the 4 MHz to 11 MHz range. A TDM integrated circuit (IC) with 8:1 multiplexer is interfaced with a fast ADC through a micro-coaxial catheter cable bundle, and processed with an FPGA RTL simulation. Input signals to the TDM IC are recovered with −40 dB crosstalk between channels on the same micro-coax, showing the feasibility of this system for ultrasound imaging applications. PMID:27116738

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.

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.

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

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.

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.

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.

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...

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.

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.

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.

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

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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.

Animal models of aging research: implications for human aging and age-related diseases.

PubMed

Mitchell, Sarah J; Scheibye-Knudsen, Morten; Longo, Dan L; de Cabo, Rafael

2015-01-01

Aging is characterized by an increasing morbidity and functional decline that eventually results in the death of an organism. Aging is the largest risk factor for numerous human diseases, and understanding the aging process may thereby facilitate the development of new treatments for age-associated diseases. The use of humans in aging research is complicated by many factors, including ethical issues; environmental and social factors; and perhaps most importantly, their long natural life span. Although cellular models of human disease provide valuable mechanistic information, they are limited in that they may not replicate the in vivo biology. Almost all organisms age, and thus animal models can be useful for studying aging. Herein, we review some of the major models currently used in aging research and discuss their benefits and pitfalls, including interventions known to extend life span and health span. Finally, we conclude by discussing the future of animal models in aging research.

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.

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

Modeled ground water age distributions

USGS Publications Warehouse

Woolfenden, Linda R.; Ginn, Timothy R.

2009-01-01

The age of ground water in any given sample is a distributed quantity representing distributed provenance (in space and time) of the water. Conventional analysis of tracers such as unstable isotopes or anthropogenic chemical species gives discrete or binary measures of the presence of water of a given age. Modeled ground water age distributions provide a continuous measure of contributions from different recharge sources to aquifers. A numerical solution of the ground water age equation of Ginn (1999) was tested both on a hypothetical simplified one-dimensional flow system and under real world conditions. Results from these simulations yield the first continuous distributions of ground water age using this model. Complete age distributions as a function of one and two space dimensions were obtained from both numerical experiments. Simulations in the test problem produced mean ages that were consistent with the expected value at the end of the model domain for all dispersivity values tested, although the mean ages for the two highest dispersivity values deviated slightly from the expected value. Mean ages in the dispersionless case also were consistent with the expected mean ages throughout the physical model domain. Simulations under real world conditions for three dispersivity values resulted in decreasing mean age with increasing dispersivity. This likely is a consequence of an edge effect. However, simulations for all three dispersivity values tested were mass balanced and stable demonstrating that the solution of the ground water age equation can provide estimates of water mass density distributions over age under real world conditions.

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

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.

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

Age and tectonic implications of Paleoproterozoic Deo Khe Granitoids within the Phan Si Pan Zone, Vietnam

NASA Astrophysics Data System (ADS)

Anh, Hoang Thi Hong; Hieu, Pham Trung; Tu, Vu Le; Son, La Mai; Choi, Sung Hi; Yu, Yongjae

2015-11-01

We report the first U-Pb zircon ages of 1855-1873 Ma for the Deo Khe Granitoids (DKG) in the Phan Si Pan Zone (PSPZ) of northern Vietnam. The DKG are medium-grained two-mica granitoids predominantly composed of quartz, K-feldspar, and muscovite. Trace element analyses indicate that the DKG are enriched in large ion lithophile elements but depleted in high field strength elements. Zircons from the granitoids have negative εHf(t) values ranging from -23.6 to -17.5. The magmatic zircons from the DKG have single-stage Hf model ages (TDM1) that range from 3.3 to 2.8 Ga and their εHf(t) data all plot well below the evolution trend of 2800 Ma average juvenile mantle. Observed Hf model ages are contemporaneous with the emplacement of 2.90-2.84 Ga tonalite-trondhjemite-granodiorite (TTG) gneiss observed in a nearby Ca Vinh Complex, suggesting that PSPZ in northern Vietnam is a product of partial melting of Archean crust. A sequence of similar tectonic events including initial emplacement of TTG protolith at 2.8-2.9 Ga, metamorphic development of TTG gneiss at 1.9-2.0 Ga, and magmatic activity at 1.8-2.0 Ga are now recognized both in northern Vietnam and Yangtze block which we interpret to indicate basement rocks in northern Vietnam are similar to those found along southern China.

Modelling the molecular mechanisms of aging

PubMed Central

Mc Auley, Mark T.; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M.; Morgan, Amy E.

2017-01-01

The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field. PMID:28096317

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.

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.

Mixed models, linear dependency, and identification in age-period-cohort models.

PubMed

O'Brien, Robert M

2017-07-20

This paper examines the identification problem in age-period-cohort models that use either linear or categorically coded ages, periods, and cohorts or combinations of these parameterizations. These models are not identified using the traditional fixed effect regression model approach because of a linear dependency between the ages, periods, and cohorts. However, these models can be identified if the researcher introduces a single just identifying constraint on the model coefficients. The problem with such constraints is that the results can differ substantially depending on the constraint chosen. Somewhat surprisingly, age-period-cohort models that specify one or more of ages and/or periods and/or cohorts as random effects are identified. This is the case without introducing an additional constraint. I label this identification as statistical model identification and show how statistical model identification comes about in mixed models and why which effects are treated as fixed and which are treated as random can substantially change the estimates of the age, period, and cohort effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

C. elegans model of neuronal aging

PubMed Central

Peng, Chiu-Ying; Chen, Chun-Hao; Hsu, Jiun-Min

2011-01-01

Aging of the nervous system underlies the behavioral and cognitive decline associated with senescence. Understanding the molecular and cellular basis of neuronal aging will therefore contribute to the development of effective treatments for aging and age-associated neurodegenerative disorders. Despite this pressing need, there are surprisingly few animal models that aim at recapitulating neuronal aging in a physiological context. We recently developed a C. elegans model of neuronal aging, and showed that age-dependent neuronal defects are regulated by insulin signaling. We identified electrical activity and epithelial attachment as two critical factors in the maintenance of structural integrity of C. elegans touch receptor neurons. These findings open a new avenue for elucidating the molecular mechanisms that maintain neuronal structures during the course of aging. PMID:22446530

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.

Biological Aging - Criteria for Modeling and a New Mechanistic Model

NASA Astrophysics Data System (ADS)

Pletcher, Scott D.; Neuhauser, Claudia

To stimulate interaction and collaboration across scientific fields, we introduce a minimum set of biological criteria that theoretical models of aging should satisfy. We review results of several recent experiments that examined changes in age-specific mortality rates caused by genetic and environmental manipulation. The empirical data from these experiments is then used to test mathematical models of aging from several different disciplines, including molecular biology, reliability theory, physics, and evolutionary biology/population genetics. We find that none of the current models are consistent with all of the published experimental findings. To provide an example of how our criteria might be applied in practice, we develop a new conceptual model of aging that is consistent with our observations.

Towards an Analytical Age-Dependent Model of Contrast Sensitivity Functions for an Ageing Society

PubMed Central

Joulan, Karine; Brémond, Roland

2015-01-01

The Contrast Sensitivity Function (CSF) describes how the visibility of a grating depends on the stimulus spatial frequency. Many published CSF data have demonstrated that contrast sensitivity declines with age. However, an age-dependent analytical model of the CSF is not available to date. In this paper, we propose such an analytical CSF model based on visual mechanisms, taking into account the age factor. To this end, we have extended an existing model from Barten (1999), taking into account the dependencies of this model's optical and physiological parameters on age. Age-dependent models of the cones and ganglion cells densities, the optical and neural MTF, and optical and neural noise are proposed, based on published data. The proposed age-dependent CSF is finally tested against available experimental data, with fair results. Such an age-dependent model may be beneficial when designing real-time age-dependent image coding and display applications. PMID:26078994

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

Exactly solvable models of growing interfaces and lattice gases: the Arcetri models, ageing and logarithmic sub-ageing

NASA Astrophysics Data System (ADS)

Durang, Xavier; Henkel, Malte

2017-12-01

Motivated by an analogy with the spherical model of a ferromagnet, the three Arcetri models are defined. They present new universality classes, either for the growth of interfaces, or else for lattice gases. They are distinct from the common Edwards-Wilkinson and Kardar-Parisi-Zhang universality classes. Their non-equilibrium evolution can be studied by the exact computation of their two-time correlators and responses. In both interpretations, the first model has a critical point in any dimension and shows simple ageing at and below criticality. The exact universal exponents are found. The second and third model are solved at zero temperature, in one dimension, where both show logarithmic sub-ageing, of which several distinct types are identified. Physically, the second model describes a lattice gas and the third model describes interface growth. A clear physical picture on the subsequent time and length scales of the sub-ageing process emerges.

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

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.

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.

System Models and Aging: A Driving Example.

ERIC Educational Resources Information Center

Melichar, Joseph F.

Chronological age is a marker in time but it fails to measure accurately the performance or behavioral characteristics of individuals. This paper models the complexity of aging by using a system model and a human function paradigm. These models help facilitate representation of older adults, integrate research agendas, and enhance remediative…

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.

Progeroid syndromes: models for stem cell aging?

PubMed

Bellantuono, I; Sanguinetti, G; Keith, W N

2012-02-01

Stem cells are responsible for tissue repair and maintenance and it is assumed that changes observed in the stem cell compartment with age underlie the concomitant decline in tissue function. Studies in murine models have highlighted the importance of intrinsic changes occurring in stem cells with age. They have also drawn the attention to other factors, such as changes in the local or systemic environment as the primary cause of stem cell dysfunction. Whilst knowledge in murine models has been advancing rapidly there has been little translation of these data to human aging. This is most likely due to the difficulties of testing the regenerative capacity of human stem cells in vivo and to substantial differences in the aging phenotype within humans. Here we summarize evidence to show how progeroid syndromes, integrated with other models, can be valuable tools in addressing questions about the role of stem cell aging in human degenerative diseases of older age and the molecular pathways involved.

Shared Ageing Research Models (ShARM): a new facility to support ageing research.

PubMed

Duran, Adele L; Potter, Paul; Wells, Sara; Kirkwood, Tom; von Zglinicki, Thomas; McArdle, Anne; Scudamore, Cheryl; Meng, Qing-Jun; de Haan, Gerald; Corcoran, Anne; Bellantuono, Ilaria

2013-12-01

In order to manage the rise in life expectancy and the concomitant increased occurrence of age-related diseases, research into ageing has become a strategic priority. Mouse models are commonly utilised as they share high homology with humans and show many similar signs and diseases of ageing. However, the time and cost needed to rear aged cohorts can limit research opportunities. Sharing of resources can provide an ethically and economically superior framework to overcome some of these issues but requires dedicated infrastructure. Shared Ageing Research Models (ShARM) ( www.ShARMUK.org ) is a new, not-for-profit organisation funded by Wellcome Trust, open to all investigators. It collects, stores and distributes flash frozen tissues from aged murine models through its biorepository and provides a database of live ageing mouse colonies available in the UK and abroad. It also has an online environment (MICEspace) for collation and analysis of data from communal models and discussion boards on subjects such as the welfare of ageing animals and common endpoints for intervention studies. Since launching in July 2012, thanks to the generosity of researchers in UK and Europe, ShARM has collected more than 2,500 tissues and has in excess of 2,000 mice registered in live ageing colonies. By providing the appropriate support, ShARM has been able to bring together the knowledge and experience of investigators in the UK and Europe to maximise research outputs with little additional cost and minimising animal use in order to facilitate progress in ageing research.

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.

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.

The potential of artificial aging for modelling of natural aging processes of ballpoint ink.

PubMed

Weyermann, Céline; Spengler, Bernhard

2008-08-25

Artificial aging has been used to reproduce natural aging processes in an accelerated pace. Questioned documents were exposed to light or high temperature in a well-defined manner in order to simulate an increased age. This may be used to study the aging processes or to date documents by reproducing their aging curve. Ink was studied especially because it is deposited on the paper when a document, such as a contract, is produced. Once on the paper, aging processes start through degradation of dyes, solvents drying and resins polymerisation. Modelling of dye's and solvent's aging was attempted. These processes, however, follow complex pathways, influenced by many factors which can be classified as three major groups: ink composition, paper type and storage conditions. The influence of these factors is such that different aging states can be obtained for an identical point in time. Storage conditions in particular are difficult to simulate, as they are dependent on environmental conditions (e.g. intensity and dose of light, temperature, air flow, humidity) and cannot be controlled in the natural aging of questioned documents. The problem therefore lies more in the variety of different conditions a questioned document might be exposed to during its natural aging, rather than in the simulation of such conditions in the laboratory. Nevertheless, a precise modelling of natural aging curves based on artificial aging curves is obtained when performed on the same paper and ink. A standard model for aging processes of ink on paper is therefore presented that is based on a fit of aging curves to a power law of solvent concentrations as a function of time. A mathematical transformation of artificial aging curves into modelled natural aging curves results in excellent overlap with data from real natural aging processes.

Animal and human models to understand ageing.

PubMed

Lees, Hayley; Walters, Hannah; Cox, Lynne S

2016-11-01

Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing. Copyright © 2016. Published by Elsevier Ireland Ltd.

The yeast replicative aging model.

PubMed

He, Chong; Zhou, Chuankai; Kennedy, Brian K

2018-03-08

It has been nearly three decades since the budding yeast Saccharomyces cerevisiae became a significant model organism for aging research and it has emerged as both simple and powerful. The replicative aging assay, which interrogates the number of times a "mother" cell can divide and produce "daughters", has been a stalwart in these studies, and genetic approaches have led to the identification of hundreds of genes impacting lifespan. More recently, cell biological and biochemical approaches have been developed to determine how cellular processes become altered with age. Together, the tools are in place to develop a holistic view of aging in this single-celled organism. Here, we summarize the current state of understanding of yeast replicative aging with a focus on the recent studies that shed new light on how aging pathways interact to modulate lifespan in yeast. Copyright © 2018. Published by Elsevier B.V.

The heuristic value of redundancy models of aging.

PubMed

Boonekamp, Jelle J; Briga, Michael; Verhulst, Simon

2015-11-01

Molecular studies of aging aim to unravel the cause(s) of aging bottom-up, but linking these mechanisms to organismal level processes remains a challenge. We propose that complementary top-down data-directed modelling of organismal level empirical findings may contribute to developing these links. To this end, we explore the heuristic value of redundancy models of aging to develop a deeper insight into the mechanisms causing variation in senescence and lifespan. We start by showing (i) how different redundancy model parameters affect projected aging and mortality, and (ii) how variation in redundancy model parameters relates to variation in parameters of the Gompertz equation. Lifestyle changes or medical interventions during life can modify mortality rate, and we investigate (iii) how interventions that change specific redundancy parameters within the model affect subsequent mortality and actuarial senescence. Lastly, as an example of data-directed modelling and the insights that can be gained from this, (iv) we fit a redundancy model to mortality patterns observed by Mair et al. (2003; Science 301: 1731-1733) in Drosophila that were subjected to dietary restriction and temperature manipulations. Mair et al. found that dietary restriction instantaneously reduced mortality rate without affecting aging, while temperature manipulations had more transient effects on mortality rate and did affect aging. We show that after adjusting model parameters the redundancy model describes both effects well, and a comparison of the parameter values yields a deeper insight in the mechanisms causing these contrasting effects. We see replacement of the redundancy model parameters by more detailed sub-models of these parameters as a next step in linking demographic patterns to underlying molecular mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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.

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.

[Active ageing and success: A brief history of conceptual models].

PubMed

Petretto, Donatella Rita; Pili, Roberto; Gaviano, Luca; Matos López, Cristina; Zuddas, Carlo

2016-01-01

The aim of this paper is to analyse and describe different conceptual models of successful ageing, active and healthy ageing developed in Europe and in America in the 20° century, starting from Rowe and Kahn's original model (1987, 1997). A narrative review was conducted on the literature on successful ageing. Our review included definition of successful ageing from European and American scholars. Models were found that aimed to describe indexes of active and healthy ageing, models devoted to describe processes involved in successful ageing, and additional views that emphasise subjective and objective perception of successful ageing. A description is also given of critiques on previous models and remedies according to Martin et al. (2014) and strategies for successful ageing according to Jeste and Depp (2014). The need is discussed for the enhancement of Rowe and Kahn's model and other models with a more inclusive, universal description of ageing, incorporating scientific evidence regarding active ageing. Copyright © 2015 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Re-evaluating neonatal-age models for ungulates: Does model choice affect survival estimates?

USGS Publications Warehouse

Grovenburg, Troy W.; Monteith, Kevin L.; Jacques, Christopher N.; Klaver, Robert W.; DePerno, Christopher S.; Brinkman, Todd J.; Monteith, Kyle B.; Gilbert, Sophie L.; Smith, Joshua B.; Bleich, Vernon C.; Swanson, Christopher C.; Jenks, Jonathan A.

2014-01-01

New-hoof growth is regarded as the most reliable metric for predicting age of newborn ungulates, but variation in estimated age among hoof-growth equations that have been developed may affect estimates of survival in staggered-entry models. We used known-age newborns to evaluate variation in age estimates among existing hoof-growth equations and to determine the consequences of that variation on survival estimates. During 2001–2009, we captured and radiocollared 174 newborn (≤24-hrs old) ungulates: 76 white-tailed deer (Odocoileus virginianus) in Minnesota and South Dakota, 61 mule deer (O. hemionus) in California, and 37 pronghorn (Antilocapra americana) in South Dakota. Estimated age of known-age newborns differed among hoof-growth models and varied by >15 days for white-tailed deer, >20 days for mule deer, and >10 days for pronghorn. Accuracy (i.e., the proportion of neonates assigned to the correct age) in aging newborns using published equations ranged from 0.0% to 39.4% in white-tailed deer, 0.0% to 3.3% in mule deer, and was 0.0% for pronghorns. Results of survival modeling indicated that variability in estimates of age-at-capture affected short-term estimates of survival (i.e., 30 days) for white-tailed deer and mule deer, and survival estimates over a longer time frame (i.e., 120 days) for mule deer. Conversely, survival estimates for pronghorn were not affected by estimates of age. Our analyses indicate that modeling survival in daily intervals is too fine a temporal scale when age-at-capture is unknown given the potential inaccuracies among equations used to estimate age of neonates. Instead, weekly survival intervals are more appropriate because most models accurately predicted ages within 1 week of the known age. Variation among results of neonatal-age models on short- and long-term estimates of survival for known-age young emphasizes the importance of selecting an appropriate hoof-growth equation and appropriately defining intervals (i.e., weekly

Aging Research Using Mouse Models

PubMed Central

Ackert-Bicknell, Cheryl L.; Anderson, Laura; Sheehan, Susan; Hill, Warren G.; Chang, Bo; Churchill, Gary A.; Chesler, Elissa J.; Korstanje, Ron; Peters, Luanne L.

2015-01-01

Despite the dramatic increase in human lifespan over the past century, there remains pronounced variability in “health-span”, or the period of time in which one is generally healthy and free of disease. Much of the variability in health-span and lifespan is thought to be genetic in origin. Understanding the genetic mechanisms of aging and identifying ways to boost longevity is a primary goal in aging research. Here, we describe a pipeline of phenotypic assays for assessing mouse models of aging. This pipeline includes behavior/cognition testing, body composition analysis, and tests of kidney function, hematopoiesis, immune function and physical parameters. We also describe study design methods for assessing lifespan and health-span, and other important considerations when conducting aging research in the laboratory mouse. The tools and assays provided can assist researchers with understanding the correlative relationships between age-associated phenotypes and, ultimately, the role of specific genes in the aging process. PMID:26069080

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.

Aging Well on the Autism Spectrum: An Examination of the Dominant Model of Successful Aging.

PubMed

Hwang, Ye In; Foley, Kitty-Rose; Trollor, Julian N

2018-05-02

There is a gap in our knowledge of aging with autism. The present study examined the applicability of the popular gerontology concept of "aging well" to autistic adults. Using survey data, a model of "aging well" was operationalised and applied to 92 autistic adults and 60 controls. A very small proportion (3.3%) of autistic adults were found to be aging well. Significantly less autistic adults were "maintaining physical and cognitive functioning" and "actively engaging with life" in comparison to controls. Whilst important differences in health and functioning status were found, the current dominant model of "aging well" is limited for examining autistic individuals. Suggested adjustments include development of a broader, more flexible and strengths -based model.

An age-specific biokinetic model for iodine

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

Leggett, Richard Wayne

This study reviews age-specific biokinetic data for iodine in humans and extends to pre-adult ages the baseline parameter values of the author’s previously published model for systemic iodine in adult humans. Compared with the ICRP’s current age-specific model for iodine introduced in Publication 56 (1989), the present model provides a more detailed description of the behavior of iodine in the human body; predicts greater cumulative (integrated) activity in the thyroid for short-lived isotopes of iodine; predicts similar cumulative activity in the thyroid for isotopes with half-time greater than a few hours; and, for most iodine isotopes, predicts much greater cumulativemore » activity in salivary glands, stomach wall, liver, and kidneys.« less

An age-specific biokinetic model for iodine

DOE PAGES

Leggett, Richard Wayne

2017-10-26

This study reviews age-specific biokinetic data for iodine in humans and extends to pre-adult ages the baseline parameter values of the author’s previously published model for systemic iodine in adult humans. Compared with the ICRP’s current age-specific model for iodine introduced in Publication 56 (1989), the present model provides a more detailed description of the behavior of iodine in the human body; predicts greater cumulative (integrated) activity in the thyroid for short-lived isotopes of iodine; predicts similar cumulative activity in the thyroid for isotopes with half-time greater than a few hours; and, for most iodine isotopes, predicts much greater cumulativemore » activity in salivary glands, stomach wall, liver, and kidneys.« less

A Model of Spirituality for Ageing Muslims.

PubMed

Ahmad, Mahjabeen; Khan, Shamsul

2016-06-01

Spirituality's influence on general well-being and its association with healthy ageing has been studied extensively. However, a different perspective has to be brought in when dealing with spirituality issues of ageing Muslims. Central to this perspective is the intertwining of religion and spirituality in Islam. This article will contribute to the understanding of the nature of Islamic spirituality and its immense importance in the life of a practicing ageing Muslim. Consequently, it will help care providers to include appropriate spiritual care in the care repertoire of a Muslim care recipient. It is assumed that the framework for a model of spirituality based on Islamic religious beliefs would help contextualise the relationship between spirituality and ageing Muslims. Not only challenges, but also the opportunities that old age provides for charting the spiritual journey have underpinned this model.

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...

Modeling and measuring extravascular hemoglobin: aging contusions

NASA Astrophysics Data System (ADS)

Lines, Collin; Kim, Oleg; Duffy, Susan; Alber, Mark; Crawford, Gregory P.

2011-07-01

Medical expertise is frequently elicited to aid in determining the age and the cause of the trauma or injury. Child protection and law enforcement frequently rely on the physical assessment of the trauma which involves delineating intentional from unintentional types of trauma. Recent studies have shown that current methods to assess the age of traumatic injuries are highly inaccurate and do not give reasonable predictions. Hemoglobin is one of the strongest chromophores in human tissues. Transport of hemoglobin and its breakdown products in tissue determines the spectrophotometric characteristics of the skin and its variations in time. Therefore, measurements of diffuse reflective spectra of the skin allow noninvasive screening. This paper reviews potential transmission and diffusive reflection spectroscopy based techniques and predictive and quantitative modeling methods assisting in efficient retrieval of the age of extravascular contusions. This paper then presents a novel Monte Carlo technique for 3D photon tracking and blood transport model. In future studies, clinically obtained spectra will be used to validate the model as well as fine-tune coefficients for absorption. It is the goal of this study to develop a model that would allow a non-invasive, accurate determination of the age of a bruise.

Stem Cell Models: A Guide to Understand and Mitigate Aging?

PubMed

Brunauer, Regina; Alavez, Silvestre; Kennedy, Brian K

2017-01-01

Aging is studied either on a systemic level using life span and health span of animal models, or on the cellular level using replicative life span of yeast or mammalian cells. While useful in identifying general and conserved pathways of aging, both approaches provide only limited information about cell-type specific causes and mechanisms of aging. Stem cells are the regenerative units of multicellular life, and stem cell aging might be a major cause for organismal aging. Using the examples of hematopoietic stem cell aging and human pluripotent stem cell models, we propose that stem cell models of aging are valuable for studying tissue-specific causes and mechanisms of aging and can provide unique insights into the mammalian aging process that may be inaccessible in simple model organisms. © 2016 S. Karger AG, Basel.

Creating Better School-Age Care Jobs: Model Work Standards.

ERIC Educational Resources Information Center

Haack, Peggy

Built on the premise that good school-age care jobs are the cornerstone of high-quality services for school-age youth and their families, this guide presents model work standards for school-age care providers. The guide begins with a description of the strengths and challenges of the school-age care profession. The model work standards are…

Travelling Wave Solutions in Multigroup Age-Structured Epidemic Models

NASA Astrophysics Data System (ADS)

Ducrot, Arnaut; Magal, Pierre; Ruan, Shigui

2010-01-01

Age-structured epidemic models have been used to describe either the age of individuals or the age of infection of certain diseases and to determine how these characteristics affect the outcomes and consequences of epidemiological processes. Most results on age-structured epidemic models focus on the existence, uniqueness, and convergence to disease equilibria of solutions. In this paper we investigate the existence of travelling wave solutions in a deterministic age-structured model describing the circulation of a disease within a population of multigroups. Individuals of each group are able to move with a random walk which is modelled by the classical Fickian diffusion and are classified into two subclasses, susceptible and infective. A susceptible individual in a given group can be crisscross infected by direct contact with infective individuals of possibly any group. This process of transmission can depend upon the age of the disease of infected individuals. The goal of this paper is to provide sufficient conditions that ensure the existence of travelling wave solutions for the age-structured epidemic model. The case of two population groups is numerically investigated which applies to the crisscross transmission of feline immunodeficiency virus (FIV) and some sexual transmission diseases.

Syn-orogenic magmatism over 100 m.y. in high crustal levels of the central Grenville Province: Characteristics, age and tectonic significance

NASA Astrophysics Data System (ADS)

Groulier, Pierre-Arthur; Indares, Aphrodite; Dunning, Gregory; Moukhsil, Abdelali; Jenner, George

2018-07-01

The Escoumins Supracrustal Belt (ESB) represents higher levels of the infrastructure of a large hot orogen, exposed in a broadly dome and basin pattern. It consists of remnants of a Pinwarian-age (1.52-1.46 Ga) oceanic arc and arc-rift sequence, preserved in the low-P Belt of the central Grenville Province, and was intruded by diverse Grenvillian-age plutons. The plutonic rocks range from quartz monzodiorite to granite and have intrusion ages covering a time interval of 100 My, that represents the entire range of the Grenvillian orogeny. Moreover, the ages, field relations and geochemical signatures of the different intrusions can be matched with different documented stages of the orogeny. The oldest pluton, the magnesian, biotite-bearing Bon-Désir granite (1086 ± 2 Ma), has positive εNd (+0.6), TDM = 1.52 Ga, and is attributed to melting of a juvenile Pinwarian crust as a result of slab break-off, at the onset of continental collision. The ferroan and Ba-Sr enriched, biotite-, amphibole- and clinopyroxene-bearing Michaud plutonic suite (1063 ± 3 Ma) and biotite-rich felsic sill (1045 ± 3 Ma) have εNd (-0.01 - +0.8) and TDM = 1.45-1.48 Ga. Their geochemistry is consistent with fractionation of a mafic magma derived from melting of a Geon 14 subduction-modified subcontinental lithospheric mantle. This magmatism is consistent with convective thinning of subcontinental lithosphere, potentially linked to tectonic extrusion and orogenic collapse. This collapse ultimately led to the juxtaposition of the low-P Belt with the high-T mid-P Belt in the hinterland of the Grenville Province and to amphibolite-facies metamorphism in the former, producing metamorphic zircon overgrowths at 1037 ± 10 Ma. Finally, 988 ± 5 Ma to 983 ± 5 Ma syn-kinematic peraluminous two-mica garnetiferous leucogranite bodies and pegmatites with inherited 1055 ± 2 Ma metamorphic monazite were derived from melting of previously metamorphosed deeper levels of the low-P Belt. This is consistent

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.

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.

Aging models of acute seizures and epilepsy.

PubMed

Kelly, Kevin M

2010-01-01

Aged animals have been used by researchers to better understand the differences between the young and the aged brain and how these differences may provide insight into the mechanisms of acute seizures and epilepsy in the elderly. To date, there have been relatively few studies dedicated to the modeling of acute seizures and epilepsy in aged, healthy animals. Inherent challenges to this area of research include the costs associated with the purchase and maintenance of older animals and, at times, the unexpected and potentially confounding comorbidities associated with aging. However, recent studies using a variety of in vivo and in vitro models of acute seizures and epilepsy in mice and rats have built upon early investigations in the field, all of which has provided an expanded vision of seizure generation and epileptogenesis in the aged brain. Results of these studies could potentially translate to new and tailored interventional approaches that limit or prevent the development of epilepsy in the elderly.

Canadian government's framing of ageing at work and older workers: Echoing positive ageing models.

PubMed

Lagacé, Martine; Nahon-Serfaty, Isaac; Laplante, Joelle

2015-01-01

Public representations of ageing can influence how individuals perceive their own experience of ageing. Results of studies on the OECD (Organisation for Economic Co-operation and Development)'s governmental messages on older workers suggest that they are mainly constructed around economic productivity and personal responsibility. The goal of this study is to examine how the Canadian government frames issues around ageing, work and older workers. Canada is facing a rapidly ageing workforce, hence the importance of examining how the government discusses ageing at work. A thematic content analysis was conducted on a total of 154 government web pages. Results revealed that predominant themes revolve around economic challenges resulting from an ageing workforce. Older workers are depicted as a key component for the (economic) management of an ageing workforce. More specifically, older workers who intend to continue working are highly valued in the government's messages which present them as productive citizens and role models for "ageing well". Canada's response to the challenges of an ageing workforce echoes the underlying standards of positive ageing models, which may generate, perhaps inadvertently, a new form of ageism by creating intra-and intergenerational divides in the workplace.

An Empirical Comparison of Different Models of Active Aging in Canada: The International Mobility in Aging Study

PubMed Central

Ahmed, Tamer; Filiatrault, Johanne; Yu, Hsiu-Ting; Zunzunegui, Maria Victoria

2017-01-01

Abstract Purpose: Active aging is a concept that lacks consensus. The WHO defines it as a holistic concept that encompasses the overall health, participation, and security of older adults. Fernández-Ballesteros and colleagues propose a similar concept but omit security and include mood and cognitive function. To date, researchers attempting to validate conceptual models of active aging have obtained mixed results. The goal of this study was to examine the validity of existing models of active aging with epidemiological data from Canada. Methods: The WHO model of active aging and the psychological model of active aging developed by Fernández-Ballesteros and colleagues were tested with confirmatory factor analysis. The data used included 799 community-dwelling older adults between 65 and 74 years old, recruited from the patient lists of family physicians in Saint-Hyacinthe, Quebec and Kingston, Ontario. Results: Neither model could be validated in the sample of Canadian older adults. Although a concept of healthy aging can be modeled adequately, social participation and security did not fit a latent factor model. A simple binary index indicated that 27% of older adults in the sample did not meet the active aging criteria proposed by the WHO. Implications: Our results suggest that active aging might represent a human rights policy orientation rather than an empirical measurement tool to guide research among older adult populations. Binary indexes of active aging may serve to highlight what remains to be improved about the health, participation, and security of growing populations of older adults. PMID:26350153

Age-Of Dependent Mutation Rate and Weak Children in the Penna Model in Biological Ageing

NASA Astrophysics Data System (ADS)

Berntsen, K. Nikolaj

We investigate the effect of an age-dependent mutation rate in the Penna model of ageing and then we observe that the high mortality for human babies can be reproduced by the model if one assumes babies to be weaker than adults.

Some analytical models to estimate maternal age at birth using age-specific fertility rates.

PubMed

Pandey, A; Suchindran, C M

1995-01-01

"A class of analytical models to study the distribution of maternal age at different births from the data on age-specific fertility rates has been presented. Deriving the distributions and means of maternal age at birth of any specific order, final parity and at next-to-last birth, we have extended the approach to estimate parity progression ratios and the ultimate parity distribution of women in the population.... We illustrate computations of various components of the model expressions with the current fertility experiences of the United States for 1970." excerpt

Age and gender specific biokinetic model for strontium in humans

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

Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.

A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitation for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on 90Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic modelmore » for strontium (Sr-AGe model). The Sr-AGe model has similar structure as the ICRP model for the alkaline earth elements. The following parameters were mainly reevaluated: gastro-intestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (0–80 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general population exposed to ingested strontium radioisotopes.« less

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

An Empirical Comparison of Different Models of Active Aging in Canada: The International Mobility in Aging Study.

PubMed

Bélanger, Emmanuelle; Ahmed, Tamer; Filiatrault, Johanne; Yu, Hsiu-Ting; Zunzunegui, Maria Victoria

2017-04-01

Active aging is a concept that lacks consensus. The WHO defines it as a holistic concept that encompasses the overall health, participation, and security of older adults. Fernández-Ballesteros and colleagues propose a similar concept but omit security and include mood and cognitive function. To date, researchers attempting to validate conceptual models of active aging have obtained mixed results. The goal of this study was to examine the validity of existing models of active aging with epidemiological data from Canada. The WHO model of active aging and the psychological model of active aging developed by Fernández-Ballesteros and colleagues were tested with confirmatory factor analysis. The data used included 799 community-dwelling older adults between 65 and 74 years old, recruited from the patient lists of family physicians in Saint-Hyacinthe, Quebec and Kingston, Ontario. Neither model could be validated in the sample of Canadian older adults. Although a concept of healthy aging can be modeled adequately, social participation and security did not fit a latent factor model. A simple binary index indicated that 27% of older adults in the sample did not meet the active aging criteria proposed by the WHO. Our results suggest that active aging might represent a human rights policy orientation rather than an empirical measurement tool to guide research among older adult populations. Binary indexes of active aging may serve to highlight what remains to be improved about the health, participation, and security of growing populations of older adults. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Selection Experiments in the Penna Model for Biological Aging

NASA Astrophysics Data System (ADS)

Medeiros, G.; Idiart, M. A.; de Almeida, R. M. C.

We consider the Penna model for biological aging to investigate correlations between early fertility and late life survival rates in populations at equilibrium. We consider inherited initial reproduction ages together with a reproduction cost translated in a probability that mother and offspring die at birth, depending on the mother age. For convenient sets of parameters, the equilibrated populations present genetic variability in what regards both genetically programmed death age and initial reproduction age. In the asexual Penna model, a negative correlation between early life fertility and late life survival rates naturally emerges in the stationary solutions. In the sexual Penna model, selection experiments are performed where individuals are sorted by initial reproduction age from the equilibrated populations and the separated populations are evolved independently. After a transient, a negative correlation between early fertility and late age survival rates also emerges in the sense that populations that start reproducing earlier present smaller average genetically programmed death age. These effects appear due to the age structure of populations in the steady state solution of the evolution equations. We claim that the same demographic effects may be playing an important role in selection experiments in the laboratory.

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.

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.

Animal models of age related macular degeneration

PubMed Central

Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

2013-01-01

Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

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.

Ages, geochemistry and tectonic implications of the Cambrian igneous rocks in the northern Great Xing'an Range, NE China

NASA Astrophysics Data System (ADS)

Feng, Zhiqiang; Liu, Yongjiang; Li, Yanrong; Li, Weimin; Wen, Quanbo; Liu, Binqiang; Zhou, Jianping; Zhao, Yingli

2017-08-01

The Xinlin-Xiguitu suture zone, located in the Great Xing'an Range, NE China, in the eastern segment of the Central Asian Orogenic Belt (CAOB), represents the boundary between the Erguna and Xing'an micro-continental blocks. The exact location of the Xinlin-Xiguitu suture zone has been debated, especially, the location of the northern extension of the suture zone. In this study, based on a detailed field, geochemical, geochronological and Sr-Nd-Hf isotope study, we focus our work on the Cambrian igneous rocks in the Erguna-Xing'an block. The Xinglong granitoids, mainly include ∼520 Ma diorite, ∼470 Ma monzogranite and ∼480 Ma pyroxene diorite. The granitoids show medium to high-K calc-alkaline series characteristics with post-collision granite affinity. The circa 500 Ma granitoids have low εHf (t) values (-16.6 to +2.2) and ancient two-stage model (TDM2) ages between 1317 Ma and 2528 Ma. These results indicate the primary magmas of the Xinglong granitoids were probably derived from the partial melting of a dominantly Paleo-Mesoproterozoic ;old; crustal source with possible different degrees of addition of juvenile materials, and formed in a post-collision tectonic setting after the amalgamation of the Erguna and Xing'an blocks. Compared with the Xinglong granitoids, the Duobaoshan igneous rocks are consisted of the approximately coeval rhyolitic tuffs (491 ± 5 Ma) and ultramafic intrusions (497 ± 5 Ma) within the Duobaoshan Formation. They are generally enriched in large ion lithophile elements (LILEs) and depleted in high field strength elements (HFSEs; e.g., Nb, Ta, and Ti), consistent with the geochemistry of igneous rocks from island arcs or active continental margins. The ultramafic rocks have high positive εHf (t) values (+1.3 to +15) and εNd (t) (+1.86 to +2.28), and relatively young two-stage model (TDM2) ages and low initial 87Sr/86Sr ratios (0.70628-0.70853), indicating the partial melting of a depleted mantle source from a subducted slab in

Radiocarbon ages and age models for the past 30,000 years in Bear Lake, Utah and Idaho

USGS Publications Warehouse

Colman, Steven M.; Rosenbaum, J.G.; Kaufman, D.S.; Dean, W.E.; McGeehin, J.P.

2009-01-01

Radiocarbon analyses of pollen, ostracodes, and total organic carbon (TOC) provide a reliable chronology for the sediments deposited in Bear Lake over the past 30,000 years. The differences in apparent age between TOC, pollen, and carbonate fractions are consistent and in accord with the origins of these fractions. Comparisons among different fractions indicate that pollen sample ages are the most reliable, at least for the past 15,000 years. The post-glacial radiocarbon data also agree with ages independently estimated from aspartic acid racemization in ostracodes. Ages in the red, siliclastic unit, inferred to be of last glacial age, appear to be several thousand years too old, probably because of a high proportion of reworked, refractory organic carbon in the pollen samples. Age-depth models for five piston cores and the Bear Lake drill core (BL00-1) were constructed by using two methods: quadratic equations and smooth cubic-splinefits. The two types of age models differ only in detail for individual cores, and each approach has its own advantages. Specific lithological horizons were dated in several cores and correlated among them, producing robust average ages for these horizons. The age of the correlated horizons in the red, siliclastic unit can be estimated from the age model for BL00-1, which is controlled by ages above and below the red, siliclastic unit. These ages were then transferred to the correlative horizons in the shorter piston cores, providing control for the sections of the age models in those cores in the red, siliclastic unit. These age models are the backbone for reconstructions of past environmental conditions in Bear Lake. In general, sedimentation rates in Bear Lake have been quite uniform, mostly between 0.3 and 0.8 mm yr-1 in the Holocene, and close to 0.5 mm yr-1 for the longer sedimentary record in the drill core from the deepest part of the lake. Copyright ?? 2009 The Geological Society of America.

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.

Does active ageing contribute to life satisfaction for older people? Testing a new model of active ageing.

PubMed

Marsillas, Sara; De Donder, Liesbeth; Kardol, Tinie; van Regenmortel, Sofie; Dury, Sarah; Brosens, Dorien; Smetcoren, An-Sofie; Braña, Teresa; Varela, Jesús

2017-09-01

Several debates have emerged across the literature about the conceptualisation of active ageing. The aim of this study is to develop a model of the construct that is focused on the individual, including different elements of people's lives that have the potential to be modified by intervention programs. Moreover, the paper examines the contributions of active ageing to life satisfaction, as well as the possible predictive role of coping styles on active ageing. For this purpose, a representative sample of 404 Galician (Spain) community-dwelling older adults (aged ≥60 years) were interviewed using a structured survey. The results demonstrate that the proposed model composed of two broad categories is valid. The model comprises status variables (related to physical, psychological, and social health) as well as different types of activities, called processual variables. This model is tested using partial least squares (PLS) regression. The findings show that active ageing is a fourth-order, formative construct. In addition, PLS analyses indicate that active ageing has a moderate and positive path on life satisfaction and that coping styles may predict active ageing. The discussion highlights the potential of active ageing as a relevant concept for people's lives, drawing out policy implications and suggestions for further research.

[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.

Age- and sex-specific thorax finite element model development and simulation.

PubMed

Schoell, Samantha L; Weaver, Ashley A; Vavalle, Nicholas A; Stitzel, Joel D

2015-01-01

The shape, size, bone density, and cortical thickness of the thoracic skeleton vary significantly with age and sex, which can affect the injury tolerance, especially in at-risk populations such as the elderly. Computational modeling has emerged as a powerful and versatile tool to assess injury risk. However, current computational models only represent certain ages and sexes in the population. The purpose of this study was to morph an existing finite element (FE) model of the thorax to depict thorax morphology for males and females of ages 30 and 70 years old (YO) and to investigate the effect on injury risk. Age- and sex-specific FE models were developed using thin-plate spline interpolation. In order to execute the thin-plate spline interpolation, homologous landmarks on the reference, target, and FE model are required. An image segmentation and registration algorithm was used to collect homologous rib and sternum landmark data from males and females aged 0-100 years. The Generalized Procrustes Analysis was applied to the homologous landmark data to quantify age- and sex-specific isolated shape changes in the thorax. The Global Human Body Models Consortium (GHBMC) 50th percentile male occupant model was morphed to create age- and sex-specific thoracic shape change models (scaled to a 50th percentile male size). To evaluate the thoracic response, 2 loading cases (frontal hub impact and lateral impact) were simulated to assess the importance of geometric and material property changes with age and sex. Due to the geometric and material property changes with age and sex, there were observed differences in the response of the thorax in both the frontal and lateral impacts. Material property changes alone had little to no effect on the maximum thoracic force or the maximum percent compression. With age, the thorax becomes stiffer due to superior rotation of the ribs, which can result in increased bone strain that can increase the risk of fracture. For the 70-YO models

An artificial intelligence tool for complex age-depth models

NASA Astrophysics Data System (ADS)

Bradley, E.; Anderson, K. A.; de Vesine, L. R.; Lai, V.; Thomas, M.; Nelson, T. H.; Weiss, I.; White, J. W. C.

2017-12-01

CSciBox is an integrated software system for age modeling of paleoenvironmental records. It incorporates an array of data-processing and visualization facilities, ranging from 14C calibrations to sophisticated interpolation tools. Using CSciBox's GUI, a scientist can build custom analysis pipelines by composing these built-in components or adding new ones. Alternatively, she can employ CSciBox's automated reasoning engine, Hobbes, which uses AI techniques to perform an in-depth, autonomous exploration of the space of possible age-depth models and presents the results—both the models and the reasoning that was used in constructing and evaluating them—to the user for her inspection. Hobbes accomplishes this using a rulebase that captures the knowledge of expert geoscientists, which was collected over the course of more than 100 hours of interviews. It works by using these rules to generate arguments for and against different age-depth model choices for a given core. Given a marine-sediment record containing uncalibrated 14C dates, for instance, Hobbes tries CALIB-style calibrations using a choice of IntCal curves, with reservoir age correction values chosen from the 14CHRONO database using the lat/long information provided with the core, and finally composes the resulting age points into a full age model using different interpolation methods. It evaluates each model—e.g., looking for outliers or reversals—and uses that information to guide the next steps of its exploration, and presents the results to the user in human-readable form. The most powerful of CSciBox's built-in interpolation methods is BACON, a Bayesian sedimentation-rate algorithm—a powerful but complex tool that can be difficult to use. Hobbes adjusts BACON's many parameters autonomously to match the age model to the expectations of expert geoscientists, as captured in its rulebase. It then checks the model against the data and iteratively re-calculates until it is a good fit to the data.

Mouse models of ageing and their relevance to disease.

PubMed

Kõks, Sulev; Dogan, Soner; Tuna, Bilge Guvenc; González-Navarro, Herminia; Potter, Paul; Vandenbroucke, Roosmarijn E

2016-12-01

Ageing is a process that gradually increases the organism's vulnerability to death. It affects different biological pathways, and the underlying cellular mechanisms are complex. In view of the growing disease burden of ageing populations, increasing efforts are being invested in understanding the pathways and mechanisms of ageing. We review some mouse models commonly used in studies on ageing, highlight the advantages and disadvantages of the different strategies, and discuss their relevance to disease susceptibility. In addition to addressing the genetics and phenotypic analysis of mice, we discuss examples of models of delayed or accelerated ageing and their modulation by caloric restriction. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Cellular senescence in the Penna model of aging

NASA Astrophysics Data System (ADS)

Periwal, Avikar

2013-11-01

Cellular senescence is thought to play a major role in age-related diseases, which cause nearly 67% of all human deaths worldwide. Recent research in mice showed that exercising mice had higher levels of telomerase, an enzyme that helps maintain telomere length, than nonexercising mice. A commonly used model for biological aging was proposed by Penna. I propose a modification of the Penna model that incorporates cellular senescence and find an analytical steady-state solution following Coe, Mao, and Cates [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.89.288103 89, 288103 (2002)]. I find that models corresponding to delayed cellular senescence have younger populations that live longer. I fit the model to the United Kingdom's death distribution, which the original Penna model cannot do.

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.

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.

Modeling the brain morphology distribution in the general aging population

NASA Astrophysics Data System (ADS)

Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

2016-03-01

Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

An age-structured extension to the vectorial capacity model.

PubMed

Novoseltsev, Vasiliy N; Michalski, Anatoli I; Novoseltseva, Janna A; Yashin, Anatoliy I; Carey, James R; Ellis, Alicia M

2012-01-01

Vectorial capacity and the basic reproductive number (R(0)) have been instrumental in structuring thinking about vector-borne pathogen transmission and how best to prevent the diseases they cause. One of the more important simplifying assumptions of these models is age-independent vector mortality. A growing body of evidence indicates that insect vectors exhibit age-dependent mortality, which can have strong and varied affects on pathogen transmission dynamics and strategies for disease prevention. Based on survival analysis we derived new equations for vectorial capacity and R(0) that are valid for any pattern of age-dependent (or age-independent) vector mortality and explore the behavior of the models across various mortality patterns. The framework we present (1) lays the groundwork for an extension and refinement of the vectorial capacity paradigm by introducing an age-structured extension to the model, (2) encourages further research on the actuarial dynamics of vectors in particular and the relationship of vector mortality to pathogen transmission in general, and (3) provides a detailed quantitative basis for understanding the relative impact of reductions in vector longevity compared to other vector-borne disease prevention strategies. Accounting for age-dependent vector mortality in estimates of vectorial capacity and R(0) was most important when (1) vector densities are relatively low and the pattern of mortality can determine whether pathogen transmission will persist; i.e., determines whether R(0) is above or below 1, (2) vector population growth rate is relatively low and there are complex interactions between birth and death that differ fundamentally from birth-death relationships with age-independent mortality, and (3) the vector exhibits complex patterns of age-dependent mortality and R(0) ∼ 1. A limiting factor in the construction and evaluation of new age-dependent mortality models is the paucity of data characterizing vector mortality patterns

An age dependent model for radium metabolism in man.

PubMed

Johnson, J R

1983-01-01

The model developed by a Task Group of Committee 2 of ICRP to describe Alkaline Earth Metabolism in Adult Man (ICRP Publication 20) has been modified so that recycling is handled explicitly, and retention in mineral bone is represented by second compartments rather than by the product of a power function and an exponential. This model has been extended to include all ages from birth to adult man, and has been coupled with modified "ICRP" lung and G.I. tract models so that activity in organs can be calculated as functions of time during or after exposures. These activities, and age dependent "specific effective energy" factors, are then used to calculate age dependent dose rates, and dose commitments. This presentation describes this work, with emphasis on the model parameters and results obtained for radium.

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.

Evaluation and clinical significance of the stomach age model for evaluating aging of the stomach-a multicenter study in China

PubMed Central

2014-01-01

Background A higher prevalence of chronic atrophic gastritis (CAG) occurs in younger adults in Asia. We used Stomach Age to examine the different mechanisms of CAG between younger adults and elderly individuals, and established a simple model of cancer risk that can be applied to CAG surveillance. Methods Stomach Age was determined by FISH examination of telomere length in stomach biopsies. Δψm was also determined by flow cytometry. Sixty volunteers were used to confirm the linear relationship between telomere length and age while 120 subjects were used to build a mathematical model by a multivariate analysis. Overall, 146 subjects were used to evaluate the validity of the model, and 1,007 subjects were used to evaluate the relationship between prognosis and Δage (calculated from the mathematical model). ROC curves were used to evaluate the relationship between prognosis and Δage and to determine the cut-off point for Δage. Results We established that a tight linear relationship between the telomere length and the age. The telomere length was obvious different between patients with and without CAG even in the same age. Δψm decreased in individuals whose Stomach Age was greater than real age, especially in younger adults. A mathematical model of Stomach Age (real age + Δage) was successfully constructed which was easy to apply in clinical work. A higher Δage was correlated with a worse outcome. The criterion of Δage >3.11 should be considered as the cut-off to select the subgroup of patients who require endoscopic surveillance. Conclusion Variation in Stomach Age between individuals of the same biological age was confirmed. Attention should be paid to those with a greater Stomach Age, especially in younger adults. The Δage in the Simple Model can be used as a criterion to select CAG patients for gastric cancer surveillance. PMID:25057261

An evaluation of sex-age-kill (SAK) model performance

USGS Publications Warehouse

Millspaugh, Joshua J.; Skalski, John R.; Townsend, Richard L.; Diefenbach, Duane R.; Boyce, Mark S.; Hansen, Lonnie P.; Kammermeyer, Kent

2009-01-01

The sex-age-kill (SAK) model is widely used to estimate abundance of harvested large mammals, including white-tailed deer (Odocoileus virginianus). Despite a long history of use, few formal evaluations of SAK performance exist. We investigated how violations of the stable age distribution and stationary population assumption, changes to male or female harvest, stochastic effects (i.e., random fluctuations in recruitment and survival), and sampling efforts influenced SAK estimation. When the simulated population had a stable age distribution and λ > 1, the SAK model underestimated abundance. Conversely, when λ < 1, the SAK overestimated abundance. When changes to male harvest were introduced, SAK estimates were opposite the true population trend. In contrast, SAK estimates were robust to changes in female harvest rates. Stochastic effects caused SAK estimates to fluctuate about their equilibrium abundance, but the effect dampened as the size of the surveyed population increased. When we considered both stochastic effects and sampling error at a deer management unit scale the resultant abundance estimates were within ±121.9% of the true population level 95% of the time. These combined results demonstrate extreme sensitivity to model violations and scale of analysis. Without changes to model formulation, the SAK model will be biased when λ ≠ 1. Furthermore, any factor that alters the male harvest rate, such as changes to regulations or changes in hunter attitudes, will bias population estimates. Sex-age-kill estimates may be precise at large spatial scales, such as the state level, but less so at the individual management unit level. Alternative models, such as statistical age-at-harvest models, which require similar data types, might allow for more robust, broad-scale demographic assessments.

Development of a bioenergetics model for age-0 American Shad

USGS Publications Warehouse

Sauter, Sally T.

2011-01-01

Bioenergetics modeling can be used as a tool to investigate the impact of non-native age-0 American shad (Alosa sapidissima) on reservoir and estuary food webs. The model can increase our understanding of how these fish influence lower trophic levels as well as predatory fish populations that feed on juvenile salmonids. Bioenergetics modeling can be used to investigate ecological processes, evaluate alternative research hypotheses, provide decision support, and quantitative prediction. Bioenergetics modeling has proven to be extremely useful in fisheries research (Ney et al. 1993,Chips and Wahl 2008, Petersen et al. 2008). If growth and diet parameters are known, the bioenergetics model can be used to quantify the relative amount of zooplankton or insects consumed by age-0 American shad. When linked with spatial and temporal information on fish abundance, model output can guide inferential hypothesis development to demonstrate where the greatest impacts of age-0 American shad might occur.

Bioenergetics modeling is particularly useful when research questions involve multiple species and trophic levels (e.g. plankton communities). Bioenergetics models are mass-balance equations where the energy acquired from food is partitioned between maintenance costs, waste products, and growth (Winberg 1956). Specifically, the Wisconsin bioenergetics model (Hanson et al. 1997) is widely used in fisheries science. Researchers have extensively tested, reviewed, and improved on this modeling approach for over 30 years (Petersen et al. 2008). Development of a bioenergetics model for any species requires three key components: 1) determine physiological parameters for the model through laboratory experiments or incorporate data from a closely related species, 2) corroboration of the model with growth and consumption estimates from independent research, and 3) error analysis of model parameters.

Wisconsin bioenergetics models have been parameterized for

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.

The short-lived African turquoise killifish: an emerging experimental model for ageing.

PubMed

Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

2016-02-01

Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. © 2016. Published by The Company of Biologists Ltd.

The short-lived African turquoise killifish: an emerging experimental model for ageing

PubMed Central

Kim, Yumi; Nam, Hong Gil; Valenzano, Dario Riccardo

2016-01-01

ABSTRACT Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. PMID:26839399

Age or stage structure? A comparison of dynamic outcomes from discrete age- and stage-structured population models.

PubMed

Wikan, Arild

2012-06-01

Discrete stage-structured density-dependent and discrete age-structured density-dependent population models are considered. Regarding the former, we prove that the model at hand is permanent (i.e., that the population will neither go extinct nor exhibit explosive oscillations) and given density dependent fecundity terms we also show that species with delayed semelparous life histories tend to be more stable than species which possess precocious semelparous life histories. Moreover, our findings together with results obtained from other stage-structured models seem to illustrate a fairly general ecological principle, namely that iteroparous species are more stable than semelparous species. Our analysis of various age-structured models does not necessarily support the conclusions above. In fact, species with precocious life histories now appear to possess better stability properties than species with delayed life histories, especially in the iteroparous case. We also show that there are dynamical outcomes from semelparous age-structured models which we are not able to capture in corresponding stage-structured cases. Finally, both age- and stage-structured population models may generate periodic dynamics of low period (either exact or approximate). The important prerequisite is to assume density-dependent survival probabilities.

Age dependent mortality in the pilocarpine model of status epilepticus

PubMed Central

Blair, Robert E.; Deshpande, Laxmikant S.; Holbert, William H.; Churn, Severn B.; DeLorenzo, Robert J.

2010-01-01

Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 to 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week old animals, mortality due to SE increased progressively with age and reached 90% in 28-week old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death. PMID:19429042

Age-dependent mortality in the pilocarpine model of status epilepticus.

PubMed

Blair, Robert E; Deshpande, Laxmikant S; Holbert, William H; Churn, Severn B; DeLorenzo, Robert J

2009-04-10

Status epilepticus (SE) is an acute neurological emergency associated with significant morbidity and mortality. Age has been shown to be a critical factor in determining outcome after SE. Understanding the causes of this increased mortality with aging by developing an animal model to study this condition would play a major role in studying mechanisms to limit the mortality due to SE. Here we employed pilocarpine to induce SE in rats aged between 5 and 28 weeks. Similar to clinical studies in man, we observed that age was a significant predictor of mortality following SE. While no deaths were observed in 5-week-old animals, mortality due to SE increased progressively with age and reached 90% in 28-week-old animals. There was no correlation between the age of animals and severity of SE. With increasing age mortality occurred earlier after the onset of SE. These results indicate that pilocarpine-induced SE in the rat provides a useful model to study age-dependent SE-induced mortality and indicates the importance of using animal models to elucidate the mechanisms contributing to SE-induced mortality and the development of novel therapeutic interventions to prevent SE-induced death.

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.

Novel polyglutamine model uncouples proteotoxicity from aging.

PubMed

Christie, Nakeirah T M; Lee, Amy L; Fay, Hannah G; Gray, Amelia A; Kikis, Elise A

2014-01-01

Polyglutamine expansions in certain proteins are the genetic determinants for nine distinct progressive neurodegenerative disorders and resultant age-related dementia. In these cases, neurodegeneration is due to the aggregation propensity and resultant toxic properties of the polyglutamine-containing proteins. We are interested in elucidating the underlying mechanisms of toxicity of the protein ataxin-3, in which a polyglutamine expansion is the genetic determinant for Machado-Joseph Disease (MJD), also referred to as spinocerebellar ataxia 3 (SCA3). To this end, we have developed a novel model for ataxin-3 protein aggregation, by expressing a disease-related polyglutamine-containing fragment of ataxin-3 in the genetically tractable body wall muscle cells of the model system C. elegans. Here, we demonstrate that this ataxin-3 fragment aggregates in a polyQ length-dependent manner in C. elegans muscle cells and that this aggregation is associated with cellular dysfunction. However, surprisingly, this aggregation and resultant toxicity was not influenced by aging. This is in contrast to polyglutamine peptides alone whose aggregation/toxicity is highly dependent on age. Thus, the data presented here not only describe a new polyglutamine model, but also suggest that protein context likely influences the cellular interactions of the polyglutamine-containing protein and thereby modulates its toxic properties.

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.

A living model for obesity and aging research: Caenorhabditis elegans.

PubMed

Shen, Peiyi; Yue, Yiren; Park, Yeonhwa

2018-03-24

Caenorhabditis elegans (C. elegans) is a free-living nematode that has been extensively utilized as an animal model for research involving aging and neurodegenerative diseases, like Alzheimer's and Parkinson's, etc. Compared with traditional animal models, this small nematode possesses many benefits, such as small body size, short lifespan, completely sequenced genome, and more than 65% of the genes associated with human disease. All these characteristics make this organism an ideal living system for obesity and aging studies. This review gives a brief introduction of C. elegans as an animal model, highlights some advantages of research using this model and describes methods to evaluate the effect of treatments on obesity and aging of this organism.

Detrital zircon age patterns from turbidites of the Balagne and Piedmont nappes of Alpine Corsica (France): Evidence for an European margin source

NASA Astrophysics Data System (ADS)

Lin, Wei; Rossi, Philippe; Faure, Michel; Li, Xian-Hua; Ji, Wenbin; Chu, Yang

2018-01-01

At the front of metamorphic Cenozoic Alpine nappe of Schistes Lustrés, Western Alpine Corsica (France) exposes non- to very low grade metamorphic nappes, such as the Piedmont nappes, Upper nappes, and the Balagne nappe. The provenance of the Balagne nappe remains still opened: an origin close to the Corsican continental margin; or an origin far East from the Corsican margin toward the "Apenninic" oceanic domain. This would constrain that the Balagne ophiolite be derived from the opposite OCT (Ocean - Continent transition), close to a microcontinent located to the East of the Mesozoic Corsican margin. A systematic U-Pb dating of 586 detrital zircon grains collected from the turbidites in the Balagne and Piedmont nappes has been performed to constrain the source of sediments. The zircon grains yield U-Pb age spectra ranging from Neoarchean to Late Paleozoic with age peaks at 2600 Ma, 2080 Ma, 1830 Ma, 910 Ma, 600 Ma, 560 Ma, 450 Ma, 330 Ma and 280 Ma with different continental model ages (TDM2) from 3.5 Ga to 1.0 Ga. The variety of composition of the Corsican batholith, unique in its present Mediterranean environment, and in spite of Alpine transcurrent movements, provide a key to analyze the detrital zircon age distribution patterns of sedimentary rocks. These new results i) confirm the lack of any Cretaceous zircon that validates absence of a magmatic arc of this age, at least in the surroundings of the turbiditic formations from the Balagne and the Piedmont nappes; ii) fully support an European provenance of detritus of the Balagne nappe, iii) put forward evidence that no ophiolitic zircon was contained neither in the Cretaceous nor in the Eocene turbidites samples, and iv) question both the deposition of the Piedmont Narbinco flysch within the ocean continent transition and its possible relationships with the Late Cretaceous Pyrenean basins.

Autophagy drives epidermal deterioration in a Drosophila model of tissue aging.

PubMed

Scherfer, Christoph; Han, Violet C; Wang, Yan; Anderson, Aimee E; Galko, Michael J

2013-04-01

Organismal lifespan has been the primary readout in aging research. However, how longevity genes control tissue-specific aging remains an open question. To examine the crosstalk between longevity programs and specific tissues during aging, biomarkers of organ-specific aging are urgently needed. Since the earliest signs of aging occur in the skin, we sought to examine skin aging in a genetically tractable model. Here we introduce a Drosophila model of skin aging. The epidermis undergoes a dramatic morphological deterioration with age that includes membrane and nuclear loss. These changes were decelerated in a long-lived mutant and accelerated in a short-lived mutant. An increase in autophagy markers correlated with epidermal aging. Finally, the epidermis of Atg7 mutants retained younger characteristics, suggesting that autophagy is a critical driver of epidermal aging. This is surprising given that autophagy is generally viewed as protective during aging. Since Atg7 mutants are short-lived, the deceleration of epidermal aging in this mutant suggests that in the epidermis healthspan can be uncoupled from longevity. Because the aging readout we introduce here has an early onset and is easily visualized, genetic dissection using our model should identify other novel mechanisms by which lifespan genes feed into tissue-specific aging.

[Cognitive advantages of the third age: a neural network model of brain aging].

PubMed

Karpenko, M P; Kachalova, L M; Budilova, E V; Terekhin, A T

2009-01-01

We consider a neural network model of age-related cognitive changes in aging brain based on Hopfield network with a sigmoid function of neuron activation. Age is included in the activation function as a parameter in the form of exponential rate denominator, which makes it possible to take into account the weakening of interneuronal links really observed in the aging brain. Analysis of properties of the Lyapunov function associated with the network shows that, with increasing parameter of age, its relief becomes smoother and the number of local minima (network attractors) decreases. As a result, the network gets less frequently stuck in the nearest local minima of the Lyapunov function and reaches a global minimum corresponding to the most effective solution of the cognitive task. It is reasonable to assume that similar changes really occur in the aging brain. Phenomenologically, these changes can be manifested as emergence in aged people of a cognitive quality such as wisdom i.e. ability to find optimal decisions in difficult controversial situations, to distract from secondary aspects and to see the problem as a whole.

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.

An agent-based computational model for tuberculosis spreading on age-structured populations

NASA Astrophysics Data System (ADS)

Graciani Rodrigues, C. C.; Espíndola, Aquino L.; Penna, T. J. P.

2015-06-01

In this work we present an agent-based computational model to study the spreading of the tuberculosis (TB) disease on age-structured populations. The model proposed is a merge of two previous models: an agent-based computational model for the spreading of tuberculosis and a bit-string model for biological aging. The combination of TB with the population aging, reproduces the coexistence of health states, as seen in real populations. In addition, the universal exponential behavior of mortalities curves is still preserved. Finally, the population distribution as function of age shows the prevalence of TB mostly in elders, for high efficacy treatments.

Parental Age and the Effectiveness of Modeled Behavior and Modeling Cues.

ERIC Educational Resources Information Center

Kearney, Deborah; And Others

A two-group independent design was employed to study the relationship between parental age and modeling effectiveness. Subjects were 50 mother-father-child triads. The child's baseline data was recorded on a task that involved constructing a specified geometric shape on a pegboard. Then the child was asked to construct another shape modeling his…

An Age-Structured Extension to the Vectorial Capacity Model

PubMed Central

Novoseltsev, Vasiliy N.; Michalski, Anatoli I.; Novoseltseva, Janna A.; Yashin, Anatoliy I.; Carey, James R.; Ellis, Alicia M.

2012-01-01

Background Vectorial capacity and the basic reproductive number (R0) have been instrumental in structuring thinking about vector-borne pathogen transmission and how best to prevent the diseases they cause. One of the more important simplifying assumptions of these models is age-independent vector mortality. A growing body of evidence indicates that insect vectors exhibit age-dependent mortality, which can have strong and varied affects on pathogen transmission dynamics and strategies for disease prevention. Methodology/Principal Findings Based on survival analysis we derived new equations for vectorial capacity and R0 that are valid for any pattern of age-dependent (or age–independent) vector mortality and explore the behavior of the models across various mortality patterns. The framework we present (1) lays the groundwork for an extension and refinement of the vectorial capacity paradigm by introducing an age-structured extension to the model, (2) encourages further research on the actuarial dynamics of vectors in particular and the relationship of vector mortality to pathogen transmission in general, and (3) provides a detailed quantitative basis for understanding the relative impact of reductions in vector longevity compared to other vector-borne disease prevention strategies. Conclusions/Significance Accounting for age-dependent vector mortality in estimates of vectorial capacity and R0 was most important when (1) vector densities are relatively low and the pattern of mortality can determine whether pathogen transmission will persist; i.e., determines whether R0 is above or below 1, (2) vector population growth rate is relatively low and there are complex interactions between birth and death that differ fundamentally from birth-death relationships with age-independent mortality, and (3) the vector exhibits complex patterns of age-dependent mortality and R0∼1. A limiting factor in the construction and evaluation of new age-dependent mortality models is the

Ages and transit times as important diagnostics of model performance for predicting C allocation in ecosystem models

NASA Astrophysics Data System (ADS)

Ceballos-Núñez, Verónika; Richardson, Andrew; Sierra, Carlos

2017-04-01

The global carbon cycle is strongly controlled by the source/sink strength of vegetation as well as the capacity of terrestrial ecosystems to retain this carbon. However, it is uncertain how some vegetation dynamics such as the allocation of carbon to different ecosystem compartments should be represented in models. The assumptions behind model structures may result in highly divergent model predictions. Here, we asses model performance by calculating the age of the carbon in the system and in each compartment, and the overall transit time of C in the system. We used these diagnostics to assess the influence of three different carbon allocation schemes on the rates of C cycling in vegetation. First, we used published measurements of ecosystem C compartments from the Harvard Forest Environmental Measurement Site to find the best set of parameters for the different model structures. Second, we calculated C stocks, respiration fluxes, radiocarbon values, ages, and transit times. We found a good fit of the three model structures to the available data, but the time series of C in foliage and wood need to be complemented with other ecosystem compartments in order to reduce the high parameter collinearity that we observed and reduce model equifinality. Differences in model structures had a small impact on predicting ecosystem C compartments, but overall they resulted in very different predictions of age and transit time distributions. In particular, the inclusion of a storage compartment had an important impact on predicting system ages and transit times. In the case of the models with 1 or 2 storage compartments, the age of carbon in the system and in each of the compartments was distributed more towards younger ages than in the model that had no storage; the mean system age of these two models with storage was 80 years younger than in the model without storage. As expected from these age distributions, the mean transit time for the two models with storage compartments

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.

Block Constraints in Age-Period-Cohort Models with Unequal-Width Intervals

ERIC Educational Resources Information Center

Luo, Liying; Hodges, James S.

2016-01-01

Age-period-cohort (APC) models are designed to estimate the independent effects of age, time periods, and cohort membership. However, APC models suffer from an identification problem: There are no unique estimates of the independent effects that fit the data best because of the exact linear dependency among age, period, and cohort. Among methods…

Development of a bioenergetics model for age-0 American Shad

USGS Publications Warehouse

Sauter, Sally T.

2011-01-01

Bioenergetics modeling can be used as a tool to investigate the impact of non-native age-0 American shad (Alosa sapidissima) on reservoir and estuary food webs. The model can increase our understanding of how these fish influence lower trophic levels as well as predatory fish populations that feed on juvenile salmonids. Bioenergetics modeling can be used to investigate ecological processes, evaluate alternative research hypotheses, provide decision support, and quantitative prediction. Bioenergetics modeling has proven to be extremely useful in fisheries research (Ney et al. 1993,Chips and Wahl 2008, Petersen et al. 2008). If growth and diet parameters are known, the bioenergetics model can be used to quantify the relative amount of zooplankton or insects consumed by age-0 American shad. When linked with spatial and temporal information on fish abundance, model output can guide inferential hypothesis development to demonstrate where the greatest impacts of age-0 American shad might occur.

Central Antarctic provenance of Permian sandstones in Dronning Maud Land and the Karoo Basin: Integration of U Pb and TDM ages and host-rock affinity from detrital zircons

NASA Astrophysics Data System (ADS)

Veevers, J. J.; Saeed, A.

2007-12-01

In conjugate SE Africa and Antarctica, Early Permian sandstones of the Swartrant Formation of the Ellisras Basin, Vryheid Formation of the Karoo Basin, and Amelang Plateau Formation of Dronning Maud Land (DML) were deposited after Gondwanan glaciation on a westward paleoslope. We analysed detrital zircons for U-Pb ages by a laser ablation microprobe-inductively coupled plasma mass spectrometer (LAM-ICPMS) and attached age significance only to clusters of three or more overlapping analyses. We analysed Hf-isotope compositions by a multi-collector spectrometer (LAM-MC-ICPMS) and trace elements by electron microprobe (EMP) and ICPMS. These analyses indicate the rock type and source (whether crustal or juvenile mantle) of the host magma, and a "crustal" model age ( TDMC). The integrated analysis gives a more distinctive, and more easily interpreted, picture of crustal evolution in the provenance area than age data alone. Zircons from the Ellisras Basin are aged 2700-2540 Ma with minor populations about 2815 Ma and 2040 Ma, which correspond with the ages of the upslope parts of the proximal Kaapvaal Craton and Limpopo Belt. Mafic rock is the dominant host rock, and it reflects the Archean granite-greenstone terrane of the Kaapvaal Craton. The three Karoo Basin samples and the two DML samples have zircons with these common properties: (1) 1160-880 Ma, host magma mafic granitoid (< 65% SiO 2) derived from juvenile depleted mantle sources ( ɛHf positive) at 1.65 Ga and 1.35 Ga, with TDMC of 2.0-0.9 Ga; (2) 760 to 480 Ma, host magma granitoid and low-heavy rare earth element rock (?alkaline rock-carbonatite), derived from mixed crustal and juvenile depleted mantle sources ( ɛHf positive and negative) at 1.50 Ga and 1.35 Ga, with TDMC of 2.0-0.9 Ga. Together with similar detrital zircons in Triassic sandstone of SE Australia, these properties reflect those in upslope central Antarctica, indicating a provenance of ˜ 1000 Ma (Grenville) cratons embedded in 700-500 Ma (Pan

Skin aging by glycation: lessons from the reconstructed skin model.

PubMed

Pageon, Hervé; Zucchi, Hélène; Rousset, Françoise; Monnier, Vincent M; Asselineau, Daniel

2014-01-01

Aging is the result of several mechanisms which operate simultaneously. Among them, glycation is of particular interest because it is a reaction which affects slowly renewing tissues and macromolecules with elevated half-life, like the dermis, a skin compartment highly affected by aging. Glycation produces crosslinks between macromolecules thereby providing an explanation for the increased age-related stiffness of the skin. Glycation products, also called AGEs (advanced glycation end products), accumulate primarily in extracellular matrix molecules like collagen or elastin. In order to reproduce this phenomenon in vitro we have created a model of reconstructed skin modified by glycation of the collagen used to fabricate the dermal compartment. This system allowed us to uncover biological modifications of dermal markers, and more surprisingly epidermal markers, as well as an increase of metalloproteinases responsible for degradation of the dermal matrix. Consequently, the imbalance between synthesis and degradation that results from glycation, may contribute to skin aging, as shown in this model. Moreover these modifications were shown to be prevented by the addition of aminoguanidine, a well-known inhibitor of glycation. Using this experimental approach our results taken together stress the importance and possibly central role of glycation in skin aging and the usefulness of the reconstructed skin as a model of physiological aging.

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.

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.

Developing a dimensional model for successful cognitive and emotional aging.

PubMed

Vahia, Ipsit V; Thompson, Wesley K; Depp, Colin A; Allison, Matthew; Jeste, Dilip V

2012-04-01

There is currently a lack of consensus on the definition of successful aging (SA) and existing implementations have omitted constructs associated with SA. We used empirical methods to develop a dimensional model of SA that incorporates a wider range of associated variables, and we examined the relationship among these components using factor analysis and Bayesian Belief Nets. We administered a successful aging questionnaire comprising several standardized measures related to SA to a sample of 1948 older women enrolled in the San Diego site of the Women's Health Initiative study. The SA-related variables we included in the model were self-rated successful aging, depression severity, physical and emotional functioning, optimism, resilience, attitude towards own aging, self-efficacy, and cognitive ability. After adjusting for age, education and income, we fitted an exploratory factor analysis model to the SA-related variables and then, in order to address relationships among these factors, we computed a Bayesian Belief Net (BBN) using rotated factor scores. The SA-related variables loaded onto five factors. Based on the loading, we labeled the factors as follows: self-rated successful aging, cognition, psychosocial protective factors, physical functioning, and emotional functioning. In the BBN, self-rated successful aging emerged as the primary downstream factor and exhibited significant partial correlations with psychosocial protective factors, physical/general status and mental/emotional status but not with cognitive ability. Our study represents a step forward in developing a dimensional model of SA. Our findings also point to a potential role for psychiatry in improving successful aging by managing depressive symptoms and developing psychosocial interventions to improve self-efficacy, resilience, and optimism.

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.

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

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

Nothobranchius as a model for aging studies. A review

PubMed Central

Lucas-Sánchez, Alejandro; Almaida-Pagán, Pedro Francisco; Mendiola, Pilar; de Costa, Jorge

2014-01-01

In recent decades, the increase in human longevity has made it increasingly important to expand our knowledge on aging. To accomplish this, the use of animal models is essential, with the most common being mouse (phylogenetically similar to humans, and a model with a long life expectancy) and Caenorhabditis elegans (an invertebrate with a short life span, but quite removed from us in evolutionary terms). However, some sort of model is needed to bridge the differences between those mentioned above, achieving a balance between phylogenetic distance and life span. Fish of the genus Nothobranchius were suggested 10 years ago as a possible alternative for the study of the aging process. In the meantime, numerous studies have been conducted at different levels: behavioral (including the study of the rest-activity rhythm), populational, histochemical, biochemical and genetic, among others, with very positive results. This review compiles what we know about Nothobranchius to date, and examines its future prospects as a true alternative to the classic models for studies on aging. PMID:25110612

Lattice Modeling of Early-Age Behavior of Structural Concrete.

PubMed

Pan, Yaming; Prado, Armando; Porras, Rocío; Hafez, Omar M; Bolander, John E

2017-02-25

The susceptibility of structural concrete to early-age cracking depends on material composition, methods of processing, structural boundary conditions, and a variety of environmental factors. Computational modeling offers a means for identifying primary factors and strategies for reducing cracking potential. Herein, lattice models are shown to be adept at simulating the thermal-hygral-mechanical phenomena that influence early-age cracking. In particular, this paper presents a lattice-based approach that utilizes a model of cementitious materials hydration to control the development of concrete properties, including stiffness, strength, and creep resistance. The approach is validated and used to simulate early-age cracking in concrete bridge decks. Structural configuration plays a key role in determining the magnitude and distribution of stresses caused by volume instabilities of the concrete material. Under restrained conditions, both thermal and hygral effects are found to be primary contributors to cracking potential.

Lattice Modeling of Early-Age Behavior of Structural Concrete

PubMed Central

Pan, Yaming; Prado, Armando; Porras, Rocío; Hafez, Omar M.; Bolander, John E.

2017-01-01

The susceptibility of structural concrete to early-age cracking depends on material composition, methods of processing, structural boundary conditions, and a variety of environmental factors. Computational modeling offers a means for identifying primary factors and strategies for reducing cracking potential. Herein, lattice models are shown to be adept at simulating the thermal-hygral-mechanical phenomena that influence early-age cracking. In particular, this paper presents a lattice-based approach that utilizes a model of cementitious materials hydration to control the development of concrete properties, including stiffness, strength, and creep resistance. The approach is validated and used to simulate early-age cracking in concrete bridge decks. Structural configuration plays a key role in determining the magnitude and distribution of stresses caused by volume instabilities of the concrete material. Under restrained conditions, both thermal and hygral effects are found to be primary contributors to cracking potential. PMID:28772590

Applying the age-shift approach to model responses to midrotation fertilization

Treesearch

Colleen A. Carlson; Thomas R. Fox; H. Lee Allen; Timothy J. Albaugh

2010-01-01

Growth and yield models used to evaluate midrotation fertilization economics require adjustments to account for the typically observed responses. This study investigated the use of age-shift models to predict midrotation fertilizer responses. Age-shift prediction models were constructed from a regional study consisting of 43 installations of a nitrogen (N) by...

The Fruit Fly Drosophila melanogaster as a Model for Aging Research.

PubMed

Brandt, Annely; Vilcinskas, Andreas

2013-01-01

: Average human life expectancy is increasing and so is the impact on society of aging and age-related diseases. Here we highlight recent advances in the diverse and multidisciplinary field of aging research, focusing on the fruit fly Drosophila melanogaster, an excellent model system in which to dissect the genetic and molecular basis of the aging processes. The conservation of human disease genes in D. melanogaster allows the functional analysis of orthologues implicated in human aging and age-related diseases. D. melanogaster models have been developed for a variety of age-related processes and disorders, including stem cell decline, Alzheimer's disease, and cardiovascular deterioration. Understanding the detailed molecular events involved in normal aging and age-related diseases could facilitate the development of strategies and treatments that reduce their impact, thus improving human health and increasing longevity.

Aging, neurogenesis, and caloric restriction in different model organisms.

PubMed

Arslan-Ergul, Ayca; Ozdemir, A Tugrul; Adams, Michelle M

2013-08-01

Brain aging is a multifactorial process that is occurring across multiple cognitive domains. A significant complaint that occurs in the elderly is a decrement in learning and memory ability. Both rodents and zebrafish exhibit a similar problem with memory during aging. The neurobiological changes that underlie this cognitive decline are complex and undoubtedly influenced by many factors. Alterations in the birth of new neurons and neuron turnover may contribute to age-related cognitive problems. Caloric restriction is the only non-genetic intervention that reliably increases life span and healthspan across multiple organisms although the molecular mechanisms are not well-understood. Recently the zebrafish has become a popular model organism for understanding the neurobiological consequences but to date very little work has been performed. Similarly, few studies have examined the effects of dietary restriction in zebrafish. Here we review the literature related to memory decline, neurogenesis, and caloric restriction across model organisms and suggest that zebrafish has the potential to be an important animal model for understanding the complex interactions between age, neurobiological changes in the brain, and dietary regimens or their mimetics as interventions.

Hydra, a powerful model for aging studies

PubMed Central

Tomczyk, Szymon; Fischer, Kathleen; Austad, Steven; Galliot, Brigitte

2015-01-01

Cnidarian Hydra polyps escape senescence, most likely due to the robust activity of their three stem cell populations. These stem cells continuously self-renew in the body column and differentiate at the extremities following a tightly coordinated spatial pattern. Paul Brien showed in 1953 that in one particular species, Hydra oligactis, cold-dependent sexual differentiation leads to rapid aging and death. Here, we review the features of this inducible aging phenotype. These cellular alterations, detected several weeks after aging was induced, are characterized by a decreasing density of somatic interstitial cell derivatives, a disorganization of the apical nervous system, and a disorganization of myofibers of the epithelial cells. Consequently, tissue replacement required to maintain homeostasis, feeding behavior, and contractility of the animal are dramatically affected. Interestingly, this aging phenotype is not observed in all H. oligactis strains, thus providing a powerful experimental model for investigations of the genetic control of aging. Given the presence in the cnidarian genome of a large number of human orthologs that have been lost in ecdysozoans, such approaches might help uncover novel regulators of aging in vertebrates. PMID:26120246

Drosophila as a model to study cardiac aging

PubMed Central

Nishimura, Mayuko; Ocorr, Karen; Bodmer, Rolf; Cartry, Jérôme

2010-01-01

With age, cardiac performance declines progressively and the risk of heart disease, a primary cause of mortality, rises dramatically. As the elderly population continues to increase, it is critical to gain a better understanding of the genetic influences and modulatory factors that impact cardiac aging. In an attempt to determine the relevance and utility of the Drosophila heart in unraveling the genetic mechanisms underlying cardiac aging, a variety of heart performance assays have recently been developed to quantify Drosophila heart performance that permit the use of the fruit fly to investigate the heart’s decline with age. As for the human heart, Drosophila heart function also deteriorates with age. Notably, with progressive age the incidence of cardiac arrhythmias, myofibrillar disorganization and susceptibility to heart dysfunction and failure all increase significantly. We review here the evidence for an involvement of the insulin-TOR pathway, the KATP channel subunit dSur, the KCNQ potassium channel, as well as Dystrophin and Myosin in fly cardiac aging, and discuss the utility of the Drosophila heart model for cardiac aging studies. PMID:21130861

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.

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.

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

Risk assessment model for development of advanced age-related macular degeneration.

PubMed

Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E

2011-12-01

To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

ACCELERATED FAILURE TIME MODELS PROVIDE A USEFUL STATISTICAL FRAMEWORK FOR AGING RESEARCH

PubMed Central

Swindell, William R.

2009-01-01

Survivorship experiments play a central role in aging research and are performed to evaluate whether interventions alter the rate of aging and increase lifespan. The accelerated failure time (AFT) model is seldom used to analyze survivorship data, but offers a potentially useful statistical approach that is based upon the survival curve rather than the hazard function. In this study, AFT models were used to analyze data from 16 survivorship experiments that evaluated the effects of one or more genetic manipulations on mouse lifespan. Most genetic manipulations were found to have a multiplicative effect on survivorship that is independent of age and well-characterized by the AFT model “deceleration factor”. AFT model deceleration factors also provided a more intuitive measure of treatment effect than the hazard ratio, and were robust to departures from modeling assumptions. Age-dependent treatment effects, when present, were investigated using quantile regression modeling. These results provide an informative and quantitative summary of survivorship data associated with currently known long-lived mouse models. In addition, from the standpoint of aging research, these statistical approaches have appealing properties and provide valuable tools for the analysis of survivorship data. PMID:19007875

Accelerated failure time models provide a useful statistical framework for aging research.

PubMed

Swindell, William R

2009-03-01

Survivorship experiments play a central role in aging research and are performed to evaluate whether interventions alter the rate of aging and increase lifespan. The accelerated failure time (AFT) model is seldom used to analyze survivorship data, but offers a potentially useful statistical approach that is based upon the survival curve rather than the hazard function. In this study, AFT models were used to analyze data from 16 survivorship experiments that evaluated the effects of one or more genetic manipulations on mouse lifespan. Most genetic manipulations were found to have a multiplicative effect on survivorship that is independent of age and well-characterized by the AFT model "deceleration factor". AFT model deceleration factors also provided a more intuitive measure of treatment effect than the hazard ratio, and were robust to departures from modeling assumptions. Age-dependent treatment effects, when present, were investigated using quantile regression modeling. These results provide an informative and quantitative summary of survivorship data associated with currently known long-lived mouse models. In addition, from the standpoint of aging research, these statistical approaches have appealing properties and provide valuable tools for the analysis of survivorship data.

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.

A New Approach of Juvenile Age Estimation using Measurements of the Ilium and Multivariate Adaptive Regression Splines (MARS) Models for Better Age Prediction.

PubMed

Corron, Louise; Marchal, François; Condemi, Silvana; Chaumoître, Kathia; Adalian, Pascal

2017-01-01

Juvenile age estimation methods used in forensic anthropology generally lack methodological consistency and/or statistical validity. Considering this, a standard approach using nonparametric Multivariate Adaptive Regression Splines (MARS) models were tested to predict age from iliac biometric variables of male and female juveniles from Marseilles, France, aged 0-12 years. Models using unidimensional (length and width) and bidimensional iliac data (module and surface) were constructed on a training sample of 176 individuals and validated on an independent test sample of 68 individuals. Results show that MARS prediction models using iliac width, module and area give overall better and statistically valid age estimates. These models integrate punctual nonlinearities of the relationship between age and osteometric variables. By constructing valid prediction intervals whose size increases with age, MARS models take into account the normal increase of individual variability. MARS models can qualify as a practical and standardized approach for juvenile age estimation. © 2016 American Academy of Forensic Sciences.

Revisiting dark energy models using differential ages of galaxies

NASA Astrophysics Data System (ADS)

Rani, Nisha; Jain, Deepak; Mahajan, Shobhit; Mukherjee, Amitabha; Biesiada, Marek

2017-03-01

In this work, we use a test based on the differential ages of galaxies for distinguishing the dark energy models. As proposed by Jimenez and Loeb in [1], relative ages of galaxies can be used to put constraints on various cosmological parameters. In the same vein, we reconstruct H0dt/dz and its derivative (H0d2t/dz2) using a model independent technique called non-parametric smoothing. Basically, dt/dz is the change in the age of the object as a function of redshift which is directly linked with the Hubble parameter. Hence for reconstruction of this quantity, we use the most recent H(z) data. Further, we calculate H0dt/dz and its derivative for several models like Phantom, Einstein de Sitter (EdS), ΛCDM, Chevallier-Polarski-Linder (CPL) parametrization, Jassal-Bagla-Padmanabhan (JBP) parametrization and Feng-Shen-Li-Li (FSLL) parametrization. We check the consistency of these models with the results of reconstruction obtained in a model independent way from the data. It is observed that H0dt/dz as a tool is not able to distinguish between the ΛCDM, CPL, JBP and FSLL parametrizations but, as expected, EdS and Phantom models show noticeable deviation from the reconstructed results. Further, the derivative of H0dt/dz for various dark energy models is more sensitive at low redshift. It is found that the FSLL model is not consistent with the reconstructed results, however, the ΛCDM model is in concordance with the 3σ region of the reconstruction at redshift z>= 0.3.

Why is the dog an ideal model for aging research?

PubMed

Gilmore, Keiva M; Greer, Kimberly A

2015-11-01

With many caveats to the traditional vertebrate species pertaining to biogerontology investigations, it has been suggested that a most informative model is the one which: 1) examines closely related species, or various members of the same species with naturally occurring lifespan variation, 2) already has adequate medical procedures developed, 3) has a well annotated genome, 4) does not require artificial housing, and can live in its natural environment while being investigated, and 5) allows considerable information to be gathered within a relatively short period of time. The domestic dog unsurprisingly fits each criterion mentioned. The dog has already become a key model system in which to evaluate surgical techniques and novel medications because of the remarkable similarity between human and canine conditions, treatments, and response to therapy. The dog naturally serves as a disease model for study, obviating the need to construct artificial genetically modified examples of disease. Just as the dog offers a natural model for human conditions and diseases, simple observation leads to the conclusion that the canine aging phenotype also mimics that of the human. Genotype information, biochemical information pertaining to the GH/IGF-1 pathway, and some limited longitudinal investigations have begun the establishment of the domestic dog as a model of aging. Although we find that dogs indeed are a model to study aging and there are many independent pieces of canine aging data, there are many more "open" areas, ripe for investigation. Published by Elsevier Inc.

Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging.

PubMed

Petrini, Stefania; Borghi, Rossella; D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia

2017-05-31

Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging.

Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging

PubMed Central

D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia

2017-01-01

Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging. PMID:28562315

Investigating the prostate specific antigen, body mass index and age relationship: is an age-BMI-adjusted PSA model clinically useful?

PubMed

Harrison, Sean; Tilling, Kate; Turner, Emma L; Lane, J Athene; Simpkin, Andrew; Davis, Michael; Donovan, Jenny; Hamdy, Freddie C; Neal, David E; Martin, Richard M

2016-12-01

Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age-BMI-adjusted PSA model would be clinically useful for detecting prostate cancer. Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50-69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m 2 . Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status. In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7-2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m 2 (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m 2 increase in BMI (95% CI 3.4-6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0-15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age-BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer. Age and BMI were associated with small changes in PSA. An age-BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

Love Kills:. Simulations in Penna Ageing Model

NASA Astrophysics Data System (ADS)

Stauffer, Dietrich; Cebrat, Stanisław; Penna, T. J. P.; Sousa, A. O.

The standard Penna ageing model with sexual reproduction is enlarged by adding additional bit-strings for love: Marriage happens only if the male love strings are sufficiently different from the female ones. We simulate at what level of required difference the population dies out.

Age and Pathway Diagnostics for a Stratospheric General Circulation Model

NASA Technical Reports Server (NTRS)

Schoeberl, Mark R.; Douglass, Anne R.; Polansky, Brian

2004-01-01

Using a variety of age diagnostic experiments we examine the stratospheric age spectrum of the Goddard Finite Volume Generd Circulation Model. Pulse tracer release age-of-air computations are compared to forward and backward trajectory computations. These comparisons show good agreement, and the age-of-air also compares well with observed long lived tracers. Pathway diagnostics show how air arrives in the lowermost stratosphere and the age structure of that region. Using tracers with different lifetimes we can estimate the age spectrum - this technique should be useful in diagnosing transport from various trace gas observations.

Phenomenological Modeling and Laboratory Simulation of Long-Term Aging of Asphalt Mixtures

NASA Astrophysics Data System (ADS)

Elwardany, Michael Dawoud

The accurate characterization of asphalt mixture properties as a function of pavement service life is becoming more important as more powerful pavement design and performance prediction methods are implemented. Oxidative aging is a major distress mechanism of asphalt pavements. Aging increases the stiffness and brittleness of the material, which leads to a high cracking potential. Thus, an improved understanding of the aging phenomenon and its effect on asphalt binder chemical and rheological properties will allow for the prediction of mixture properties as a function of pavement service life. Many researchers have conducted laboratory binder thin-film aging studies; however, this approach does not allow for studying the physicochemical effects of mineral fillers on age hardening rates in asphalt mixtures. Moreover, aging phenomenon in the field is governed by kinetics of binder oxidation, oxygen diffusion through mastic phase, and oxygen percolation throughout the air voids structure. In this study, laboratory aging trials were conducted on mixtures prepared using component materials of several field projects throughout the USA and Canada. Laboratory aged materials were compared against field cores sampled at different ages. Results suggested that oven aging of loose mixture at 95°C is the most promising laboratory long-term aging method. Additionally, an empirical model was developed in order to account for the effect of mineral fillers on age hardening rates in asphalt mixtures. Kinetics modeling was used to predict field aging levels throughout pavement thickness and to determine the required laboratory aging duration to match field aging. Kinetics model outputs are calibrated using measured data from the field to account for the effects of oxygen diffusion and percolation. Finally, the calibrated model was validated using independent set of field sections. This work is expected to provide basis for improved asphalt mixture and pavement design procedures in

Ages and transit times as important diagnostics of model performance for predicting carbon dynamics in terrestrial vegetation models

NASA Astrophysics Data System (ADS)

Ceballos-Núñez, Verónika; Richardson, Andrew D.; Sierra, Carlos A.

2018-03-01

The global carbon cycle is strongly controlled by the source/sink strength of vegetation as well as the capacity of terrestrial ecosystems to retain this carbon. These dynamics, as well as processes such as the mixing of old and newly fixed carbon, have been studied using ecosystem models, but different assumptions regarding the carbon allocation strategies and other model structures may result in highly divergent model predictions. We assessed the influence of three different carbon allocation schemes on the C cycling in vegetation. First, we described each model with a set of ordinary differential equations. Second, we used published measurements of ecosystem C compartments from the Harvard Forest Environmental Measurement Site to find suitable parameters for the different model structures. And third, we calculated C stocks, release fluxes, radiocarbon values (based on the bomb spike), ages, and transit times. We obtained model simulations in accordance with the available data, but the time series of C in foliage and wood need to be complemented with other ecosystem compartments in order to reduce the high parameter collinearity that we observed, and reduce model equifinality. Although the simulated C stocks in ecosystem compartments were similar, the different model structures resulted in very different predictions of age and transit time distributions. In particular, the inclusion of two storage compartments resulted in the prediction of a system mean age that was 12-20 years older than in the models with one or no storage compartments. The age of carbon in the wood compartment of this model was also distributed towards older ages, whereas fast cycling compartments had an age distribution that did not exceed 5 years. As expected, models with C distributed towards older ages also had longer transit times. These results suggest that ages and transit times, which can be indirectly measured using isotope tracers, serve as important diagnostics of model structure

Age and geochemistry of Neoproterozoic granitoids in the Songnen-Zhangguangcai Range Massif, NE China: Petrogenesis and tectonic implications

NASA Astrophysics Data System (ADS)

Luan, Jin-Peng; Xu, Wen-Liang; Wang, Feng; Wang, Zhi-Wei; Guo, Peng

2017-10-01

This study presents new zircon U-Pb ages and geochemical data for Neoproterozoic granitoids in the Songnen-Zhangguangcai Range Massif (SZRM) of NE China. This dataset provides insights into the Neoproterozoic tectonic setting of the SZRM and the links between this magmatism and the evolution of the Rodinia supercontinent. The zircon U-Pb dating indicates that the Neoproterozoic magmatism within the SZRM can be subdivided into two stages: (1) a ∼917-911 Ma suite of syenogranites and monzogranites, and (2) an ∼841 Ma suite of granodiorites. The 917-911 Ma granitoids contain high concentrations of SiO2 (67.89-71.18 wt.%), K2O (4.24-6.91 wt.%), and Al2O3 (14.89-16.14 wt.%), and low concentrations of TFe2O3 (1.63-3.70 wt.%) and MgO (0.53-0.88 wt.%). They are enriched in the light rare earth elements (LREE) and the large ion lithophile elements (LILE), are depleted in the heavy REE (HREE) and the high field strength elements (HFSE; e.g., Nb, Ta, and Ti), and have slightly positive Eu anomalies, indicating that they are geochemically similar to high-K adakitic rocks. They have zircon εHf (t) values and TDM2 ages from -4.4 to +1.5 and 1915 Ma to 1592 Ma, respectively, suggesting that they were derived from a primary magma generated by the partial melting of ancient thickened lower crustal material. In comparison, the 841 Ma granodiorites contain relatively low concentrations of Al2O3 (14.50-14.58 wt.%) and K2O (3.27-3.29 wt.%), relatively high concentrations of TFe2O3 (3.78-3.81 wt.%) and the HREE, have negative Eu anomalies, and have zircon εHf (t) values and TDM2 ages from -4.7 to +1.0 and 1875 to 1559 Ma, respectively. These granodiorites formed from a primary magma generated by the partial melting of ancient crustal material. The ∼917-911 Ma magmatism within the SZRM is inferred to have formed in an orogenic setting, whereas the ∼841 Ma magmatism formed in an anorogenic setting related to either a post-orogenic tectonic event or the onset of Neoproterozoic

Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy.

PubMed

Lai, Ming-Ming; Lein, Shi-Ying; Lau, Siok-Hwa; Lai, Ming-Ling

2016-01-01

This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above) in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96) indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population.

Modeling Age-Friendly Environment, Active Aging, and Social Connectedness in an Emerging Asian Economy

PubMed Central

Lai, Ming-Ming; Lein, Shi-Ying; Lau, Siok-Hwa; Lai, Ming-Ling

2016-01-01

This paper empirically tested eight key features of WHO guidelines to age-friendly community by surveying 211 informal caregivers and 402 self-care adults (aged 45 to 85 and above) in Malaysia. We examined the associations of these eight features with active aging and social connectedness through exploratory and confirmatory factor analyses. A structural model with satisfactory goodness-of-fit indices (CMIN/df = 1.11, RMSEA = 0.02, NFI = 0.97, TLI = 1.00, CFI = 1.00, and GFI = 0.96) indicates that transportation and housing, community support and health services, and outdoor spaces and buildings are statistically significant in creating an age-friendly environment. We found a statistically significant positive relationship between an age-friendly environment and active aging. This relationship is mediated by social connectedness. The results indicate that built environments such as accessible public transportations and housing, affordable and accessible healthcare services, and elderly friendly outdoor spaces and buildings have to be put into place before social environment in building an age-friendly environment. Otherwise, the structural barriers would hinder social interactions for the aged. The removal of the environmental barriers and improved public transportation services provide short-term solutions to meet the varied and growing needs of the older population. PMID:27293889

An analysis of age-prevalence data by catalytic models

PubMed Central

Hairston, Nelson G.

1965-01-01

The analysis of age-prevalence curves obtained from bilharziasis surveys is not usually carried out to the maximum depth the data allow for. With a view to obtaining greater value from the available information, the author analyses age-prevalence data for three common human schistosomes by Muench's catalytic models. The two-stage model is found the most appropriate. Use of this model assumes constant rates of becoming positive and of becoming negative. Two separate analyses are required, one for the first few years of life of the human host and one for the remainder. Satisfactory fits to the data are obtained only when the proportion of older people who remain positive is determined. This proportion varies with the intensity of transmission. The calculated rates of becoming positive agree very well with rates obtained by observing originally negative children for 12 months or longer. The parameters in the model are used in interpreting data from skin-test surveys. It is concluded tentatively that in order to be positive by the skin test, a person must have had both sexes of worms at some time in the past and to be carrying living female worms or to have been exposed recently to female cercariae. It may become possible to use the model to predict the entire age-prevalence curve from data on children, thus saving much effort in parasitological surveys. PMID:5294588

Markov Chain-Like Quantum Biological Modeling of Mutations, Aging, and Evolution.

PubMed

Djordjevic, Ivan B

2015-08-24

Recent evidence suggests that quantum mechanics is relevant in photosynthesis, magnetoreception, enzymatic catalytic reactions, olfactory reception, photoreception, genetics, electron-transfer in proteins, and evolution; to mention few. In our recent paper published in Life, we have derived the operator-sum representation of a biological channel based on codon basekets, and determined the quantum channel model suitable for study of the quantum biological channel capacity. However, this model is essentially memoryless and it is not able to properly model the propagation of mutation errors in time, the process of aging, and evolution of genetic information through generations. To solve for these problems, we propose novel quantum mechanical models to accurately describe the process of creation spontaneous, induced, and adaptive mutations and their propagation in time. Different biological channel models with memory, proposed in this paper, include: (i) Markovian classical model, (ii) Markovian-like quantum model, and (iii) hybrid quantum-classical model. We then apply these models in a study of aging and evolution of quantum biological channel capacity through generations. We also discuss key differences of these models with respect to a multilevel symmetric channel-based Markovian model and a Kimura model-based Markovian process. These models are quite general and applicable to many open problems in biology, not only biological channel capacity, which is the main focus of the paper. We will show that the famous quantum Master equation approach, commonly used to describe different biological processes, is just the first-order approximation of the proposed quantum Markov chain-like model, when the observation interval tends to zero. One of the important implications of this model is that the aging phenotype becomes determined by different underlying transition probabilities in both programmed and random (damage) Markov chain-like models of aging, which are mutually

Markov Chain-Like Quantum Biological Modeling of Mutations, Aging, and Evolution

PubMed Central

Djordjevic, Ivan B.

2015-01-01

Recent evidence suggests that quantum mechanics is relevant in photosynthesis, magnetoreception, enzymatic catalytic reactions, olfactory reception, photoreception, genetics, electron-transfer in proteins, and evolution; to mention few. In our recent paper published in Life, we have derived the operator-sum representation of a biological channel based on codon basekets, and determined the quantum channel model suitable for study of the quantum biological channel capacity. However, this model is essentially memoryless and it is not able to properly model the propagation of mutation errors in time, the process of aging, and evolution of genetic information through generations. To solve for these problems, we propose novel quantum mechanical models to accurately describe the process of creation spontaneous, induced, and adaptive mutations and their propagation in time. Different biological channel models with memory, proposed in this paper, include: (i) Markovian classical model, (ii) Markovian-like quantum model, and (iii) hybrid quantum-classical model. We then apply these models in a study of aging and evolution of quantum biological channel capacity through generations. We also discuss key differences of these models with respect to a multilevel symmetric channel-based Markovian model and a Kimura model-based Markovian process. These models are quite general and applicable to many open problems in biology, not only biological channel capacity, which is the main focus of the paper. We will show that the famous quantum Master equation approach, commonly used to describe different biological processes, is just the first-order approximation of the proposed quantum Markov chain-like model, when the observation interval tends to zero. One of the important implications of this model is that the aging phenotype becomes determined by different underlying transition probabilities in both programmed and random (damage) Markov chain-like models of aging, which are mutually

[Induced thymus aging: radiation model and application perspective for low intensive laser radiation].

PubMed

Sevost'ianova, N N; Trofimov, A V; Lin'kova, N S; Poliakova, V O; Kvetnoĭ, I M

2010-01-01

The influence of gamma-radiation on morphofunctional state of thymus is rather like as natural thymus aging. However gamma-radiation model of thymus aging widely used to investigate geroprotectors has many shortcomings and limitations. Gamma-radiation can induce irreversible changes in thymus very often. These changes are more intensive in comparison with changes, which can be observed at natural thymus aging. Low intensive laser radiation can not destroy structure of thymus and its effects are rather like as natural thymus aging in comparison with gamma-radiation effects. There are many parameters of low intensive laser radiation, which can be changed to improve morphofunctional thymus characteristics in aging model. Using low intensive laser radiation in thymus aging model can be very perspective for investigations of aging immune system.

Revisiting dark energy models using differential ages of galaxies

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

Rani, Nisha; Mahajan, Shobhit; Mukherjee, Amitabha

In this work, we use a test based on the differential ages of galaxies for distinguishing the dark energy models. As proposed by Jimenez and Loeb in [1], relative ages of galaxies can be used to put constraints on various cosmological parameters. In the same vein, we reconstruct H {sub 0} {sub dt} / dz and its derivative ( H {sub 0} {sub d} {sup 2} {sup t} / dz {sup 2}) using a model independent technique called non-parametric smoothing . Basically, dt / dz is the change in the age of the object as a function of redshift whichmore » is directly linked with the Hubble parameter. Hence for reconstruction of this quantity, we use the most recent H ( z ) data. Further, we calculate H {sub 0} {sub dt} / dz and its derivative for several models like Phantom, Einstein de Sitter (EdS), ΛCDM, Chevallier-Polarski-Linder (CPL) parametrization, Jassal-Bagla-Padmanabhan (JBP) parametrization and Feng-Shen-Li-Li (FSLL) parametrization. We check the consistency of these models with the results of reconstruction obtained in a model independent way from the data. It is observed that H {sub 0} {sub dt} / dz as a tool is not able to distinguish between the ΛCDM, CPL, JBP and FSLL parametrizations but, as expected, EdS and Phantom models show noticeable deviation from the reconstructed results. Further, the derivative of H {sub 0} {sub dt} / dz for various dark energy models is more sensitive at low redshift. It is found that the FSLL model is not consistent with the reconstructed results, however, the ΛCDM model is in concordance with the 3σ region of the reconstruction at redshift z ≥ 0.3.« less

Drug repurposing for aging research using model organisms.

PubMed

Ziehm, Matthias; Kaur, Satwant; Ivanov, Dobril K; Ballester, Pedro J; Marcus, David; Partridge, Linda; Thornton, Janet M

2017-10-01

Many increasingly prevalent diseases share a common risk factor: age. However, little is known about pharmaceutical interventions against aging, despite many genes and pathways shown to be important in the aging process and numerous studies demonstrating that genetic interventions can lead to a healthier aging phenotype. An important challenge is to assess the potential to repurpose existing drugs for initial testing on model organisms, where such experiments are possible. To this end, we present a new approach to rank drug-like compounds with known mammalian targets according to their likelihood to modulate aging in the invertebrates Caenorhabditis elegans and Drosophila. Our approach combines information on genetic effects on aging, orthology relationships and sequence conservation, 3D protein structures, drug binding and bioavailability. Overall, we rank 743 different drug-like compounds for their likelihood to modulate aging. We provide various lines of evidence for the successful enrichment of our ranking for compounds modulating aging, despite sparse public data suitable for validation. The top ranked compounds are thus prime candidates for in vivo testing of their effects on lifespan in C. elegans or Drosophila. As such, these compounds are promising as research tools and ultimately a step towards identifying drugs for a healthier human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

A Comparison of the Age-Spectra from Data Assimilation Models

NASA Technical Reports Server (NTRS)

Schoeberl, Mark R.; Douglass, Anne R.; Zhu, Zheng-Xin; Pawson, Steven; Einaudi, Franco (Technical Monitor)

2002-01-01

We use kinematic and diabatic back trajectory calculations, driven by winds from a general circulation model (GCM) and two different data assimilation systems (DAS), to compute the age spectrum at three latitudes in the lower stratosphere. The age-spectra are compared to chemical transport model (CTM) calculations, and the mean ages from all of these studies are compared to observations. The age spectra computed using the GCM winds show a reasonably well-isolated tropics in good agreement with observations; however, the age spectra determined from the DAS differ from the GCM spectra. For the diabatic trajectory calculations, the age spectrum is too broad as a result of too much exchange between the tropics and mid-latitudes. The age spectrum determined using the kinematic trajectory calculation is less broad and lacks an age offset; both of these features are due to excessive vertical dispersion of parcels. The tropical and mid-latitude mean age difference between the diabatically and kinematically determined age-spectra is about one year, the former being older. The CTM calculation of the age spectrum using the DAS winds shows the same dispersive characteristics of the kinematic trajectory calculation. These results suggest that the current DAS products will not give realistic trace gas distributions for long integrations; they also help explain why the mean ages determined in a number of previous DAS driven CTM's are too young compared with observations. Finally, we note trajectory-generated age spectra show significant age anomalies correlated with the seasonal cycles, and these anomalies can be linked to year-to-year variations in the tropical heating rate. These anomalies are suppressed in the CTM spectra suggesting that the CTM transport is too diffusive.

Automatic age and gender classification using supervised appearance model

NASA Astrophysics Data System (ADS)

Bukar, Ali Maina; Ugail, Hassan; Connah, David

2016-11-01

Age and gender classification are two important problems that recently gained popularity in the research community, due to their wide range of applications. Research has shown that both age and gender information are encoded in the face shape and texture, hence the active appearance model (AAM), a statistical model that captures shape and texture variations, has been one of the most widely used feature extraction techniques for the aforementioned problems. However, AAM suffers from some drawbacks, especially when used for classification. This is primarily because principal component analysis (PCA), which is at the core of the model, works in an unsupervised manner, i.e., PCA dimensionality reduction does not take into account how the predictor variables relate to the response (class labels). Rather, it explores only the underlying structure of the predictor variables, thus, it is no surprise if PCA discards valuable parts of the data that represent discriminatory features. Toward this end, we propose a supervised appearance model (sAM) that improves on AAM by replacing PCA with partial least-squares regression. This feature extraction technique is then used for the problems of age and gender classification. Our experiments show that sAM has better predictive power than the conventional AAM.

Different macaque models of cognitive aging exhibit task-dependent behavioral disparities.

PubMed

Comrie, Alison E; Gray, Daniel T; Smith, Anne C; Barnes, Carol A

2018-05-15

Deficits in cognitive functions that rely on the integrity of the frontal and temporal lobes are characteristic of normative human aging. Due to similar aging phenotypes and homologous cortical organization between nonhuman primates and humans, several species of macaque monkeys are used as models to explore brain senescence. These macaque species are typically regarded as equivalent models of cognitive aging, yet no direct comparisons have been made to support this assumption. Here we used adult and aged rhesus and bonnet macaques (Macaca mulatta and Macaca radiata) to characterize the effect of age on acquisition and retention of information across delays in a battery of behavioral tasks that rely on prefrontal cortex and medial temporal lobe networks. The cognitive functions that were tested include visuospatial short-term memory, object recognition memory, and object-reward association memory. In general, bonnet macaques at all ages outperformed rhesus macaques on tasks thought to rely primarily on the prefrontal cortex, and were more resilient to age-related deficits in these behaviors. On the other hand, both species were comparably impaired by age on tasks thought to preferentially engage the medial temporal lobe. Together, these results suggest that rhesus and bonnet macaques are not equivalent models of cognitive aging and highlight the value of cross-species comparisons. These observations should enable improved design and interpretation of future experiments aimed at understanding changes in cognition across the lifespan. Copyright © 2018 Elsevier B.V. All rights reserved.

Social Breakdown and Competence. A Model of Normal Aging

ERIC Educational Resources Information Center

Kuypers, J. A.; Bengtson, V. L.

1973-01-01

Presents a model emphasizing the interactions between reorganization of social systems and individual competencies in old age. The model suggests the process by which loss of coping abilities and feelings of worthlessness develop. Implications for effective intervention with the elderly are discussed. (DP)

Econometric model for age- and population-dependent radiation exposures

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

Sandquist, G.M.; Slaughter, D.M.; Rogers, V.C.

1991-01-01

The economic impact associated with ionizing radiation exposures in a given human population depends on numerous factors including the individual's mean economic status as a function age, the age distribution of the population, the future life expectancy at each age, and the latency period for the occurrence of radiation-induced health effects. A simple mathematical model has been developed that provides an analytical methodology for estimating the societal econometrics associated with radiation effects are to be assessed and compared for economic evaluation.

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.

[Central female hypogonadism as a model of premature aging].

PubMed

Ilovayskaya, I A; Lazebnik, L B; Kulikov, A V

Central (hypogonadotropic) hypogonadism in women could also be a cause of persistent amenorrhea and hypoestrogenemia. The aim of this study was to evaluate symptoms of premature aging in women of young age with central hypogonadism. 88 young women (25 [21; 30] y.o.) with central hypogonadism (with isolated hypogonadotropic hypogonadism n=42, and associated with the other types of pituitary insufficiencies n=46), 53 healthy young women (24 [23; 28] y.o.) and 50 healthy postmenopausal women (56 [53; 58] y.o.) were examined. In young women with central hypogonadism frequency of psychoemotional, neurovegetative and urogenital disorders, peripheral sex steroid concentrations, lipid and mineral homeostasis parameters differed significantly from the healthy young women of similar age and were comparable with postmenopausal women of middle/older age. Thus, according to clinical, hormonal and biochemical abnormalities biological age of female patients with central hypogonadism advanced significantly chronological young age and corresponded to middle/older age. The central female hypogonadism is a model of premature aging.

Toward Reducing Ageism: PEACE (Positive Education about Aging and Contact Experiences) Model.

PubMed

Levy, Sheri R

2018-03-19

The population of older adults is growing worldwide. Negative ageism (negative attitudes and behavior toward older adults) is a serious international concern that negatively influences not only older adults but also individuals across the age continuum. This article proposes and examines the application of an integrative theoretical model across empirical evidence in the literature on ageism in psychology, medicine, social work, and sociology. The proposed Positive Education about Aging and Contact Experiences (PEACE) model focuses on 2 key contributing factors expected to reduce negative ageism: (a) education about aging including facts on aging along with positive older role models that dispel negative and inaccurate images of older adulthood; and (b) positive contact experiences with older adults that are individualized, provide or promote equal status, are cooperative, involve sharing of personal information, and are sanctioned within the setting. These 2 key contributing factors have the potential to be interconnected and work together to reduce negative stereotypes, aging anxiety, prejudice, and discrimination associated with older adults and aging. This model has implications for policies and programs that can improve the health and well-being of individuals, as well as expand the residential, educational, and career options of individuals across the age continuum.

Cscibox: A Software System for Age-Model Construction and Evaluation

NASA Astrophysics Data System (ADS)

Bradley, E.; Anderson, K. A.; Marchitto, T. M., Jr.; de Vesine, L. R.; White, J. W. C.; Anderson, D. M.

2014-12-01

CSciBox is an integrated software system for the construction and evaluation of age models of paleo-environmetal archives, both directly dated and cross dated. The time has come to encourage cross-pollinization between earth science and computer science in dating paleorecords. This project addresses that need. The CSciBox code, which is being developed by a team of computer scientists and geoscientists, is open source and freely available on github. The system employs modern database technology to store paleoclimate proxy data and analysis results in an easily accessible and searchable form. This makes it possible to do analysis on the whole core at once, in an interactive fashion, or to tailor the analysis to a subset of the core without loading the entire data file. CSciBox provides a number of 'components' that perform the common steps in age-model construction and evaluation: calibrations, reservoir-age correction, interpolations, statistics, and so on. The user employs these components via a graphical user interface (GUI) to go from raw data to finished age model in a single tool: e.g., an IntCal09 calibration of 14C data from a marine sediment core, followed by a piecewise-linear interpolation. CSciBox's GUI supports plotting of any measurement in the core against any other measurement, or against any of the variables in the calculation of the age model-with or without explicit error representations. Using the GUI, CSciBox's user can import a new calibration curve or other background data set and define a new module that employs that information. Users can also incorporate other software (e.g., Calib, BACON) as 'plug ins.' In the case of truly large data or significant computational effort, CSciBox is parallelizable across modern multicore processors, or clusters, or even the cloud. The next generation of the CSciBox code, currently in the testing stages, includes an automated reasoning engine that supports a more-thorough exploration of plausible age models

Face aging effect simulation model based on multilayer representation and shearlet transform

NASA Astrophysics Data System (ADS)

Li, Yuancheng; Li, Yan

2017-09-01

In order to extract detailed facial features, we build a face aging effect simulation model based on multilayer representation and shearlet transform. The face is divided into three layers: the global layer of the face, the local features layer, and texture layer, which separately establishes the aging model. First, the training samples are classified according to different age groups, and we use active appearance model (AAM) at the global level to obtain facial features. The regression equations of shape and texture with age are obtained by fitting the support vector machine regression, which is based on the radial basis function. We use AAM to simulate the aging of facial organs. Then, for the texture detail layer, we acquire the significant high-frequency characteristic components of the face by using the multiscale shearlet transform. Finally, we get the last simulated aging images of the human face by the fusion algorithm. Experiments are carried out on the FG-NET dataset, and the experimental results show that the simulated face images have less differences from the original image and have a good face aging simulation effect.

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.

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.

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

PubMed Central

McAuley, Mark T; Kenny, Rose Anne; Kirkwood, Thomas BL; Wilkinson, Darren J; Jones, Janette JL; Miller, Veronica M

2009-01-01

Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people. PMID:19320982

Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose.

PubMed

Zhang, Shengchang; Dong, Ziqing; Peng, Zhangsong; Lu, Feng

2014-01-01

Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs) are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism. Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 106 green fluorescent protein (GFP)-expressing ASCs, aminoguanidine (AG) or phosphate-buffered saline (PBS). Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD) and malondialdehyde (MDA). Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE) levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect. These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.

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.

Age structure and capital dilution effects in neo-classical growth models.

PubMed

Blanchet, D

1988-01-01

Economists often over estimate capital dilution effects when applying neoclassical growth models which use age structured population and depreciation of capital stock. This occurs because capital stock is improperly characterized. A standard model which assumes a constant depreciation of capital intimates that a population growth rate equal to a negative constant savings ratio is preferable to any higher growth rate. Growth rates which are lower than a negative constant savings ratio suggest an ever growing capital/labor ratio and an ever growing standard of living, even if people do not save. This is suggested because the natural reduction of the capital stock through depreciation is slower than the population decrease which is simply unrealistic. This model overlooks the fact that low or negative growth rates result in an ageing of the capital stock, and this ageing subsequently results in an increase of the overall rate of capital depreciation. In that overly simplistic model, depreciation was assumed independent of the age of the captial stock. Incorporating depreciation as a variable into a model allows a more symmetric treatment of capital. Using models with heterogenous capital, this article explores what occurs when more than 1 kind of capital good is involved in production and when these various captial goods have different lengths of life. Applying economic models, it also examines what occurs when the length of life of capital may vary. These variations correct the negative impact that population growth can have on per capital production and consumption.

Reactive Radial Diffusion Model for the Aging/Sequestration Process

NASA Astrophysics Data System (ADS)

Ginn, T. R.; Basagaoglu, H.; McCoy, B. J.; Scow, K. M.

2001-12-01

A radial diffusion model has been formulated to simulate age-dependent bioavailability of chemical compounds to micro-organisms residing outside (and/or inside) the porous soil particles. Experimental findings in the literature indicate that the sequestration and reduction in bioavailability of contaminants are controlled presumably by the diffusion-limited sorption kinetics and the time-variant desorption process. Here we combine radial-diffusion mass transfer modeling with the exposure-time concept to generate mass-balance equations for the intra- and extra-particle concentrations. The model accomodates reversible sorption kinetics involving sorption time-dependence of the rate coefficients, distinct intra- and extra-particle biodegradation rates; and a dynamic mass interaction between the intra- and extra-particle concentrations arising from the radial diffusion concept. The model explicitly treats multiple particle classes distributed in size and chemical properties in a bulk aquifer or soil volume, which allows the simulation of the sequestration and bioavailability of contaminants in different particle size classes that have distinct diffusion, reaction, and aging properties.

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.

Development and validation of age-dependent FE human models of a mid-sized male thorax.

PubMed

El-Jawahri, Raed E; Laituri, Tony R; Ruan, Jesse S; Rouhana, Stephen W; Barbat, Saeed D

2010-11-01

The increasing number of people over 65 years old (YO) is an important research topic in the area of impact biomechanics, and finite element (FE) modeling can provide valuable support for related research. There were three objectives of this study: (1) Estimation of the representative age of the previously-documented Ford Human Body Model (FHBM) -- an FE model which approximates the geometry and mass of a mid-sized male, (2) Development of FE models representing two additional ages, and (3) Validation of the resulting three models to the extent possible with respect to available physical tests. Specifically, the geometry of the model was compared to published data relating rib angles to age, and the mechanical properties of different simulated tissues were compared to a number of published aging functions. The FHBM was determined to represent a 53-59 YO mid-sized male. The aforementioned aging functions were used to develop FE models representing two additional ages: 35 and 75 YO. The rib model was validated against human rib specimens and whole rib tests, under different loading conditions, with and without modeled fracture. In addition, the resulting three age-dependent models were validated by simulating cadaveric tests of blunt and sled impacts. The responses of the models, in general, were within the cadaveric response corridors. When compared to peak responses from individual cadavers similar in size and age to the age-dependent models, some responses were within one standard deviation of the test data. All the other responses, but one, were within two standard deviations.

Poverty dynamics, poverty thresholds and mortality: An age-stage Markovian model

PubMed Central

Rehkopf, David; Tuljapurkar, Shripad; Horvitz, Carol C.

2018-01-01

Recent studies have examined the risk of poverty throughout the life course, but few have considered how transitioning in and out of poverty shape the dynamic heterogeneity and mortality disparities of a cohort at each age. Here we use state-by-age modeling to capture individual heterogeneity in crossing one of three different poverty thresholds (defined as 1×, 2× or 3× the “official” poverty threshold) at each age. We examine age-specific state structure, the remaining life expectancy, its variance, and cohort simulations for those above and below each threshold. Survival and transitioning probabilities are statistically estimated by regression analyses of data from the Health and Retirement Survey RAND data-set, and the National Longitudinal Survey of Youth. Using the results of these regression analyses, we parameterize discrete state, discrete age matrix models. We found that individuals above all three thresholds have higher annual survival than those in poverty, especially for mid-ages to about age 80. The advantage is greatest when we classify individuals based on 1× the “official” poverty threshold. The greatest discrepancy in average remaining life expectancy and its variance between those above and in poverty occurs at mid-ages for all three thresholds. And fewer individuals are in poverty between ages 40-60 for all three thresholds. Our findings are consistent with results based on other data sets, but also suggest that dynamic heterogeneity in poverty and the transience of the poverty state is associated with income-related mortality disparities (less transience, especially of those above poverty, more disparities). This paper applies the approach of age-by-stage matrix models to human demography and individual poverty dynamics. In so doing we extend the literature on individual poverty dynamics across the life course. PMID:29768416

The Healthy Aging Research Network: Modeling Collaboration for Community Impact.

PubMed

Belza, Basia; Altpeter, Mary; Smith, Matthew Lee; Ory, Marcia G

2017-03-01

As the first Centers for Disease Control and Prevention (CDC) Prevention Research Centers Program thematic network, the Healthy Aging Research Network was established to better understand the determinants of healthy aging within older adult populations, identify interventions that promote healthy aging, and assist in translating research into sustainable community-based programs throughout the nation. To achieve these goals requires concerted efforts of a collaborative network of academic, community, and public health organizational partnerships. For the 2001-2014 Prevention Research Center funding cycles, the Healthy Aging Research Network conducted prevention research and promoted the wide use of practices known to foster optimal health. Organized around components necessary for successful collaborations (i.e., governance and infrastructure, shaping focus, community involvement, and evaluation and improvement), this commentary highlights exemplars that demonstrate the Healthy Aging Research Network's unique contributions to the field. The Healthy Aging Research Network's collaboration provided a means to collectively build capacity for practice and policy, reduce fragmentation and duplication in health promotion and aging research efforts, maximize the efficient use of existing resources and generate additional resources, and ultimately, create synergies for advancing the healthy aging agenda. This collaborative model was built upon a backbone organization (coordinating center); setting of common agendas and mutually reinforcing activities; and continuous communications. Given its successes, the Healthy Aging Research Network model could be used to create new and evaluate existing thematic networks to guide the translation of research into policy and practice. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Drosophila melanogaster as a model system for the evaluation of anti-aging compounds.

PubMed

Jafari, Mahtab

2010-01-01

Understanding the causes of aging is a complex problem due to the multiple factors that influence aging, which include genetics, environment, metabolism and reproduction, among others. These multiple factors create logistical difficulties in the evaluation of anti-aging agents. There is a need for good model systems to evaluate potential anti-aging compounds. The model systems used should represent the complexities of aging in humans, so that the findings may be extrapolated to human studies, but they should also present an opportunity to minimize the variables so that the experimental results can be accurately interpreted. In addition to positively affecting lifespan, the impact of the compound on the physiologic confounders of aging, including fecundity and the health span--the period of life where an organism is generally healthy and free from serious or chronic illness--of the model organism needs to be evaluated. Fecundity is considered a major confounder of aging in fruit flies. It is well established that female flies that are exposed to toxic substances typically reduce their dietary intake and their reproductive output and display an artifactual lifespan extension. As a result, drugs that achieve longevity benefits by reducing fecundity as a result of diminished food intake are probably not useful candidates for eventual treatment of aging in humans and should be eliminated during the screening process. Drosophila melanogaster provides a suitable model system for the screening of anti-aging compounds as D. melanogaster and humans have many conserved physiological and biological pathways. In this paper, I propose an algorithm to screen anti-aging compounds using Drosophila melanogaster as a model system.

A new model integrating short- and long-term aging of copper added to soils

PubMed Central

Zeng, Saiqi; Li, Jumei; Wei, Dongpu

2017-01-01

Aging refers to the processes by which the bioavailability/toxicity, isotopic exchangeability, and extractability of metals added to soils decline overtime. We studied the characteristics of the aging process in copper (Cu) added to soils and the factors that affect this process. Then we developed a semi-mechanistic model to predict the lability of Cu during the aging process with descriptions of the diffusion process using complementary error function. In the previous studies, two semi-mechanistic models to separately predict short-term and long-term aging of Cu added to soils were developed with individual descriptions of the diffusion process. In the short-term model, the diffusion process was linearly related to the square root of incubation time (t1/2), and in the long-term model, the diffusion process was linearly related to the natural logarithm of incubation time (lnt). Both models could predict short-term or long-term aging processes separately, but could not predict the short- and long-term aging processes by one model. By analyzing and combining the two models, we found that the short- and long-term behaviors of the diffusion process could be described adequately using the complementary error function. The effect of temperature on the diffusion process was obtained in this model as well. The model can predict the aging process continuously based on four factors—soil pH, incubation time, soil organic matter content and temperature. PMID:28820888

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

Dynamic analysis of a hepatitis B model with three-age-classes

NASA Astrophysics Data System (ADS)

Zhang, Suxia; Zhou, Yicang

2014-07-01

Based on the fact that the likelihood of becoming chronically infected is dependent on age at primary infection Kane (1995) [2], Edmunds et al. (1993) [3], Medley et al. (2001) [4], and Ganem and Prince (2004) [6], we formulate a hepatitis B transmission model with three age classes. The reproduction number, R0 is defined and the dynamical behavior of the model is analyzed. It is proved that the disease-free equilibrium is globally stable if R0<1, and there exists at least one endemic equilibrium and that the disease is uniformly persistent if R0>1. The unique endemic equilibrium and its global stability is obtained in a special case. Simulations are also conducted to compare the dynamical behavior of the model with and without age classes.

The mare model for follicular maturation and reproductive aging in the woman.

PubMed

Carnevale, E M

2008-01-01

Reproductive aging and assisted reproduction are becoming progressively more relevant in human medicine. Research with human subjects is limited in many aspects, and consequently animal models may have considerable utility. Such models have provided insight into follicular function, oocyte maturation, and reproductive aging. However, models are often selected based on factors other than physiological or functional similarities. Although the mare has received limited attention as a model for reproduction in women, comparisons between these species indicate that the mare has many attributes of a good model. As the mare ages, cyclic and hormonal changes parallel those of older women. The initial sign of reproductive aging in both species is a shortening of the reproductive cycle with elevated concentrations of FSH. Subsequently, cycles become longer with intermittent ovulations and elevated concentrations of FSH and LH. Reproduction ceases with failure of follicular growth and elevated gonadotropins, apparently because of ovarian failure. In the older woman and mare, oocytes have been maintained in meiotic arrest for decades -- approximately four to five for the woman and two to three for the mare; in both species, reduced oocyte quality is the end factor identified in age-associated infertility. After induction of oocyte maturation in vivo, the timeline to ovulation is the same for the mare and woman, suggesting a comparable sequence of events. The mare's anatomy, long follicular phase and single dominant follicle provide a foundation for studies in oocyte and follicular development. The aim of this review is to evaluate the mare as an animal model to study age-associated changes in reproduction and to improve our understanding of oocyte and follicular maturation in vivo.

Age-Related Effects of Alcohol from Adolescent, Adult, and Aged Populations Using Human and Animal Models

PubMed Central

Squeglia, Lindsay M.; Boissoneault, Jeff; Van Skike, Candice E.; Nixon, Sara Jo; Matthews, Douglas B.

2014-01-01

Background This review incorporates current research examining alcohol's differential effects on adolescents, adults, and aged populations in both animal and clinical models. Methods The studies presented range from cognitive, behavioral, molecular, and neuroimaging techniques, leading to a more comprehensive understanding of how acute and chronic alcohol use affects the brain throughout the life span. Results Age of life is a significant factor in determining the effect of alcohol on brain functioning. Adolescents and aged populations may be more negatively affected by heavy alcohol use when compared to adults. Conclusions Investigations limiting alcohol effects to a single age group constrains understanding of differential trajectories and outcomes following acute and chronic use. To meaningfully address the sequencing and interaction effects of alcohol and age, the field must incorporate collaborative and integrated research efforts focused on interdisciplinary questions facilitated by engaging basic and applied scientists with expertise in a range of disciplines including alcohol, neurodevelopment, and aging. PMID:25156779

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.

Modeling the Information Age Combat Model: An Agent-Based Simulation of Network Centric Operations

NASA Technical Reports Server (NTRS)

Deller, Sean; Rabadi, Ghaith A.; Bell, Michael I.; Bowling, Shannon R.; Tolk, Andreas

2010-01-01

The Information Age Combat Model (IACM) was introduced by Cares in 2005 to contribute to the development of an understanding of the influence of connectivity on force effectiveness that can eventually lead to quantitative prediction and guidelines for design and employment. The structure of the IACM makes it clear that the Perron-Frobenius Eigenvalue is a quantifiable metric with which to measure the organization of a networked force. The results of recent experiments presented in Deller, et aI., (2009) indicate that the value of the Perron-Frobenius Eigenvalue is a significant measurement of the performance of an Information Age combat force. This was accomplished through the innovative use of an agent-based simulation to model the IACM and represents an initial contribution towards a new generation of combat models that are net-centric instead of using the current platform-centric approach. This paper describes the intent, challenges, design, and initial results of this agent-based simulation model.

Age- and bite-structured models for vector-borne diseases.

PubMed

Rock, K S; Wood, D A; Keeling, M J

2015-09-01

The biology and behaviour of biting insects is a vitally important aspect in the spread of vector-borne diseases. This paper aims to determine, through the use of mathematical models, what effect incorporating vector senescence and realistic feeding patterns has on disease. A novel model is developed to enable the effects of age- and bite-structure to be examined in detail. This original PDE framework extends previous age-structured models into a further dimension to give a new insight into the role of vector biting and its interaction with vector mortality and spread of disease. Through the PDE model, the roles of the vector death and bite rates are examined in a way which is impossible under the traditional ODE formulation. It is demonstrated that incorporating more realistic functions for vector biting and mortality in a model may give rise to different dynamics than those seen under a more simple ODE formulation. The numerical results indicate that the efficacy of control methods that increase vector mortality may not be as great as predicted under a standard host-vector model, whereas other controls including treatment of humans may be more effective than previously thought. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Spectral ageing in the era of big data: integrated versus resolved models

NASA Astrophysics Data System (ADS)

Harwood, Jeremy J.

2017-04-01

Continuous injection models of spectral ageing have long been used to determine the age of radio galaxies from their integrated spectrum; however, many questions about their reliability remain unanswered. With various large area surveys imminent (e.g. LOw Frequency ARray, MeerKAT, Murchison Widefield Array) and planning for the next generation of radio interferometers are well underway (e.g. next generation VLA, Square Kilometre Array), investigations of radio galaxy physics are set to shift away from studies of individual sources to the population as a whole. Determining if and how integrated models of spectral ageing can be applied in the era of big data is therefore crucial. In this paper, I compare classical integrated models of spectral ageing to recent well-resolved studies that use modern analysis techniques on small spatial scales to determine their robustness and validity as a source selection method. I find that integrated models are unable to recover key parameters and, even when known a priori, provide a poor, frequency-dependent description of a source's spectrum. I show a disparity of up to a factor of 6 in age between the integrated and resolved methods but suggest, even with these inconsistencies, such models still provide a potential method of candidate selection in the search for remnant radio galaxies and in providing a cleaner selection of high redshift radio galaxies in z - α selected samples.

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.

[The use of biological age on mental work capacity model in accelerated aging assessment of professional lorry-drivers].

PubMed

Bashkireva, A S

2012-01-01

The studies of biological age, aging rate, mental work capacity in professional drivers were conducted. The examination revealed peculiarities of system organization of functions determining the mental work capacity levels. Dynamics of the aging process of professional driver's organism in relation with calendar age and driving experience were shown using the biological age model. The results point at the premature decrease of the mental work capacity in professional drivers. It was proved, that premature age-related changes of physiologic and psychophysiologic indices in drivers are just "risk indicators", while long driving experience is a real risk factor, accelerating the aging process. The "risk group" with manifestations of accelerating aging was observed in 40-49-year old drivers with 15-19 years of professional experience. The expediency of using the following methods for the age rate estimation according to biologic age indices and necessity of prophylactic measures for premature and accelerated aging prevention among working population was demonstrated.

Atomistic Model of Physical Ageing in Se-rich As-Se Glasses

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

Golovchak,R.; Shpotyuk, O.; Kozdras, A.

2007-01-01

Thermal, optical, X-ray excited and magnetic methods were used to develop a microstructural model of physical ageing in Se-rich glasses. The glass composition As10Se90, possessing a typical cross-linked chain structure, was chosen as a model object for the investigations. The effect of physical ageing in this glass was revealed by differential scanning calorimetry, whereas the corresponding changes in its atomic arrangement were studied by extended X-ray absorption fine structure, Raman and solid-state 77Se nuclear magnetic resonance spectroscopy. Straightening-shrinkage processes are shown to be responsible for the physical ageing in this Se-rich As-Se glass.

Building from a conceptual model of the resilience process during ageing, towards the Groningen Aging Resilience Inventory.

PubMed

van Abbema, Renske; Bielderman, Annemiek; De Greef, Mathieu; Hobbelen, Hans; Krijnen, Wim; van der Schans, Cees

2015-09-01

To develop and psychometrically test the Groningen Ageing Resilience Inventory. Ageing is a process that is often accompanied by functional limitation, disabilities and losses. Instead of focusing on these negative events of ageing, there are opportunities in focusing on adaptation mechanisms, like resilience, that are helpful to cope with those adversities. Cross-sectional study. The study was conducted from 2011-2012. First, a conceptual model of resilience during the ageing process was constructed. Next, items were formulated that made up a comprehensive template questionnaire reflecting the model. Finally, a cross-sectional study was performed to evaluate the construct validity and internal consistency of this template 16-item questionnaire. Participants (N = 229) with a mean age of 71·5 years, completed the template 16-item Groningen Ageing Resilience Inventory, and performance based tests and psychological questionnaires. Exploratory factor analysis resulted in a two factor solution of internal and external resources of resilience. Three items did not discriminate well between the two factors and were deleted, remaining a final 13-item questionnaire that shows evidence of good internal consistency. The direction and magnitude of the correlations with other measures support the construct validity. The Groningen Ageing Resilience Inventory is a useful instrument that can help nurses, other healthcare workers, researchers and providers of informal care to identify the internal and external resources of resilience in individuals and groups. In a multidisciplinary biopsychosocial approach this knowledge provides tools for empowering older patients in performing health promoting behaviors and self-care tasks. © 2015 John Wiley & Sons Ltd.

Nonlinear programming models to optimize uneven-aged loblolly pine management

Treesearch

Benedict J. Schulte; Joseph. Buongiorno; Kenneth Skog

1999-01-01

Nonlinear programming models of uneven-aged loblolly pine (Pinus taeda L.) management were developed to identify sustainable management regimes which optimize: 1) soil expectation value (SEV), 2) tree diversity, or 3) annual sawtimber yields. The models use the equations of SouthPro, a site- and density-dependent, multi-species matrix growth and yield model that...

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.

Modeling old-age wealth with endogenous early-life outcomes: The case of Mexico

PubMed Central

DeGraff, Deborah S.; Wong, Rebeca

2014-01-01

This paper contributes to the literature on the life course and aging by examining the association between early-life outcomes and late-life well being, using data from the Mexican Health and Aging Study. Empirical research in this area has been challenged by the potential endogeneity of the early-life outcomes of interest, an issue which most studies ignore or downplay. Our contribution takes two forms: (1) we examine in detail the potential importance of two key life-cycle outcomes, age at marriage (a measure of family formation) and years of educational attainment (a measure of human capital investment) for old-age wealth, and (2) we illustrate the empirical value of past context variables that could help model the association between early-life outcomes and late-life well being. Our illustrative approach, matching macro-level historical policy and census variables to individual records to use as instruments in modeling the endogeneity of early-life behaviors, yields a statistically identified two-stage model of old-age wealth with minimum bias. We use simulations to show that the results for the model of wealth in old age are meaningfully different when comparing the approach that accounts for endogeneity with an approach that assumes exogeneity of early-life outcomes. Furthermore, our results suggest that in the Mexican case, models which ignore the potential endogeneity of early-life outcomes are likely to under-estimate the effects of such variables on old-age wealth. PMID:25170434

Genetic mouse models of brain ageing and Alzheimer's disease.

PubMed

Bilkei-Gorzo, Andras

2014-05-01

Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

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.

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

Site index model for naturally regenerated even-aged longleaf pine

Treesearch

Dwight K. Lauer; John S. Kush

2013-01-01

Data from the Regional Longleaf Growth Study (339 permanent sample plots) were used to develop a site index model for naturally regenerated, even-aged longleaf pine (Pinus palustris Mill.). The site index equation was derived using the generalized algebraic difference approach and is base-age invariant. Using height as a measure of site productivity...

Anomalous scaling in an age-dependent branching model.

PubMed

Keller-Schmidt, Stephanie; Tuğrul, Murat; Eguíluz, Víctor M; Hernández-García, Emilio; Klemm, Konstantin

2015-02-01

We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ(-α). Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)(2). This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point.

Modeling Fetal Weight for Gestational Age: A Comparison of a Flexible Multi-level Spline-based Model with Other Approaches

PubMed Central

Villandré, Luc; Hutcheon, Jennifer A; Perez Trejo, Maria Esther; Abenhaim, Haim; Jacobsen, Geir; Platt, Robert W

2011-01-01

We present a model for longitudinal measures of fetal weight as a function of gestational age. We use a linear mixed model, with a Box-Cox transformation of fetal weight values, and restricted cubic splines, in order to flexibly but parsimoniously model median fetal weight. We systematically compare our model to other proposed approaches. All proposed methods are shown to yield similar median estimates, as evidenced by overlapping pointwise confidence bands, except after 40 completed weeks, where our method seems to produce estimates more consistent with observed data. Sex-based stratification affects the estimates of the random effects variance-covariance structure, without significantly changing sex-specific fitted median values. We illustrate the benefits of including sex-gestational age interaction terms in the model over stratification. The comparison leads to the conclusion that the selection of a model for fetal weight for gestational age can be based on the specific goals and configuration of a given study without affecting the precision or value of median estimates for most gestational ages of interest. PMID:21931571

Statistical Models for Predicting Automobile Driving Postures for Men and Women Including Effects of Age.

PubMed

Park, Jangwoon; Ebert, Sheila M; Reed, Matthew P; Hallman, Jason J

2016-03-01

Previously published statistical models of driving posture have been effective for vehicle design but have not taken into account the effects of age. The present study developed new statistical models for predicting driving posture. Driving postures of 90 U.S. drivers with a wide range of age and body size were measured in laboratory mockup in nine package conditions. Posture-prediction models for female and male drivers were separately developed by employing a stepwise regression technique using age, body dimensions, vehicle package conditions, and two-way interactions, among other variables. Driving posture was significantly associated with age, and the effects of other variables depended on age. A set of posture-prediction models is presented for women and men. The results are compared with a previously developed model. The present study is the first study of driver posture to include a large cohort of older drivers and the first to report a significant effect of age. The posture-prediction models can be used to position computational human models or crash-test dummies for vehicle design and assessment. © 2015, Human Factors and Ergonomics Society.

A statistical model including age to predict passenger postures in the rear seats of automobiles.

PubMed

Park, Jangwoon; Ebert, Sheila M; Reed, Matthew P; Hallman, Jason J

2016-06-01

Few statistical models of rear seat passenger posture have been published, and none has taken into account the effects of occupant age. This study developed new statistical models for predicting passenger postures in the rear seats of automobiles. Postures of 89 adults with a wide range of age and body size were measured in a laboratory mock-up in seven seat configurations. Posture-prediction models for female and male passengers were separately developed by stepwise regression using age, body dimensions, seat configurations and two-way interactions as potential predictors. Passenger posture was significantly associated with age and the effects of other two-way interaction variables depended on age. A set of posture-prediction models are presented for women and men, and the prediction results are compared with previously published models. This study is the first study of passenger posture to include a large cohort of older passengers and the first to report a significant effect of age for adults. The presented models can be used to position computational and physical human models for vehicle design and assessment. Practitioner Summary: The significant effects of age, body dimensions and seat configuration on rear seat passenger posture were identified. The models can be used to accurately position computational human models or crash test dummies for older passengers in known rear seat configurations.

Age-dependent Fourier model of the shape of the isolated ex vivo human crystalline lens.

PubMed

Urs, Raksha; Ho, Arthur; Manns, Fabrice; Parel, Jean-Marie

2010-06-01

To develop an age-dependent mathematical model of the zero-order shape of the isolated ex vivo human crystalline lens, using one mathematical function, that can be subsequently used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. Profiles of whole isolated human lenses (n=30) aged 20-69, were measured from shadow-photogrammetric images. The profiles were fit to a 10th-order Fourier series consisting of cosine functions in polar-co-ordinate system that included terms for tilt and decentration. The profiles were corrected using these terms and processed in two ways. In the first, each lens was fit to a 10th-order Fourier series to obtain thickness and diameter, while in the second, all lenses were simultaneously fit to a Fourier series equation that explicitly include linear terms for age to develop an age-dependent mathematical model for the whole lens shape. Thickness and diameter obtained from Fourier series fits exhibited high correlation with manual measurements made from shadow-photogrammetric images. The root-mean-squared-error of the age-dependent fit was 205 microm. The age-dependent equations provide a reliable lens model for ages 20-60 years. The contour of the whole human crystalline lens can be modeled with a Fourier series. Shape obtained from the age-dependent model described in this paper can be used to facilitate the development of other models for specific purposes such as optical modeling and analytical and numerical modeling of the lens. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Adaptive model of the aging emmetropic eye and its changes with accommodation.

PubMed

Navarro, Rafael

2014-11-20

A general schematic model of the optical system of the emmetropic human eye is proposed, capable of adapting to changes with age and accommodation through adjustment of the optical surfaces and the internal gradient index structure of the lens. The specific models of the cornea and lens consist of minor generalizations of previous work by assuming them to be the sum of a biconic plus three higher order Zernike modes. The internal gradient index distribution adapts to the external shape so that the analytical expression is invariant with the changes with age and accommodation. The model also includes tips, tilts, and decentrations of the surfaces according to experimental findings. The specific parameters of these models are either constants or functions of age and/or accommodation. The model is polychromatic, and its optical performance was evaluated along the keratometric axis. Chromatic aberrations (longitudinal and transverse), astigmatism, coma, trefoil, and spherical aberration show good agreement with experimental averages. The change of these aberrations as a function of age or accommodation is also consistent with experimental findings (except for trefoil in eyes older than 50 years). This means that the average structure seems to predict the average performance. Nevertheless, the present model is too schematic to account for other higher order aberrations, such as tetrafoil, also present in real eyes. © 2014 ARVO.

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.

Advanced age negatively impacts survival in an experimental brain tumor model.

PubMed

Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

2016-09-06

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Is HIV a model of accelerated or accentuated aging?

PubMed

Pathai, Sophia; Bajillan, Hendren; Landay, Alan L; High, Kevin P

2014-07-01

Antiretroviral therapy has reduced the incidence of adverse events and early mortality in HIV-infected persons. Despite these benefits, important comorbidities that increase with age (eg, diabetes, cardiovascular disease, cancer, liver disease, and neurocognitive impairment) are more prevalent in HIV-infected persons than in HIV-uninfected persons at every age, and geriatric syndromes such as falls and frailty occur earlier in HIV-infected persons. This raises a critical research question: Does HIV accelerate aging through pathways and mechanisms common to the aging process or is HIV simply an additional risk factor for a wide number of chronic conditions, thus accentuating aging? Extensive literature review. The purpose of this review is to briefly outline the evidence that age-related clinical syndromes are exacerbated by HIV, examine the ways in which HIV is similar, and dissimilar from natural aging, and assess the validity of HIV as a model of premature aging. Specific biomarkers of aging are limited in HIV-infected hosts and impacted by antiretroviral therapy, and a high rate of modifiable life style confounders (eg, smoking, substance abuse, alcohol) and coinfections (eg, hepatitis) in HIV-infected participants. There is a need for validated biomarkers of aging in the context of HIV. Despite these differences, welldesigned studies of HIV-infected participants are likely to provide new opportunities to better understand the mechanisms that lead to aging and age-related diseases. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The importance of age-related decline in forest NPP for modeling regional carbon balances.

PubMed

Zaehle, Sönke; Sitch, Stephen; Prentice, I Colin; Liski, Jari; Cramer, Wolfgang; Erhard, Markus; Hickler, Thomas; Smith, Benjamin

2006-08-01

We show the implications of the commonly observed age-related decline in aboveground productivity of forests, and hence forest age structure, on the carbon dynamics of European forests in response to historical changes in environmental conditions. Size-dependent carbon allocation in trees to counteract increasing hydraulic resistance with tree height has been hypothesized to be responsible for this decline. Incorporated into a global terrestrial biosphere model (the Lund-Potsdam-Jena model, LPJ), this hypothesis improves the simulated increase in biomass with stand age. Application of the advanced model, including a generic representation of forest management in even-aged stands, for 77 European provinces shows that model-based estimates of biomass development with age compare favorably with inventory-based estimates for different tree species. Model estimates of biomass densities on province and country levels, and trends in growth increment along an annual mean temperature gradient are in broad agreement with inventory data. However, the level of agreement between modeled and inventory-based estimates varies markedly between countries and provinces. The model is able to reproduce the present-day age structure of forests and the ratio of biomass removals to increment on a European scale based on observed changes in climate, atmospheric CO2 concentration, forest area, and wood demand between 1948 and 2000. Vegetation in European forests is modeled to sequester carbon at a rate of 100 Tg C/yr, which corresponds well to forest inventory-based estimates.

U.S. Telecommunications and Trade Policies: The Need for an Effective Information Age Model.

ERIC Educational Resources Information Center

Tirman, W. Robert

This paper examines the need for telecommunications and international trade policies in the Information Age and presents a model for developing such policies. The first of seven sections discusses the need for an Information Age Model, and the technological changes that are giving rise to increasingly integrated Information Age networks are…

A genome-wide longitudinal transcriptome analysis of the aging model Podospora anserina.

PubMed

Philipp, Oliver; Hamann, Andrea; Servos, Jörg; Werner, Alexandra; Koch, Ina; Osiewacz, Heinz D

2013-01-01

Aging of biological systems is controlled by various processes which have a potential impact on gene expression. Here we report a genome-wide transcriptome analysis of the fungal aging model Podospora anserina. Total RNA of three individuals of defined age were pooled and analyzed by SuperSAGE (serial analysis of gene expression). A bioinformatics analysis identified different molecular pathways to be affected during aging. While the abundance of transcripts linked to ribosomes and to the proteasome quality control system were found to decrease during aging, those associated with autophagy increase, suggesting that autophagy may act as a compensatory quality control pathway. Transcript profiles associated with the energy metabolism including mitochondrial functions were identified to fluctuate during aging. Comparison of wild-type transcripts, which are continuously down-regulated during aging, with those down-regulated in the long-lived, copper-uptake mutant grisea, validated the relevance of age-related changes in cellular copper metabolism. Overall, we (i) present a unique age-related data set of a longitudinal study of the experimental aging model P. anserina which represents a reference resource for future investigations in a variety of organisms, (ii) suggest autophagy to be a key quality control pathway that becomes active once other pathways fail, and (iii) present testable predictions for subsequent experimental investigations.

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

Porosity estimation of aged mortar using a micromechanical model.

PubMed

Hernández, M G; Anaya, J J; Sanchez, T; Segura, I

2006-12-22

Degradation of concrete structures located in high humidity atmospheres or under flowing water is a very important problem. In this study, a method for ultrasonic non-destructive characterization in aged mortar is presented. The proposed method makes a prediction of the behaviour of aged mortar accomplished with a three phase micromechanical model using ultrasonic measurements. Aging mortar was accelerated by immersing the probes in ammonium nitrate solution. Both destructive and non-destructive characterization of mortar was performed. Destructive tests of porosity were performed using a vacuum saturation method and non-destructive characterization was carried out using ultrasonic velocities. Aging experiments show that mortar degradation not only involves a porosity increase, but also microstructural changes in the cement matrix. Experimental results show that the estimated porosity using the proposed non-destructive methodology had a comparable performance to classical destructive techniques.

Premature aging-related peripheral neuropathy in a mouse model of progeria.

PubMed

Goss, James R; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D; Glorioso, Joseph C; Niedernhofer, Laura J

2011-08-01

Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Bivalve models of aging and the determination of molluscan lifespans.

PubMed

Abele, Doris; Brey, Thomas; Philipp, Eva

2009-05-01

Bivalves are newly discovered models of natural aging. This invertebrate group includes species with the longest metazoan lifespan approaching 400 y, as well as species of swimming and sessile lifestyles that live just for 1 y. Bivalves from natural populations can be aged by shell growth bands formed at regular intervals of time. This enables the study of abiotic and biotic environment factors (temperature, salinity, predator and physical disturbance) on senescence and fitness in natural populations, and distinguishes the impact of extrinsic effectors from intrinsic (genetic) determinants of animal aging. Extreme longevity of some bivalve models may help to analyze general metabolic strategies thought to be life prolonging, like the transient depression of metabolism, which forms part of natural behaviour in these species. Thus, seasonal food shortage experienced by benthic filter feeding bivalves in polar and temperate seas may mimic caloric restriction in vertebrates. Incidence of malignant neoplasms in bivalves needs to be investigated, to determine the implication of late acting mutations for bivalve longevity. Finally, bivalves are applicable models for testing the implication of heterozygosity of multiple genes for physiological tolerance, adaptability (heterozygote superiority), and life expectancy.

Mathematical modelling the age dependence of Epstein-Barr virus associated infectious mononucleosis.

PubMed

Huynh, Giao T; Adler, Frederick R

2012-09-01

Most people get Epstein-Barr virus (EBV) infection at young age and are asymptomatic. Primary EBV infection in adolescents and young adults, however, often leads to infectious mononucleosis (IM) with symptoms including fever, fatigue and sore throat that can persist for months. Expansion in the number of CD8(+) T cells, especially against EBV lytic proteins, are the main cause of these symptoms. We propose a mathematical model for the regulation of EBV infection within a host to address the dependence of IM on age. This model tracks the number of virus, infected B cell and epithelial cell and CD8(+) T-cell responses to the infection. We use this model to investigate three hypotheses for the high incidence of IM in teenagers and young adults: saliva and antibody effects that increase with age, high cross-reactive T-cell responses and a high initial viral load. The model supports the first two of these hypotheses and suggests that variation in host antibody responses and the complexity of the pre-existing cross-reactive T-cell repertoire, both of which depend on age, may play important roles in the etiology of IM.

Aging and crystallization in a lattice glass model

NASA Astrophysics Data System (ADS)

Seif, Alejandro; Loscar, Ernesto S.; Grigera, Tomás S.

2015-04-01

We have studied the three-dimensional lattice glass of Pica Ciamarra et al. [Phys. Rev. E 67, 057105 (2003), 10.1103/PhysRevE.67.057105], which has been shown to reproduce several features of the structural glass phenomenology, such as the cage effect, exponential increase of relaxation times, and aging. We show, using short-time dynamics, that the metastability limit is above the estimated Kauzmann temperature. We also find that in the region where the metastable liquid exists the aging exponent is lower than 0.5, indicating that equilibrium is reached relatively quickly. We conclude that the usefulness of this model to study the deeply supercooled regime is rather limited.

Experimental models for aging and their potential for novel drug discovery.

PubMed

Folch, Jaume; Busquets, Oriol; Sánchez-López, Miren EttchetoElena; Pallàs, Mercè; Beas-Zarate, Carlos; Marin, Miguel; Casadesus, Gemma; Olloquequi, Jordi; Auladell, Carme; Camins, Antoni

2017-07-07

The development of antiaging drugs is an interesting area of scientific research. In order to evaluate the beneficial effects of new potential drugs, it is necessary to gather the specific knowledge on the adequate preclinical models that are available. This review focuses on invertebrate and vertebrate preclinical models used to evaluate the efficacy of antiaging compounds, with the objective to extend lifespan and health span. Dietary restriction (DR), a common experimental process to extend lifespan in all organisms, is also discussed. Besides, classical antiaging drugs such as resveratrol, rapamycin and metformin, denominated DR mimetics, are reviewed. The main therapeutic targets of these drugs include sirtuins, IGF-1, and mTOR, all of them being modulated by DR. The National Institute on Aging (NIA) developed the Interventions Testing Program (ITP). At the preclinical level, the ITP uses genetically heterogeneous mice model (HET), which is probably the most suitable rodent model to study potential drugs preventing aging-related diseases. The accelerated-senescence mouse P8 is also an interesting rodent model for the research in the field of aging. Notwithstanding, non-human primates are still necessary prior to clinical trials, since they allow an easier extrapolation to humans due to their anatomical and physiological similarities. In this review, the different models and approaches for antiaging studies were evaluated. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Modeling and Analysis of a Nonlinear Age-Structured Model for Tumor Cell Populations with Quiescence

NASA Astrophysics Data System (ADS)

Liu, Zijian; Chen, Jing; Pang, Jianhua; Bi, Ping; Ruan, Shigui

2018-05-01

We present a nonlinear first-order hyperbolic partial differential equation model to describe age-structured tumor cell populations with proliferating and quiescent phases at the avascular stage in vitro. The division rate of the proliferating cells is assumed to be nonlinear due to the limitation of the nutrient and space. The model includes a proportion of newborn cells that enter directly the quiescent phase with age zero. This proportion can reflect the effect of treatment by drugs such as erlotinib. The existence and uniqueness of solutions are established. The local and global stabilities of the trivial steady state are investigated. The existence and local stability of the positive steady state are also analyzed. Numerical simulations are performed to verify the results and to examine the impacts of parameters on the nonlinear dynamics of the model.

The mouse as a model organism in aging research: usefulness, pitfalls and possibilities.

PubMed

Vanhooren, Valerie; Libert, Claude

2013-01-01

The mouse has become the favorite mammalian model. Among the many reasons for this privileged position of mice is their genetic proximity to humans, the possibilities of genetically manipulating their genomes and the availability of many tools, mutants and inbred strains. Also in the field of aging, mice have become very robust and reliable research tools. Since laboratory mice have a life expectancy of only a few years, genetic approaches and other strategies for intervening in aging can be tested by examining their effects on life span and aging parameters during the relatively short period of, for example, a PhD project. Moreover, experiments on mice with an extended life span as well as on mice demonstrating signs of (segmental) premature aging, together with genetic mapping strategies, have provided novel insights into the fundamental processes that drive aging. Finally, the results of studies on caloric restriction and pharmacological anti-aging treatments in mice have a high degree of relevance to humans. In this paper, we review a number of recent genetic mapping studies that have yielded novel insights into the aging process. We discuss the value of the mouse as a model for testing interventions in aging, such as caloric restriction, and we critically discuss mouse strains with an extended or a shortened life span as models of aging. Copyright © 2012 Elsevier B.V. All rights reserved.

Nonlinear Programming Models to Optimize Uneven-Aged Shortleaf Pine Management

Treesearch

Benedict J. Schulte; Joseph Buongiorno

2002-01-01

Nonlinear programming models of uneven-aged shortleaf pine (Pinus echinata Mill.) management were developed to identify sustainable management regimes that optimize soil expectation value (SEV) or annual sawtimber yields. The models recognize three species groups (shortleaf pine and other softwoods, soft hardwoods and hard hardwoods) and 13 2-inch...

ON THE RELIABILITY OF STELLAR AGES AND AGE SPREADS INFERRED FROM PRE-MAIN-SEQUENCE EVOLUTIONARY MODELS

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

Hosokawa, Takashi; Offner, Stella S. R.; Krumholz, Mark R., E-mail: Takashi.Hosokawa@jpl.nasa.gov, E-mail: hosokwtk@gmail.com

2011-09-10

We revisit the problem of low-mass pre-main-sequence stellar evolution and its observational consequences for where stars fall on the Hertzsprung-Russell diagram (HRD). In contrast to most previous work, our models follow stars as they grow from small masses via accretion, and we perform a systematic study of how the stars' HRD evolution is influenced by their initial radius, by the radiative properties of the accretion flow, and by the accretion history, using both simple idealized accretion histories and histories taken from numerical simulations of star cluster formation. We compare our numerical results to both non-accreting isochrones and to the positionsmore » of observed stars in the HRD, with a goal of determining whether both the absolute ages and the age dispersions inferred from non-accreting isochrones are reliable. We show that non-accreting isochrones can sometimes overestimate stellar ages for more massive stars (those with effective temperatures above {approx}3500 K), thereby explaining why non-accreting isochrones often suggest a systematic age difference between more and less massive stars in the same cluster. However, we also find the only way to produce a similar overestimate for the ages of cooler stars is if these stars grow from {approx}0.01 M{sub sun} seed protostars that are an order of magnitude smaller than predicted by current theoretical models, and if the size of the seed protostar correlates systematically with the final stellar mass at the end of accretion. We therefore conclude that, unless both of these conditions are met, inferred ages and age spreads for cool stars are reliable, at least to the extent that the observed bolometric luminosities and temperatures are accurate. Finally, we note that the time dependence of the mass accretion rate has remarkably little effect on low-mass stars' evolution on the HRD, and that such time dependence may be neglected for all stars except those with effective temperatures above {approx}4000

Lithium-ion Open Circuit Voltage (OCV) curve modelling and its ageing adjustment

NASA Astrophysics Data System (ADS)

Lavigne, L.; Sabatier, J.; Francisco, J. Mbala; Guillemard, F.; Noury, A.

2016-08-01

This paper is a contribution to lithium-ion batteries modelling taking into account aging effects. It first analyses the impact of aging on electrode stoichiometry and then on lithium-ion cell Open Circuit Voltage (OCV) curve. Through some hypotheses and an appropriate definition of the cell state of charge, it shows that each electrode equilibrium potential, but also the whole cell equilibrium potential can be modelled by a polynomial that requires only one adjustment parameter during aging. An adjustment algorithm, based on the idea that for two fixed OCVs, the state of charge between these two equilibrium states is unique for a given aging level, is then proposed. Its efficiency is evaluated on a battery pack constituted of four cells.

COMPUTATION OF ℛ IN AGE-STRUCTURED EPIDEMIOLOGICAL MODELS WITH MATERNAL AND TEMPORARY IMMUNITY.

PubMed

Feng, Zhilan; Han, Qing; Qiu, Zhipeng; Hill, Andrew N; Glasser, John W

2016-03-01

For infectious diseases such as pertussis, susceptibility is determined by immunity, which is chronological age-dependent. We consider an age-structured epidemiological model that accounts for both passively acquired maternal antibodies that decay and active immunity that wanes, permitting reinfection. The model is a 6-dimensional system of partial differential equations (PDE). By assuming constant rates within each age-group, the PDE system can be reduced to an ordinary differential equation (ODE) system with aging from one age-group to the next. We derive formulae for the effective reproduction number ℛ and provide their biological interpretation in some special cases. We show that the disease-free equilibrium is stable when ℛ < 1 and unstable if ℛ > 1.

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.

Ageing of polymer bonds: a coupled chemomechanical modelling approach

NASA Astrophysics Data System (ADS)

Dippel, Benedikt; Johlitz, Michael; Lion, Alexander

2014-05-01

With the increasing number of requirements on joinings, it gets more and more important to understand and predict an assemblies properties. Nowadays, in industrial applications, combinations of different materials get more common. In most of those cases, it is, besides other advantages, useful to connect such parts with adhesives to avoid local cells. Thus, the knowledge about the mechanical behaviour of adhesives over the whole time of utilisation is an essential element of engineering. As it is well known, ageing due to environmental influences such as oxygen, radiation, ozone and others plays a major role in polymers properties. So, for the prediction of applicability over the whole lifetime of a technical component, the change in mechanical properties due to ageing is necessary. In this contribution, we introduce a material model which takes into account the internal structure of an adhesive. Therefore, an interphase zone is introduced. In the interphase, which is developed due to the contact of an adhesive with an adherent, the materials properties change continuously from the surface to the centre of the joint, where the polymer is in a bulky state. Built up on this geometry dependency, the materials ageing as a function of the position is described. To model the change of the polymers state, we use a parameter representing chain scission processes and another one for the reformation of a new network. In a last step, the model is transferred into a finite element code for exemplary calculations.

Discrete Dynamical Modeling of Influenza Virus Infection Suggests Age-Dependent Differences in Immunity.

PubMed

Keef, Ericka; Zhang, Li Ang; Swigon, David; Urbano, Alisa; Ermentrout, G Bard; Matuszewski, Michael; Toapanta, Franklin R; Ross, Ted M; Parker, Robert S; Clermont, Gilles

2017-12-01

Immunosenescence, an age-related decline in immune function, is a major contributor to morbidity and mortality in the elderly. Older hosts exhibit a delayed onset of immunity and prolonged inflammation after an infection, leading to excess damage and a greater likelihood of death. Our study applies a rule-based model to infer which components of the immune response are most changed in an aged host. Two groups of BALB/c mice (aged 12 to 16 weeks and 72 to 76 weeks) were infected with 2 inocula: a survivable dose of 50 PFU and a lethal dose of 500 PFU. Data were measured at 10 points over 19 days in the sublethal case and at 6 points over 7 days in the lethal case, after which all mice had died. Data varied primarily in the onset of immunity, particularly the inflammatory response, which led to a 2-day delay in the clearance of the virus from older hosts in the sublethal cohort. We developed a Boolean model to describe the interactions between the virus and 21 immune components, including cells, chemokines, and cytokines, of innate and adaptive immunity. The model identifies distinct sets of rules for each age group by using Boolean operators to describe the complex series of interactions that activate and deactivate immune components. Our model accurately simulates the immune responses of mice of both ages and with both inocula included in the data (95% accurate for younger mice and 94% accurate for older mice) and shows distinct rule choices for the innate immunity arm of the model between younger and aging mice in response to influenza A virus infection. IMPORTANCE Influenza virus infection causes high morbidity and mortality rates every year, especially in the elderly. The elderly tend to have a delayed onset of many immune responses as well as prolonged inflammatory responses, leading to an overall weakened response to infection. Many of the details of immune mechanisms that change with age are currently not well understood. We present a rule-based model of the

Age-dependent cognitive impairment in a Drosophila fragile X model and its pharmacological rescue.

PubMed

Choi, Catherine H; McBride, Sean M J; Schoenfeld, Brian P; Liebelt, David A; Ferreiro, David; Ferrick, Neal J; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L; Terlizzi, Allison M; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T; Bell, Aaron J; McDonald, Thomas V; Jongens, Thomas A

2010-06-01

Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms.

Determination of timescales of nitrate contamination by groundwater age models in a complex aquifer system

NASA Astrophysics Data System (ADS)

Koh, E. H.; Lee, E.; Kaown, D.; Lee, K. K.; Green, C. T.

2017-12-01

Timing and magnitudes of nitrate contamination are determined by various factors like contaminant loading, recharge characteristics and geologic system. Information of an elapsed time since recharged water traveling to a certain outlet location, which is defined as groundwater age, can provide indirect interpretation related to the hydrologic characteristics of the aquifer system. There are three major methods (apparent ages, lumped parameter model, and numerical model) to date groundwater ages, which differently characterize groundwater mixing resulted by various groundwater flow pathways in a heterogeneous aquifer system. Therefore, in this study, we compared the three age models in a complex aquifer system by using observed age tracer data and reconstructed history of nitrate contamination by long-term source loading. The 3H-3He and CFC-12 apparent ages, which did not consider the groundwater mixing, estimated the most delayed response time and a highest period of the nitrate loading had not reached yet. However, the lumped parameter model could generate more recent loading response than the apparent ages and the peak loading period influenced the water quality. The numerical model could delineate various groundwater mixing components and its different impacts on nitrate dynamics in the complex aquifer system. The different age estimation methods lead to variations in the estimated contaminant loading history, in which the discrepancy in the age estimation was dominantly observed in the complex aquifer system.

Modeling the formation and aging of secondary organic aerosols during CalNex 2010

NASA Astrophysics Data System (ADS)

Hayes, P. L.; Ortega, A. M.; Ahmadov, R.; McKeen, S. A.; Washenfelder, R. A.; Alvarez, S.; Rappenglueck, B.; Holloway, J. S.; Gilman, J. B.; Kuster, W. C.; De Gouw, J. A.; Zotter, P.; Prevot, A. S.; Kleindienst, T. E.; Offenberg, J. H.; Jimenez, J. L.

2012-12-01

Several traditional and recently proposed models are applied to predict the concentrations and properties of secondary organic aerosols (SOA) and organic gases at the Pasadena ground site during the CalNex campaign. The models are constrained with and compared against results from available observations. The CalNex campaign and specifically the Pasadena ground site featured a large and sophisticated suite of aerosol and gas phase instrumentation, and thus, it provides a unique opportunity to test SOA models under conditions of strong urban emissions at a range of low photochemical ages. The oxidation of volatile organic compounds (VOCs) using an updated traditional model cannot explain the observed ambient SOA, and under-predicts the measurements by a factor of ~40. Similarly, after accounting for the multi-generation oxidation of VOCs using a volatility basis set (VBS) approach as described by Tsimpidi et al. (2010), SOA is still under-predicted by a factor of ~8. For SOA formed from VOCs (V-SOA) the dominant precursors are aromatics (xylenes, toluene, and trimethylbenzenes). The model SOA formed from the oxidation of primary semivolatile and intermediate volatility organic compounds (P-S/IVOCs, producing SI-SOA) is also predicted using the parameterizations of Robinson et al. (2007) and Grieshop et al. (2009), and the properties of V-SOA + SI-SOA are compared against the measured O:C and volatility. We also compare the results of the different models against fossil/non-fossil carbon measurements as well as tracers of different SOA precursors. Potential Aerosol Mass (PAM) measurements of the SOA forming potential of the Pasadena air masses are also compared against that predicted by the models. The PAM analysis allows for model/measurement comparisons of SOA properties over a range of photochemical ages spanning almost two weeks. Using the V-SOA model, at low photochemical ages (< 1 day) the modeled PAM V-SOA is less than the measured PAM SOA, similar to the

Precise age for the Permian-Triassic boundary in South China from high-precision U-Pb geochronology and Bayesian age-depth modeling

NASA Astrophysics Data System (ADS)

Baresel, Björn; Bucher, Hugo; Brosse, Morgane; Cordey, Fabrice; Guodun, Kuang; Schaltegger, Urs

2017-03-01

This study is based on zircon U-Pb ages of 12 volcanic ash layers and volcanogenic sandstones from two deep water sections with conformable and continuous formational Permian-Triassic boundaries (PTBs) in the Nanpanjiang Basin (South China). Our dates of single, thermally annealed and chemically abraded zircons bracket the PTB in Dongpan and Penglaitan and provide the basis for a first proof-of-concept study utilizing a Bayesian chronology model comparing the three sections of Dongpan, Penglaitan and the Global Stratotype Section and Point (GSSP) at Meishan. Our Bayesian modeling demonstrates that the formational boundaries in Dongpan (251.939 ± 0.030 Ma), Penglaitan (251.984 ± 0.031 Ma) and Meishan (251.956 ± 0.035 Ma) are synchronous within analytical uncertainty of ˜ 40 ka. It also provides quantitative evidence that the ages of the paleontologically defined boundaries, based on conodont unitary association zones in Meishan and on macrofaunas in Dongpan, are identical and coincide with the age of the formational boundaries. The age model also confirms the extreme condensation around the PTB in Meishan, which distorts the projection of any stratigraphic points or intervals onto other more expanded sections by means of Bayesian age-depth models. Dongpan and Penglaitan possess significantly higher sediment accumulation rates and thus offer a greater potential for high-resolution studies of environmental proxies and correlations around the PTB than Meishan. This study highlights the power of high-resolution radio-isotopic ages that allow a robust intercalibration of patterns of biotic changes and fluctuating environmental proxies and will help recognizing their global, regional or local significance.

The companion dog as a model for human aging and mortality.

PubMed

Hoffman, Jessica M; Creevy, Kate E; Franks, Alexander; O'Neill, Dan G; Promislow, Daniel E L

2018-06-01

Around the world, human populations have experienced large increases in average lifespan over the last 150 years, and while individuals are living longer, they are spending more years of life with multiple chronic morbidities. Researchers have used numerous laboratory animal models to understand the biological and environmental factors that influence aging, morbidity, and longevity. However, the most commonly studied animal species, laboratory mice and rats, do not experience environmental conditions similar to those to which humans are exposed, nor do we often diagnose them with many of the naturally occurring pathologies seen in humans. Recently, the companion dog has been proposed as a powerful model to better understand the genetic and environmental determinants of morbidity and mortality in humans. However, it is not known to what extent the age-related dynamics of morbidity, comorbidity, and mortality are shared between humans and dogs. Here, we present the first large-scale comparison of human and canine patterns of age-specific morbidity and mortality. We find that many chronic conditions that commonly occur in human populations (obesity, arthritis, hypothyroidism, and diabetes), and which are associated with comorbidities, are also associated with similarly high levels of comorbidity in companion dogs. We also find significant similarities in the effect of age on disease risk in humans and dogs, with neoplastic, congenital, and metabolic causes of death showing similar age trajectories between the two species. Overall, our study suggests that the companion dog may be an ideal translational model to study the many complex facets of human morbidity and mortality. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Preparing the workforce for healthy aging programs: the Skills for Healthy Aging Resources and Programs (SHARP) model.

PubMed

Frank, Janet C; Altpeter, Mary; Damron-Rodriguez, JoAnn; Driggers, Joann; Lachenmayr, Susan; Manning, Colleen; Martinez, Dana M; Price, Rachel M; Robinson, Patricia

2014-10-01

Current public health and aging service agency personnel have little training in gerontology, and virtually no training in evidence-based health promotion and disease management programs for older adults. These programs are rapidly becoming the future of our community-based long-term care support system. The purpose of this project was to develop and test a model community college career technical education program, Skills for Healthy Aging Resources and Programs (SHARP), for undergraduate college students, current personnel in aging service and community organizations, and others interested in retraining. A multidisciplinary cross-sector team from disciplines of public health, sociology, gerontology and nursing developed four competency-based courses that focus on healthy aging, behavior change strategies, program management, an internship, and an option for leader training in the Chronic Disease Self-Management Program. To enhance implementation and fidelity, intensive faculty development training was provided to all instructors and community agency partners. Baseline and postprogram evaluation of competencies for faculty and students was conducted. Process evaluation for both groups focused on satisfaction with the curricula and suggestions for program improvement. SHARP has been piloted five times at two community colleges. Trainees (n = 113) were primarily community college students (n = 108) and current aging service personnel (n = 5). Statistically significant improvements in all competencies were found for both faculty and students. Process evaluation outcomes identified the needed logical and component adaptations to enhance the feasibility of program implementation, dissemination, and student satisfaction. The SHARP program provides a well-tested, evidence-based effective model for addressing workforce preparation in support of healthy aging service program expansion and delivery. © 2014 Society for Public Health Education.

Development of the Thai healthy aging model: A grounded theory study.

PubMed

Thiamwong, Ladda; McManus, Michael S; Suwanno, Jom

2013-06-01

To develop a model of healthy aging from the perspective of Thais, a grounded theory approach, including in-depth interviews and focus groups, was used. A purposive sample of 39 community-dwelling adults aged 40-85 years old was interviewed. The Thai healthy aging model composed of three themes: normality, nature, and dharma. In Thai, they are called tham-ma-da, tham-ma-chat, and tham-ma, or "Thai 3Ts". The theme of normality encompasses subthemes of staying physically active by being involved in plenty of physical activities, and being mentally active with creative and thoughtful hobbies and work. The theme of nature encompasses subthemes of living simply and being careful with money. The theme of dharma encompasses subthemes of enjoyment through helping family and participating in community activities, staying away from stress and worries by talking openly and honestly with someone, making merit, and helping other people without expecting anything in return. A greater understanding of healthy aging is a benefit for older adults and healthcare providers in an intervention-design process. Research can contribute valuable information to shape policy for healthy aging as well. © 2013 Wiley Publishing Asia Pty Ltd.

Comparing Four Age Model Techniques using Nine Sediment Cores from the Iberian Margin

NASA Astrophysics Data System (ADS)

Lisiecki, L. E.; Jones, A. M.; Lawrence, C.

2017-12-01

Interpretations of paleoclimate records from ocean sediment cores rely on age models, which provide estimates of age as a function of core depth. Here we compare four methods used to generate age models for sediment cores for the past 140 kyr. The first method is based on radiocarbon dating using the Bayesian statistical software, Bacon [Blaauw and Christen, 2011]. The second method aligns benthic δ18O to a target core using the probabilistic alignment algorithm, HMM-Match, which also generates age uncertainty estimates [Lin et al., 2014]. The third and fourth methods are planktonic δ18O and sea surface temperature (SST) alignments to the same target core, using the alignment algorithm Match [Lisiecki and Lisiecki, 2002]. Unlike HMM-Match, Match requires parameter tuning and does not produce uncertainty estimates. The results of these four age model techniques are compared for nine high-resolution cores from the Iberian margin. The root mean square error between the individual age model results and each core's average estimated age is 1.4 kyr. Additionally, HMM-Match and Bacon age estimates agree to within uncertainty and have similar 95% confidence widths of 1-2 kyr for the highest resolution records. In one core, the planktonic and SST alignments did not fall within the 95% confidence intervals from HMM-Match. For this core, the surface proxy alignments likely produce more reliable results due to millennial-scale SST variability and the presence of several gaps in the benthic δ18O data. Similar studies of other oceanographic regions are needed to determine the spatial extents over which these climate proxies may be stratigraphically correlated.

Models for predicting turnover of residential aged care nurses: a structural equation modelling analysis of secondary data.

PubMed

Gao, Fengsong; Newcombe, Peter; Tilse, Cheryl; Wilson, Jill; Tuckett, Anthony

2014-09-01

Nurse turnover in the residential aged care industry is a pressing issue. Researchers have shown ongoing interest in exploring how the factors that are amendable to change in aged care policy, regulation and funding and in organizational procedures (e.g. job demands, coping resources and psychological health of nurses) impact on turnover. However, the findings are mixed. This study tested two theoretical models of turnover to examine the structural relationships among job demands, coping resources, psychological health and turnover of residential aged care nurses. Although many previous studies operationalized turnover as intention to leave, the present study investigated actual turnover by following up with the same individuals over time, and thus provided more accurate predictive models of turnover behaviour. The sample, 239 Australian residential aged care nurses, came from the Nurses and Midwives e-cohort Study. Job demands, coping resources, and psychological health were measured using standardized instruments. Structural equation modelling was used to test the measurement and structural models. Controlling for a number of workforce and individual characteristics, coping resources (measured by job control, supervisor support, and co-worker support) were negatively and directly associated with turnover. Additionally, the findings supported the Job Demand-Control-Support model in that higher coping resources and lower job demands (indicated by psychological demands, physical demands, and effort) were related to better psychological health (measured by vitality, social functioning, role emotional, and mental health), and higher job demands were related to lower coping resources. Findings suggest that aged care policy makers and service providers might consider increasing coping resources available to nurses and minimizing job demands of care work to reduce turnover and improve nurses' psychological health. Moreover, findings from this Australian study may provide

Accommodation and age-dependent eye model based on in vivo measurements.

PubMed

Zapata-Díaz, Juan F; Radhakrishnan, Hema; Charman, W Neil; López-Gil, Norberto

2018-03-21

To develop a flexible model of the average eye that incorporates changes with age and accommodation in all optical parameters, including entrance pupil diameter, under photopic, natural, environmental conditions. We collated retrospective in vivo measurements of all optical parameters, including entrance pupil diameter. Ray-tracing was used to calculate the wavefront aberrations of the eye model as a function of age, stimulus vergence and pupil diameter. These aberrations were used to calculate objective refraction using paraxial curvature matching. This was also done for several stimulus positions to calculate the accommodation response/stimulus curve. The model predicts a hyperopic change in distance refraction as the eye ages (+0.22D every 10 years) between 20 and 65 years. The slope of the accommodation response/stimulus curve was 0.72 for a 25 years-old subject, with little change between 20 and 45 years. A trend to a more negative value of primary spherical aberration as the eye accommodates is predicted for all ages (20-50 years). When accommodation is relaxed, a slight increase in primary spherical aberration (0.008μm every 10 years) between 20 and 65 years is predicted, for an age-dependent entrance pupil diameter ranging between 3.58mm (20 years) and 3.05mm (65 years). Results match reasonably well with studies performed in real eyes, except that spherical aberration is systematically slightly negative as compared with the practical data. The proposed eye model is able to predict changes in objective refraction and accommodation response. It has the potential to be a useful design and testing tool for devices (e.g. intraocular lenses or contact lenses) designed to correct the eye's optical errors. Copyright © 2018 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Modelling safety of multistate systems with ageing components

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

Kołowrocki, Krzysztof; Soszyńska-Budny, Joanna

An innovative approach to safety analysis of multistate ageing systems is presented. Basic notions of the ageing multistate systems safety analysis are introduced. The system components and the system multistate safety functions are defined. The mean values and variances of the multistate systems lifetimes in the safety state subsets and the mean values of their lifetimes in the particular safety states are defined. The multi-state system risk function and the moment of exceeding by the system the critical safety state are introduced. Applications of the proposed multistate system safety models to the evaluation and prediction of the safty characteristics ofmore » the consecutive “m out of n: F” is presented as well.« less

Dynamical analysis of cellular ageing by modeling of gene regulatory network based attractor landscape.

PubMed

Chong, Ket Hing; Zhang, Xiaomeng; Zheng, Jie

2018-01-01

Ageing is a natural phenomenon that is inherently complex and remains a mystery. Conceptual model of cellular ageing landscape was proposed for computational studies of ageing. However, there is a lack of quantitative model of cellular ageing landscape. This study aims to investigate the mechanism of cellular ageing in a theoretical model using the framework of Waddington's epigenetic landscape. We construct an ageing gene regulatory network (GRN) consisting of the core cell cycle regulatory genes (including p53). A model parameter (activation rate) is used as a measure of the accumulation of DNA damage. Using the bifurcation diagrams to estimate the parameter values that lead to multi-stability, we obtained a conceptual model for capturing three distinct stable steady states (or attractors) corresponding to homeostasis, cell cycle arrest, and senescence or apoptosis. In addition, we applied a Monte Carlo computational method to quantify the potential landscape, which displays: I) one homeostasis attractor for low accumulation of DNA damage; II) two attractors for cell cycle arrest and senescence (or apoptosis) in response to high accumulation of DNA damage. Using the Waddington's epigenetic landscape framework, the process of ageing can be characterized by state transitions from landscape I to II. By in silico perturbations, we identified the potential landscape of a perturbed network (inactivation of p53), and thereby demonstrated the emergence of a cancer attractor. The simulated dynamics of the perturbed network displays a landscape with four basins of attraction: homeostasis, cell cycle arrest, senescence (or apoptosis) and cancer. Our analysis also showed that for the same perturbed network with low DNA damage, the landscape displays only the homeostasis attractor. The mechanistic model offers theoretical insights that can facilitate discovery of potential strategies for network medicine of ageing-related diseases such as cancer.

[MEDICAL SOCIAL MODELING TECHNOLOGIES FOR ACTIVE AGING IN KAZAKHSTAN].

PubMed

Benberin, V V; Akhetov, A A; Tanbaeva, G Z

2015-01-01

The article discusses a new model for active ageing in Republic of Kazakhstan with participation the state, population and medical social services. Achieving active longevity will lead to positive trends in the development of human capital of the state, because it enables to use experience and knowledge of senior generation in enhancing the effectiveness of socio-economic transformation in health care. The study was carried out on the base of the Central clinical hospital of the President's affairs administration in Republic of Kazakhstan, with the participation of 147 admitted patients of elderly and senile age.

Geophysical Age Dating of Seamounts using Dense Core Flexure Model

NASA Astrophysics Data System (ADS)

Hwang, Gyuha; Kim, Seung-Sep

2016-04-01

Lithospheric flexure of oceanic plate is thermo-mechanical response of an elastic plate to the given volcanic construct (e.g., seamounts and ocean islands). If the shape and mass of such volcanic loads are known, the flexural response is governed by the thickness of elastic plate, Te. As the age of oceanic plate increases, the elastic thickness of oceanic lithosphere becomes thicker. Thus, we can relate Te with the age of plate at the time of loading. To estimate the amount of the driving force due to seamounts on elastic plate, one needs to approximate their density structure. The most common choice is uniform density model, which utilizes constant density value for a seamount. This approach simplifies computational processes for gravity prediction and error estimates. However, the uniform density model tends to overestimate the total mass of the seamount and hence produces more positive gravitational contributions from the load. Minimization of gravity misfits using uniform density, therefore, favors thinner Te in order to increase negative contributions from the lithospheric flexure, which can compensate for the excessive positives from the seamount. An alternative approach is dense core model, which approximate the heterogeneity nature of seamount density as three bodies of infill sediment, edifice, and dense core. In this study, we apply the dense core model to the Louisville Seamount Chain for constraining flexural deformation. We compare Te estimates with the loading time of the examined seamounts to redefine empirical geophysical age dating of seamounts.

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

Evaluation of three statistical prediction models for forensic age prediction based on DNA methylation.

PubMed

Smeers, Inge; Decorte, Ronny; Van de Voorde, Wim; Bekaert, Bram

2018-05-01

DNA methylation is a promising biomarker for forensic age prediction. A challenge that has emerged in recent studies is the fact that prediction errors become larger with increasing age due to interindividual differences in epigenetic ageing rates. This phenomenon of non-constant variance or heteroscedasticity violates an assumption of the often used method of ordinary least squares (OLS) regression. The aim of this study was to evaluate alternative statistical methods that do take heteroscedasticity into account in order to provide more accurate, age-dependent prediction intervals. A weighted least squares (WLS) regression is proposed as well as a quantile regression model. Their performances were compared against an OLS regression model based on the same dataset. Both models provided age-dependent prediction intervals which account for the increasing variance with age, but WLS regression performed better in terms of success rate in the current dataset. However, quantile regression might be a preferred method when dealing with a variance that is not only non-constant, but also not normally distributed. Ultimately the choice of which model to use should depend on the observed characteristics of the data. Copyright © 2018 Elsevier B.V. All rights reserved.

Network model of human aging: Frailty limits and information measures

NASA Astrophysics Data System (ADS)

Farrell, Spencer G.; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

2016-11-01

Aging is associated with the accumulation of damage throughout a persons life. Individual health can be assessed by the Frailty Index (FI). The FI is calculated simply as the proportion f of accumulated age-related deficits relative to the total, leading to a theoretical maximum of f ≤1 . Observational studies have generally reported a much more stringent bound, with f ≤fmax<1 . The value of fmax in observational studies appears to be nonuniversal, but fmax≈0.7 is often reported. A previously developed network model of individual aging was unable to recover fmax<1 while retaining the other observed phenomenology of increasing f and mortality rates with age. We have developed a computationally accelerated network model that also allows us to tune the scale-free network exponent α . The network exponent α significantly affects the growth of mortality rates with age. However, we are only able to recover fmax by also introducing a deficit sensitivity parameter 1 -q , which is equivalent to a false-negative rate q . Our value of q =0.3 is comparable to finite sensitivities of age-related deficits with respect to mortality that are often reported in the literature. In light of nonzero q , we use mutual information I to provide a nonparametric measure of the predictive value of the FI with respect to individual mortality. We find that I is only modestly degraded by q <1 , and this degradation is mitigated when increasing number of deficits are included in the FI. We also find that the information spectrum, i.e., the mutual information of individual deficits versus connectivity, has an approximately power-law dependence that depends on the network exponent α . Mutual information I is therefore a useful tool for characterizing the network topology of aging populations.

A two-component Bayesian mixture model to identify implausible gestational age.

PubMed

Mohammadian-Khoshnoud, Maryam; Moghimbeigi, Abbas; Faradmal, Javad; Yavangi, Mahnaz

2016-01-01

Background: Birth weight and gestational age are two important variables in obstetric research. The primary measure of gestational age is based on a mother's recall of her last menstrual period. This recall may cause random or systematic errors. Therefore, the objective of this study is to utilize Bayesian mixture model in order to identify implausible gestational age. Methods: In this cross-sectional study, medical documents of 502 preterm infants born and hospitalized in Hamadan Fatemieh Hospital from 2009 to 2013 were gathered. Preterm infants were classified to less than 28 weeks and 28 to 31 weeks. A two-component Bayesian mixture model was utilized to identify implausible gestational age; the first component shows the probability of correct and the second one shows the probability of incorrect classification of gestational ages. The data were analyzed through OpenBUGS 3.2.2 and 'coda' package of R 3.1.1. Results: The mean (SD) of the second component of less than 28 weeks and 28 to 31 weeks were 1179 (0.0123) and 1620 (0.0074), respectively. These values were larger than the mean of the first component for both groups which were 815.9 (0.0123) and 1061 (0.0074), respectively. Conclusion: Errors occurred in recording the gestational ages of these two groups of preterm infants included recording the gestational age less than the actual value at birth. Therefore, developing scientific methods to correct these errors is essential to providing desirable health services and adjusting accurate health indicators.

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

Description of cervical cancer mortality in Belgium using Bayesian age-period-cohort models

PubMed Central

2009-01-01

Objective To correct cervical cancer mortality rates for death cause certification problems in Belgium and to describe the corrected trends (1954-1997) using Bayesian models. Method Cervical cancer (cervix uteri (CVX), corpus uteri (CRP), not otherwise specified (NOS) uterus cancer and other very rare uterus cancer (OTH) mortality data were extracted from the WHO mortality database together with population data for Belgium and the Netherlands. Different ICD (International Classification of Diseases) were used over time for death cause certification. In the Netherlands, the proportion of not-otherwise specified uterine cancer deaths was small over large periods and therefore internal reallocation could be used to estimate the corrected rates cervical cancer mortality. In Belgium, the proportion of improperly defined uterus deaths was high. Therefore, the age-specific proportions of uterus cancer deaths that are probably of cervical origin for the Netherlands was applied to Belgian uterus cancer deaths to estimate the corrected number of cervix cancer deaths (corCVX). A Bayesian loglinear Poisson-regression model was performed to disentangle the separate effects of age, period and cohort. Results The corrected age standardized mortality rate (ASMR) decreased regularly from 9.2/100 000 in the mid 1950s to 2.5/100,000 in the late 1990s. Inclusion of age, period and cohort into the models were required to obtain an adequate fit. Cervical cancer mortality increases with age, declines over calendar period and varied irregularly by cohort. Conclusion Mortality increased with ageing and declined over time in most age-groups, but varied irregularly by birth cohort. In global, with some discrete exceptions, mortality decreased for successive generations up to the cohorts born in the 1930s. This decline stopped for cohorts born in the 1940s and thereafter. For the youngest cohorts, even a tendency of increasing risk of dying from cervical cancer could be observed, reflecting

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

Transcriptional profiling reveals progeroid Ercc1-/Δ mice as a model system for glomerular aging

PubMed Central

2013-01-01

Background Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1-/Δ progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. Results In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1-/Δ mice showed cluster formation between young WT and Ercc1-/Δ as well as old WT and Ercc1-/Δ samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1-/Δ mice (p < 0.0001). GO term enrichment analysis revealed these genes to be involved in immune and inflammatory response, cell death, and chemotaxis. In a network analysis, these genes were part of insulin signaling, chemokine and cytokine signaling and extracellular matrix pathways. Conclusion Beyond insulin signaling, we find chemokine and cytokine signaling as well as modifiers of extracellular matrix composition to be subject to major changes in the aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1-/Δ mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies. PMID:23947592

Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

PubMed

Schermer, Bernhard; Bartels, Valerie; Frommolt, Peter; Habermann, Bianca; Braun, Fabian; Schultze, Joachim L; Roodbergen, Marianne; Hoeijmakers, Jan Hj; Schumacher, Björn; Nürnberg, Peter; Dollé, Martijn Et; Benzing, Thomas; Müller, Roman-Ulrich; Kurschat, Christine E

2013-08-16

Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/Δ) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease. In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1(-/Δ) mice showed cluster formation between young WT and Ercc1(-/Δ) as well as old WT and Ercc1(-/Δ) samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1(-/Δ) mice (p < 0.0001). GO term enrichment analysis revealed these genes to be involved in immune and inflammatory response, cell death, and chemotaxis. In a network analysis, these genes were part of insulin signaling, chemokine and cytokine signaling and extracellular matrix pathways. Beyond insulin signaling, we find chemokine and cytokine signaling as well as modifiers of extracellular matrix composition to be subject to major changes in the aging glomerulus. At the level of the transcriptome, the pattern of gene activities is similar in the progeroid Ercc1(-/Δ) mouse model constituting a valuable tool for future studies of aging-associated glomerular pathologies.

A novel strategy for forensic age prediction by DNA methylation and support vector regression model

PubMed Central

Xu, Cheng; Qu, Hongzhu; Wang, Guangyu; Xie, Bingbing; Shi, Yi; Yang, Yaran; Zhao, Zhao; Hu, Lan; Fang, Xiangdong; Yan, Jiangwei; Feng, Lei

2015-01-01

High deviations resulting from prediction model, gender and population difference have limited age estimation application of DNA methylation markers. Here we identified 2,957 novel age-associated DNA methylation sites (P < 0.01 and R2 > 0.5) in blood of eight pairs of Chinese Han female monozygotic twins. Among them, nine novel sites (false discovery rate < 0.01), along with three other reported sites, were further validated in 49 unrelated female volunteers with ages of 20–80 years by Sequenom Massarray. A total of 95 CpGs were covered in the PCR products and 11 of them were built the age prediction models. After comparing four different models including, multivariate linear regression, multivariate nonlinear regression, back propagation neural network and support vector regression, SVR was identified as the most robust model with the least mean absolute deviation from real chronological age (2.8 years) and an average accuracy of 4.7 years predicted by only six loci from the 11 loci, as well as an less cross-validated error compared with linear regression model. Our novel strategy provides an accurate measurement that is highly useful in estimating the individual age in forensic practice as well as in tracking the aging process in other related applications. PMID:26635134

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.

Experimental characterization and modeling of isothermal and nonisothermal physical aging in glassy polymer films

NASA Astrophysics Data System (ADS)

Guo, Yunlong

This dissertation focuses on nonisothermal physical aging of polymers from both experimental and theoretical aspects. The study concentrates on pure polymers rather than fiber-reinforced composites; this step removes several complicating factors to simplify the study. It is anticipated that the findings of this work can then be applied to composite materials applications. The physical aging tests in this work are performed using a dynamic mechanical analyzer (DMA). The viscoelastic response of glassy polymers under various loading and thermal histories are observed as stress-strain data at a series of time points. The first stage of the experimental work involves the characterization of the isothermal physical aging behavior of two advanced thermoplastics. The second stage conducts tests on the same materials with varying thermal histories and with long-term test duration. This forms the basis to assess and modify a nonisothermal physical aging model (KAHR-ate model). Based on the experimental findings, the KAHR-ate model has been revised by new correlations between aging shift factors and volume response; this revised model performed well in predicting the nonisothermal physical aging behavior of glassy polymers. In the work on isothermal physical aging, short-term creep and stress relaxation tests were performed at several temperatures within 15-35°C below the glass transition temperature (Tg) at various aging times, using the short-term test method established by Struik. Stress and strain levels were such that the materials remained in the linear viscoelastic regime. These curves were then shifted together to determine momentary master curves and shift rates. In order to validate the obtained isothermal physical aging behavior, the results of creep and stress relaxation testing were compared and shown to be consistent with one another using appropriate interconversion of the viscoelastic material functions. Time-temperature superposition of the master curves

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.

Verification of relationship model between Korean new elderly class's recovery resilience and productive aging.

PubMed

Cho, Gun-Sang; Kim, Dae-Sung; Yi, Eun-Surk

2015-12-01

The purpose of this study is to verification of relationship model between Korean new elderly class's recovery resilience and productive aging. As of 2013, this study sampled preliminary elderly people in Gyeonggi-do and other provinces nationwide. Data from a total of effective 484 subjects was analyzed. The collected data was processed using the IBM SPSS 20.0 and AMOS 20.0, and underwent descriptive statistical analysis, confirmatory factor analysis, and structure model verification. The path coefficient associated with model fitness was examined. The standardization path coefficient between recovery resilience and productive aging is β=0.975 (t=14.790), revealing a statistically significant positive effect. Thus, it was found that the proposed basic model on the direct path of recovery resilience and productive aging was fit for the model.

Evaluating the All-Ages Lead Model Using SiteSpecific Data ...

EPA Pesticide Factsheets

Lead (Pb) exposure continues to be a problem in the United States. Even after years of progress in reducing environmental levels, CDC estimates at least 500,000 U.S. children ages 1-5 years have blood Pb levels (BLL) above the CDC reference level of 5 µg/dL. Childhood Pb exposure is associated with neurological consequences and public health professionals continue to work to reduce Pb exposures. To better understand the relationship between exposure and BLL, the USEPA has developed a beta version of the All-Ages Lead Model (AALM). Compared to the Integrated Exposure Uptake Biokinetics (IEUBK) Model for lead in children, the AALM provides greater flexibility to describe Pb exposures (acute or chronic, constant or intermittent) for any age. At this time, the AALM has the capability to predict exposure in each of the following media: dust/soil, water, air, food, and other. As part of an interagency test group, we evaluated the ability of the AALM beta v4.2 (Leggett version) to predict BLLs for children that were exposed to Pb in their environment near the John T. Lewis and Bros Lead Smelter Superfund site. The model predicted that fourteen children met our inclusion criteria that spent less than 20 hours a week away from the home (e.g., no daycare or school) and had paired BLL and environmental sampling data (i.e., Pb in soil, window sill dust, front door dust, floor dust, and drinking water). The model can predict average BLLs, but it remains difficult to predic

Aging in the three-dimensional random-field Ising model

NASA Astrophysics Data System (ADS)

von Ohr, Sebastian; Manssen, Markus; Hartmann, Alexander K.

2017-07-01

We studied the nonequilibrium aging behavior of the random-field Ising model in three dimensions for various values of the disorder strength. This allowed us to investigate how the aging behavior changes across the ferromagnetic-paramagnetic phase transition. We investigated a large system size of N =2563 spins and up to 108 Monte Carlo sweeps. To reach these necessary long simulation times, we employed an implementation running on Intel Xeon Phi coprocessors, reaching single-spin-flip times as short as 6 ps. We measured typical correlation functions in space and time to extract a growing length scale and corresponding exponents.

A Lagrangian model for the age of tracer in surface water

NASA Astrophysics Data System (ADS)

Ding, Yu; Liu, Haifei; Yi, Yujun

The age of tracer is a spatio-temporal scale, indicating the transition time of solute particles, which is helpful to monitor and manage the pollutant leakage accidents. In this study, an effective Lagrangian model for the age of tracer is developed based on the lattice Boltzmann method in D2Q5 lattices. A tracer age problem in an asymmetrical circular reservoir is then employed as a benchmark test to verify this method. Then it is applied to computing the age of tracers under two different reservoir operation schemes in the Danjiangkou Reservoir, the drinking water source for the Middle Route of South-to-North Water Transfer Project.

The effects of aging on the BTBR mouse model of autism spectrum disorder

PubMed Central

Jasien, Joan M.; Daimon, Caitlin M.; Wang, Rui; Shapiro, Bruce K.; Martin, Bronwen; Maudsley, Stuart

2014-01-01

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including “Neural synaptic plasticity regulation” and “Neurotransmitter secretion regulation.” Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype. PMID:25225482

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.

Using remotely-sensed multispectral imagery to build age models for alluvial fan surfaces

NASA Astrophysics Data System (ADS)

D'Arcy, Mitch; Mason, Philippa J.; Roda Boluda, Duna C.; Whittaker, Alexander C.; Lewis, James

2016-04-01

Accurate exposure age models are essential for much geomorphological field research, and generally depend on laboratory analyses such as radiocarbon, cosmogenic nuclide, or luminescence techniques. These approaches continue to revolutionise geomorphology, however they cannot be deployed remotely or in situ in the field. Therefore other methods are still needed for producing preliminary age models, performing relative dating of surfaces, or selecting sampling sites for the laboratory analyses above. With the widespread availability of detailed multispectral imagery, a promising approach is to use remotely-sensed data to discriminate surfaces with different ages. Here, we use new Landsat 8 Operational Land Imager (OLI) multispectral imagery to characterise the reflectance of 35 alluvial fan surfaces in the semi-arid Owens Valley, California. Alluvial fans are useful landforms to date, as they are widely used to study the effects of tectonics, climate and sediment transport processes on source-to-sink sedimentation. Our target fan surfaces have all been mapped in detail in the field, and have well-constrained exposure ages ranging from modern to ~ 125 ka measured using a high density of 10Be cosmogenic nuclide samples. Despite all having similar granitic compositions, the spectral properties of these surfaces vary systematically with their exposure ages. Older surfaces demonstrate a predictable shift in reflectance across the visible and short-wave infrared spectrum. Simple calculations, such as the brightness ratios of different wavelengths, generate sensitive power law relationships with exposure age that depend on post-depositional alteration processes affecting these surfaces. We investigate what these processes might be in this dryland location, and evaluate the potential for using remotely-sensed multispectral imagery for developing surface age models. The ability to remotely sense relative exposure ages has useful implications for preliminary mapping, selecting

The zebrafish as a gerontology model in nervous system aging, disease, and repair.

PubMed

Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

2015-11-01

Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age. Copyright © 2015 Elsevier B.V. All rights reserved.

Comprehensive stellar population models and the disentanglement of age and metallicity effects

NASA Technical Reports Server (NTRS)

Worthey, Guy

1994-01-01

The construction of detailed models for intermediate and old stellar populations is described. Input parameters include metallicity (-2 less than (Fe/H) less than 0.5), single-burst age (between 1.5 and 17 Gyr), and initial mass function (IMF) exponent. Quantities output include broadband magnitudes, spectral energy distributions, surface brightness fluctuation magnitudes, and a suite of 21 absorption feature indices. The models are checked against a wide variety of available observations. Examinations of model output yield the following conclusions. (1) If the percentage change delta age/delta Z approximately equals 3/2 for two populations, they will appear almost identical in most indices. A few indices break this degeneracy by being either more abundance sensitive (Fe4668, Fe5015, Fe5709, and Fe5782) or more age sensitive (G4300, H beta, and presumably higher order Balmer lines) than usual. (2) Present uncertainties in stellar evolution are of the same magnitude as the effects of IMF and Y in the indices studied. (3) Changes in abundance ratios (like (Mg/Fe)) are predicted to be readily apparent in the spectra of old stellar populations. (4) The I-band flux of a stellar population is predicted to be nearly independent of metallicity and only modestly sensitive to age. The I band is therefore recommended for standard candle work or studies of M/L in galaxies. Other conclusions stem from this work. (1) Intercomparison of models and observations of two TiO indices seem to indicate variation of the (V/Ti) ratio among galaxies, but it is not clear how this observation ties into the standard picture of chemical enrichment. (2) Current estimates of (Fe/H) for the most metal-rich globulars that are based on integrated indices are probably slightly too high. (3) Colors of population models from different authors exhibit a substantial range. At solar metallicity and 13 Gyr, this range corresponds to an age error of roughly +/- 7 Gyr. Model colors from different authors

The autophagy interaction network of the aging model Podospora anserina.

PubMed

Philipp, Oliver; Hamann, Andrea; Osiewacz, Heinz D; Koch, Ina

2017-03-27

Autophagy is a conserved molecular pathway involved in the degradation and recycling of cellular components. It is active either as response to starvation or molecular damage. Evidence is emerging that autophagy plays a key role in the degradation of damaged cellular components and thereby affects aging and lifespan control. In earlier studies, it was found that autophagy in the aging model Podospora anserina acts as a longevity assurance mechanism. However, only little is known about the individual components controlling autophagy in this aging model. Here, we report a biochemical and bioinformatics study to detect the protein-protein interaction (PPI) network of P. anserina combining experimental and theoretical methods. We constructed the PPI network of autophagy in P. anserina based on the corresponding networks of yeast and human. We integrated PaATG8 interaction partners identified in an own yeast two-hybrid analysis using ATG8 of P. anserina as bait. Additionally, we included age-dependent transcriptome data. The resulting network consists of 89 proteins involved in 186 interactions. We applied bioinformatics approaches to analyze the network topology and to prove that the network is not random, but exhibits biologically meaningful properties. We identified hub proteins which play an essential role in the network as well as seven putative sub-pathways, and interactions which are likely to be evolutionary conserved amongst species. We confirmed that autophagy-associated genes are significantly often up-regulated and co-expressed during aging of P. anserina. With the present study, we provide a comprehensive biological network of the autophagy pathway in P. anserina comprising PPI and gene expression data. It is based on computational prediction as well as experimental data. We identified sub-pathways, important hub proteins, and evolutionary conserved interactions. The network clearly illustrates the relation of autophagy to aging processes and enables

Compact modeling of total ionizing dose and aging effects in MOS technologies

DOE PAGES

Esqueda, Ivan S.; Barnaby, Hugh J.; King, Michael Patrick

2015-06-18

This paper presents a physics-based compact modeling approach that incorporates the impact of total ionizing dose (TID) and stress-induced defects into simulations of metal-oxide-semiconductor (MOS) devices and integrated circuits (ICs). This approach utilizes calculations of surface potential (ψs) to capture the charge contribution from oxide trapped charge and interface traps and to describe their impact on MOS electrostatics and device operating characteristics as a function of ionizing radiation exposure and aging effects. The modeling approach is demonstrated for bulk and silicon-on-insulator (SOI) MOS device. The formulation is verified using TCAD simulations and through the comparison of model calculations and experimentalmore » I-V characteristics from irradiated devices. The presented approach is suitable for modeling TID and aging effects in advanced MOS devices and ICs.« less

Age model for a continuous, ca 250-ka Quaternary lacustrine record from Bear Lake, Utah-Idaho

USGS Publications Warehouse

Colman, Steven M.; Kaufman, D.S.; Bright, Jordon; Heil, C.; King, J.W.; Dean, W.E.; Rosenbaum, J.G.; Forester, R.M.; Bischoff, J.L.; Perkins, Marie; McGeehin, J.P.

2006-01-01

The Quaternary sediments sampled by continuous 120-m-long drill cores from Bear Lake (Utah-Idaho) comprise one of the longest lacustrine sequences recovered from an extant lake. The cores serve as a good case study for the construction of an age model for sequences that extend beyond the range of radiocarbon dating. From a variety of potential age indicators, we selected a combination of radiocarbon ages, one magnetic excursion (correlated to a standard sequence), and a single Uranium-series age to develop an initial data set. The reliability of the excursion and U-series data require consideration of their position with respect to sediments of inferred interglacial character, but not direct correlation with other paleoclimate records. Data omitted from the age model include amino acid age estimates, which have a large amount of scatter, and tephrochronology correlations, which have relatively large uncertainties. Because the initial data set was restricted to the upper half of the BL00-1 core, we inferred additional ages by direct correlation to the independently dated paleoclimate record from Devils Hole. We developed an age model for the entire core using statistical methods that consider both the uncertainties of the original data and that of the curve-fitting process, with a combination of our initial data set and the climate correlations as control points. This age model represents our best estimate of the chronology of deposition in Bear Lake. Because the age model contains assumptions about the correlation of Bear Lake to other climate records, the model cannot be used to address some paleoclimate questions, such as phase relationships with other areas.

Modeling Intraindividual Dynamics Using Stochastic Differential Equations: Age Differences in Affect Regulation.

PubMed

Wood, Julie; Oravecz, Zita; Vogel, Nina; Benson, Lizbeth; Chow, Sy-Miin; Cole, Pamela; Conroy, David E; Pincus, Aaron L; Ram, Nilam

2017-12-15

Life-span theories of aging suggest improvements and decrements in individuals' ability to regulate affect. Dynamic process models, with intensive longitudinal data, provide new opportunities to articulate specific theories about individual differences in intraindividual dynamics. This paper illustrates a method for operationalizing affect dynamics using a multilevel stochastic differential equation (SDE) model, and examines how those dynamics differ with age and trait-level tendencies to deploy emotion regulation strategies (reappraisal and suppression). Univariate multilevel SDE models, estimated in a Bayesian framework, were fit to 21 days of ecological momentary assessments of affect valence and arousal (average 6.93/day, SD = 1.89) obtained from 150 adults (age 18-89 years)-specifically capturing temporal dynamics of individuals' core affect in terms of attractor point, reactivity to biopsychosocial (BPS) inputs, and attractor strength. Older age was associated with higher arousal attractor point and less BPS-related reactivity. Greater use of reappraisal was associated with lower valence attractor point. Intraindividual variability in regulation strategy use was associated with greater BPS-related reactivity and attractor strength, but in different ways for valence and arousal. The results highlight the utility of SDE models for studying affect dynamics and informing theoretical predictions about how intraindividual dynamics change over the life course. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Modeled tephra ages from lake sediments, base of Redoubt Volcano, Alaska

USGS Publications Warehouse

Schiff, C.J.; Kaufman, D.S.; Wallace, K.L.; Werner, A.; Ku, T.-L.; Brown, T.A.

2008-01-01

A 5.6-m-long lake sediment core from Bear Lake, Alaska, located 22 km southeast of Redoubt Volcano, contains 67 tephra layers deposited over the last 8750 cal yr, comprising 15% of the total thickness of recovered sediment. Using 12 AMS 14C ages, along with the 137Cs and 210Pb activities of recent sediment, we evaluated different models to determine the age-depth relation of the core, and to determine the age of each tephra deposit. The selected age model is based on a mixed-effect regression that was passed through the adjusted tephra-free depth of each dated layer. The estimated age uncertainty of the 67 tephras averages ??105 yr (95% confidence intervals). Tephra-fall frequency at Bear Lake was among the highest during the past 500 yr, with eight tephras deposited compared to an average of 3.7/500 yr over the last 8500 yr. Other periods of increased tephra fall occurred 2500-3500, 4500-5000, and 7000-7500 cal yr. Our record suggests that Bear Lake experienced extended periods (1000-2000 yr) of increased tephra fall separated by shorter periods (500-1000 yr) of apparent quiescence. The Bear Lake sediment core affords the most comprehensive tephrochronology from the base of the Redoubt Volcano to date, with an average tephra-fall frequency of one every 130 yr. ?? 2007 Elsevier Ltd. All rights reserved.

Accounting for Age Uncertainty in Growth Modeling, the Case Study of Yellowfin Tuna (Thunnus albacares) of the Indian Ocean

PubMed Central

Dortel, Emmanuelle; Massiot-Granier, Félix; Rivot, Etienne; Million, Julien; Hallier, Jean-Pierre; Morize, Eric; Munaron, Jean-Marie; Bousquet, Nicolas; Chassot, Emmanuel

2013-01-01

Age estimates, typically determined by counting periodic growth increments in calcified structures of vertebrates, are the basis of population dynamics models used for managing exploited or threatened species. In fisheries research, the use of otolith growth rings as an indicator of fish age has increased considerably in recent decades. However, otolith readings include various sources of uncertainty. Current ageing methods, which converts an average count of rings into age, only provide periodic age estimates in which the range of uncertainty is fully ignored. In this study, we describe a hierarchical model for estimating individual ages from repeated otolith readings. The model was developed within a Bayesian framework to explicitly represent the sources of uncertainty associated with age estimation, to allow for individual variations and to include knowledge on parameters from expertise. The performance of the proposed model was examined through simulations, and then it was coupled to a two-stanza somatic growth model to evaluate the impact of the age estimation method on the age composition of commercial fisheries catches. We illustrate our approach using the saggital otoliths of yellowfin tuna of the Indian Ocean collected through large-scale mark-recapture experiments. The simulation performance suggested that the ageing error model was able to estimate the ageing biases and provide accurate age estimates, regardless of the age of the fish. Coupled with the growth model, this approach appeared suitable for modeling the growth of Indian Ocean yellowfin and is consistent with findings of previous studies. The simulations showed that the choice of the ageing method can strongly affect growth estimates with subsequent implications for age-structured data used as inputs for population models. Finally, our modeling approach revealed particularly useful to reflect uncertainty around age estimates into the process of growth estimation and it can be applied to any

Efficient Workflows for Curation of Heterogeneous Data Supporting Modeling of U-Nb Alloy Aging

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

Ward, Logan Timothy; Hackenberg, Robert Errol

These are slides from a presentation summarizing a graduate research associate's summer project. The following topics are covered in these slides: data challenges in materials, aging in U-Nb Alloys, Building an Aging Model, Different Phase Trans. in U-Nb, the Challenge, Storing Materials Data, Example Data Source, Organizing Data: What is a Schema?, What does a "XML Schema" look like?, Our Data Schema: Nice and Simple, Storing Data: Materials Data Curation System (MDCS), Problem with MDCS: Slow Data Entry, Getting Literature into MDCS, Staging Data in Excel Document, Final Result: MDCS Records, Analyzing Image Data, Process for Making TTT Diagram, Bottleneckmore » Number 1: Image Analysis, Fitting a TTP Boundary, Fitting a TTP Curve: Comparable Results, How Does it Compare to Our Data?, Image Analysis Workflow, Curating Hardness Records, Hardness Data: Two Key Decisions, Before Peak Age? - Automation, Interactive Viz, Which Transformation?, Microstructure-Informed Model, Tracking the Entire Process, General Problem with Property Models, Pinyon: Toolkit for Managing Model Creation, Tracking Individual Decisions, Jupyter: Docs and Code in One File, Hardness Analysis Workflow, Workflow for Aging Models, and conclusions.« less

Asteroid age distributions determined by space weathering and collisional evolution models

NASA Astrophysics Data System (ADS)

Willman, Mark; Jedicke, Robert

2011-01-01

We provide evidence of consistency between the dynamical evolution of main belt asteroids and their color evolution due to space weathering. The dynamical age of an asteroid's surface (Bottke, W.F., Durda, D.D., Nesvorný, D., Jedicke, R., Morbidelli, A., Vokrouhlický, D., Levison, H. [2005]. Icarus 175 (1), 111-140; Nesvorný, D., Jedicke, R., Whiteley, R.J., Ivezić, Ž. [2005]. Icarus 173, 132-152) is the time since its last catastrophic disruption event which is a function of the object's diameter. The age of an S-complex asteroid's surface may also be determined from its color using a space weathering model (e.g. Willman, M., Jedicke, R., Moskovitz, N., Nesvorný, D., Vokrouhlický, D., Mothé-Diniz, T. [2010]. Icarus 208, 758-772; Jedicke, R., Nesvorný, D., Whiteley, R.J., Ivezić, Ž., Jurić, M. [2004]. Nature 429, 275-277; Willman, M., Jedicke, R., Nesvorny, D., Moskovitz, N., Ivezić, Ž., Fevig, R. [2008]. Icarus 195, 663-673. We used a sample of 95 S-complex asteroids from SMASS and obtained their absolute magnitudes and u, g, r, i, z filter magnitudes from SDSS. The absolute magnitudes yield a size-derived age distribution. The u, g, r, i, z filter magnitudes lead to the principal component color which yields a color-derived age distribution by inverting our color-age relationship, an enhanced version of the 'dual τ' space weathering model of Willman et al. (2010). We fit the size-age distribution to the enhanced dual τ model and found characteristic weathering and gardening times of τw = 2050 ± 80 Myr and τg=4400-500+700Myr respectively. The fit also suggests an initial principal component color of -0.05 ± 0.01 for fresh asteroid surface with a maximum possible change of the probable color due to weathering of Δ PC = 1.34 ± 0.04. Our predicted color of fresh asteroid surface matches the color of fresh ordinary chondritic surface of PC1 = 0.17 ± 0.39.

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

Modelling Precipitation Kinetics During Aging of Al-Mg-Si Alloys

NASA Astrophysics Data System (ADS)

Du, Qiang; Friis, Jepser

A classical Kaufmann-Wagner numerical model is employed to predict the evolution of precipitate size distribution during the aging treatment of Al-Mg-Si alloys. One feature of the model is its fully coupling with CALPHAD database, and with the input of interfacial energy from ab-initial calculation, it is able to capture the morphological change of the precipitates. The simulation results will be compared with the experimental measurements.

The relative age effect in sport: a developmental systems model.

PubMed

Wattie, Nick; Schorer, Jörg; Baker, Joseph

2015-01-01

The policies that dictate the participation structure of many youth sport systems involve the use of a set selection date (e.g. 31 December), which invariably produces relative age differences between those within the selection year (e.g. 1 January to 31 December). Those born early in the selection year (e.g. January) are relatively older—by as much as 12 months minus 1 day—than those born later in the selection year (e.g. December). Research in the area of sport has identified a number of significant developmental effects associated with such relative age differences. However, a theoretical framework that describes the breadth and complexity of relative age effects (RAEs) in sport does not exist in the literature. This paper reviews and summarizes the existing literature on relative age in sport, and proposes a constraints-based developmental systems model for RAEs in sport.

Testing Multidimensional Models of Youth Civic Engagement: Model Comparisons, Measurement Invariance, and Age Differences

ERIC Educational Resources Information Center

Wray-Lake, Laura; Metzger, Aaron; Syvertsen, Amy K.

2017-01-01

Despite recognition that youth civic engagement is multidimensional, different modeling approaches are rarely compared or tested for measurement invariance. Using a diverse sample of 2,467 elementary, middle, and high school-aged youth, we measured eight dimensions of civic engagement: social responsibility values, informal helping, political…

Individual-tree diameter growth model for managed, even-aged, upland oak stands

Treesearch

Donald E. Hilt

1983-01-01

A distance-independent, individual-tree diameter growth model was developed for managed, even-aged, upland oak stands. The 5-year basal-area growth of individual trees is first modeled as a function of dbh squared for given stands. Parameters from these models are then modeled as a function of mean stand diameter, percent stocking of the stand, and site index. A...

Development of a lifetime prediction model for lithium-ion batteries based on extended accelerated aging test data

NASA Astrophysics Data System (ADS)

Ecker, Madeleine; Gerschler, Jochen B.; Vogel, Jan; Käbitz, Stefan; Hust, Friedrich; Dechent, Philipp; Sauer, Dirk Uwe

2012-10-01

Battery lifetime prognosis is a key requirement for successful market introduction of electric and hybrid vehicles. This work aims at the development of a lifetime prediction approach based on an aging model for lithium-ion batteries. A multivariable analysis of a detailed series of accelerated lifetime experiments representing typical operating conditions in hybrid electric vehicle is presented. The impact of temperature and state of charge on impedance rise and capacity loss is quantified. The investigations are based on a high-power NMC/graphite lithium-ion battery with good cycle lifetime. The resulting mathematical functions are physically motivated by the occurring aging effects and are used for the parameterization of a semi-empirical aging model. An impedance-based electric-thermal model is coupled to the aging model to simulate the dynamic interaction between aging of the battery and the thermal as well as electric behavior. Based on these models different drive cycles and management strategies can be analyzed with regard to their impact on lifetime. It is an important tool for vehicle designers and for the implementation of business models. A key contribution of the paper is the parameterization of the aging model by experimental data, while aging simulation in the literature usually lacks a robust empirical foundation.

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.

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

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

Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

PubMed Central

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-01-01

The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

Oxidative damage and cellular defense mechanisms in sea urchin models of aging.

PubMed

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-10-01

The free radical, or oxidative stress, theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging because of the existence of species with tremendously different natural life spans, including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity, and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus, and Strongylocentrotus purpuratus, which has an intermediate life span. Levels of protein carbonyls and 4-hydroxynonenal measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2'-deoxyguanosine measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age pigment lipofuscin, measured in muscle, nerve, and esophagus, increased with age; however, it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species; however, further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age, and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. Copyright © 2013 Elsevier Inc. All

A model framework for mortality and health data classified by age, area, and time.

PubMed

Congdon, Peter

2006-03-01

This article sets out a modeling framework for modeling health outcomes over area, age, and time dimensions that takes account of spatial correlation, interactions between dimensions, and cohort as well as age effects. The goals of the framework include parsimony and parameter interpretability. Multivariate extensions may be made allowing interdependent or shared effects between different outcomes (e.g., ill health and mortality). A particular focus is on assessing the proportionality assumption whereby separate age and area effects multiply to produce age-area mortality or illness rates, and age-area interactions are assumed not to exist. A trivariate (mortality-health) application of the framework involves cross-sectional data in the 33 London boroughs, while a longitudinal univariate application involves deaths for the same areas over four 5-year periods starting in 1979.

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

Verification of relationship model between Korean new elderly class’s recovery resilience and productive aging

PubMed Central

Cho, Gun-Sang; Kim, Dae-Sung; Yi, Eun-Surk

2015-01-01

The purpose of this study is to verification of relationship model between Korean new elderly class’s recovery resilience and productive aging. As of 2013, this study sampled preliminary elderly people in Gyeonggi-do and other provinces nationwide. Data from a total of effective 484 subjects was analyzed. The collected data was processed using the IBM SPSS 20.0 and AMOS 20.0, and underwent descriptive statistical analysis, confirmatory factor analysis, and structure model verification. The path coefficient associated with model fitness was examined. The standardization path coefficient between recovery resilience and productive aging is β=0.975 (t=14.790), revealing a statistically significant positive effect. Thus, it was found that the proposed basic model on the direct path of recovery resilience and productive aging was fit for the model. PMID:26730383

Computational Modeling of Age-Differences In a Visually Demanding Driving Task: Vehicle Detection

DTIC Science & Technology

1997-10-07

overall estimate of d’ for each scene was calculated from the two levels using the method described in MacMillan and Creelman [13]. MODELING VEHICLE...Scialfa, "Visual and auditory aging," In J. Birren & K. W. Schaie (Eds.) Handbook of the Psychology of Aging (4th edition), 1996, New York: Academic...Computational models of Visual Processing, 1991, Boston MA: MIT Press. [13] N. A. MacMillan & C. D. Creelman , Detection Theory: A User’s Guide, 1991

A holistic aging model for Li(NiMnCo)O2 based 18650 lithium-ion batteries

NASA Astrophysics Data System (ADS)

Schmalstieg, Johannes; Käbitz, Stefan; Ecker, Madeleine; Sauer, Dirk Uwe

2014-07-01

Knowledge on lithium-ion battery aging and lifetime estimation is a fundamental aspect for successful market introduction in high-priced goods like electric mobility. This paper illustrates the parameterization of a holistic aging model from accelerated aging tests. More than 60 cells of the same type are tested to analyze different impact factors. In calendar aging tests three temperatures and various SOC are applied to the batteries. For cycle aging tests especially different cycle depths and mean SOC are taken into account. Capacity loss and resistance increase are monitored as functions of time and charge throughput during the tests. From these data physical based functions are obtained, giving a mathematical description of aging. To calculate the stress factors like temperature or voltage, an impedance based electric-thermal model is coupled to the aging model. The model accepts power and current profiles as input, furthermore an ambient air temperature profile can be applied. Various drive cycles and battery management strategies can be tested and optimized using the lifetime prognosis of this tool. With the validation based on different realistic driving profiles and temperatures, a robust foundation is provided.

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

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.

Advanced age diminishes tendon-to-bone healing in a rat model of rotator cuff repair.

PubMed

Plate, Johannes F; Brown, Philip J; Walters, Jordan; Clark, John A; Smith, Thomas L; Freehill, Michael T; Tuohy, Christopher J; Stitzel, Joel D; Mannava, Sandeep

2014-04-01

Advanced patient age is associated with recurrent tearing and failure of rotator cuff repairs clinically; however, basic science studies have not evaluated the influence of aging on tendon-to-bone healing after rotator cuff repair in an animal model. Hypothesis/ This study examined the effect of aging on tendon-to-bone healing in an established rat model of rotator cuff repair using the aged animal colony from the National Institute on Aging of the National Institutes of Health. The authors hypothesized that normal aging decreases biomechanical strength and histologic organization at the tendon-to-bone junction after acute repair. Controlled laboratory study. In 56 F344xBN rats, 28 old and 28 young (24 and 8 months of age, respectively), the supraspinatus tendon was transected and repaired. At 2 or 8 weeks after surgery, shoulder specimens underwent biomechanical testing to compare load-to-failure and load-relaxation response between age groups. Histologic sections of the tendon-to-bone interface were assessed with hematoxylin and eosin staining, and collagen fiber organization was assessed by semiquantitative analysis of picrosirius red birefringence under polarized light. Peak failure load was similar between young and old animals at 2 weeks after repair (31% vs 26% of age-matched uninjured controls, respectively; P > .05) but significantly higher in young animals compared with old animals 8 weeks after repair (86% vs 65% of age-matched uninjured controls, respectively; P < .01). Eight weeks after repair, fibroblasts appeared more organized and uniformly aligned in young animals on hematoxylin and eosin slides compared with old animals. Collagen birefringence analysis of the tendon-to-bone junction demonstrated that young animals had increased collagen fiber organization and similar histologic structure compared with age-matched controls (53.7 ± 2.4 gray scales; P > .05). In contrast, old animals had decreased collagen fiber organization and altered structure

Early-life stress and reproductive cost: A two-hit developmental model of accelerated aging?

PubMed

Shalev, Idan; Belsky, Jay

2016-05-01

Two seemingly independent bodies of research suggest a two-hit model of accelerated aging, one highlighting early-life stress and the other reproduction. The first, informed by developmental models of early-life stress, highlights reduced longevity effects of early adversity on telomere erosion, whereas the second, informed by evolutionary theories of aging, highlights such effects with regard to reproductive cost (in females). The fact that both early-life adversity and reproductive effort are associated with shorter telomeres and increased oxidative stress raises the prospect, consistent with life-history theory, that these two theoretical frameworks currently informing much research are tapping into the same evolutionary-developmental process of increased senescence and reduced longevity. Here we propose a mechanistic view of a two-hit model of accelerated aging in human females through (a) early-life adversity and (b) early reproduction, via a process of telomere erosion, while highlighting mediating biological embedding mechanisms that might link these two developmental aging processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Modeling aging effects on two-choice tasks: response signal and response time data.

PubMed

Ratcliff, Roger

2008-12-01

In the response signal paradigm, a test stimulus is presented, and then at one of a number of experimenter-determined times, a signal to respond is presented. Response signal, standard response time (RT), and accuracy data were collected from 19 college-age and 19 60- to 75-year-old participants in a numerosity discrimination task. The data were fit with 2 versions of the diffusion model. Response signal data were modeled by assuming a mixture of processes, those that have terminated before the signal and those that have not terminated; in the latter case, decisions are based on either partial information or guessing. The effects of aging on performance in the regular RT task were explained the same way in the models, with a 70- to 100-ms increase in the nondecision component of processing, more conservative decision criteria, and more variability across trials in drift and the nondecision component of processing, but little difference in drift rate (evidence). In the response signal task, the primary reason for a slower rise in the response signal functions for older participants was variability in the nondecision component of processing. Overall, the results were consistent with earlier fits of the diffusion model to the standard RT task for college-age participants and to the data from aging studies using this task in the standard RT procedure. Copyright (c) 2009 APA, all rights reserved.

Modeling Aging Effects on Two-Choice Tasks: Response Signal and Response Time Data

PubMed Central

Ratcliff, Roger

2009-01-01

In the response signal paradigm, a test stimulus is presented, and then at one of a number of experimenter-determined times, a signal to respond is presented. Response signal, standard response time (RT), and accuracy data were collected from 19 college-age and 19 60- to 75-year-old participants in a numerosity discrimination task. The data were fit with 2 versions of the diffusion model. Response signal data were modeled by assuming a mixture of processes, those that have terminated before the signal and those that have not terminated; in the latter case, decisions are based on either partial information or guessing. The effects of aging on performance in the regular RT task were explained the same way in the models, with a 70- to 100-ms increase in the nondecision component of processing, more conservative decision criteria, and more variability across trials in drift and the nondecision component of processing, but little difference in drift rate (evidence). In the response signal task, the primary reason for a slower rise in the response signal functions for older participants was variability in the nondecision component of processing. Overall, the results were consistent with earlier fits of the diffusion model to the standard RT task for college-age participants and to the data from aging studies using this task in the standard RT procedure. PMID:19140659

Effort-reward imbalance and organisational injustice among aged nurses: a moderated mediation model.

PubMed

Topa, Gabriela; Guglielmi, Dina; Depolo, Marco

2016-09-01

To test the effort-reward imbalance model among older nurses, expanding it to include the moderation of overcommitment and age in the stress-health complaints relationship, mediated by organisational injustice. The theoretical framework included the effort-reward imbalance, the uncertainty management and the socio-emotional selectivity models. Employing a two-wave design, the participants were 255 nurses aged 45 years and over, recruited from four large hospitals in Spain (Madrid and Basque Country). The direct effect of imbalance on health complaints was supported: it was significant when overcommitment was low but not when it was high. Organisational injustice mediated the influence of effort-reward imbalance on health complaints. The conditional effect of the mediation of organisational injustice was significant in three of the overcommitment/age conditions but it weakened, becoming non-significant, when the level of overcommitment was low and age was high. The study tested the model in nursing populations and expanded it to the settings of occupational health and safety at work. The results of this study highlight the importance of effort-reward imbalance and organisational justice for creating healthy work environments. © 2016 John Wiley & Sons Ltd.

A Diffusion Model Analysis of the Effects of Aging on Recognition Memory

ERIC Educational Resources Information Center

Ratcliff, Roger; Thapar, Anjali; McKoon, Gail

2004-01-01

The effects of aging on response time were examined in a recognition memory experiment with young, college age subjects and older, 60-75 year old subjects. The older subjects were slower than the young subjects but almost as accurate. Ratcliff's (1978) diffusion model was fit to the data and it provided a good account of response times, their…

Activated aging dynamics and effective trap model description in the random energy model

NASA Astrophysics Data System (ADS)

Baity-Jesi, M.; Biroli, G.; Cammarota, C.

2018-01-01

We study the out-of-equilibrium aging dynamics of the random energy model (REM) ruled by a single spin-flip Metropolis dynamics. We focus on the dynamical evolution taking place on time-scales diverging with the system size. Our aim is to show to what extent the activated dynamics displayed by the REM can be described in terms of an effective trap model. We identify two time regimes: the first one corresponds to the process of escaping from a basin in the energy landscape and to the subsequent exploration of high energy configurations, whereas the second one corresponds to the evolution from a deep basin to the other. By combining numerical simulations with analytical arguments we show why the trap model description does not hold in the former but becomes exact in the second.

Keep Up the Good Work! Age-Moderated Mediation Model on Intention to Retire.

PubMed

Dordoni, Paola; Van der Heijden, Beatrice; Peters, Pascale; Kraus-Hoogeveen, Sascha; Argentero, Piergiorgio

2017-01-01

In European nations, the aging of the workforce is a major issue which is increasingly addressed both in national and organizational policies in order to sustain older workers' employability and to encourage longer working lives. Particularly older workers' employability can be viewed an important issue as this has the potential to motivate them for their work and change their intention to retire. Based on lifespan development theories and Van der Heijden's 'employability enhancement model', this paper develops and tests an age-moderated mediation model (which refers to the processes that we want to test in this model), linking older workers' (55 years old and over) perceptions of job support for learning (job-related factor) and perceptions of negative age stereotypes on productivity (organizational factor), on the one hand, and their intention to retire, on the other hand, via their participation in employability enhancing activities, being the mediator in our model. A total of 2,082 workers aged 55 years and above were included in the analyses. Results revealed that the two proposed relationships between the predictors and intention to retire were mediated by participation in employability enhancing activities, reflecting two mechanisms through which work context affects intention to retire (namely 'a gain spiral and a loss spiral'). Multi-Group SEM analyses, distinguishing between two age groups (55-60 and 61-65 years old), revealed different paths for the two distinguished groups of older workers. Employability mediated the relationship between perceptions of job support for learning and intention to retire in both age groups, whereas it only mediated the relationship between perceptions of negative age stereotypes and intention to retire in the 55-60 group. From our empirical study, we may conclude that employability is an important factor in the light of older workers' intention to retire. In order to motivate this category of workers to participate in

Molybdenite Re/Os dating, zircon U-Pb age and geochemistry of granitoids in the Yangchuling porphyry W-Mo deposit (Jiangnan tungsten ore belt), China: Implications for petrogenesis, mineralization and geodynamic setting

NASA Astrophysics Data System (ADS)

Mao, Jingwen; Xiong, Bikang; Liu, Jun; Pirajno, Franco; Cheng, Yanbo; Ye, Huishou; Song, Shiwei; Dai, Pan

2017-08-01

The Yangchuling W-Mo deposit, located in the Jiangnan porphyry-skarn (JNB) tungsten ore belt, is the first recognized typical porphyry W-Mo deposit in China in the 1980's. Stockworks and disseminated W-Mo mineralization occur in the roof pendant of a 0.3 km2 monzogranitic porphyry stock that intruded into a granodiorite stock, hosted by Neoproterozoic phyllite and slate. LA-ICPMS zircon U-Pb analyses suggest that of the monzogranitic porphyry and granodiorite were formed at 143.8 ± 0.5 Ma and 149.8 ± 0.6 Ma, respectively. Six molybdenite samples yielded a Re-Os weighted mean age of 146.4 ± 1.0 Ma. Geochemical data show that both granodiorite and monzogranitic porphyry are characterized by enrichment of large ion lithophile elements (LILE) relative to high field strength elements (HFSE), indicating a peraluminous nature (A/CNK = 1.01-1.08). Two granitoids are characterized by a negative slope with significant light REE/heavy REE fractionation [(La/Yb)N = 8.38-23.20] and negative Eu anomalies (Eu/Eu* = 0.69-0.76). The P2O5 contents of the Yangchuling granitoids range from 0.12% to 0.17% and exhibit a negative correlation with SiO2, reflecting that they are highly fractionated I-type. They have high initial 87Sr/86Sr ratios (0.7104-0.7116), low negative εNd(t) (- 5.05 to - 5.67), and homogeneous εHf(t) between - 1.39 and - 2.17, indicating similar sources. Additionally, two-stage Nd model ages (TDM2) of 1.3-1.4 Ga and two-stage Hf model ages (TDM2) of 1.2-1.3 Ga are consistent, indicating that Neoproterozoic crustal rocks of the Shuangqiaoshan Group could have contributed to form the Yangchuling magmas. Considering the two groups of parallel Late Mesozoic ore belts, namely the Jiangnan porphyry-skarn tungsten belt (JNB) in the south and the Middle-Lower Yangtze River porphyry-skarn Cu-Au-Mo-Fe ore belt (YRB) in the north, the Nanling granite-related W-Sn ore belt (NLB) in the south, the neighboring Qin-Hang porphyry-skarn Cu-Mo-hydrothermal Pb-Zn-Ag ore belt (QHB

Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

PubMed

Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

2014-01-01

The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

Comparison of particle-tracking and lumped-parameter age-distribution models for evaluating vulnerability of production wells to contamination

USGS Publications Warehouse

Eberts, S.M.; Böhlke, J.K.; Kauffman, L.J.; Jurgens, B.C.

2012-01-01

Environmental age tracers have been used in various ways to help assess vulnerability of drinking-water production wells to contamination. The most appropriate approach will depend on the information that is available and that which is desired. To understand how the well will respond to changing nonpoint-source contaminant inputs at the water table, some representation of the distribution of groundwater ages in the well is needed. Such information for production wells is sparse and difficult to obtain, especially in areas lacking detailed field studies. In this study, age distributions derived from detailed groundwater-flow models with advective particle tracking were compared with those generated from lumped-parameter models to examine conditions in which estimates from simpler, less resource-intensive lumped-parameter models could be used in place of estimates from particle-tracking models. In each of four contrasting hydrogeologic settings in the USA, particle-tracking and lumped-parameter models yielded roughly similar age distributions and largely indistinguishable contaminant trends when based on similar conceptual models and calibrated to similar tracer data. Although model calibrations and predictions were variably affected by tracer limitations and conceptual ambiguities, results illustrated the importance of full age distributions, rather than apparent tracer ages or model mean ages, for trend analysis and forecasting.

Dynamical properties of the Penna aging model applied to the population of wolves

NASA Astrophysics Data System (ADS)

Makowiec, Danuta

1997-02-01

The parameters of th Penna bit-string model of aging of biological systems are systematically tested to better understand the model itself as well as the results arising from applying this model to studies of the development of the stationary population of Alaska wolves.

Improving age-depth models using sedimentary proxies for accumulation rates in fluvio-lacustrine deposits

NASA Astrophysics Data System (ADS)

Minderhoud, Philip S. J.; Cohen, Kim M.; Toonen, Willem. H. J.; Erkens, Gilles; Hoek, Wim Z.

2017-04-01

Lacustrine fills, including those of oxbow lakes in river floodplains, often hold valuable sedimentary and biological proxy records of palaeo-environmental change. Precise dating of accumulated sediments at levels throughout these records is crucial for interpretation and correlation of (proxy) data existing within the fills. Typically, dates are gathered from multiple sampled levels and their results are combined in age-depth models to estimate the ages of events identified between the datings. In this paper, a method of age-depth modelling is presented that varies the vertical accumulation rate of the lake fill based on continuous sedimentary data. In between Bayesian calibrated radiocarbon dates, this produces a modified non-linear age-depth relation based on sedimentology rather than linear or spline interpolation. The method is showcased on a core of an infilled palaeomeander at the floodplain edge of the river Rhine near Rheinberg (Germany). The sequence spans from 4.7 to 2.9 ka cal BP and consists of 5.5 meters of laminated lacustrine, organo-clastic mud, covered by 1 meter of peaty clay. Four radiocarbon dates provide direct dating control, mapping and dating in the wider surroundings provide additional control. The laminated, organo-clastic facies of the oxbow fill contains a record of nearby fluvial-geomorphological activity, including meander reconfiguration events and passage of rare large floods, recognized as fluctuations in coarseness and amount of allochthonous clastic sediment input. Continuous along-core sampling and measurement of loss-on-ignition (LOI) provided a fast way of expressing the variation in clastic sedimentation influx from the nearby river versus autochthonous organic deposition derived from biogenic production in the lake itself. This low-cost sedimentary proxy data feeds into the age-depth modelling. The sedimentology-modelled age-depth relation (re)produces the distinct lithological boundaries in the fill as marked changes in

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

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.

Estimating child mortality and modelling its age pattern for India.

PubMed

Roy, S G

1989-06-01

"Using data [for India] on proportions of children dead...estimates of infant and child mortality are...obtained by Sullivan and Trussell modifications of [the] Brass basic method. The estimate of child survivorship function derived after logit smoothing appears to be more reliable than that obtained by the Census Actuary. The age pattern of childhood mortality is suitably modelled by [a] Weibull function defining the probability of surviving from birth to a specified age and involving two parameters of level and shape. A recently developed linearization procedure based on [a] graphical approach is adopted for estimating the parameters of the function." excerpt

Application of third molar development and eruption models in estimating dental age in Malay sub-adults.

PubMed

Mohd Yusof, Mohd Yusmiaidil Putera; Cauwels, Rita; Deschepper, Ellen; Martens, Luc

2015-08-01

The third molar development (TMD) has been widely utilized as one of the radiographic method for dental age estimation. By using the same radiograph of the same individual, third molar eruption (TME) information can be incorporated to the TMD regression model. This study aims to evaluate the performance of dental age estimation in individual method models and the combined model (TMD and TME) based on the classic regressions of multiple linear and principal component analysis. A sample of 705 digital panoramic radiographs of Malay sub-adults aged between 14.1 and 23.8 years was collected. The techniques described by Gleiser and Hunt (modified by Kohler) and Olze were employed to stage the TMD and TME, respectively. The data was divided to develop three respective models based on the two regressions of multiple linear and principal component analysis. The trained models were then validated on the test sample and the accuracy of age prediction was compared between each model. The coefficient of determination (R²) and root mean square error (RMSE) were calculated. In both genders, adjusted R² yielded an increment in the linear regressions of combined model as compared to the individual models. The overall decrease in RMSE was detected in combined model as compared to TMD (0.03-0.06) and TME (0.2-0.8). In principal component regression, low value of adjusted R(2) and high RMSE except in male were exhibited in combined model. Dental age estimation is better predicted using combined model in multiple linear regression models. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Forecasting selected specific age mortality rate of Malaysia by using Lee-Carter model

NASA Astrophysics Data System (ADS)

Shukri Kamaruddin, Halim; Ismail, Noriszura

2018-03-01

Observing mortality pattern and trend is an important subject for any country to maintain a good social-economy in the next projection years. The declining in mortality trend gives a good impression of what a government has done towards macro citizen in one nation. Selecting a particular mortality model can be a tricky based on the approached method adapting. Lee-Carter model is adapted because of its simplicity and reliability of the outcome results with approach of regression. Implementation of Lee-Carter in finding a fitted model and hence its projection has been used worldwide in most of mortality research in developed countries. This paper studies the mortality pattern of Malaysia in the past by using original model of Lee-Carter (1992) and hence its cross-sectional observation for a single age. The data is indexed by age of death and year of death from 1984 to 2012, in which are supplied by Department of Statistics Malaysia. The results are modelled by using RStudio and the keen analysis will focus on the trend and projection of mortality rate and age specific mortality rate in the future. This paper can be extended to different variants extensions of Lee-Carter or any stochastic mortality tool by using Malaysia mortality experience as a centre of the main issue.

Flexible parametric survival models built on age-specific antimüllerian hormone percentiles are better predictors of menopause.

PubMed

Ramezani Tehrani, Fahimeh; Mansournia, Mohammad Ali; Solaymani-Dodaran, Masoud; Steyerberg, Ewout; Azizi, Fereidoun

2016-06-01

This study aimed to improve existing prediction models for age at menopause. We identified all reproductive aged women with regular menstrual cycles who met our eligibility criteria (n = 1,015) in the Tehran Lipid and Glucose Study-an ongoing population-based cohort study initiated in 1998. Participants were examined every 3 years and their reproductive histories were recorded. Blood levels of antimüllerian hormone (AMH) were measured at the time of recruitment. Age at menopause was estimated based on serum concentrations of AMH using flexible parametric survival models. The optimum model was selected according to Akaike Information Criteria and the realness of the range of predicted median menopause age. We followed study participants for a median of 9.8 years during which 277 women reached menopause and found that a spline-based proportional odds model including age-specific AMH percentiles as the covariate performed well in terms of statistical criteria and provided the most clinically relevant and realistic predictions. The range of predicted median age at menopause for this model was 47.1 to 55.9 years. For those who reached menopause, the median of the absolute mean difference between actual and predicted age at menopause was 1.9 years (interquartile range 2.9). The model including the age-specific AMH percentiles as the covariate and using proportional odds as its covariate metrics meets all the statistical criteria for the best model and provides the most clinically relevant and realistic predictions for age at menopause for reproductive-aged women.