Extension of quality-by-design concept to the early development phase of pharmaceutical R&D processes.

PubMed

Csóka, Ildikó; Pallagi, Edina; Paál, Tamás L

2018-03-27

Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a 'zero' preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders' (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analysis of Dibenzothiophene Desulfurization in a Recombinant Pseudomonas putida Strain▿

PubMed Central

Calzada, Javier; Zamarro, María T.; Alcón, Almudena; Santos, Victoria E.; Díaz, Eduardo; García, José L.; Garcia-Ochoa, Felix

2009-01-01

Biodesulfurization was monitored in a recombinant Pseudomonas putida CECT5279 strain. DszB desulfinase activity reached a sharp maximum at the early exponential phase, but it rapidly decreased at later growth phases. A model two-step resting-cell process combining sequentially P. putida cells from the late and early exponential growth phases was designed to significantly increase biodesulfurization. PMID:19047400

The Impact of Early Design Phase Risk Identification Biases on Space System Project Performance

NASA Technical Reports Server (NTRS)

Reeves, John D., Jr.; Eveleigh, Tim; Holzer, Thomas; Sarkani, Shahryar

2012-01-01

Risk identification during the early design phases of complex systems is commonly implemented but often fails to result in the identification of events and circumstances that truly challenge project performance. Inefficiencies in cost and schedule estimation are usually held accountable for cost and schedule overruns, but the true root cause is often the realization of programmatic risks. A deeper understanding of frequent risk identification trends and biases pervasive during space system design and development is needed, for it would lead to improved execution of existing identification processes and methods.

Risk Evaluation in the Pre-Phase A Conceptual Design of Spacecraft

NASA Technical Reports Server (NTRS)

Fabisinski, Leo L., III; Maples, Charlotte Dauphne

2010-01-01

Typically, the most important decisions in the design of a spacecraft are made in the earliest stages of its conceptual design the Pre-Phase A stages. It is in these stages that the greatest number of design alternatives is considered, and the greatest number of alternatives is rejected. The focus of Pre-Phase A conceptual development is on the evaluation and comparison of whole concepts and the larger-scale systems comprising those concepts. This comparison typically uses general Figures of Merit (FOMs) to quantify the comparative benefits of designs and alternative design features. Along with mass, performance, and cost, risk should be one of the major FOMs in evaluating design decisions during the conceptual design phases. However, risk is often given inadequate consideration in conceptual design practice. The reasons frequently given for this lack of attention to risk include: inadequate mission definition, lack of rigorous design requirements in early concept phases, lack of fidelity in risk assessment methods, and under-evaluation of risk as a viable FOM for design evaluation. In this paper, the role of risk evaluation in early conceptual design is discussed. The various requirements of a viable risk evaluation tool at the Pre-Phase A level are considered in light of the needs of a typical spacecraft design study. A technique for risk identification and evaluation is presented. The application of the risk identification and evaluation approach to the conceptual design process is discussed. Finally, a computational tool for risk profiling is presented and applied to assess the risk for an existing Pre-Phase A proposal. The resulting profile is compared to the risks identified for the proposal by other means.

The Development of Attention and Response Inhibition in Early Childhood

ERIC Educational Resources Information Center

Bartgis, Jami; Thomas, David G.; Lefler, Elizabeth K.; Hartung, Cynthia M.

2008-01-01

The goal of this study was to examine the development of attention and response inhibition from ages 5 to 7. Forty children (20 5-year-olds and 20 7-year-olds) completed four counterbalanced phases of a continuous performance task. Phase 1 was designed to measure attention without distraction, Phase 2 was designed to measure attention with…

Use of Probabilistic Engineering Methods in the Detailed Design and Development Phases of the NASA Ares Launch Vehicle

NASA Technical Reports Server (NTRS)

Fayssal, Safie; Weldon, Danny

2008-01-01

The United States National Aeronautics and Space Administration (NASA) is in the midst of a space exploration program called Constellation to send crew and cargo to the international Space Station, to the moon, and beyond. As part of the Constellation program, a new launch vehicle, Ares I, is being developed by NASA Marshall Space Flight Center. Designing a launch vehicle with high reliability and increased safety requires a significant effort in understanding design variability and design uncertainty at the various levels of the design (system, element, subsystem, component, etc.) and throughout the various design phases (conceptual, preliminary design, etc.). In a previous paper [1] we discussed a probabilistic functional failure analysis approach intended mainly to support system requirements definition, system design, and element design during the early design phases. This paper provides an overview of the application of probabilistic engineering methods to support the detailed subsystem/component design and development as part of the "Design for Reliability and Safety" approach for the new Ares I Launch Vehicle. Specifically, the paper discusses probabilistic engineering design analysis cases that had major impact on the design and manufacturing of the Space Shuttle hardware. The cases represent important lessons learned from the Space Shuttle Program and clearly demonstrate the significance of probabilistic engineering analysis in better understanding design deficiencies and identifying potential design improvement for Ares I. The paper also discusses the probabilistic functional failure analysis approach applied during the early design phases of Ares I and the forward plans for probabilistic design analysis in the detailed design and development phases.

Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual

PubMed Central

Massett, Holly A.; Mishkin, Grace; Rubinstein, Larry; Ivy, S. Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A.; Abrams, Jeffrey S.

2016-01-01

Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAPs) received for slow-accruing Phase 1 and 2 trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for Phase 1 trials and 66 for Phase 2 trials. Primary reasons cited for slow accrual were safety/toxicity (Phase 1: 48%), design/protocol concerns (Phase 1: 42%, Phase 2: 33%), and eligibility criteria (Phase 1: 41%, Phase 2: 35%). The most commonly proposed corrective actions were adding institutions (Phase 1: 43%, Phase 2: 85%) and amending the trial to change eligibility or design (Phase 1: 55%, Phase 2: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (Phase 1=48; Phase 2=46). Of these, 67% of Phase 1 and 70% of Phase 2 trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial lifecycles, but it may be more beneficial to invest in earlier accrual planning. PMID:27401246

Mars Rover/Sample Return - Phase A cost estimation

NASA Technical Reports Server (NTRS)

Stancati, Michael L.; Spadoni, Daniel J.

1990-01-01

This paper presents a preliminary cost estimate for the design and development of the Mars Rover/Sample Return (MRSR) mission. The estimate was generated using a modeling tool specifically built to provide useful cost estimates from design parameters of the type and fidelity usually available during early phases of mission design. The model approach and its application to MRSR are described.

Definition of technology development missions for early space stations. Large space structures, phase 2, midterm review

NASA Technical Reports Server (NTRS)

1984-01-01

The large space structures technology development missions to be performed on an early manned space station was studied and defined and the resources needed and the design implications to an early space station to carry out these large space structures technology development missions were determined. Emphasis is being placed on more detail in mission designs and space station resource requirements.

Test Design Optimization in CAT Early Stage with the Nominal Response Model

ERIC Educational Resources Information Center

Passos, Valeria Lima; Berger, Martijn P. F.; Tan, Frans E.

2007-01-01

The early stage of computerized adaptive testing (CAT) refers to the phase of the trait estimation during the administration of only a few items. This phase can be characterized by bias and instability of estimation. In this study, an item selection criterion is introduced in an attempt to lessen this instability: the D-optimality criterion. A…

Psychotropic and Anticonvulsant Drug Usage in Early Childhood Special Education Programs I. Phase One: A Preliminary Report: Prevalence, Attitude, Training, and Problems.

ERIC Educational Resources Information Center

Gadow, Kenneth D.

As part of a three phase study designed to survey the teachers and parents of children receiving psychotropic and anticonvulsant drugs, 208 teachers of preschool special education children on medication were mailed questionnaires. The Early Childhood Medication Questionnaire used in the survey included items relating to teacher, program, and…

QoS Composition and Decomposition Model in Uniframe

DTIC Science & Technology

2003-08-01

Architecture Tradeoff Analysis Method.………………….19 2.2 Analysis of Non-Functional Requirements at the Early Design Phase………19 2.2.1 Parmenides Framework...early design phase are discussed in the following sections. 2.2.1 Parmenides Framework In [22], an architecture-based framework is proposed for

Early Risk Reduction Phase 1 FLIR/Laser Designator Window. Revision

DTIC Science & Technology

1991-12-31

Sandwich-Type FLIR Windows," Air Force AFWAL-TR-83- 4122, Nov 1983. 4-1 Hughes Danbury Optical Systems Final Report, "ATA Window Technology Program," PRBll...Risk Reduction -- Phase I, Optical Properties Measurement Techniques of Three Wide Band Window Materials," 22 August 1991. xii I i 86PR0869 30... Optical Systems, Lexington, MA, 02173, 1 Feb 1991. 5-7 McDonnell Aircraft Company Technical Memorandum TM 256.91.0056.01, "Early Risk Reduction -- Phase

Integrating nutrition and early child-development interventions among infants and preschoolers in rural India.

PubMed

Fernandez-Rao, Sylvia; Hurley, Kristen M; Nair, Krishnapillai Madhavan; Balakrishna, Nagalla; Radhakrishna, Kankipati V; Ravinder, Punjal; Tilton, Nicholas; Harding, Kimberly B; Reinhart, Greg A; Black, Maureen M

2014-01-01

This article describes the development, design, and implementation of an integrated randomized double-masked placebo-controlled trial (Project Grow Smart) that examines how home/preschool fortification with multiple micronutrient powder (MNP) combined with an early child-development intervention affects child development, growth, and micronutrient status among infants and preschoolers in rural India. The 1-year trial has an infant phase (enrollment age: 6-12 months) and a preschool phase (enrollment age: 36-48 months). Infants are individually randomized into one of four groups: placebo, placebo plus early learning, MNP alone, and MNP plus early learning (integrated intervention), conducted through home visits. The preschool phase is a cluster-randomized trial conducted in Anganwadi centers (AWCs), government-run preschools sponsored by the Integrated Child Development System of India. AWCs are randomized into MNP or placebo, with the MNP or placebo mixed into the children's food. The evaluation examines whether the effects of the MNP intervention vary by the quality of the early learning opportunities and communication within the AWCs. Study outcomes include child development, growth, and micronutrient status. Lessons learned during the development, design, and implementation of the integrated trial can be used to guide large-scale policy and programs designed to promote the developmental, educational, and economic potential of children in developing countries. © 2013 New York Academy of Sciences.

Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.

PubMed

Massett, Holly A; Mishkin, Grace; Rubinstein, Larry; Ivy, S Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A; Abrams, Jeffrey S

2016-11-15

Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397. ©2016 American Association for Cancer Research.

Enabling Parametric Optimal Ascent Trajectory Modeling During Early Phases of Design

NASA Technical Reports Server (NTRS)

Holt, James B.; Dees, Patrick D.; Diaz, Manuel J.

2015-01-01

During the early phases of engineering design, the costs committed are high, costs incurred are low, and the design freedom is high. It is well documented that decisions made in these early design phases drive the entire design's life cycle. In a traditional paradigm, key design decisions are made when little is known about the design. As the design matures, design changes become more difficult -- in both cost and schedule -- to enact. Indeed, the current capability-based paradigm that has emerged because of the constrained economic environment calls for the infusion of knowledge acquired during later design phases into earlier design phases, i.e. bring knowledge acquired during preliminary and detailed design into pre-conceptual and conceptual design. An area of critical importance to launch vehicle design is the optimization of its ascent trajectory, as the optimal trajectory will be able to take full advantage of the launch vehicle's capability to deliver a maximum amount of payload into orbit. Hence, the optimal ascent trajectory plays an important role in the vehicle's affordability posture as the need for more economically viable access to space solutions are needed in today's constrained economic environment. The problem of ascent trajectory optimization is not a new one. There are several programs that are widely used in industry that allows trajectory analysts to, based on detailed vehicle and insertion orbit parameters, determine the optimal ascent trajectory. Yet, little information is known about the launch vehicle early in the design phase - information that is required of many different disciplines in order to successfully optimize the ascent trajectory. Thus, the current paradigm of optimizing ascent trajectories involves generating point solutions for every change in a vehicle's design parameters. This is often a very tedious, manual, and time-consuming task for the analysts. Moreover, the trajectory design space is highly non-linear and multi-modal due to the interaction of various constraints. Additionally, when these obstacles are coupled with The Program to Optimize Simulated Trajectories [1] (POST), an industry standard program to optimize ascent trajectories that is difficult to use, it requires expert trajectory analysts to effectively optimize a vehicle's ascent trajectory. As it has been pointed out, the paradigm of trajectory optimization is still a very manual one because using modern computational resources on POST is still a challenging problem. The nuances and difficulties involved in correctly utilizing, and therefore automating, the program presents a large problem. In order to address these issues, the authors will discuss a methodology that has been developed. The methodology is two-fold: first, a set of heuristics will be introduced and discussed that were captured while working with expert analysts to replicate the current state-of-the-art; secondly, leveraging the power of modern computing to evaluate multiple trajectories simultaneously, and therefore, enable the exploration of the trajectory's design space early during the pre-conceptual and conceptual phases of design. When this methodology is coupled with design of experiments in order to train surrogate models, the authors were able to visualize the trajectory design space, enabling parametric optimal ascent trajectory information to be introduced with other pre-conceptual and conceptual design tools. The potential impact of this methodology's success would be a fully automated POST evaluation suite for the purpose of conceptual and preliminary design trade studies. This will enable engineers to characterize the ascent trajectory's sensitivity to design changes in an arbitrary number of dimensions and for finding settings for trajectory specific variables, which result in optimal performance for a "dialed-in" launch vehicle design. The effort described in this paper was developed for the Advanced Concepts Office [2] at NASA Marshall Space Flight Center

Efficient runner safety assessment during early design phase and root cause analysis

NASA Astrophysics Data System (ADS)

Liang, Q. W.; Lais, S.; Gentner, C.; Braun, O.

2012-11-01

Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for other types of turbines, such as pump turbines and Pelton runners.

The Integrated Airframe/Propulsion Control System Architecture program (IAPSA)

NASA Technical Reports Server (NTRS)

Palumbo, Daniel L.; Cohen, Gerald C.; Meissner, Charles W.

1990-01-01

The Integrated Airframe/Propulsion Control System Architecture program (IAPSA) is a two-phase program which was initiated by NASA in the early 80s. The first phase, IAPSA 1, studied different architectural approaches to the problem of integrating engine control systems with airframe control systems in an advanced tactical fighter. One of the conclusions of IAPSA 1 was that the technology to construct a suitable system was available, yet the ability to create these complex computer architectures has outpaced the ability to analyze the resulting system's performance. With this in mind, the second phase of IAPSA approached the same problem with the added constraint that the system be designed for validation. The intent of the design for validation requirement is that validation requirements should be shown to be achievable early in the design process. IAPSA 2 has demonstrated that despite diligent efforts, integrated systems can retain characteristics which are difficult to model and, therefore, difficult to validate.

Results from conceptual design study of potential early commercial MHD/steam power plants

NASA Technical Reports Server (NTRS)

Hals, F.; Kessler, R.; Swallom, D.; Westra, L.; Zar, J.; Morgan, W.; Bozzuto, C.

1981-01-01

This paper presents conceptual design information for a potential early MHD power plant developed in the second phase of a joint study of such plants. Conceptual designs of plant components and equipment with performance, operational characteristics and costs are reported on. Plant economics and overall performance including full and part load operation are reviewed. Environmental aspects and the methods incorporated in plant design for emission control of sulfur and nitrogen oxides are reviewed. Results from reliability/availability analysis conducted are also included.

Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

PubMed Central

2014-01-01

This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

A Bayesian-frequentist two-stage single-arm phase II clinical trial design.

PubMed

Dong, Gaohong; Shih, Weichung Joe; Moore, Dirk; Quan, Hui; Marcella, Stephen

2012-08-30

It is well-known that both frequentist and Bayesian clinical trial designs have their own advantages and disadvantages. To have better properties inherited from these two types of designs, we developed a Bayesian-frequentist two-stage single-arm phase II clinical trial design. This design allows both early acceptance and rejection of the null hypothesis ( H(0) ). The measures (for example probability of trial early termination, expected sample size, etc.) of the design properties under both frequentist and Bayesian settings are derived. Moreover, under the Bayesian setting, the upper and lower boundaries are determined with predictive probability of trial success outcome. Given a beta prior and a sample size for stage I, based on the marginal distribution of the responses at stage I, we derived Bayesian Type I and Type II error rates. By controlling both frequentist and Bayesian error rates, the Bayesian-frequentist two-stage design has special features compared with other two-stage designs. Copyright © 2012 John Wiley & Sons, Ltd.

Design for Safety - The Ares Launch Vehicles Paradigm Change

NASA Technical Reports Server (NTRS)

Safie, Fayssal M.; Maggio, Gaspare

2010-01-01

The lessons learned from the S&MA early involvement in the Ares I launch vehicle design phases proved that performing an in-line function jointly with engineering is critical for S&MA to have an effective role in supporting the system, element, and component design. These lessons learned were used to effectively support the Ares V conceptual design phase and planning for post conceptual design phases. The Top level Conceptual LOM assessment for Ares V performed by the S&MA community jointly with the engineering Advanced Concept Office (ACO) was influential in the final selection of the Ares V system configuration. Post conceptual phase, extensive reliability effort should be planned to support future Heavy Lift Launch Vehicles (HLLV) design. In-depth reliability analysis involving the design, manufacturing, and system engineering communities is critical to understand design and process uncertainties and system integrated failures.

Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

PubMed

Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

2014-05-01

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

Safety Guided Design Based on Stamp/STPA for Manned Vehicle in Concept Design Phase

NASA Astrophysics Data System (ADS)

Ujiie, Ryo; Katahira, Masafumi; Miyamoto, Yuko; Umeda, Hiroki; Leveson, Nancy; Hoshino, Nobuyuki

2013-09-01

In manned vehicles, such as the Soyuz and the Space Shuttle, the crew and computer system cooperate to succeed in returning to the earth. While computers increase the functionality of system, they also increase the complexity of the interaction between the controllers (human and computer) and the target dynamics. In some cases, the complexity can produce a serious accident. To prevent such losses, traditional hazard analysis such as FTA has been applied to system development, however it can be used after creating a detailed system because it focuses on detailed component failures. As a result, it's more difficult to eliminate hazard cause early in the process when it is most feasible.STAMP/STPA is a new hazard analysis that can be applied from the early development phase, with the analysis being refined as more detailed decisions are made. In essence, the analysis and design decisions are intertwined and go hand-in-hand. We have applied STAMP/STPA to a concept design of a new JAXA manned vehicle and tried safety guided design of the vehicle. As a result of this trial, it has been shown that STAMP/STPA can be accepted easily by system engineers and the design has been made more sophisticated from a safety viewpoint. The result also shows that the consequences of human errors on system safety can be analysed in the early development phase and the system designed to prevent them. Finally, the paper will discuss an effective way to harmonize this safety guided design approach with system engineering process based on the result of this experience in this project.

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain.

PubMed

Whitehead, John; Valdés-Márquez, Elsa; Lissmats, Agneta

2009-01-01

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to be stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase II and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail. Copyright 2008 John Wiley & Sons, Ltd.

Gathering Design References from Nature

ERIC Educational Resources Information Center

Debs, Luciana; Kelley, Todd

2015-01-01

Teaching design to middle and high school students can be challenging. One of the first procedures in teaching design is to help students gather information that will be useful in the design phase. An early stage of engineering design as described by Lewis (2005), calls for the designer to establish the state of the art of the problem. During this…

Design Tools for Cost-Effective Implementation of Planetary Protection Requirements

NASA Technical Reports Server (NTRS)

Hamlin, Louise; Belz, Andrea; Evans, Michael; Kastner, Jason; Satter, Celeste; Spry, Andy

2006-01-01

Since the Viking missions to Mars in the 1970s, accounting for the costs associated with planetary protection implementation has not been done systematically during early project formulation phases, leading to unanticipated costs during subsequent implementation phases of flight projects. The simultaneous development of more stringent planetary protection requirements, resulting from new knowledge about the limits of life on Earth, together with current plans to conduct life-detection experiments on a number of different solar system target bodies motivates a systematic approach to integrating planetary protection requirements and mission design. A current development effort at NASA's Jet Propulsion Laboratory is aimed at integrating planetary protection requirements more fully into the early phases of mission architecture formulation and at developing tools to more rigorously predict associated cost and schedule impacts of architecture options chosen to meet planetary protection requirements.

A Risk Management Framework to Characterize Black Swan Risks: A Case Study of Lightning Effects on Insensitive High Explosives

NASA Astrophysics Data System (ADS)

Sanders, Gary A.

Effective and efficient risk management processes include the use of high fidelity modeling and simulation during the concept exploration phase as part of the technology and risk assessment activities, with testing and evaluation tasks occurring in later design development phases. However, some safety requirements and design architectures may be dominated by the low probability/high consequence "Black Swan" vulnerabilities that require very early testing to characterize and efficiently mitigate. Failure to address these unique risks has led to catastrophic systems failures including the space shuttle Challenger, Deepwater Horizon, Fukushima nuclear reactor, and Katrina dike failures. Discovering and addressing these risks later in the design and development process can be very costly or even lead to project cancellation. This paper examines the need for risk management process adoption of early hazard phenomenology testing to inform the technical risk assessment, requirements definition and conceptual design. A case study of the lightning design vulnerability of the insensitive high explosives being used in construction, mining, demolition, and defense industries will be presented to examine the impact of this vulnerability testing during the concept exploration phase of the design effort. While these insensitive high explosives are far less sensitive to accidental initiation by fire, impact, friction or even electrical stimuli, their full range of sensitivities have not been characterized and ensuring safe engineering design and operations during events such as lightning storms requires vulnerability testing during the risk assessment phase.

Goals and Strategies for the Human Lunar Reference Architecture

NASA Technical Reports Server (NTRS)

Seaman, Calvin H.

2010-01-01

The presentation examines common goals for human lunar exploration and strategic guidance. Three major sections include illustrative example goals, introduction to the GPoD campaign, and GPoD overview. The first section includes slides about strategic view of partnerships, the moon as a stepping stone and a uniquely preserved record, human-robotic partnership, innovative engagement, strategic considerations, and evaluation of campaigns against common goals. The second section examines campaigns considered, the philosophy of GPoD, GPoD campaign phase definitions, and GPoD design decision points. The third section examines lunar exploration capabilities, extended stay-relocation exploration mode, notional campaign destinations for GPoD, early robotics phase, development of the GPoD early robotics phase, polar exploration/system validation phase, polar relocatability phase, non-polar relocatability phase, long duration phase, and return to evaluation of campaigns.

Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design.

PubMed

Levin, Bruce; Thompson, John L P; Chakraborty, Bibhas; Levy, Gilberto; MacArthur, Robert; Haley, E Clarke

2011-08-01

TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs. In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05. Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis. Design complexity and evolving regulatory requirements lengthened the review process. (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols for futility stopping may not be followed may be allayed by submitting interim analysis results to them as these analyses occur.

Simplified spacecraft vulnerability assessments at component level in early design phase at the European Space Agency's Concurrent Design Facility

NASA Astrophysics Data System (ADS)

Kempf, Scott; Schäfer, Frank K.; Cardone, Tiziana; Ferreira, Ivo; Gerené, Sam; Destefanis, Roberto; Grassi, Lilith

2016-12-01

During recent years, the state-of-the-art risk assessment of the threat posed to spacecraft by micrometeoroids and space debris has been expanded to the analysis of failure modes of internal spacecraft components. This method can now be used to perform risk analyses for satellites to assess various failure levels - from failure of specific sub-systems to catastrophic break-up. This new assessment methodology is based on triple-wall ballistic limit equations (BLEs), specifically the Schäfer-Ryan-Lambert (SRL) BLE, which is applicable for describing failure threshold levels for satellite components following a hypervelocity impact. The methodology is implemented in the form of the software tool Particle Impact Risk and vulnerability Analysis Tool (PIRAT). During a recent European Space Agency (ESA) funded study, the PIRAT functionality was expanded in order to provide an interface to ESA's Concurrent Design Facility (CDF). The additions include a geometry importer and an OCDT (Open Concurrent Design Tool) interface. The new interface provides both the expanded geometrical flexibility, which is provided by external computer aided design (CAD) modelling, and an ease of import of existing data without the need for extensive preparation of the model. The reduced effort required to perform vulnerability analyses makes it feasible for application during early design phase, at which point modifications to satellite design can be undertaken with relatively little extra effort. The integration of PIRAT in the CDF represents the first time that vulnerability analyses can be performed in-session in ESA's CDF and the first time that comprehensive vulnerability studies can be applied cost-effectively in early design phase in general.

Developing an inventor support service which performs early stage market and manufacturing evaluations. Final report

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

Not Available

1991-10-01

American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was tomore » establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.« less

Developing an inventor support service which performs early stage market and manufacturing evaluations. [Final Report

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

Not Available

1991-10-01

American businesses are learning the difficult high cost lesson of ignoring production and market factors (producibility, unit product cost (UPC), marketability, etc) during the engineering design phase of product development. Studies have shown that the Japanese spend three times as long as Americans in the design feasibility and decision process of new product introductions and one third the amount of time in the implementation of those products. There is a 20 to 1 cost benefit on effort applied in the design phase versus the production phase of the product life cycle. The number one goal of this project was tomore » establish an organization that has, as one of its purposes, the providing of services responsive to the needs of independent inventors. The number two goal was to demonstrate the value of providing marketing and manufacturing counsel at an early stage in the product development process. The first study goal was met by providing the materials and information necessary to establish an evaluation team and an organization to handle such evaluations. The second study goal was met by demonstrating the impact of early market analysis and manufacturing considerations on product design and therefore on the description of the invention for four different inventions. These inventions were selected at various stages of development. Regardless of stage of development, the marketing and manufacturing reviews resulted in significant changes in design and/or market positioning.« less

An NAFP Project: Use of Object Oriented Methodologies and Design Patterns to Refactor Software Design

NASA Technical Reports Server (NTRS)

Shaykhian, Gholam Ali; Baggs, Rhoda

2007-01-01

In the early problem-solution era of software programming, functional decompositions were mainly used to design and implement software solutions. In functional decompositions, functions and data are introduced as two separate entities during the design phase, and are followed as such in the implementation phase. Functional decompositions make use of refactoring through optimizing the algorithms, grouping similar functionalities into common reusable functions, and using abstract representations of data where possible; all these are done during the implementation phase. This paper advocates the usage of object-oriented methodologies and design patterns as the centerpieces of refactoring software solutions. Refactoring software is a method of changing software design while explicitly preserving its external functionalities. The combined usage of object-oriented methodologies and design patterns to refactor should also benefit the overall software life cycle cost with improved software.

Optimization of Primary Drying in Lyophilization during Early Phase Drug Development using a Definitive Screening Design with Formulation and Process Factors.

PubMed

Goldman, Johnathan M; More, Haresh T; Yee, Olga; Borgeson, Elizabeth; Remy, Brenda; Rowe, Jasmine; Sadineni, Vikram

2018-06-08

Development of optimal drug product lyophilization cycles is typically accomplished via multiple engineering runs to determine appropriate process parameters. These runs require significant time and product investments, which are especially costly during early phase development when the drug product formulation and lyophilization process are often defined simultaneously. Even small changes in the formulation may require a new set of engineering runs to define lyophilization process parameters. In order to overcome these development difficulties, an eight factor definitive screening design (DSD), including both formulation and process parameters, was executed on a fully human monoclonal antibody (mAb) drug product. The DSD enables evaluation of several interdependent factors to define critical parameters that affect primary drying time and product temperature. From these parameters, a lyophilization development model is defined where near optimal process parameters can be derived for many different drug product formulations. This concept is demonstrated on a mAb drug product where statistically predicted cycle responses agree well with those measured experimentally. This design of experiments (DoE) approach for early phase lyophilization cycle development offers a workflow that significantly decreases the development time of clinically and potentially commercially viable lyophilization cycles for a platform formulation that still has variable range of compositions. Copyright © 2018. Published by Elsevier Inc.

Army-NASA aircrew/aircraft integration program. Phase 5: A3I Man-Machine Integration Design and Analysis System (MIDAS) software concept document

NASA Technical Reports Server (NTRS)

Banda, Carolyn; Bushnell, David; Chen, Scott; Chiu, Alex; Neukom, Christian; Nishimura, Sayuri; Prevost, Michael; Shankar, Renuka; Staveland, Lowell; Smith, Greg

1992-01-01

This is the Software Concept Document for the Man-machine Integration Design and Analysis System (MIDAS) being developed as part of Phase V of the Army-NASA Aircrew/Aircraft Integration (A3I) Progam. The approach taken in this program since its inception in 1984 is that of incremental development with clearly defined phases. Phase 1 began in 1984 and subsequent phases have progressed at approximately 10-16 month intervals. Each phase of development consists of planning, setting requirements, preliminary design, detailed design, implementation, testing, demonstration and documentation. Phase 5 began with an off-site planning meeting in November, 1990. It is expected that Phase 5 development will be complete and ready for demonstration to invited visitors from industry, government and academia in May, 1992. This document, produced during the preliminary design period of Phase 5, is intended to record the top level design concept for MIDAS as it is currently conceived. This document has two main objectives: (1) to inform interested readers of the goals of the MIDAS Phase 5 development period, and (2) to serve as the initial version of the MIDAS design document which will be continuously updated as the design evolves. Since this document is written fairly early in the design period, many design issues still remain unresolved. Some of the unresolved issues are mentioned later in this document in the sections on specific components. Readers are cautioned that this is not a final design document and that, as the design of MIDAS matures, some of the design ideas recorded in this document will change. The final design will be documented in a detailed design document published after the demonstrations.

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

Rehder, J.B.

The project focuses on an appropriate technology for small-scale hydro power: floating waterwheels and turbines. For background, relic and existing systems such as early floating mills, traditional Amish waterwheels, and micro-hydro systems are examined. In the design phase of the project, new designs for Floating Hydro Power Systems include: an analysis of floatation materials and systems; a floating undershot waterwheel design; a floating cylinder (fiberglass storage tank) design; a submerged tube design; and a design for a floating platform with submerged propellers. Finally, in the applications phase, stream flow data from East Tennessee streams are used in a discussion ofmore » the potential applications of floating hydro power systems in small streams.« less

Evolutionary Design of a Phased Array Antenna Element

NASA Technical Reports Server (NTRS)

Globus, Al; Linden, Derek; Lohn, Jason

2006-01-01

We present an evolved S-band phased array antenna element design that meets the requirements of NASA's TDRS-C communications satellite scheduled for launch early next decade. The original specification called for two types of elements, one for receive only and one for transmit/receive. We were able to evolve a single element design that meets both specifications thereby simplifying the antenna and reducing testing and integration costs. The highest performance antenna found using a genetic algorithm and stochastic hill-climbing has been fabricated and tested. Laboratory results are largely consistent with simulation. Researchers have been investigating evolutionary antenna design and optimization since the early 1990s, and the field has grown in recent years its computer speed has increased and electromagnetic simulators have improved. Many antenna types have been investigated, including wire antennas, antenna arrays and quadrifilar helical antennas. In particular, our laboratory evolved a wire antenna design for NASA's Space Technology 5 (ST5) spacecraft. This antenna has been fabricated, tested, and is scheduled for launch on the three spacecraft in 2006.

A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

PubMed

Vormoor, B; Veal, G J; Griffin, M J; Boddy, A V; Irving, J; Minto, L; Case, M; Banerji, U; Swales, K E; Tall, J R; Moore, A S; Toguchi, M; Acton, G; Dyer, K; Schwab, C; Harrison, C J; Grainger, J D; Lancaster, D; Kearns, P; Hargrave, D; Vormoor, J

2017-06-01

Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies. © 2016 Wiley Periodicals, Inc.

Phased Array Probe Optimization for the Inspection of Titanium Billets

NASA Astrophysics Data System (ADS)

Rasselkorde, E.; Cooper, I.; Wallace, P.; Lupien, V.

2010-02-01

The manufacturing process of titanium billets can produce multiple sub-surface defects that are particularly difficult to detect during the early stages of production. Failure to detect these defects can lead to subsequent in-service failure. A new and novel automated quality control system is being developed for the inspection of titanium billets destined for use in aerospace applications. The sensors will be deployed by an automated system to minimise the use of manual inspections, which should improve the quality and reliability of these critical inspections early on in the manufacturing process. This paper presents the first part of the work, which is the design and the simulation of the phased array ultrasonic inspection of the billets. A series of phased array transducers were designed to optimise the ultrasonic inspection of a ten inch diameter billet made from Titanium 6Al-4V. A comparison was performed between different probes including a 2D annular sectorial array.

NCI–RTOG Translational Program Strategic Guidelines for the Early-Stage Development of Radiosensitizers

PubMed Central

2013-01-01

The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry’s diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trials—acute toxicity and maximum-tolerated dose—are of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II “screening” trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation. PMID:23231975

A two-stage patient enrichment adaptive design in phase II oncology trials.

PubMed

Song, James X

2014-01-01

Illustrated is the use of a patient enrichment adaptive design in a randomized phase II trial which allows the evaluation of treatment benefits by the biomarker expression level and makes interim adjustment according to the pre-specified rules. The design was applied to an actual phase II metastatic hepatocellular carcinoma (HCC) trial in which progression-free survival (PFS) in two biomarker-defined populations is evaluated at both interim and final analyses. As an extension, a short-term biomarker is used to predict the long-term PFS in a Bayesian model in order to improve the precision of hazard ratio (HR) estimate at the interim analysis. The characteristics of the extended design are examined in a number of scenarios via simulations. The recommended adaptive design is shown to be useful in a phase II setting. When a short-term maker which correlates with the long-term PFS is available, the design can be applied in smaller early phase trials in which PFS requires longer follow-up. In summary, the adaptive design offers flexibility in randomized phase II patient enrichment trials and should be considered in an overall personalized healthcare (PHC) strategy. Copyright © 2013 Elsevier Inc. All rights reserved.

Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer

NASA Astrophysics Data System (ADS)

Fitzpatrick, C. R. M.; Gordon, G. S. D.; Sawyer, T. W.; Wilkinson, T. D.; Bohndiek, S. E.

2018-02-01

Esophageal cancer has a 5-year survival rate below 20%, but can be curatively resected if it is detected early. At present, poor contrast for early lesions in white light imaging leads to a high miss rate in standard-of- care endoscopic surveillance. Early lesions in the esophagus, referred to as dysplasia, are characterized by an abundance of abnormal cells with enlarged nuclei. This tissue has a different refractive index profile to healthy tissue, which results in different light scattering properties and provides a source of endogenous contrast that can be exploited for advanced endoscopic imaging. For example, point measurements of such contrast can be made with scattering spectroscopy, while optical coherence tomography generates volumetric data. However, both require specialist interpretation for diagnostic decision making. We propose combining wide-field phase imaging with existing white light endoscopy in order to provide enhanced contrast for dysplasia and early-stage cancer in an image format that is familiar to endoscopists. Wide-field phase imaging in endoscopy can be achieved using coherent illumination combined with phase retrieval algorithms. Here, we present the design and simulation of a benchtop phase imaging system that is compatible with capsule endoscopy. We have undertaken preliminary optical modelling of the phase imaging setup, including aberration correction simulations and an investigation into distinguishing between different tissue phantom scattering coefficients. As our approach is based on phase retrieval rather than interferometry, it is feasible to realize a device with low-cost components for future clinical implementation.

Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials.

PubMed

London, Wendy B; Bagatell, Rochelle; Weigel, Brenda J; Fox, Elizabeth; Guo, Dongjing; Van Ryn, Collin; Naranjo, Arlene; Park, Julie R

2017-12-15

Early-phase trials in patients with recurrent neuroblastoma historically used an objective "response" of measureable disease (Response Evaluation Criteria In Solid Tumors [RECIST], without bone/bone marrow assessment) to select agents for further study. Historical cohorts may be small and potentially biased; to the authors' knowledge, disease recurrence studies from international registries are outdated. Using a large recent cohort of patients with recurrent/refractory neuroblastoma from Children's Oncology Group (COG) modern-era early-phase trials, the authors determined outcome and quantified parameters for designing future studies. The first early-phase COG trial enrollment (sequential) of 383 distinct patients with recurrent/refractory neuroblastoma on 23 phase 1, 3 phase 1/2, and 9 phase 2 trials (August 2002 to January 2014) was analyzed for progression-free survival (PFS), overall survival (OS), and time to disease progression (TTP). Planned frontline therapy for patients with high-risk neuroblastoma included hematopoietic stem cell transplantation (approximately two-thirds of patients underwent ≥1 hematopoietic stem cell transplantation); 13.2% of patients received dinutuximab. From the time of the patient's first early-phase trial enrollment (383 patients), the 1-year and 4-year PFS rates ( ± standard error) were 21% ± 2% and 6% ± 1%, respectively, whereas the 1-year and 4-year OS rates were 57% ± 3% and 20% ± 2%, respectively. The median TTP was 58 days (interquartile range, 31-183 days [350 patients]); the median follow-up was 25.3 months (33 patients were found to be without disease recurrence/progression). The median time from diagnosis to first disease recurrence/progression was 18.7 months (range, 1.4-64.8 months) (176 patients). MYCN amplification and 11q loss of heterozygosity were prognostic of worse PFS and OS (P = .003 and P<.0001, respectively, and P = .02 and P = .03, respectively) after early-phase trial enrollment. This recent COG cohort of patients with recurrent/refractory neuroblastoma is inclusive and representative. To the authors' knowledge, the current study is the first meta-analysis of PFS, TTP, and OS within the context of modern therapy. These results will inform the design of future phase 2 studies by providing a) historical context during the search for more effective agents; and, b) factors prognostic of PFS and OS after disease recurrence to stratify randomization. Cancer 2017;123:4914-23. © 2017 American Cancer Society. © 2017 American Cancer Society.

Learning to Be: The Modelling of Art and Design Practice in University Art and Design Teaching

ERIC Educational Resources Information Center

Budge, Kylie

2016-01-01

Learning to be an artist or designer is a complex process of becoming. Much of the early phase of "learning to be" occurs during the time emerging artists and designers are students in university art/design programmes, both undergraduate and postgraduate. Recent research reveals that a critical role in assisting students in their…

Hierarchical Thinking: A Cognitive Tool for Guiding Coherent Decision Making in Design Problem Solving

ERIC Educational Resources Information Center

Haupt, Grietjie

2018-01-01

This paper builds on two concepts, the first of which is the extended information processing model of expert design cognition. This proposes twelve internal psychological characteristics interacting with the external world of expert designers during the early phases of the design process. Here, I explore one of the characteristics, hierarchical…

The aerodynamic challenges of the design and development of the space shuttle orbiter

NASA Technical Reports Server (NTRS)

Young, J. C.; Underwood, J. M.; Hillje, E. R.; Whitnah, A. M.; Romere, P. O.; Gamble, J. D.; Roberts, B. B.; Ware, G. M.; Scallion, W. I.; Spencer, B., Jr.

1985-01-01

The major aerodynamic design challenge at the beginning of the United States Space Transportation System (STS) research and development phase was to design a vehicle that would fly as a spacecraft during early entry and as an aircraft during the final phase of entry. The design was further complicated because the envisioned vehicle was statically unstable during a portion of the aircraft mode of operation. The second challenge was the development of preflight aerodynamic predictions with an accuracy consistent with conducting a manned flight on the initial orbital flight. A brief history of the early contractual studies is presented highlighting the technical results and management decisions influencing the aerodynamic challenges. The configuration evolution and the development of preflight aerodynamic predictions will be reviewed. The results from the first four test flights shows excellent agreement with the preflight aerodynamic predictions over the majority of the flight regimes. The only regimes showing significant disagreement is confined primarily to early entry, where prediction of the basic vehicle trim and the influence of the reaction control system jets on the flow field were found to be deficient. Postflight results are analyzed to explain these prediction deficiencies.

Toward a clinically useful method of predicting early breast-feeding attrition.

PubMed

Lewallen, Lynne Porter; Dick, Margaret J; Wall, Yolanda; Zickefoose, Kimberly Taylor; Hannah, Susan Hensley; Flowers, Janet; Powell, Wanda

2006-08-01

The overall purpose of this study was to revise and test an instrument to identify, during the early postpartum period, women at risk for early breast-feeding attrition. This study was completed in two phases: the first phase tested a revision of the Breast-Feeding Attrition Prediction Tool (BAPT); the second, a new instrument, the Breast-Feeding Attitude Scale (BrAS), which was adapted from the BAPT. The two phases of this study involved 415 pregnant and postpartum women. Women answered questions either by phone (pregnant women) or in their hospital rooms after delivery (postpartum women). Data were analyzed using t tests and reliability analysis. The BAPT did not predict early breast-feeding attrition; however, the BrAS did differentiate between the attitudes of breast-feeding women and those of formula-feeding women and had adequate reliability. Women at risk for early breast-feeding attrition should be identified early so nursing interventions can be directed toward preventing early unintended weaning. Although the BrAS did not reliably identify women at risk in this sample, it did highlight important differences between breast-feeding and formula-feeding women that can be used in designing preconceptional or prenatal educational assessments and interventions.

Central region of SKKUCY-9 compact cyclotron

NASA Astrophysics Data System (ADS)

Jung, S. Y.; Kim, H. W.; Ghergherehchi, M.; Park, J. K.; Chai, J. S.; Kim, S. H.

2014-04-01

The development of a 9 MeV compact cyclotron for the production of radioisotopes for medical applications has been recently completed. The machine accelerates negative hydrogen ions generated from an internal PIG (Penning Ion Gauge) ion source following spiral orbits. Some of the structures designed for early beam acceleration, including a pair of center poles providing ions a circular direction, the head of the ion source, and the electrodes, are located in the center of the cyclotron. In this paper we discuss and evaluate the design of the central region that pulls the ions from the chimney of the ion source and directs them into the equilibrium orbit. The magnetic field produced by the center poles was analyzed using the magnetic solver in OPERA-3D TOSCA, and the phase error and ion equilibrium orbit, which is dependent on the kinetic energy within the designed field, were calculated using CYCLONE v8.4. The electric field produced in the acceleration gap was designed using an electrostatic solver. Then, the single beam trajectory was calculated by our own Cyclotron Beam Dynamics (CBD) code. The early orbits, vertical oscillation, acceptable RF phase and the energy gain during the early turns was evaluated. Final goal was to design the central region by the iterative optimization process and verify it with 1 MeV beam experiment.

Flight Test of the F/A-18 Active Aeroelastic Wing Airplane

NASA Technical Reports Server (NTRS)

Clarke, Robert; Allen, Michael J.; Dibley, Ryan P.; Gera, Joseph; Hodgkinson, John

2005-01-01

Successful flight-testing of the Active Aeroelastic Wing airplane was completed in March 2005. This program, which started in 1996, was a joint activity sponsored by NASA, Air Force Research Laboratory, and industry contractors. The test program contained two flight test phases conducted in early 2003 and early 2005. During the first phase of flight test, aerodynamic models and load models of the wing control surfaces and wing structure were developed. Design teams built new research control laws for the Active Aeroelastic Wing airplane using these flight-validated models; and throughout the final phase of flight test, these new control laws were demonstrated. The control laws were designed to optimize strategies for moving the wing control surfaces to maximize roll rates in the transonic and supersonic flight regimes. Control surface hinge moments and wing loads were constrained to remain within hydraulic and load limits. This paper describes briefly the flight control system architecture as well as the design approach used by Active Aeroelastic Wing project engineers to develop flight control system gains. Additionally, this paper presents flight test techniques and comparison between flight test results and predictions.

A Status Report on the Parachute Development for NASA's Next Manned Spacecraft

NASA Technical Reports Server (NTRS)

Sinclair, Robert

2008-01-01

NASA has determined that the parachute portion of the Landing System for the Crew Exploration Vehicle (CEV) will be Government Furnished Equipment (GFE). The Earth Landing System has been designated CEV Parachute Assembly System (CPAS). Thus a program team was developed consisting of NASA Johnson Space Center (JSC) and Jacobs Engineering through their Engineering and Science Contract Group (ESCG). Following a rigorous competitive phase, Airborne Systems North America was selected to provide the parachute design, testing and manufacturing role to support this team. The development program has begun with some early flight testing of a Generation 1 parachute system. Future testing will continue to refine the design and complete a qualification phase prior to manned flight of the spacecraft. The program team will also support early spacecraft system testing, including a Pad Abort Flight Test in the Fall of 2008

Rethinking the architectural design concept in the digital culture (in architecture's practice perspective)

NASA Astrophysics Data System (ADS)

Prawata, Albertus Galih

2017-11-01

The architectural design stages in architectural practices or in architectural design studio consist of many aspects. One of them is during the early phases of the design process, where the architects or designers try to interpret the project brief into the design concept. This paper is a report of the procedure of digital tools in the early design process in an architectural practice in Jakarta. It targets principally the use of BIM and digital modeling to generate information and transform them into conceptual forms, which is not very common in Indonesian architectural practices. Traditionally, the project brief is transformed into conceptual forms by using sketches, drawings, and physical model. The new method using digital tools shows that it is possible to do the same thing during the initial stage of the design process to create early architectural design forms. Architect's traditional tools and methods begin to be replaced effectively by digital tools, which would drive bigger opportunities for innovation.

Space Station - An integrated approach to operational logistics support

NASA Technical Reports Server (NTRS)

Hosmer, G. J.

1986-01-01

Development of an efficient and cost effective operational logistics system for the Space Station will require logistics planning early in the program's design and development phase. This paper will focus on Integrated Logistics Support (ILS) Program techniques and their application to the Space Station program design, production and deployment phases to assure the development of an effective and cost efficient operational logistics system. The paper will provide the methodology and time-phased programmatic steps required to establish a Space Station ILS Program that will provide an operational logistics system based on planned Space Station program logistics support.

Bid opening report : Federal-aid highway construction contracts : first six months 2001

DOT National Transportation Integrated Search

2000-04-01

This research update provides general human factors design information relevant to the early phases of in-vehicle icon development and design. It reflects a subset of the results to date of a Federal Highway Administration project to develop a set of...

Adaptive Façade: Variant-Finding using Shape Grammar

NASA Astrophysics Data System (ADS)

Tomasowa, Riva; Utama Sjarifudin, Firza

2017-12-01

Modular façade construction has never been better since the birth of computer-aided manufacturing which bridges the modeling phase into the manufacturing phase for escalating the mass production. This comes to a result that the identity of a product or a building façade will commonly generate in the same way that the initial design was intended to. Rectifying the early model will then greatly impact the process later. The aim of this paper is to propose a way to solve these two challenges, without risking the manufacturing process, but more to explore the potential designs. Shape grammar is used to conceive more designs in the early stage, derived from the initial product - the modular adaptive façade system. The derivations are then tested through simulation to state the efficacy of the models. We find that the workflow somehow contributes to the better design and engineering process as well as the solution allows diversification in the façade expressions.

Sustainability in the Architectural Design Studio: A Case Study of Designing On-Campus Academic Staff Housing in Konya and Izmir, Turkey

ERIC Educational Resources Information Center

Bala, Havva Alkan

2010-01-01

It is important to engender a "sustainable" architectural consciousness in the students who will be the next generation architects. In architectural education, design decisions taken during the early phases of the design process play an important role in ensuring concern for the sustainability issue. But, in general, all discussions…

The Langley Research Center CSI phase-0 evolutionary model testbed-design and experimental results

NASA Technical Reports Server (NTRS)

Belvin, W. K.; Horta, Lucas G.; Elliott, K. B.

1991-01-01

A testbed for the development of Controls Structures Interaction (CSI) technology is described. The design philosophy, capabilities, and early experimental results are presented to introduce some of the ongoing CSI research at NASA-Langley. The testbed, referred to as the Phase 0 version of the CSI Evolutionary model (CEM), is the first stage of model complexity designed to show the benefits of CSI technology and to identify weaknesses in current capabilities. Early closed loop test results have shown non-model based controllers can provide an order of magnitude increase in damping in the first few flexible vibration modes. Model based controllers for higher performance will need to be robust to model uncertainty as verified by System ID tests. Data are presented that show finite element model predictions of frequency differ from those obtained from tests. Plans are also presented for evolution of the CEM to study integrated controller and structure design as well as multiple payload dynamics.

CCCT - Investigational Drug Steering Committee

Cancer.gov

The Investigational Drug Steering Committee (IDSC) collaborates with NCI in the design and prioritization of early phase drug development trials conducted by the Experimental Therapeutics Clinical Trials Network (ETCTN).

The Third Year of the Brookline Early Education Project.

ERIC Educational Resources Information Center

Pierson, Donald E.

This is the third progress report of the Brookline Early Education Project (BEEP) which is a program designed to provide diagnostic and educational services to the family through their child's preschool years. This document provides information on (1) the BEEP center, (2) playgroups: transition phase of the education program, (3) dental screening…

Guidelines for the Clinical Evaluation of Psychoactive Drugs in Infants and Children.

ERIC Educational Resources Information Center

Food and Drug Administration (DHEW), Washington, DC.

These guidelines are intended to help those who design and conduct investigations of psychopharmacologic agents in children. A progression of studies in four phases is advocated. First, early short term studies should establish single and multiple dose safety baselines. Second, early pilot efficacy studies may be initiated jointly with longer…

Multi-Attribute Tradespace Exploration in Space System Design

NASA Astrophysics Data System (ADS)

Ross, A. M.; Hastings, D. E.

2002-01-01

The complexity inherent in space systems necessarily requires intense expenditures of resources both human and monetary. The high level of ambiguity present in the early design phases of these systems causes long, highly iterative, and costly design cycles. This paper looks at incorporating decision theory methods into the early design processes to streamline communication of wants and needs among stakeholders and between levels of design. Communication channeled through formal utility interviews and analysis enables engineers to better understand the key drivers for the system and allows a more thorough exploration of the design tradespace. Multi-Attribute Tradespace Exploration (MATE), an evolving process incorporating decision theory into model and simulation- based design, has been applied to several space system case studies at MIT. Preliminary results indicate that this process can improve the quality of communication to more quickly resolve project ambiguity, and enable the engineer to discover better value designs for multiple stakeholders. MATE is also being integrated into a concurrent design environment to facilitate the transfer knowledge of important drivers into higher fidelity design phases. Formal utility theory provides a mechanism to bridge the language barrier between experts of different backgrounds and differing needs (e.g. scientists, engineers, managers, etc). MATE with concurrent design couples decision makers more closely to the design, and most importantly, maintains their presence between formal reviews.

Shuttle free-flying teleoperator system experiment definition. Volume 3: program development requirements

NASA Technical Reports Server (NTRS)

1972-01-01

The planning data are presented for subsequent phases of free-flying teleoperator program (FFTO) and includes costs, schedules and supporting research and technology activities required to implement the free-flying teleoperator system and associated flight equipment. The purpose of the data presented is to provide NASA with the information needed to continue development of the FFTO and integrate it into the space shuttle program. The planning data describes three major program phases consisting of activities and events scheduled to effect integrated design, development, fabrication and operation of an FFTO system. Phase A, Concept Generation, represents a study effort directed toward generating and evaluating a number of feasible FFTO experiment system concepts. Phase B, Definition, will include preliminary design and supporting analysis of the FFTO, the shuttle based equipment and ground support equipment. Phase C/D, Design, Development and Operations will include detail design of the operational FFTO, its integration into the space shuttle, hardware fabrication and testing, delivery of flight hardware and support of flight operations. Emphasis is placed on the planning for Phases A and B since these studies will be implemented early in the development cycle. Phase C/D planning is more general and subject to refinement during the definition phase.

Learning from Experts: Fostering Extended Thinking in the Early Phases of the Design Process

ERIC Educational Resources Information Center

Haupt, Grietjie

2015-01-01

Empirical evidence on the way in which expert designers from different domains cognitively connect their internal processes with external resources is presented in the context of an extended cognition model. The article focuses briefly on the main trends in the extended design cognition theory and in particular on recent trends in information…

Project 8, Phase III Design: Placing an eV-Scale Limit on the Neutrino Mass using Cyclotron Radiation Emission Spectroscopy

NASA Astrophysics Data System (ADS)

Oblath, Noah; Project 8 Collaboration

2016-09-01

We report on the design concept for Phase III of the Project 8 experiment. In the third phase of Project 8 we aim to place a limit on the neutrino mass that is similar to the current limits set by tritium beta-decay experiments, mν < 2eV . From the first two phases of Project 8 we move to a novel design consisting of a 100cm3 cylindrical volume of tritium gas instrumented with two 30-element rings of inward-facing antennas. Beam-forming techniques similar to those used in radioastronomy will be employed to search for and track electron signals in the fiducial volume. This talk will present the quantitative design concept for the phased-array receiver, and illustrate how we are progressing towards the Phase IV experiment, which will have sensitivity to the neutrino mass scale allowed by the inverted mass hierarchy. This work is supported by the DOE Office of Science Early Career Research Program, and the Laboratory Directed Research and Development Program at Pacific Northwest National Laboratory.

EARLY ENTRANCE COPRODUCTION PLANT

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

David Storm; Govanon Nongbri; Steve Decanio

2004-01-12

The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase IImore » is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, Inc., GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. During Phase I, a design basis for the Fischer-Tropsch Synthesis section was developed based on limited experience with the specified feed gas and operating conditions. The objective of this Task in Phase II RD&T work was to confirm the performance of the F-T reactor at the set design conditions. Although much of the research, development, and testing work were done by TES outside of this project, several important issues were addressed in this phase of the project. They included Rejuvenation/Regeneration of the Fischer-Tropsch Catalyst, online Catalyst Withdrawal and Addition from the synthesis reactor, and the Fischer-Tropsch Design Basis Confirmation. In Phase III the results from these RD&T work will be incorporated in developing the engineering design package. This Topical Report documents the Phase II RD&T work that was completed for this task.« less

Statistical controversies in clinical research: building the bridge to phase II-efficacy estimation in dose-expansion cohorts.

PubMed

Boonstra, P S; Braun, T M; Taylor, J M G; Kidwell, K M; Bellile, E L; Daignault, S; Zhao, L; Griffith, K A; Lawrence, T S; Kalemkerian, G P; Schipper, M J

2017-07-01

Regulatory agencies and others have expressed concern about the uncritical use of dose expansion cohorts (DECs) in phase I oncology trials. Nonetheless, by several metrics-prevalence, size, and number-their popularity is increasing. Although early efficacy estimation in defined populations is a common primary endpoint of DECs, the types of designs best equipped to identify efficacy signals have not been established. We conducted a simulation study of six phase I design templates with multiple DECs: three dose-assignment/adjustment mechanisms multiplied by two analytic approaches for estimating efficacy after the trial is complete. We also investigated the effect of sample size and interim futility analysis on trial performance. Identifying populations in which the treatment is efficacious (true positives) and weeding out inefficacious treatment/populations (true negatives) are competing goals in these trials. Thus, we estimated true and false positive rates for each design. Adaptively updating the MTD during the DEC improved true positive rates by 8-43% compared with fixing the dose during the DEC phase while maintaining false positive rates. Inclusion of an interim futility analysis decreased the number of patients treated under inefficacious DECs without hurting performance. A substantial gain in efficiency is obtainable using a design template that statistically models toxicity and efficacy against dose level during expansion. Design choices for dose expansion should be motivated by and based upon expected performance. Similar to the common practice in single-arm phase II trials, cohort sample sizes should be justified with respect to their primary aim and include interim analyses to allow for early stopping. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Automatic Debugging Support for UML Designs

NASA Technical Reports Server (NTRS)

Schumann, Johann; Swanson, Keith (Technical Monitor)

2001-01-01

Design of large software systems requires rigorous application of software engineering methods covering all phases of the software process. Debugging during the early design phases is extremely important, because late bug-fixes are expensive. In this paper, we describe an approach which facilitates debugging of UML requirements and designs. The Unified Modeling Language (UML) is a set of notations for object-orient design of a software system. We have developed an algorithm which translates requirement specifications in the form of annotated sequence diagrams into structured statecharts. This algorithm detects conflicts between sequence diagrams and inconsistencies in the domain knowledge. After synthesizing statecharts from sequence diagrams, these statecharts usually are subject to manual modification and refinement. By using the "backward" direction of our synthesis algorithm. we are able to map modifications made to the statechart back into the requirements (sequence diagrams) and check for conflicts there. Fed back to the user conflicts detected by our algorithm are the basis for deductive-based debugging of requirements and domain theory in very early development stages. Our approach allows to generate explanations oil why there is a conflict and which parts of the specifications are affected.

Warfighting Concepts to Future Weapon System Designs (WARCON)

DTIC Science & Technology

2003-09-12

34* Software design documents rise to litigation. "* A Material List "Cost information that may support, or may * Final Engineering Process Maps be...document may include design the system as derived from the engineering design, software development, SRD. MTS Technologies, Inc. 26 FOR OFFICIAL USE...document, early in the development phase. It is software engineers produce the vision of important to establish a standard, formal the design effort. As

Communication of Political Information during Early Presidential Primaries: Cognition, Affect, and Uncertainty.

ERIC Educational Resources Information Center

Kennamer, J. David; Chaffee, Steven H.

As part of a larger study of political socialization in adolescence, 782 adolescents and 718 parents were surveyed to test hypotheses about political information as a function of the early phase of a presidential campaign and the news exposure level of the respondent. Despite shortcomings in the sample design and in the precision of interview…

Design of an ammonia two-phase Prototype Thermal Bus for Space Station

NASA Technical Reports Server (NTRS)

Brown, Richard F.; Gustafson, Eric; Parish, Richard

1987-01-01

The feasibility of two-phase heat transport systems for use on Space Station was demonstrated by testing the Thermal Bus Technology Demonstrator (TBTD) as part of the Integrated Two-Phase System Test in NASA-JSC's Thermal Test Bed. Under contract to NASA-JSC, Grumman is currently developing the successor to the TBTD, the Prototype Thermal Bus System (TBS). The TBS design, which uses ammonia as the working fluid, is intended to achieve a higher fidelity level than the TBTD by incorporating both improvements based on TBTD testing and realistic design margins, and by addressing Space Station issues such as redundancy and maintenance. The TBS is currently being fabricated, with testing scheduled for late 1987/early 1988. This paper describes the TBS design which features fully redundant plumbing loops, five evaporators designed to represent different heat acquisition interfaces, 14 condensers which mate with either space radiators or facility heat exchangers, and several modular components.

Scenario for concurrent conceptual assembly line design: A case study

NASA Astrophysics Data System (ADS)

Mas, F.; Ríos, J.; Menéndez, J. L.

2012-04-01

The decision to design and build a new aircraft is preceded by years of research and study. Different disciplines work together throughout the lifecycle to ensure not only a complete functional definition of the product, but also a complete industrialization, a marketing plan, a maintenance plan, etc. This case study focuses on the conceptual design phase. During this phase, the design solutions that will meet the functional and industrial requirements are defined, i.e.: the basic requirements of industrialization. During this phase, several alternatives are studied, and the most attractive in terms of performance and cost requirements is selected. As a result of the study of these alternatives, it is possible to define an early conceptual design of the assembly line and its basic parameters. The plant needs, long cycle jigs & tools or industrial means and human resources with the necessary skills can be determined in advance.

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

2014-01-01

Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

The Design and Implementation of a Physical Education Program to Promote Children's Creativity in the Early Years

ERIC Educational Resources Information Center

Zachopoulou, Evridiki; Trevlas, Efthimios; Konstadinidou, Elisavet

2006-01-01

The purpose of this study was to design and implement a physical education program to promote creativity in preschool children. The study was based on the following phases: (a) to design and formulate 20 physical education lessons in order to provide children with opportunities to develop their creative thinking through the use of movement…

Mixed response and time-to-event endpoints for multistage single-arm phase II design.

PubMed

Lai, Xin; Zee, Benny Chung-Ying

2015-06-04

The objective of phase II cancer clinical trials is to determine if a treatment has sufficient activity to warrant further study. The efficiency of a conventional phase II trial design has been the object of considerable debate, particularly when the study regimen is characteristically cytostatic. At the time of development of a phase II cancer trial, we accumulated clinical experience regarding the time to progression (TTP) for similar classes of drugs and for standard therapy. By considering the time to event (TTE) in addition to the tumor response endpoint, a mixed-endpoint phase II design may increase the efficiency and ability of selecting promising cytotoxic and cytostatic agents for further development. We proposed a single-arm phase II trial design by extending the Zee multinomial method to fully use mixed endpoints with tumor response and the TTE. In this design, the dependence between the probability of response and the TTE outcome is modeled through a Gaussian copula. Given the type I and type II errors and the hypothesis as defined by the response rate (RR) and median TTE, such as median TTP, the decision rules for a two-stage phase II trial design can be generated. We demonstrated through simulation that the proposed design has a smaller expected sample size and higher early stopping probability under the null hypothesis than designs based on a single-response endpoint or a single TTE endpoint. The proposed design is more efficient for screening new cytotoxic or cytostatic agents and less likely to miss an effective agent than the alternative single-arm design.

Instructional Media Production for Early Childhood Education: A. B. C. Jig-Saw Puzzle, a Model

ERIC Educational Resources Information Center

Yusuf, Mudashiru Olalere; Olanrewaju, Olatayo Solomon; Soetan, Aderonke K.

2015-01-01

In this paper, a. b. c. jig-saw puzzle was produced for early childhood education using local materials. This study was a production based type of research, to serve as a supplemental or total learning resource. Its production followed four phases of development referred to as information, design, production and evaluation. The storyboard cards,…

40 CFR 300.515 - Requirements for state involvement in remedial and enforcement response.

Code of Federal Regulations, 2012 CFR

2012-07-01

... not limited to, remedial investigations, feasibility studies, and remedial designs, the state agency... later than the early stages of the comparative analysis described in § 300.430(e)(9), such that... separate phase or activity, for supervising the remedial design and construction of the entire remedy. (2...

40 CFR 300.515 - Requirements for state involvement in remedial and enforcement response.

Code of Federal Regulations, 2010 CFR

2010-07-01

... not limited to, remedial investigations, feasibility studies, and remedial designs, the state agency... later than the early stages of the comparative analysis described in § 300.430(e)(9), such that... separate phase or activity, for supervising the remedial design and construction of the entire remedy. (2...

40 CFR 300.515 - Requirements for state involvement in remedial and enforcement response.

Code of Federal Regulations, 2014 CFR

2014-07-01

... not limited to, remedial investigations, feasibility studies, and remedial designs, the state agency... later than the early stages of the comparative analysis described in § 300.430(e)(9), such that... separate phase or activity, for supervising the remedial design and construction of the entire remedy. (2...

40 CFR 300.515 - Requirements for state involvement in remedial and enforcement response.

Code of Federal Regulations, 2013 CFR

2013-07-01

... not limited to, remedial investigations, feasibility studies, and remedial designs, the state agency... later than the early stages of the comparative analysis described in § 300.430(e)(9), such that... separate phase or activity, for supervising the remedial design and construction of the entire remedy. (2...

40 CFR 300.515 - Requirements for state involvement in remedial and enforcement response.

Code of Federal Regulations, 2011 CFR

2011-07-01

... not limited to, remedial investigations, feasibility studies, and remedial designs, the state agency... later than the early stages of the comparative analysis described in § 300.430(e)(9), such that... separate phase or activity, for supervising the remedial design and construction of the entire remedy. (2...

Correlation of causal factors that influence construction safety performance: A model.

PubMed

Rodrigues, F; Coutinho, A; Cardoso, C

2015-01-01

The construction sector has presented positive development regarding the decrease in occupational accident rates in recent years. Regardless, the construction sector stands out systematically from other industries due to its high number of fatalities. The aim of this paper is to deeply understand the causality of construction accidents from the early design phase through a model. This study reviewed several research papers presenting various analytical models that correlate the contributing factors to occupational accidents in this sector. This study also analysed different construction projects and conducted a survey of design and site supervision teams. This paper proposes a model developed from the analysis of existing ones, which correlates the causal factors through all the construction phases. It was concluded that effective risk prevention can only be achieved by a global correlation of causal factors including not only production ones but also client requirements, financial climate, design team competence, project and risk management, financial capacity, health and safety policy and early planning. Accordingly, a model is proposed.

MOD-5A wind turbine generator program design report: Volume 1: Executive Summary

NASA Technical Reports Server (NTRS)

1984-01-01

The design, development and analysis of the 7.3 MW MOD-5A wind turbine generator covering work performed between July 1980 and June 1984 is discussed. The report is divided into four volumes: Volume 1 summarizes the entire MOD-5A program, Volume 2 discusses the conceptual and preliminary design phases, Volume 3 describes the final design of the MOD-5A, and Volume 4 contains the drawings and specifications developed for the final design. Volume 1, the Executive Summary, summarizes all phases of the MOD-5A program. The performance and cost of energy generated by the MOD-5A are presented. Each subsystem - the rotor, drivetrain, nacelle, tower and foundation, power generation, and control and instrumentation subsystems - is described briefly. The early phases of the MOD-5A program, during which the design was analyzed and optimized, and new technologies and materials were developed, are discussed. Manufacturing, quality assurance, and safety plans are presented. The volume concludes with an index of volumes 2 and 3.

Exploring Three-Phase Systems and Synchronous Motors: A Low-Voltage and Low-Cost Experiment at the Sophomore Level

ERIC Educational Resources Information Center

Schubert, T. F., Jr.; Jacobitz, F. G.; Kim, E. M.

2011-01-01

In order to meet changing curricular and societal needs, a three-phase system and synchronous motor laboratory experience for sophomore-level students in a wide variety of engineering majors was designed, implemented, and assessed. The experiment is unusual in its early placement in the curriculum, and in that it focuses primarily on basic…

Canadian and Siberian Boreal Fire Activity during ARCTAS Spring and Summer Phases

NASA Astrophysics Data System (ADS)

Stocks, B. J.; Fromm, M. D.; Soja, A. J.; Servranckx, R.; Lindsey, D.; Hyer, E.

2009-12-01

The summer phase of ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites) was designed specifically around forest fire activity in the Canadian boreal forest, and located in areas of northern Canada where summer forest fires are ubiquitous. Lightning fires are most often allowed to burn naturally in these regions, and a number of large free-burning fires in northern Saskatchewan in late June/early July 2008 provided excellent targets during the summer phase of ARCTAS. Smoke generated by a large number of early spring fires in Kazakhstan and southern Siberia unexpectedly made a significant contribution to arctic haze during the Alaska-based spring phase of ARCTAS, Numerous smoke plumes were sampled during the spring phase of ARCTAS, creating interest in the origin and characteristics of the fires in the source regions of East Asia. This presentation is designed to connect aircraft and satellite smoke chemistry/transport measurements with ground-based measurements of fire activity during the spring and summer phases of ARCTAS. The Canadian Forest Fire Danger Rating System (CFFDRS) is used to determine forest fire danger conditions in regions of fire activity, and these measurements are in turn used to project fire behavior characteristics. Fuel consumption, spread rates, and frontal fire intensity are calculated using the CFFDRS. Energy release rates at ground level are related to convection/smoke column development and smoke injection heights.

Space Station ECLSS Integration Analysis

NASA Technical Reports Server (NTRS)

1993-01-01

The Space Station Environmental Control and Life Support System (ECLSS) contract with NASA MSFC covered the time frame from 9 May 1985 to 31 Dec. 1992. The contract roughly covered the period of Space Station Freedom (SSF) development from early Phase B through Phase C/D Critical Design Review (CDR). During this time, McDonnell Douglas Aerospace-Huntsville (formerly McDonnell Douglas Space Systems Company) performed an analytical support role to MSFC for the development of analytical math models and engineering trade studies related to the design of the ECLSS for the SSF.

Advanced Life Support Water Recycling Technologies Case Studies: Vapor Phase Catalytic Ammonia Removal and Direct Osmotic Concentration

NASA Technical Reports Server (NTRS)

Flynn, Michael

2004-01-01

Design for microgravity has traditionally not been well integrated early on into the development of advanced life support (ALS) technologies. NASA currently has a many ALS technologies that are currently being developed to high technology readiness levels but have not been formally evaluated for microgravity compatibility. Two examples of such technologies are the Vapor Phase Catalytic Ammonia Removal Technology and the Direct Osmotic Concentration Technology. This presentation will cover the design of theses two systems and will identify potential microgravity issues.

Payload Instrument Design Rules for Safe and Efficient Flight Operations

NASA Astrophysics Data System (ADS)

Montagnon, E.; Ferri, P.

2004-04-01

Payload operations are often being neglected in favour of optimisation of scientific performance of the instrument design. This has major drawbacks in terms of cost, safety, efficiency of operations and finally science return. By taking operational aspects into account in the early phases of the instrument design, with a minimum more cultural than financial or technological additional effort, many problems can be avoided or minimized, with significant benefits to be gained in the mission execution phases. This paper presents possible improvements based on the use of the telemetry and telecommand packet standard, proper sharing of autonomy functions between instrument and platform, and enhanced interface documents.

Application of modern tools and techniques to maximize engineering productivity in the development of orbital operations plans for the space station progrm

NASA Technical Reports Server (NTRS)

Manford, J. S.; Bennett, G. R.

1985-01-01

The Space Station Program will incorporate analysis of operations constraints and considerations in the early design phases to avoid the need for later modifications to the Space Station for operations. The application of modern tools and administrative techniques to minimize the cost of performing effective orbital operations planning and design analysis in the preliminary design phase of the Space Station Program is discussed. Tools and techniques discussed include: approach for rigorous analysis of operations functions, use of the resources of a large computer network, and providing for efficient research and access to information.

A Phase I/II adaptive design for heterogeneous groups with application to a stereotactic body radiation therapy trial.

PubMed

Wages, Nolan A; Read, Paul W; Petroni, Gina R

2015-01-01

Dose-finding studies that aim to evaluate the safety of single agents are becoming less common, and advances in clinical research have complicated the paradigm of dose finding in oncology. A class of more complex problems, such as targeted agents, combination therapies and stratification of patients by clinical or genetic characteristics, has created the need to adapt early-phase trial design to the specific type of drug being investigated and the corresponding endpoints. In this article, we describe the implementation of an adaptive design based on a continual reassessment method for heterogeneous groups, modified to coincide with the objectives of a Phase I/II trial of stereotactic body radiation therapy in patients with painful osseous metastatic disease. Operating characteristics of the Institutional Review Board approved design are demonstrated under various possible true scenarios via simulation studies. Copyright © 2015 John Wiley & Sons, Ltd.

Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.

PubMed

Paoletti, X; Ezzalfani, M; Le Tourneau, C

2015-09-01

More than 95% of published phase I trials have used the 3 + 3 design to identify the dose to be recommended for phase II trials. However, the statistical community agrees on the limitations of the 3 + 3 design compared with model-based approaches. Moreover, the mechanisms of action of targeted agents strongly challenge the hypothesis that the maximum tolerated dose constitutes the optimal dose, and more outcomes including clinical and biological activity increasingly need to be taken into account to identify the optimal dose. We review key elements from clinical publications and from the statistical literature to show that the 3 + 3 design lacks the necessary flexibility to address the challenges of targeted agents. The design issues raised by expansion cohorts, new definitions of dose-limiting toxicity and trials of combinations are not easily addressed by the 3 + 3 design or its extensions. Alternative statistical proposals have been developed to make a better use of the complex data generated by phase I trials. Their applications require a close collaboration between all actors of early phase clinical trials. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Standardized Radiation Shield Design Methods: 2005 HZETRN

NASA Technical Reports Server (NTRS)

Wilson, John W.; Tripathi, Ram K.; Badavi, Francis F.; Cucinotta, Francis A.

2006-01-01

Research committed by the Langley Research Center through 1995 resulting in the HZETRN code provides the current basis for shield design methods according to NASA STD-3000 (2005). With this new prominence, the database, basic numerical procedures, and algorithms are being re-examined with new methods of verification and validation being implemented to capture a well defined algorithm for engineering design processes to be used in this early development phase of the Bush initiative. This process provides the methodology to transform the 1995 HZETRN research code into the 2005 HZETRN engineering code to be available for these early design processes. In this paper, we will review the basic derivations including new corrections to the codes to insure improved numerical stability and provide benchmarks for code verification.

Preliminary design document: Ground based testbed for avionics systems

NASA Technical Reports Server (NTRS)

1989-01-01

The design and interface requirements for an avionics Ground Based Test bed (GBT) to support Heavy Lift Cargo Vehicles (HLCV) is presented. It also contains data on the vehicle subsystem configurations that are to be supported during their early, pre-PDR developmental phases. Several emerging technologies are also identified for support. A Preliminary Specification Tree is also presented.

Scientific white paper on concentration-QTc modeling.

PubMed

Garnett, Christine; Bonate, Peter L; Dang, Qianyu; Ferber, Georg; Huang, Dalong; Liu, Jiang; Mehrotra, Devan; Riley, Steve; Sager, Philip; Tornoe, Christoffer; Wang, Yaning

2018-06-01

The International Council for Harmonisation revised the E14 guideline through the questions and answers process to allow concentration-QTc (C-QTc) modeling to be used as the primary analysis for assessing the QTc interval prolongation risk of new drugs. A well-designed and conducted QTc assessment based on C-QTc modeling in early phase 1 studies can be an alternative approach to a thorough QT study for some drugs to reliably exclude clinically relevant QTc effects. This white paper provides recommendations on how to plan and conduct a definitive QTc assessment of a drug using C-QTc modeling in early phase clinical pharmacology and thorough QT studies. Topics included are: important study design features in a phase 1 study; modeling objectives and approach; exploratory plots; the pre-specified linear mixed effects model; general principles for model development and evaluation; and expectations for modeling analysis plans and reports. The recommendations are based on current best modeling practices, scientific literature and personal experiences of the authors. These recommendations are expected to evolve as their implementation during drug development provides additional data and with advances in analytical methodology.

Obtaining Valid Safety Data for Software Safety Measurement and Process Improvement

NASA Technical Reports Server (NTRS)

Basili, Victor r.; Zelkowitz, Marvin V.; Layman, Lucas; Dangle, Kathleen; Diep, Madeline

2010-01-01

We report on a preliminary case study to examine software safety risk in the early design phase of the NASA Constellation spaceflight program. Our goal is to provide NASA quality assurance managers with information regarding the ongoing state of software safety across the program. We examined 154 hazard reports created during the preliminary design phase of three major flight hardware systems within the Constellation program. Our purpose was two-fold: 1) to quantify the relative importance of software with respect to system safety; and 2) to identify potential risks due to incorrect application of the safety process, deficiencies in the safety process, or the lack of a defined process. One early outcome of this work was to show that there are structural deficiencies in collecting valid safety data that make software safety different from hardware safety. In our conclusions we present some of these deficiencies.

Microstructural Developments Leading to New Advanced High Strength Sheet Steels: A Historical Assessment of Critical Metallographic Observations

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

Matlock, David K; Thomas, Larrin S; Taylor, Mark D

In the past 30+ years significant advancements have been made in the development of higher strength sheet steels with improved combinations of strength and ductility that have enabled important product improvements leading to safer, lighter weight, and more fuel efficient automobiles and in other applications. Properties of the primarily low carbon, low alloy steels are derived through careful control of time-temperature processing histories designed to produce multiphase ferritic based microstructures that include martensite and other constituents including retained austenite. The basis for these developments stems from the early work on dual-phase steels which was the subject of much interest. Inmore » response to industry needs, dual-phase steels have evolved as a unique class of advanced high strength sheet steels (AHSS) in which the thermal and mechanical processing histories have been specifically designed to produce constituent combinations for the purpose of simultaneously controlling strength and deformation behavior, i.e. stress-strain curve shapes. Improvements continue as enhanced dual-phase steels have recently been produced with finer microstructures, higher strengths, and better overall formability. Today, dual phase steels are the primary AHSS products used in vehicle manufacture, and several companies have indicated that the steels will remain as important design materials well into the future. In this presentation, fundamental results from the early work on dual-phase steels will be reviewed and assessed in light of recent steel developments. Specific contributions from industry/university cooperative research leading to product improvements will be highlighted. The historical perspective provided in the evolution of dual-phase steels represents a case-study that provides important framework and lessons to be incorporated in next generation AHSS products.« less

‘Much clearer with pictures’: using community-based participatory research to design and test a Picture Option Grid for underserved patients with breast cancer

PubMed Central

Durand, Marie-Anne; Alam, Shama; Grande, Stuart W; Elwyn, Glyn

2016-01-01

Objective Women of low socioeconomic status (SES) diagnosed with early stage breast cancer experience decision-making, treatment and outcome disparities. Evidence suggests that decision aids can benefit underserved patients, when tailored to their needs. Our aim was to develop and test the usability, acceptability and accessibility of a pictorial encounter decision aid targeted at women of low SES diagnosed with early stage breast cancer. Design Community-based participatory research (CBPR) using think-aloud protocols (phases 1 and 2) and semistructured interviews (phase 3). Setting Underserved community settings (eg, knitting groups, bingo halls, senior centres) and breast clinics. Participants In phase 1, we recruited a convenience sample of clinicians and academics. In phase 2, we targeted women over 40 years of age, of low SES, regardless of breast cancer history, and in phase 3, women of low SES, recently diagnosed with breast cancer. Intervention The pictorial encounter decision aid was derived from an evidence-based table comparing treatment options for breast cancer (http://www.optiongrid.org). Outcome measures We assessed the usability, acceptability and accessibility of the pictorial decision aid prototypes using the think-aloud protocol and semistructured interviews. Results After initial testing of the first prototype with 18 academics and health professionals, new versions were developed and tested with 53 lay individuals in community settings. Usability was high. In response to feedback indicating that the use of cartoon characters was considered insensitive, a picture-only version was developed and tested with 23 lay people in phase 2, and 10 target users in phase 3. Conclusions and relevance Using CBPR methods and iterative user testing cycles improved usability and accessibility, and led to the development of the Picture Option Grid, entirely guided by multiple stakeholder feedback. All women of low SES recently diagnosed with early stage breast cancer found the Picture Option Grid usable, acceptable and accessible. PMID:26839014

Immediate Effects of a Single Session of Motor Skill Training on the Lumbar Movement Pattern During a Functional Activity in People With Low Back Pain: A Repeated-Measures Study.

PubMed

Marich, Andrej V; Lanier, Vanessa M; Salsich, Gretchen B; Lang, Catherine E; Van Dillen, Linda R

2018-04-06

People with low back pain (LBP) may display an altered lumbar movement pattern of early lumbar motion compared to people with healthy backs. Modifying this movement pattern during a clinical test decreases pain. It is unknown whether similar effects would be seen during a functional activity. The objective of this study is was to examine the lumbar movement patterns before and after motor skill training, effects on pain, and characteristics that influenced the ability to modify movement patterns. The design consisted of a repeated-measures study examining early-phase lumbar excursion in people with LBP during a functional activity test. Twenty-six people with chronic LBP received motor skill training, and 16 people with healthy backs were recruited as a reference standard. Twenty minutes of motor skill training to decrease early-phase lumbar excursion during the performance of a functional activity were used as a treatment intervention. Early-phase lumbar excursion was measured before and after training. Participants verbally reported increased pain, decreased pain, or no change in pain during performance of the functional activity test movement in relation to their baseline pain. The characteristics of people with LBP that influenced the ability to decrease early-phase lumbar excursion were examined. People with LBP displayed greater early-phase lumbar excursion before training than people with healthy backs (LBP: mean = 11.2°, 95% CI = 9.3°-13.1°; healthy backs: mean = 7.1°, 95% CI = 5.8°-8.4°). Following training, the LBP group showed a decrease in the amount of early-phase lumbar excursion (mean change = 4.1°, 95% CI = 2.4°-5.8°); 91% of people with LBP reported that their pain decreased from baseline following training. The longer the duration of LBP (β = - 0.22) and the more early-phase lumbar excursion before training (β = - 0.82), the greater the change in early-phase lumbar excursion following training. The long-term implications of modifying the movement pattern and whether the decrease in pain attained was clinically significant are unknown. People with LBP were able to modify their lumbar movement pattern and decrease their pain with the movement pattern within a single session of motor skill training.

Evaluation of early efficacy endpoints for proof-of-concept trials.

PubMed

Chen, Cong; Sun, Linda; Li, Chih-Lin

2013-03-11

A Phase II proof-of-concept (POC) trial usually uses an early efficacy endpoint other than a clinical endpoint as the primary endpoint. Because of the advancement in bioscience and technology, which has yielded a number of new surrogate biomarkers, drug developers often have more candidate endpoints to choose from than they can handle. As a result, selection of endpoint and its effect size as well as choice of type I/II error rates are often at the center of heated debates in design of POC trials. While optimization of the trade-off between benefit and cost is the implicit objective in such a decision-making process, it is seldom explicitly accounted for in practice. In this research note, motivated by real examples from the oncology field, we provide practical measures for evaluation of early efficacy endpoints (E4) for POC trials. We further provide optimal design strategies for POC trials that include optimal Go-No Go decision criteria for initiation of Phase III and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology is used for illustration purpose, the same idea developed in this research note also applies to similar situations in other therapeutic areas or in early-stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.

Life cycle assessment based environmental impact estimation model for pre-stressed concrete beam bridge in the early design phase

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

Kim, Kyong Ju, E-mail: kjkim@cau.ac.kr; Yun, Won Gun, E-mail: ogun78@naver.com; Cho, Namho, E-mail: nhc51@cau.ac.kr

The late rise in global concern for environmental issues such as global warming and air pollution is accentuating the need for environmental assessments in the construction industry. Promptly evaluating the environmental loads of the various design alternatives during the early stages of a construction project and adopting the most environmentally sustainable candidate is therefore of large importance. Yet, research on the early evaluation of a construction project's environmental load in order to aid the decision making process is hitherto lacking. In light of this dilemma, this study proposes a model for estimating the environmental load by employing only the mostmore » basic information accessible during the early design phases of a project for the pre-stressed concrete (PSC) beam bridge, the most common bridge structure. Firstly, a life cycle assessment (LCA) was conducted on the data from 99 bridges by integrating the bills of quantities (BOQ) with a life cycle inventory (LCI) database. The processed data was then utilized to construct a case based reasoning (CBR) model for estimating the environmental load. The accuracy of the estimation model was then validated using five test cases; the model's mean absolute error rates (MAER) for the total environmental load was calculated as 7.09%. Such test results were shown to be superior compared to those obtained from a multiple-regression based model and a slab area base-unit analysis model. Henceforth application of this model during the early stages of a project is expected to highly complement environmentally friendly designs and construction by facilitating the swift evaluation of the environmental load from multiple standpoints. - Highlights: • This study is to develop the model of assessing the environmental impacts on LCA. • Bills of quantity from completed designs of PSC Beam were linked with the LCI DB. • Previous cases were used to estimate the environmental load of new case by CBR model. • CBR model produces more accurate estimations (7.09%) than other conventional models. • This study supports decision making process in the early stage of a new construction case.« less

Inhibition of Late and Early Phases of Cancer Metastasis by the NF-κB Inhibitor DHMEQ Derived from Microbial Bioactive Metabolite Epoxyquinomicin: A Review.

PubMed

Lin, Yinzhi; Ukaji, Tamami; Koide, Naoki; Umezawa, Kazuo

2018-03-03

We previously designed and synthesized dehydroxyepoxyquinomicin (DHMEQ) as an inhibitor of NF-κB based on the structure of microbial secondary metabolite epoxyquinomicin C. DHMEQ showed anti-inflammatory and anticancer activity in various in vivo disease models without toxicity. On the other hand, the process of cancer metastasis consists of cell detachment from the primary tumor, invasion, transportation by blood or lymphatic vessels, invasion, attachment, and formation of secondary tumor. Cell detachment from the primary tumor and subsequent invasion are considered to be early phases of metastasis, while tumor cell attachment to the tissue and secondary tumor formation the late phases. The assay system for the latter phase was set up with intra-portal-vein injection of pancreatic cancer cells. Intraperitoneal administration of DHMEQ was found to inhibit liver metastasis possibly by decreasing the expression of MMP-9 and IL-8. Also, when the pancreatic cancer cells treated with DHMEQ were inoculated into the peritoneal cavity of mice, the metastatic foci formation was inhibited. These results indicate that DHMEQ is likely to inhibit the late phase of metastasis. Meanwhile, we have recently employed three-dimensional (3D) culture of breast cancer cells for the model of early phase metastasis, since the 3D invasion just includes cell detachment and invasion into the matrix. DHMEQ inhibited the 3D invasion of breast cancer cells at 3D-nontoxic concentrations. In this way, DHMEQ was shown to inhibit the late and early phases of metastasis. Thus, DHMEQ is likely to be useful for the suppression of cancer metastasis.

Maximizing Launch Vehicle and Payload Design Via Early Communications

NASA Technical Reports Server (NTRS)

Morris, Bruce

2010-01-01

The United States? current fleet of launch vehicles is largely derived from decades-old designs originally made for payloads that no longer exist. They were built primarily for national security or human exploration missions. Today that fleet can be divided roughly into small-, medium-, and large-payload classes based on mass and volume capability. But no vehicle in the U.S. fleet is designed to accommodate modern payloads. It is usually the payloads that must accommodate the capabilities of the launch vehicles. This is perhaps most true of science payloads. It was this paradigm that the organizers of two weekend workshops in 2008 at NASA's Ames Research Center sought to alter. The workshops brought together designers of NASA's Ares V cargo launch vehicle (CLV) with scientists and payload designers in the astronomy and planetary sciences communities. Ares V was still in a pre-concept development phase as part of NASA?s Constellation Program for exploration beyond low Earth orbit (LEO). The space science community was early in a Decadal Survey that would determine future priorities for research areas, observations, and notional missions to make those observations. The primary purpose of the meetings in April and August of 2008, including the novel format, was to bring vehicle designers together with space scientists to discuss the feasibility of using a heavy lift capability to launch large observatories and explore the Solar System. A key question put to the science community was whether this heavy lift capability enabled or enhanced breakthrough science. The meetings also raised the question of whether some trade-off between mass/volume and technical complexity existed that could reduce technical and programmatic risk. By engaging the scientific community early in the vehicle design process, vehicle engineers sought to better understand potential limitations and requirements that could be added to the Ares V from the mission planning community. From the vehicle standpoint, while the human exploration mission could not be compromised to accommodate other payloads, the design might otherwise be tailored to not exclude other payload requirements. This paper summarizes the findings of the workshops and discusses the benefits of bringing together the vehicle design and science communities early in their concept phases

Lunar Ultraviolet Telescope Experiment (LUTE), phase A

NASA Technical Reports Server (NTRS)

Mcbrayer, Robert O.

1994-01-01

The Lunar Ultraviolet Telescope Experiment (LUTE) is a 1-meter telescope for imaging from the lunar surface the ultraviolet spectrum between 1,000 and 3,500 angstroms. There have been several endorsements of the scientific value of a LUTE. In addition to the scientific value of LUTE, its educational value and the information it can provide on the design of operating hardware for long-term exposure in the lunar environment are important considerations. This report provides the results of the LUTE phase A activity begun at the George C. Marshall Space Flight Center in early 1992. It describes the objective of LUTE (science, engineering, and education), a feasible reference design concept that has evolved, and the subsystem trades that were accomplished during the phase A.

Transitions of Care Between Acute and Chronic Heart Failure: Critical Steps in the Design of a Multidisciplinary Care Model for the Prevention of Rehospitalization.

PubMed

Comín-Colet, Josep; Enjuanes, Cristina; Lupón, Josep; Cainzos-Achirica, Miguel; Badosa, Neus; Verdú, José María

2016-10-01

Despite advances in the treatment of heart failure, mortality, the number of readmissions, and their associated health care costs are very high. Heart failure care models inspired by the chronic care model, also known as heart failure programs or heart failure units, have shown clinical benefits in high-risk patients. However, while traditional heart failure units have focused on patients detected in the outpatient phase, the increasing pressure from hospital admissions is shifting the focus of interest toward multidisciplinary programs that concentrate on transitions of care, particularly between the acute phase and the postdischarge phase. These new integrated care models for heart failure revolve around interventions at the time of transitions of care. They are multidisciplinary and patient-centered, designed to ensure continuity of care, and have been demonstrated to reduce potentially avoidable hospital admissions. Key components of these models are early intervention during the inpatient phase, discharge planning, early postdischarge review and structured follow-up, advanced transition planning, and the involvement of physicians and nurses specialized in heart failure. It is hoped that such models will be progressively implemented across the country. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Development and functionality of a handheld computer program to improve fruit and vegetable intake among low-income youth

PubMed Central

Nollen, Nicole L.; Hutcheson, Tresza; Carlson, Susan; Rapoff, Michael; Goggin, Kathy; Mayfield, Carlene; Ellerbeck, Edward

2013-01-01

Mobile technologies hold promise for improving diet and physical activity, but little attention is given to creating programs that adolescents like and will use. This study developed a personal digital assistant (PDA) program to promote increased intake of fruits and vegetables (FV) in predominately low-income, ethnic minority girls. This study used a three-phase community-engaged process, including (i) engagement of a Student Advisory Board (SAB) to determine comfort with PDAs; (ii) early testing of Prototype I and rapid re-design by the SAB and (iii) feasibility testing of Prototype II in a new sample of girls. Phase 1 results showed that girls were comfortable with the PDA. Testing of Prototype I in Phase 2 showed that acceptability was mixed, with girls responding to 47.3% of the prompts. Girls wanted more reminders, accountability in monitoring FV, help in meeting daily goals and free music downloads based on program use. The PDA was reprogrammed and testing of Prototype II in Phase 3 demonstrated marked improvement in use (78.3%), increases in FV intake (1.8 ± 2.6 daily servings) and good overall satisfaction. Findings suggest that mobile technology designed with the early input of youth is a promising way to improve adolescent health behaviors. PMID:22949499

A Validation of Object-Oriented Design Metrics as Quality Indicators

NASA Technical Reports Server (NTRS)

Basili, Victor R.; Briand, Lionel C.; Melo, Walcelio

1997-01-01

This paper presents the results of a study in which we empirically investigated the suits of object-oriented (00) design metrics introduced in another work. More specifically, our goal is to assess these metrics as predictors of fault-prone classes and, therefore, determine whether they can be used as early quality indicators. This study is complementary to the work described where the same suite of metrics had been used to assess frequencies of maintenance changes to classes. To perform our validation accurately, we collected data on the development of eight medium-sized information management systems based on identical requirements. All eight projects were developed using a sequential life cycle model, a well-known 00 analysis/design method and the C++ programming language. Based on empirical and quantitative analysis, the advantages and drawbacks of these 00 metrics are discussed. Several of Chidamber and Kamerer's 00 metrics appear to be useful to predict class fault-proneness during the early phases of the life-cycle. Also, on our data set, they are better predictors than 'traditional' code metrics, which can only be collected at a later phase of the software development processes.

An Integrated Approach to Risk Assessment for Concurrent Design

NASA Technical Reports Server (NTRS)

Meshkat, Leila; Voss, Luke; Feather, Martin; Cornford, Steve

2005-01-01

This paper describes an approach to risk assessment and analysis suited to the early phase, concurrent design of a space mission. The approach integrates an agile, multi-user risk collection tool, a more in-depth risk analysis tool, and repositories of risk information. A JPL developed tool, named RAP, is used for collecting expert opinions about risk from designers involved in the concurrent design of a space mission. Another in-house developed risk assessment tool, named DDP, is used for the analysis.

Sidewalk undermining studies : phase III, field and model studies.

DOT National Transportation Integrated Search

1979-01-01

The results of the early studies of the undermining problems are summarized in the initial portion of this report. Additionally, the design and use of a model sidewalk for testing procedures for preventing undermining are described. Based upon tests ...

Phase III Early Restoration Public Meetings | NOAA Gulf Spill Restoration

Science.gov Websites

Archive Home Phase III Early Restoration Public Meetings Phase III Early Restoration Public Meetings share Posted on December 6, 2013 | Assessment and Early Restoration Restoration Area Title: Phase III Early on the draft plan for the third phase of Early Restoration, which proposes more than $625 million in

Human Engineering of Space Vehicle Displays and Controls

NASA Technical Reports Server (NTRS)

Whitmore, Mihriban; Holden, Kritina L.; Boyer, Jennifer; Stephens, John-Paul; Ezer, Neta; Sandor, Aniko

2010-01-01

Proper attention to the integration of the human needs in the vehicle displays and controls design process creates a safe and productive environment for crew. Although this integration is critical for all phases of flight, for crew interfaces that are used during dynamic phases (e.g., ascent and entry), the integration is particularly important because of demanding environmental conditions. This panel addresses the process of how human engineering involvement ensures that human-system integration occurs early in the design and development process and continues throughout the lifecycle of a vehicle. This process includes the development of requirements and quantitative metrics to measure design success, research on fundamental design questions, human-in-the-loop evaluations, and iterative design. Processes and results from research on displays and controls; the creation and validation of usability, workload, and consistency metrics; and the design and evaluation of crew interfaces for NASA's Crew Exploration Vehicle are used as case studies.

Early phase drug discovery: cheminformatics and computational techniques in identifying lead series.

PubMed

Duffy, Bryan C; Zhu, Lei; Decornez, Hélène; Kitchen, Douglas B

2012-09-15

Early drug discovery processes rely on hit finding procedures followed by extensive experimental confirmation in order to select high priority hit series which then undergo further scrutiny in hit-to-lead studies. The experimental cost and the risk associated with poor selection of lead series can be greatly reduced by the use of many different computational and cheminformatic techniques to sort and prioritize compounds. We describe the steps in typical hit identification and hit-to-lead programs and then describe how cheminformatic analysis assists this process. In particular, scaffold analysis, clustering and property calculations assist in the design of high-throughput screening libraries, the early analysis of hits and then organizing compounds into series for their progression from hits to leads. Additionally, these computational tools can be used in virtual screening to design hit-finding libraries and as procedures to help with early SAR exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Policy and health implications of using the U.S. Food and Drug Administration product design approach in reducing tobacco product risk.

PubMed

Givel, Michael

2008-06-01

Purported risk or harm reduction through product design change of cigarettes has occurred in three phases in the U.S. The first phase from the 1940s to the early 1960s included a gradual rise in filtered cigarettes. The second phase, which began in the early 1960s in response to the landmark 1964 U.S. Surgeon General's report that linked smoking with lung cancer and other diseases, included the introduction of purportedly low tar and nicotine cigarettes. Subsequent research found that both filters and low tar and nicotine cigarettes were ineffective approaches to reducing health risks associated with smoking. Despite this, these product design changes were used in tobacco industry marketing campaigns to allay consumer health concerns and stabilize tobacco markets and sales. Since 2004, a new risk or harm reduction phase has occurred with the backing by Philip Morris as well as major U.S. health groups of U.S. Food and Drug Administration legislation that would require disclosure of tobacco ingredients, ban misleading health claims, prohibit or reduce harmful ingredients, and require prior approval of tobacco design, performance changes, and modified risk tobacco products. However, current scientific literature indicates that there is no scientific consensus and little evidence on what tobacco ingredients are linked to particular morbidities and mortalities and at what levels. This will allow the tobacco industry to implicitly or explicitly claim their products are "safer." Instead, health advocates should advocate for scientifically proven policy measures such as smoke free public places or higher tobacco taxes that control and reduce tobacco markets and consumption.

Gene expression profiles of Vibrio parahaemolyticus in the early stationary phase.

PubMed

Meng, L; Alter, T; Aho, T; Huehn, S

2015-09-01

Vibrio (V.) parahaemolyticus is an aquatic bacterium capable of causing foodborne gastroenteritis. In the environment or the food chain, V. parahaemolyticus cells are usually forced into the stationary phase, the common phase for bacterial survival in the environment. So far, little is known about whole genomic expression of V. parahaemolyticus in the early stationary phase compared with the exponential growth phase. We performed whole transcriptomic profiling of V. parahaemolyticus cells in both phases (exponential and early stationary phase). Our data showed in total that 172 genes were induced in early stationary phase, while 61 genes were repressed in early stationary phase compared with the exponential phase. Three functional categories showed stable gene expression in the early stationary phase. Eleven functional categories showed that up-regulation of genes was dominant over down-regulation in the early stationary phase. Although genes related to endogenous metabolism were repressed in the early stationary phase, massive regulation of gene expression occurred in the early stationary phase, indicating the expressed gene set of V. parahaemolyticus in the early stationary phase impacts environmental survival. Vibrio (V.) parahaemolyticus is one of the main bacterial causes of foodborne intestinal infections. This bacterium usually is forced into stationary phase in the environment, which includes, e.g. seafood. When bacteria are in stationary phase, physiological changes can lead to a resistance to many stresses, including physical and chemical challenges during food processing. To the best of our knowledge, highlighting the whole genome expression changes in the early stationary phase compared with exponential phase, as well as the investigation of physiological changes of V. parahaemolyticus such as the survival mechanism in the stationary phase has been the very first study in this field. © 2015 The Society for Applied Microbiology.

Neurophysiological evidence (ERPs) for hemispheric processing of facial expressions of emotions: Evidence from whole face and chimeric face stimuli.

PubMed

Damaskinou, Nikoleta; Watling, Dawn

2018-05-01

This study was designed to investigate the patterns of electrophysiological responses of early emotional processing at frontocentral sites in adults and to explore whether adults' activation patterns show hemispheric lateralization for facial emotion processing. Thirty-five adults viewed full face and chimeric face stimuli. After viewing two faces, sequentially, participants were asked to decide which of the two faces was more emotive. The findings from the standard faces and the chimeric faces suggest that emotion processing is present during the early phases of face processing in the frontocentral sites. In particular, sad emotional faces are processed differently than neutral and happy (including happy chimeras) faces in these early phases of processing. Further, there were differences in the electrode amplitudes over the left and right hemisphere, particularly in the early temporal window. This research provides supporting evidence that the chimeric face test is a test of emotion processing that elicits right hemispheric processing.

Phase III of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

information about this phase of Early Restoration, including fact sheets on each project. The final Phase III 44 projects are documented in a final Record of Decision. Information about Phase III of Early Archive Home Phase III of Early Restoration Phase III of Early Restoration Beach habitat would be restored

Phase II Clinical Trial of Intraoral Grafting of Human Tissue Engineered Oral Mucosa

DTIC Science & Technology

2017-10-01

experimental arm subject in the small defect study. A protocol amendment in early 2017revised the study inclusionary criteria to include all non ...construed as an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE...group phase II study to assess the safety and efficacy for use of human EVPOME for soft tissue intraoral grafting procedures compared to the “gold

Modular space station phase B extension integrated ground operations

NASA Technical Reports Server (NTRS)

Selegue, D. F.

1971-01-01

Requirements for development test, manufacturing, facilities, GSE, training, logistics support, and launch operations are described. The prime integrating requirement is the early establishment of a common data base and its use throughout the design, development, and operational life of the station. The common data base is defined, and the concept of its use is presented. Development requirements for the station modules and subsystems are outlined along with a master development phasing chart.

Space shuttle holddown post blast shield

NASA Technical Reports Server (NTRS)

Larracas, F. B.

1991-01-01

The original and subsequent designs of the Solid Rocket Booster/Holddown Post blast shield assemblies and their associated hardware are described. It presents the major problems encountered during their early use in the Space Shuttle Program, during the Return-to-Flight Modification Phase, and during their fabrication and validation testing phases. The actions taken to correct the problems are discussed, along with the various concepts now being considered to increase the useful life of the blast shield.

Definition of technology development missions for early space stations: Large space structures

NASA Technical Reports Server (NTRS)

Gates, R. M.; Reid, G.

1984-01-01

The objectives studied are the definition of the tested role of an early Space Station for the construction of large space structures. This is accomplished by defining the LSS technology development missions (TDMs) identified in phase 1. Design and operations trade studies are used to identify the best structural concepts and procedures for each TDMs. Details of the TDM designs are then developed along with their operational requirements. Space Station resources required for each mission, both human and physical, are identified. The costs and development schedules for the TDMs provide an indication of the programs needed to develop these missions.

Is it growing exponentially fast? -- Impact of assuming exponential growth for characterizing and forecasting epidemics with initial near-exponential growth dynamics.

PubMed

Chowell, Gerardo; Viboud, Cécile

2016-10-01

The increasing use of mathematical models for epidemic forecasting has highlighted the importance of designing models that capture the baseline transmission characteristics in order to generate reliable epidemic forecasts. Improved models for epidemic forecasting could be achieved by identifying signature features of epidemic growth, which could inform the design of models of disease spread and reveal important characteristics of the transmission process. In particular, it is often taken for granted that the early growth phase of different growth processes in nature follow early exponential growth dynamics. In the context of infectious disease spread, this assumption is often convenient to describe a transmission process with mass action kinetics using differential equations and generate analytic expressions and estimates of the reproduction number. In this article, we carry out a simulation study to illustrate the impact of incorrectly assuming an exponential-growth model to characterize the early phase (e.g., 3-5 disease generation intervals) of an infectious disease outbreak that follows near-exponential growth dynamics. Specifically, we assess the impact on: 1) goodness of fit, 2) bias on the growth parameter, and 3) the impact on short-term epidemic forecasts. Designing transmission models and statistical approaches that more flexibly capture the profile of epidemic growth could lead to enhanced model fit, improved estimates of key transmission parameters, and more realistic epidemic forecasts.

Assessing Risk/Benefit for Trials Using Preclinical Evidence: A Proposal

PubMed Central

Kimmelman, Jonathan; Henderson, Valerie C.

2015-01-01

Abstract Moral evaluation of risk/benefit in early phase studies requires assessing the clinical promise of a candidate intervention using preclinical evidence. Yet there is little to guide ethics committees, investigators, sponsors or other stakeholders morally charged with making these assessments (“evaluators”). In what follows, we draw on published guidelines for preclinical study design to develop a structured process for assessing the clinical promise of new interventions. In the first step, evaluators gather all relevant preclinical studies, assess the magnitude of treatment effects, and determine clinical promise in light of various threats to valid clinical inference. In the second step, evaluators adjust assessments of clinical promise from preclinical studies by examining how other agents in the same reference class-and supported by similar evidence- have fared in clinical development. Assessments of clinical promise can then be fed into moral evaluation of risk and benefit in early phase trials. Though our approach has limitations, it offers a systematic and transparent method for assessing risk/benefit in early phase trials of novel interventions. PMID:26463620

Development of the Sri Lankan early teenagers' violence inventory: an instrument to measure peer violence in schools.

PubMed

Wijeratne, Monika; Seneviratne, Rohini; Gunawardena, Nalika; Østbye, Truls; Lynch, Catherine; Sandøy, Ingvild Fossgard

2014-01-01

This study was designed to develop an inventory to measure peer violence among early teens (13-15 years of age) in schools in Sri Lanka. Development of SLETVI was carried out in two phases. In phase I, development of an operational definition for peer violence, identification, and finalizing violent acts for inventory was done by a combination of qualitative methods: a comprehensive literature review, focus group discussions among 13-15-year-old adolescents, their teachers and parents, and consultative meetings with experts in the field. Inventory was then pretested. In phase II, elaboration of SLETVI was carried out by administering it to a sample of 1700 adolescents (13-15 years old). Exploratory factor analysis using principal component analysis was performed separately for experiences of victimization and perpetration. Test-retest reliability of SLETVI was assessed. SLETVI included 37 items in three factors: "less severe violence," "severe physical," and "severe relational" violence. Combined use of qualitative and quantitative methods enabled development of a culturally valid and reliable operational inventory to assess early teenagers' peer violence in Sri Lankan and other South Asian schools.

Early dialogue between the developers of new technologies and pricing and reimbursement agencies: a pilot study.

PubMed

Backhouse, Martin E; Wonder, Michael; Hornby, Edward; Kilburg, Anne; Drummond, Michael; Mayer, Friedrich Karl

2011-06-01

It is common practice for developers of new health care technologies to engage in early dialogue with the major regulatory agencies; such discussions frequently center around the proposed clinical trial designs to support the registration of new interventions and suggestions on their improvement. Pricing and reimbursement agencies are increasingly using the results from health technology assessments to inform their decision making for new technologies. Such assessments are invariably underpinned by the phase 3 clinical trial evidence which may not provide answers to the key questions. Technology developers are beginning to realize that direct, early dialogue on the evidence requirements of the major pricing and reimbursement agencies, before phase 3 clinical trial designs for their key development compounds have been finalized, may be beneficial. This article reports on the pioneering efforts of one technology developer in seeking early dialogue with seven pricing and reimbursement agencies in five countries globally in 2007-2008 on their likely evidence requirements for a new oral treatment for patients with chronic plaque psoriasis. The pilot project demonstrated that a feasible process of early dialogue could be established, through a face-to-face meeting with prior circulation of a briefing book. Although there was some variation in the advice the similarities far outweighed the differences. More experience of early dialogue needs to be accumulated, involving a wider range of pricing and reimbursement agencies and compounds. The conclusion of this study, however, was that early dialogue can be a worthwhile process for all parties and can lead to a common understanding about evidence development for market access. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

PubMed

Nagpal, Anjali; Choy, Fong Chan; Howell, Stuart; Hillier, Susan; Chan, Fiona; Hamilton-Bruce, Monica A; Koblar, Simon A

2017-08-30

Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

Excellent Beginnings: Evaluation of Phase I (1991-1994).

ERIC Educational Resources Information Center

Brickman, Alan

In 1991 the Plan for Social Excellence, Inc., funded three elementary schools to design and implement a comprehensive early childhood education program. This funding initiative, entitled "Excellent Beginnings," supports programs that include innovative curriculum and classroom-management strategies, extensive parent participation, the use of high…

Why Early Prevention of Childhood Obesity Is More Than a Medical Concern: A Health Economic Approach.

PubMed

Sonntag, Diana

2017-01-01

Childhood overweight and obesity are a non-deniable health concern with increasing economic attention. International studies provide robust evidence about substantial lifetime excess costs due to childhood obesity, thereby underscoring the urgent need to implement potent obesity prevention programs in early childhood. Fortunately, this is happening more and more, as evidenced by the increase in well-conducted interventions. Nevertheless, an important piece of the puzzle is often missing, that is, health economic evaluations. There are 3 main reasons for this: an insufficient number of economic approaches which consider the complexity of childhood obesity, a lack of (significant) long-term effect sizes of an intervention, and inadequate planning of health economic evaluations in the design phase of an intervention. Key Messages: It is advisable to involve health economists during the design phase of an intervention. Equally necessary is the development of a tailored toolbox for efficient data acquisition. © 2017 S. Karger AG, Basel.

Optimizing the early phase development of new analgesics by human pain biomarkers.

PubMed

Arendt-Nielsen, Lars; Hoeck, Hans Christian

2011-11-01

Human pain biomarkers are based on standardized acute activation of pain pathways/mechanisms and quantitative assessment of the evoked responses. This approach can be applied to healthy volunteers, to pain patients, and before and after pharmacological interventions to help understanding and profile the mode of action (proof-of-concept) of new and existing analgesic compounds. Standardized stimuli of different modalities can be applied to different tissues (multimodal and multi-tissue) for profiling analgesic compounds with respect to modulation of pain transduction, transmission, specific mechanisms and processing. This approach substantiates which specific compounds may work in particular clinical pain conditions. Human pain biomarkers can be translational and may bridge animal findings in clinical pain conditions, which in turn can provide new possibilities for designing more successful clinical trials. Biomarker based proof-of-concept drug studies in either volunteers or selected patient populations provide inexpensive, fast and reliable mechanism-based information about dose-efficacy relationships. This is important information in the early drug development phase and for designing large expensive clinical trials.

Bayesian Dose-Response Modeling in Sparse Data

NASA Astrophysics Data System (ADS)

Kim, Steven B.

This book discusses Bayesian dose-response modeling in small samples applied to two different settings. The first setting is early phase clinical trials, and the second setting is toxicology studies in cancer risk assessment. In early phase clinical trials, experimental units are humans who are actual patients. Prior to a clinical trial, opinions from multiple subject area experts are generally more informative than the opinion of a single expert, but we may face a dilemma when they have disagreeing prior opinions. In this regard, we consider compromising the disagreement and compare two different approaches for making a decision. In addition to combining multiple opinions, we also address balancing two levels of ethics in early phase clinical trials. The first level is individual-level ethics which reflects the perspective of trial participants. The second level is population-level ethics which reflects the perspective of future patients. We extensively compare two existing statistical methods which focus on each perspective and propose a new method which balances the two conflicting perspectives. In toxicology studies, experimental units are living animals. Here we focus on a potential non-monotonic dose-response relationship which is known as hormesis. Briefly, hormesis is a phenomenon which can be characterized by a beneficial effect at low doses and a harmful effect at high doses. In cancer risk assessments, the estimation of a parameter, which is known as a benchmark dose, can be highly sensitive to a class of assumptions, monotonicity or hormesis. In this regard, we propose a robust approach which considers both monotonicity and hormesis as a possibility. In addition, We discuss statistical hypothesis testing for hormesis and consider various experimental designs for detecting hormesis based on Bayesian decision theory. Past experiments have not been optimally designed for testing for hormesis, and some Bayesian optimal designs may not be optimal under a wrong parametric assumption. In this regard, we consider a robust experimental design which does not require any parametric assumption.

Practical characteristics of adaptive design in phase 2 and 3 clinical trials.

PubMed

Sato, A; Shimura, M; Gosho, M

2018-04-01

Adaptive design methods are expected to be ethical, reflect real medical practice, increase the likelihood of research and development success and reduce the allocation of patients into ineffective treatment groups by the early termination of clinical trials. However, the comprehensive details regarding which types of clinical trials will include adaptive designs remain unclear. We examined the practical characteristics of adaptive design used in clinical trials. We conducted a literature search of adaptive design clinical trials published from 2012 to 2015 using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, with common search terms related to adaptive design. We systematically assessed the types and characteristics of adaptive designs and disease areas employed in the adaptive design trials. Our survey identified 245 adaptive design clinical trials. The number of trials by the publication year increased from 2012 to 2013 and did not greatly change afterwards. The most frequently used adaptive design was group sequential design (n = 222, 90.6%), especially for neoplasm or cardiovascular disease trials. Among the other types of adaptive design, adaptive dose/treatment group selection (n = 21, 8.6%) and adaptive sample-size adjustment (n = 19, 7.8%) were frequently used. The adaptive randomization (n = 8, 3.3%) and adaptive seamless design (n = 6, 2.4%) were less frequent. Adaptive dose/treatment group selection and adaptive sample-size adjustment were frequently used (up to 23%) in "certain infectious and parasitic diseases," "diseases of nervous system," and "mental and behavioural disorders" in comparison with "neoplasms" (<6.6%). For "mental and behavioural disorders," adaptive randomization was used in two trials of eight trials in total (25%). Group sequential design and adaptive sample-size adjustment were used frequently in phase 3 trials or in trials where study phase was not specified, whereas the other types of adaptive designs were used more in phase 2 trials. Approximately 82% (202 of 245 trials) resulted in early termination at the interim analysis. Among the 202 trials, 132 (54% of 245 trials) had fewer randomized patients than initially planned. This result supports the motive to use adaptive design to make study durations shorter and include a smaller number of subjects. We found that adaptive designs have been applied to clinical trials in various therapeutic areas and interventions. The applications were frequently reported in neoplasm or cardiovascular clinical trials. The adaptive dose/treatment group selection and sample-size adjustment are increasingly common, and these adaptations generally follow the Food and Drug Administration's (FDA's) recommendations. © 2017 John Wiley & Sons Ltd.

Early Palliative Care-Health services research and implementation of sustainable changes: the study protocol of the EVI project.

PubMed

Meffert, Cornelia; Gaertner, Jan; Seibel, Katharina; Jors, Karin; Bardenheuer, Hubert; Buchheidt, Dieter; Mayer-Steinacker, Regine; Viehrig, Marén; Paul, Christina; Stock, Stephanie; Xander, Carola; Becker, Gerhild

2015-05-29

International medical organizations such as the American Society of Medical Oncology recommend early palliative care as the "gold standard" for palliative care in patients with advanced cancer. Nevertheless, even in Comprehensive Cancer Centers, early palliative care is not yet routine practice. The main goal of the EVI project is to evaluate whether early palliative care can be implemented-in the sense of "putting evidence into practice"-into the everyday clinical practice of Comprehensive Cancer Centers. In addition, we are interested in (1) describing the type of support that patients would like from palliative care, (2) gaining information about the effect of palliative care on patients' quality of life, and (3) understanding the economic burden of palliative care on patients and their families. The EVI project is a multi-center, prospective cohort study with a sequential control group design. The study is a project of the Palliative Care Center of Excellence (KOMPACT) in Baden-Württemberg, Germany, which was recently established to combine the expertise of five academic, specialist palliative care departments. The study is divided into two phases: preliminary phase (months 1-9) and main study phase (months 10-18). In each of all five participating academic Comprehensive Cancer Centers, an experienced palliative care physician will be hired for 18 months. During the preliminary phase, the physician will be allowed time to establish the necessary structures for early palliative care within the Comprehensive Cancer Center. In the main study phase, patients with metastatic cancer will be offered a consultation with the palliative care physician within eight weeks of diagnosis. After the initial consultation, follow-up consultations will be offered as needed. The study is built upon a convergent parallel design. In the quantitative arm, patients will be surveyed in both the preliminary and main study phase at three points in time (baseline, 12 weeks, 24 weeks). Standardized questionnaires will be used to measure patients' quality of life, symptom burden and mood. Using interviews with palliative care physicians, oncologists, department heads, patients and their caregivers, the qualitative arm will explore (1) what factors encourage and hinder the early integration of palliative care into standard oncology care, (2) what support patients and their caregivers would like from palliative care, and (3) what effect palliative care has on the economic disease burden of patients and their families. The study proposed is meant to serve as a catalyzer. Local palliative care teams should be put in position to routinely cooperate with the primary treating department at their respective cancer center. The long-term goal of this project is to create sustainable improvements in the care of patients with incurable cancer. DRKS00006162 ; date of registration: 19/05/2014.

Operator Station Design System - A computer aided design approach to work station layout

NASA Technical Reports Server (NTRS)

Lewis, J. L.

1979-01-01

The Operator Station Design System is resident in NASA's Johnson Space Center Spacecraft Design Division Performance Laboratory. It includes stand-alone minicomputer hardware and Panel Layout Automated Interactive Design and Crew Station Assessment of Reach software. The data base consists of the Shuttle Transportation System Orbiter Crew Compartment (in part), the Orbiter payload bay and remote manipulator (in part), and various anthropometric populations. The system is utilized to provide panel layouts, assess reach and vision, determine interference and fit problems early in the design phase, study design applications as a function of anthropometric and mission requirements, and to accomplish conceptual design to support advanced study efforts.

Evidence-based design in an intensive care unit: end-user perceptions.

PubMed

Ferri, Mauricio; Zygun, David A; Harrison, Alexandra; Stelfox, Henry T

2015-04-25

The objective of this study was to describe end-user impressions and experiences in a new intensive care unit built using evidence-based design. This qualitative study was comprised of early (2-3 months after opening) and late (12-15 months after opening) phase individual interviews with end-users (healthcare providers, support staff, and patient family members) of the newly constructed Foothills Medical Centre intensive care unit in Calgary, Canada. The study unit was the recipient of the Society of Critical Care Medicine Design Citation award in 2012. We conducted interviews with thirty-nine ICU end-users, twenty-four in the early phase and fifteen in the late phase. We identified four themes (eleven sub-themes): atmosphere (abundant natural light and low noise levels), physical spaces (single occupancy rooms, rooms clustered into clinical pods, medication rooms, and tradeoffs of larger spaces), family participation in care (family support areas and social networks), and equipment (usability, storage, and providers connectivity). Abundant natural light was the design feature most frequently associated with a pleasant atmosphere. Participants emphasized the tradeoffs of size and space, and reported that the benefits of additional space (e.g., fewer interruptions due to less noise) out-weighed the disadvantages (e.g., greater distances between patients, families and providers). End-users advised that local patient care policies (e.g., number of visitors allowed at a time) and staffing needed to be updated to reflect the characteristics of the new facility design. End-users identified design elements for creating a pleasant atmosphere, attention to the tradeoffs of space and size, designing family support areas to encourage family participation in care, and updating patient care policies and staffing to reflect the new physical space as important aspects to consider when building intensive care units. Evidence-based design may optimize ICU structure for patients, patient families and providers.

Design to Cost and Life Cycle Cost.

DTIC Science & Technology

1980-07-01

The data are also based on a sample of reporting squadrons. Though the VAMOSC MS offers an excellent capability to deal with design-related issues...levels as predictions in the early design phase of a program. Figure 4 presents sample FY-78 costs from the VAMOSC MS report. The costs are on a cost...equlipmlent before attachlmenlt to adjacent sectionls. Ibis allows tile work tol be performed within thC reachl of tile most1 efficient equipment and w4ithl

Software development for airborne radar

NASA Astrophysics Data System (ADS)

Sundstrom, Ingvar G.

Some aspects for development of software in a modern multimode airborne nose radar are described. First, an overview of where software is used in the radar units is presented. The development phases-system design, functional design, detailed design, function verification, and system verification-are then used as the starting point for the discussion. Methods, tools, and the most important documents are described. The importance of video flight recording in the early stages and use of a digital signal generators for performance verification is emphasized. Some future trends are discussed.

Integrating post-manufacturing issues into design and manufacturing decisions

NASA Technical Reports Server (NTRS)

Eubanks, Charles F.

1996-01-01

An investigation is conducted on research into some of the fundamental issues underlying the design for manufacturing, service and recycling that affect engineering decisions early in the conceptual design phase of mechanical systems. The investigation focuses on a system-based approach to material selection, manufacturing methods and assembly processes related to overall product requirements, performance and life-cycle costs. Particular emphasis is placed on concurrent engineering decision support for post-manufacturing issues such as serviceability, recyclability, and product retirement.

Command and Control of Guerrilla Groups in the Philippines, 1941-1945

DTIC Science & Technology

2017-05-25

However, the phasing concept in this case seems ex post facto , rather than descriptive of any initial design. Especially in its early days, the trajectory... post -independence era. They apply a framework that examines the environment, organization, tactics, doctrine, and technology of each phase of history...defenses on Mindanao and destroyed the bulk of Sharp’s force, though the command post at Del Monte remained intact.33 On May 9, Sharp met with a

3S (Safeguards, Security, Safety) based pyroprocessing facility safety evaluation plan

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

Ku, J.H.; Choung, W.M.; You, G.S.

The big advantage of pyroprocessing for the management of spent fuels against the conventional reprocessing technologies lies in its proliferation resistance since the pure plutonium cannot be separated from the spent fuel. The extracted materials can be directly used as metal fuel in a fast reactor, and pyroprocessing reduces drastically the volume and heat load of the spent fuel. KAERI has implemented the SBD (Safeguards-By-Design) concept in nuclear fuel cycle facilities. The goal of SBD is to integrate international safeguards into the entire facility design process since the very beginning of the design phase. This paper presents a safety evaluationmore » plan using a conceptual design of a reference pyroprocessing facility, in which 3S (Safeguards, Security, Safety)-By-Design (3SBD) concept is integrated from early conceptual design phase. The purpose of this paper is to establish an advanced pyroprocessing hot cell facility design concept based on 3SBD for the successful realization of pyroprocessing technology with enhanced safety and proliferation resistance.« less

Outline of a Twenty-Five Year Plan for Development and Deployment of A Catapult for A Third Generation Space Shuttle

NASA Technical Reports Server (NTRS)

Russell, John M.

2002-01-01

This report reviews the rationale for catapult assist in the launching a third generation space shuttle. It then furnishes lists of early design decisions, questions whose answers are prerequisite to later design decisions, preliminary inventories of carriage levitation and carriage propulsion concepts, phases of the project and major milestones, and some sources of expertise to support the project.

Outline Of A Twenty-Five Year Plan For Development And Deployment Of a Catapult For a Third Generation Space Shuttle

NASA Technical Reports Server (NTRS)

Russell, John M.

2001-01-01

This report reviews the rationale for catapult assist in the launching of a third generation space shuttle. It then furnishes lists of early design decisions, questions whose answers are prerequisite to later design decisions, preliminary inventories of carriage levitation and carriage propulsion concepts, phases of the project and major milestones, and some sources of expertise to support the project.

Crossing eastern cottonwood in the greenhouse

Treesearch

R. E. Farmer; W. L. Nance

1968-01-01

Eastern cottonwood (Populus deltoides Bartr.) is the subject of breeding programs designed to develop planting stock with potential for rapid growth, desirable wood properties, and pest resistance (4). Techniques for making controlled crosses within the species are essential to breeding, and their development constitutes an early phase of genetics...

Phase V of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Phase V Early Restoration Plan and Environmental Assessment. The project will acquire land along Florida million. Phase V Early Restoration Plan and Environmental Assessment (pdf, 10 MB) Draft Phase V Early Restoration Plan and Environmental Assessment (Executive Summary) (2 MB) Phase V Fact Sheet (pdf, 2 MB) Gulf

Comparison of Occlusive and Open Application in a Psoriasis Plaque Test Design, Exemplarily Using Investigations of Mapracorat 0.1% Ointment versus Vehicle and Reference Drugs.

PubMed

Wigger-Alberti, Walter; Williams, Ragna; von Mackensen, Yi-Ling; Hoffman-Wecker, Maciej; Grossmann, Ulrike; Staedtler, Gerald; Nkulikiyinka, Richard; Shakery, Kaweh

2017-01-01

Psoriasis plaque tests (PPTs) are important tools in the early phases of antipsoriatic drug development. Two distinct PPT design variants (open vs. occluded drug application) are commonly used, but no previous work has aimed to directly compare and contrast their performance. We compared the antipsoriatic efficacy of mapracorat 0.1% ointment and reference drugs reported in 2 separate studies, representing open and occluded PPT designs. The drug effect size was measured by sonography (mean change in echo-poor band thickness), chromametry, and standardized clinical assessment. Antipsoriatic effects were detectable for the study drugs in both occluded and open PPTs. Differences between the potency of antipsoriatic drugs and vehicle were observable. The total antipsoriatic effect size appeared to be higher in the occluded PPT than the open PPT, despite the shorter treatment duration (2 vs. 4 weeks). Effect dynamics over time revealed greater differences between some study drugs in the open PPT compared to the occluded PPT. Taking the higher technical challenges for the open PPT into account, we recommend the occluded PPT as a standard screening setting in early drug development. In special cases, considering certain drug aspects or study objectives that would require procedural adaptations, an open PPT could be the better-suited design. Finally, both PPT models show clear advantages: classification as phase I studies, small number of psoriatic subjects, relatively short study duration, excellent discrimination between compounds and concentrations, parallel measurement of treatment response, and go/no go decisions very early in clinical development. © 2017 S. Karger AG, Basel.

Range and trend of expected toxicity level (ETL) in standard A + B designs: a report from the Children's Oncology Group.

PubMed

Chen, Zhengjia; Krailo, Mark D; Sun, Junfeng; Azen, Stanley P

2009-03-01

The traditional algorithm-based 3+3 designs are most widely used for their practical simplicity in phase I clinical trials. At early stage, a common belief was that the expected toxicity level (ETL) at the maximum tolerated dose (MTD) should be 33% [Storer, B. Design and analysis of phase I clinical trials. Biometrics 1989;45;925-937, Gorden, N., Willson, J. Using toxicity grades in the design and analysis of cancer phase I clinical trials. Statistics in Medicine 1992; 11: 2063-2075, Mick, R. Phase I Clinical Trial Design. In Schilsky, R., Milano, G., Ratain, M., eds. Principles of Antineoplastic Drug Development and Pharmacology New York, NY: Marcel Dekker, 1996; 29-36]. Recently, Kang and Ahn [Kang, S., Ahn, C. The expected toxicity rate at the maximum tolerated dose in the standard phase I cancer clinical trial design. Drug Information Journal 2001; 35:1189-1199, Kang, S., Ahn, C. An investigation of the traditional algorithm-based designs for phase I cancer clinical trials. Drug Information Journal 2002; 36:865-873] found that the ETL is between 17% and 21% and He et al [He, W., Liu, J., Binkowitz, B., Quan, H. A model-based approach in the estimation of the maximum tolerated dose in phase I cancer clinical trials. Statistics in Medicine 2006; 25(12):2027-42] further reported that the ETL ranges from 19% to 24%. However they only investigated designs where the number of dose levels was at most 20. It has practical significance in designing and conducting phase I clinical trial to definitely assess the full range and trend of ETL by all possible number of tested dose levels in traditional algorithm-based A+B designs, especially 3+3 designs. In this simulation study, we originally find that the ETL decreases monotonically from about 30% to 0% as the number of dose levels increase from 3 to infinity, which will correct the inaccuracy in the common belief among phase I trial investigators. To help better design and conduct phase I trials, we create a table as a reference for the association between ETL and number of dose levels considered in a design when the exact shape of the dose-toxicity relationship is not well understood. We conclude that the number of specified dose levels is an important factor affecting substantially the ETL at MTD and recommend that fewer than 20 dose levels be designated.

Phased-array radar for airborne systems

NASA Astrophysics Data System (ADS)

Tahim, Raghbir S.; Foshee, James J.; Chang, Kai

2003-09-01

Phased array antenna systems, which support high pulse rates and high transmit power, are well suited for radar and large-scale surveillance. Sensors and communication systems can function as the eyes and ears for ballistic missile defense applications, providing early warning of attack, target detection and identification, target tracking, and countermeasure decision. In such applications, active array radar systems that contain solid-state transmitter sources and low-noise preamplifiers for transmission and reception are preferred over the conventional radar antennas, because the phased array radar offers the advantages of power management and efficiency, reliability, signal reception, beam steering target detection. The current phased array radar designs are very large, complex and expensive and less efficient because of high RF losses in the phase control circuits used for beam scan. Several thousands of phase shifters and drivers may be required for a single system thus making the system very complex and expensive. This paper describes the phased array radar system based on high power T/R modules, wide-band radiating planar antenna elements and very low loss wide-band phase control circuits (requiring reduced power levels) for beam scan. The phase shifter design is based on micro-strip feed lines perturbed by the proximity of voltage controlled piezoelectric transducer (PET). Measured results have shown an added insertion loss of less than 1 dB for a phase shift of 450 degrees from 2 to 20 GHz. The new wideband phased array radar design provides significant reduction in size cost and weight. Compared to the conventional phased array systems, the cost saving is more than 15 to 1.

Effect of GNSS receiver carrier phase tracking loops on earthquake monitoring performance

NASA Astrophysics Data System (ADS)

Clare, Adam; Lin, Tao; Lachapelle, Gérard

2017-06-01

This research focuses on the performance of GNSS receiver carrier phase tracking loops for early earthquake monitoring systems. An earthquake was simulated using a hardware simulator and position, velocity and acceleration displacements were obtained to recreate the dynamics of the 2011 Tohoku earthquake. Using a software defined receiver, GSNRx, tracking bandwidths of 5, 10, 15, 20, 30, 40 and 50 Hz along with integration times of 1, 5 and 10 ms were tested. Using the phase lock indicator, an adaptive tracking loop was designed and tested to maximize performance for this application.

Singularity classification as a design tool for multiblock grids

NASA Technical Reports Server (NTRS)

Jones, Alan K.

1992-01-01

A major stumbling block in interactive design of 3-D multiblock grids is the difficulty of visualizing the design as a whole. One way to make this visualization task easier is to focus, at least in early design stages, on an aspect of the grid which is inherently easy to present graphically, and to conceptualize mentally, namely the nature and location of singularities in the grid. The topological behavior of a multiblock grid design is determined by what happens at its edges and vertices. Only a few of these are in any way exceptional. The exceptional behaviors lie along a singularity graph, which is a 1-D construct embedded in 3-D space. The varieties of singular behavior are limited enough to make useful symbology on a graphics device possible. Furthermore, some forms of block design manipulation that appear appropriate to the early conceptual-modeling phase can be accomplished on this level of abstraction. An overview of a proposed singularity classification scheme and selected examples of corresponding manipulation techniques is presented.

Brain responses to food images during the early and late follicular phase of the menstrual cycle in healthy young women: relation to fasting and feeding1234

PubMed Central

Ziemke, Florencia; Magkos, Faidon; Barrios, Fernando A; Brinkoetter, Mary; Boyd, Ingrid; Rifkin-Graboi, Anne; Yannakoulia, Mary; Rojas, Rafael; Pascual-Leone, Alvaro; Mantzoros, Christos S

2011-01-01

Background: Food intake fluctuates throughout the menstrual cycle; it is greater during the early follicular and luteal phases than in the late follicular (periovulatory) phase. Ovarian steroids can influence brain areas that process food-related information, but the specific contribution of individual hormones and the importance of the prandial state remain unknown. Objective: The objective was to examine whether brain activation during food visualization is affected by changes in estradiol concentration in the fasted and fed conditions. Design: Nine eumenorrheic, lean young women [mean (±SD) age: 26.2 ± 3.2 y; body mass index (in kg/m2): 22.4 ± 1.2] completed 2 visits, one in the early (low estradiol) and one in the late (high estradiol) follicular phase of their menstrual cycle. At each visit, subjects underwent functional magnetic resonance imaging while they viewed food and nonfood images, before and after a standardized meal. Region-of-interest analysis was used to examine the effect of follicular phase and prandial state on brain activation (food > nonfood contrast) and its association with estradiol concentration. Results: Differences were identified in the inferior frontal and fusiform gyri. In these areas, visualization of food elicited greater activation in the fed state than during fasting but only in the late follicular phase, when estradiol concentration was high. The change in estradiol concentration across the follicular phase (late minus early) was inversely correlated with the change in fusiform gyrus activation in the fasted state but not in the fed state. Conclusion: Our findings suggest that estradiol may reduce food intake by decreasing sensitivity to food cues in the ventral visual pathway under conditions of energy deprivation. This trial was registered at clinicaltrials.gov as NCT00130117. PMID:21593494

Space Station Freedom Toxic and Reactive Materials Handling

NASA Technical Reports Server (NTRS)

Baugher, Charles R. (Editor)

1990-01-01

Viable research in materials processing in space requires the utilization of a wide variety of chemicals and materials, many of which are considered toxic and/or highly reactive with other substances. A realistic view of the experiments which are most likely to be accomplished in the early Space Station phases are examined and design issues addressed which are related to their safe implementation. Included are discussions of materials research on Skylab, Spacelab, and the Shuttle mid-deck; overviews of early concepts for specialized Space Station systems designed to help contain potential problems; descriptions of industrial experience with ground-based research; and an overview of the state-of-the-art in contamination detection systems.

Software Tools for Formal Specification and Verification of Distributed Real-Time Systems.

DTIC Science & Technology

1997-09-30

set of software tools for specification and verification of distributed real time systems using formal methods. The task of this SBIR Phase II effort...to be used by designers of real - time systems for early detection of errors. The mathematical complexity of formal specification and verification has

China Earthquake Relief: Participatory Action Work with Children

ERIC Educational Resources Information Center

Zeng, Emily Jie; Silverstein, Louise Bordeaux

2011-01-01

This article presents a community-focused participatory action project designed to promote children's resilience in the early aftermath of the cataclysmic May 2008 Earthquake in Beichuan, China. Thirty children aged 7- to 15-years-old participated in the project. The project encompassed four phases that evolved from adult-directed/initiated…

40 CFR 73.20 - Phase II early reduction credits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... utility, including generators that are not fossil fuel-fired) that has decreased its total coal-fired... quality of fuel being burned. (c) Initial certification of eligibility. The designated representative of a... reductions in sulfur dioxide emissions; and (2) A report listing all units in the utility system, each fossil...

Launch vehicle design and GNC sizing with ASTOS

NASA Astrophysics Data System (ADS)

Cremaschi, Francesco; Winter, Sebastian; Rossi, Valerio; Wiegand, Andreas

2018-03-01

The European Space Agency (ESA) is currently involved in several activities related to launch vehicle designs (Future Launcher Preparatory Program, Ariane 6, VEGA evolutions, etc.). Within these activities, ESA has identified the importance of developing a simulation infrastructure capable of supporting the multi-disciplinary design and preliminary guidance navigation and control (GNC) design of different launch vehicle configurations. Astos Solutions has developed the multi-disciplinary optimization and launcher GNC simulation and sizing tool (LGSST) under ESA contract. The functionality is integrated in the Analysis, Simulation and Trajectory Optimization Software for space applications (ASTOS) and is intended to be used from the early design phases up to phase B1 activities. ASTOS shall enable the user to perform detailed vehicle design tasks and assessment of GNC systems, covering all aspects of rapid configuration and scenario management, sizing of stages, trajectory-dependent estimation of structural masses, rigid and flexible body dynamics, navigation, guidance and control, worst case analysis, launch safety analysis, performance analysis, and reporting.

Early stage design decisions: the way to achieve sustainable buildings at lower costs.

PubMed

Bragança, Luís; Vieira, Susana M; Andrade, Joana B

2014-01-01

The construction industry attempts to produce buildings with as lower environmental impact as possible. However, construction activities still greatly affect environment; therefore, it is necessary to consider a sustainable project approach based on its performance. Sustainability is an important issue to consider in design, not only due to environmental concerns but also due to economic and social matters, promoting architectural quality and economic advantages. This paper aims to identify the phases through which a design project should be developed, emphasising the importance and ability of earlier stages to influence sustainability, performance, and life cycle cost. Then, a selection of sustainability key indicators, able to be used at the design conceptual phase and able to start predicting environmental sustainability performance of buildings is presented. The output of this paper aimed to enable designers to compare and evaluate the consequences of different design solutions, based on preliminary data, and facilitate the collaboration between stakeholders and clients and eventually yield a sustainable and high performance building throughout its life cycle.

Early Stage Design Decisions: The Way to Achieve Sustainable Buildings at Lower Costs

PubMed Central

Bragança, Luís; Vieira, Susana M.; Andrade, Joana B.

2014-01-01

The construction industry attempts to produce buildings with as lower environmental impact as possible. However, construction activities still greatly affect environment; therefore, it is necessary to consider a sustainable project approach based on its performance. Sustainability is an important issue to consider in design, not only due to environmental concerns but also due to economic and social matters, promoting architectural quality and economic advantages. This paper aims to identify the phases through which a design project should be developed, emphasising the importance and ability of earlier stages to influence sustainability, performance, and life cycle cost. Then, a selection of sustainability key indicators, able to be used at the design conceptual phase and able to start predicting environmental sustainability performance of buildings is presented. The output of this paper aimed to enable designers to compare and evaluate the consequences of different design solutions, based on preliminary data, and facilitate the collaboration between stakeholders and clients and eventually yield a sustainable and high performance building throughout its life cycle. PMID:24578630

The NASA pollution-reduction technology program for small jet aircraft engines

NASA Technical Reports Server (NTRS)

Fear, J. S.

1976-01-01

Three advanced combustor concepts, designed for the AiResearch TFE 731-2 turbofan engine, were evaluated in screening tests. Goals for carbon monoxide and unburned hydrocarbons were met or closely approached with two of the concepts with relatively modest departures from conventional combustor design practices. A more advanced premixing/prevaporizing combustor, while appearing to have the potential for meeting the oxides of nitrogen goal as well, will require extensive development to make it a practical combustion system. Smoke numbers for the two combustor concepts were well within the EPA smoke standard. Phase 2, Combustor-Engine Compatibility Testing, which is in its early stages, and planned Phase 3, Combustor-Engine Demonstration Testing, are also described.

Expected Science Performance of the Square Kilometre Array Phase 1 (SKA1)

NASA Astrophysics Data System (ADS)

Bourke, Tyler; Braun, Robert; Bonaldi, Anna; Garcia-Miro, Cristina; Keane, Evan; Wagg, Jeff; SKAO Science Team

2018-01-01

The Square Kilometre Array (SKA) will be the world’s largest radio telescope when Phase 1 (SKA1) is completed in the next decade. The past few years have seen great progress toward this goal, through extensive design activities, with construction to start before the end of this decade, and early operations anticipated to begin around 2026. This poster describes the SKA and presents the expected performance and capabilities of SKA1 based on the modelling and proto-typing to date.

Two-stage phase II oncology designs using short-term endpoints for early stopping.

PubMed

Kunz, Cornelia U; Wason, James Ms; Kieser, Meinhard

2017-08-01

Phase II oncology trials are conducted to evaluate whether the tumour activity of a new treatment is promising enough to warrant further investigation. The most commonly used approach in this context is a two-stage single-arm design with binary endpoint. As for all designs with interim analysis, its efficiency strongly depends on the relation between recruitment rate and follow-up time required to measure the patients' outcomes. Usually, recruitment is postponed after the sample size of the first stage is achieved up until the outcomes of all patients are available. This may lead to a considerable increase of the trial length and with it to a delay in the drug development process. We propose a design where an intermediate endpoint is used in the interim analysis to decide whether or not the study is continued with a second stage. Optimal and minimax versions of this design are derived. The characteristics of the proposed design in terms of type I error rate, power, maximum and expected sample size as well as trial duration are investigated. Guidance is given on how to select the most appropriate design. Application is illustrated by a phase II oncology trial in patients with advanced angiosarcoma, which motivated this research.

Selection of a turbine cooling system applying multi-disciplinary design considerations.

PubMed

Glezer, B

2001-05-01

The presented paper describes a multi-disciplinary cooling selection approach applied to major gas turbine engine hot section components, including turbine nozzles, blades, discs, combustors and support structures, which maintain blade tip clearances. The paper demonstrates benefits of close interaction between participating disciplines starting from early phases of the hot section development. The approach targets advancements in engine performance and cost by optimizing the design process, often requiring compromises within individual disciplines.

Development of the Sri Lankan Early Teenagers' Violence Inventory: An Instrument to Measure Peer Violence in Schools

PubMed Central

Seneviratne, Rohini; Østbye, Truls; Lynch, Catherine; Sandøy, Ingvild Fossgard

2014-01-01

This study was designed to develop an inventory to measure peer violence among early teens (13–15 years of age) in schools in Sri Lanka. Development of SLETVI was carried out in two phases. In phase I, development of an operational definition for peer violence, identification, and finalizing violent acts for inventory was done by a combination of qualitative methods: a comprehensive literature review, focus group discussions among 13–15-year-old adolescents, their teachers and parents, and consultative meetings with experts in the field. Inventory was then pretested. In phase II, elaboration of SLETVI was carried out by administering it to a sample of 1700 adolescents (13–15 years old). Exploratory factor analysis using principal component analysis was performed separately for experiences of victimization and perpetration. Test-retest reliability of SLETVI was assessed. SLETVI included 37 items in three factors: “less severe violence,” “severe physical,” and “severe relational” violence. Combined use of qualitative and quantitative methods enabled development of a culturally valid and reliable operational inventory to assess early teenagers' peer violence in Sri Lankan and other South Asian schools. PMID:25061607

Interdyad differences in early mother-infant face-to-face communication: real-time dynamics and developmental pathways.

PubMed

Lavelli, Manuela; Fogel, Alan

2013-12-01

A microgenetic research design with a multiple case study method and a combination of quantitative and qualitative analyses was used to investigate interdyad differences in real-time dynamics and developmental change processes in mother-infant face-to-face communication over the first 3 months of life. Weekly observations of 24 mother-infant dyads with analyses performed dyad by dyad showed that most dyads go through 2 qualitatively different developmental phases of early face-to-face communication: After a phase of mutual attentiveness, mutual engagement begins in Weeks 7-8, with infant smiling and cooing bidirectionally linked with maternal mirroring. This gives rise to sequences of positive feedback that, by the 3rd month, dynamically stabilizes into innovative play routines. However, when there is a lack of bidirectional positive feedback between infant and maternal behaviors, and a lack of permeability of the early communicative patterns to incorporate innovations, the development of the mutual engagement phase is compromised. The findings contribute both to theories of relationship change processes and to clinical work with at-risk mother-infant interactions. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Phase IV of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Trustees published the Final Phase IV Early Restoration Plan and Environmental Assessments. The plan habitats. Useful Links: Final Phase IV Early Restoration Plan and Environmental Assessments (pdf, 4.8 MB ) Final Phase IV Early Restoration Plan and Environmental Assessments Executive Summary (pdf, 729 KB

Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Early Restoration Plan. On April 20, 2011 we reached an agreement with BP to start restoration planning draft plan for the third phase of early restoration in December 2013. We are considering your comments : All Phase III information and documents Phase II Useful Links: Phase II Early Restoration Plan &

The impact of arthritis on the early employment experiences of young adults: A literature review.

PubMed

Jetha, Arif

2015-07-01

Young adulthood is an important transitional life phase that can determine a person's career trajectory. To date, little research has examined the influence of arthritis on early work experiences. This literature review aims at examining the impact of arthritis on the early career phase of young adults and identifying the barriers to employment. Two independent reviewers searched bibliographic databases for arthritis conditions and a series of employment-related keywords and subject headings. Information on authors, publication year; study design, sample characteristics (e.g., number of participants, age, gender, arthritis type); work outcomes measured; and specific barriers to employment was recorded. Nine studies were uncovered in the review. All studies examined young people with juvenile arthritis (9 of 9 studies) and consisted of sample sizes with less then 150 participants (6 of 9 studies) who were primarily recruited from clinics (7 of 9 studies). All were cross-sectional designs. Employment status was primarily examined and ranged from 11% to 71%. Although not always statistically significant, young adults with arthritis were less likely to be employed when compared to their healthy peers. Greater disease severity, less educational attainment and being female were related to not participating in paid work. This review brings to light the paucity of studies examining the early employment experiences of young adults with arthritis. There is a need to expand research to contribute to recommendations for sustained and productive employment across the working life course. Copyright © 2015 Elsevier Inc. All rights reserved.

Experience and Assessment of the DOE/NASA Mod-1 2000 Kw Wind Turbine Generator at Boone, North Carolina

NASA Technical Reports Server (NTRS)

Collins, J. L.; Shaltens, R. K.; Poor, R. H.; Barton, R. S.

1982-01-01

The Mod 1 program objectives are defined. The Mod 1 wind turbine is described. In addition to the steel blade operated on the wind turbine, a composite blade was designed and manufactured. During the early phase of the manufacturing cycle of Mod 1A configuration was designed that identified concepts such as partial span control, a soft tower, and upwind teetered rotors that were incorporated in second and third generation industry designs. The Mod 1 electrical system performed as designed, with voltage flicker characteristics within acceptable utility limits.

Multiobjective optimization applied to structural sizing of low cost university-class microsatellite projects

NASA Astrophysics Data System (ADS)

Ravanbakhsh, Ali; Franchini, Sebastián

2012-10-01

In recent years, there has been continuing interest in the participation of university research groups in space technology studies by means of their own microsatellites. The involvement in such projects has some inherent challenges, such as limited budget and facilities. Also, due to the fact that the main objective of these projects is for educational purposes, usually there are uncertainties regarding their in orbit mission and scientific payloads at the early phases of the project. On the other hand, there are predetermined limitations for their mass and volume budgets owing to the fact that most of them are launched as an auxiliary payload in which the launch cost is reduced considerably. The satellite structure subsystem is the one which is most affected by the launcher constraints. This can affect different aspects, including dimensions, strength and frequency requirements. In this paper, the main focus is on developing a structural design sizing tool containing not only the primary structures properties as variables but also the system level variables such as payload mass budget and satellite total mass and dimensions. This approach enables the design team to obtain better insight into the design in an extended design envelope. The structural design sizing tool is based on analytical structural design formulas and appropriate assumptions including both static and dynamic models of the satellite. Finally, a Genetic Algorithm (GA) multiobjective optimization is applied to the design space. The result is a Pareto-optimal based on two objectives, minimum satellite total mass and maximum payload mass budget, which gives a useful insight to the design team at the early phases of the design.

Design decisions from the history of the EUVE science payload

NASA Technical Reports Server (NTRS)

Marchant, W.

1993-01-01

Some of the design issues that arose during the development of the EUVE science payload and solutions to the problems involved are examined. In particular, attention is given to the use of parallel and serial busses, the selection of the the ROM approach for software storage and execution, implementation of memory error detection and correction, and the selection of command structures. The early design decisions paid off in the timely delivery of the scientific payload and in the successful completion of the survey phase of the EUVE science mission.

Design decisions from the history of the EUVE science payload

NASA Astrophysics Data System (ADS)

Marchant, W.

1993-09-01

Some of the design issues that arose during the development of the EUVE science payload and solutions to the problems involved are examined. In particular, attention is given to the use of parallel and serial busses, the selection of the the ROM approach for software storage and execution, implementation of memory error detection and correction, and the selection of command structures. The early design decisions paid off in the timely delivery of the scientific payload and in the successful completion of the survey phase of the EUVE science mission.

Radiation Hardness Assurance (RHA) for Space Systems

NASA Technical Reports Server (NTRS)

Poivey, Christian; Buchner, Stephen

2007-01-01

This presentation discusses radiation hardness assurance (RHA) for space systems, providing both the programmatic aspects of RHA and the RHA procedure. RHA consists of all activities undertaken to ensure that the electronics and materials of a space system perform to their design specifications after exposure to the space radiation environment. RHA also pertains to environment definition, part selection, part testing, spacecraft layout, radiation tolerant design, and mission/system/subsystems requirements. RHA procedure consists of establishing mission requirements, defining and evaluating the radiation hazard, selecting and categorizing the appropriate parts, and evaluating circuit response to hazard. The RHA approach is based on risk management and is confined only to parts, it includes spacecraft layout, system/subsystem/circuit design, and system requirements and system operations. RHA should be taken into account in the early phases of a program including the proposal and feasibility analysis phases.

Concurrent Design used in the Design of Space Instruments

NASA Technical Reports Server (NTRS)

Oxnevad, Knut I.

1998-01-01

At the Project Design Center at the Jet Propulsion Laboratory, a concurrent design environment is under development for supporting development and analyses of space instruments in the early, conceptual design phases. This environment is being utilized by a Team I, a multidisciplinary group of experts. Team I is providing study and proposal support. To provide the required support, the Team I concurrent design environment features effectively interconnected high-end optics, CAD, and thermal design and analysis tools. Innovative approaches for linking tools, and for transferring files between applications have been implemented. These approaches together with effective sharing of geometry between the optics, CAD, and thermal tools are already showing significant timesavings.

Supporting Universal Prevention Programs: A Two-Phased Coaching Model

ERIC Educational Resources Information Center

Becker, Kimberly D.; Darney, Dana; Domitrovich, Celene; Keperling, Jennifer Pitchford; Ialongo, Nicholas S.

2013-01-01

Schools are adopting evidence-based programs designed to enhance students' emotional and behavioral competencies at increasing rates (Hemmeter et al. in "Early Child Res Q" 26:96-109, 2011). At the same time, teachers express the need for increased support surrounding implementation of these evidence-based programs (Carter and Van Norman in "Early…

Portable Life Support System: PLSS 101

NASA Technical Reports Server (NTRS)

Thomas, Gretchen A.

2011-01-01

This presentation reviewed basic interfaces and considerations necessary for prototype suit hardware integration from an advanced spacesuit engineer perspective during the early design and test phases. The discussion included such topics such as the human interface, suit pass-throughs, keep-out zones, hardware form factors, subjective feedback from suit tests, and electricity in the suit.

Approach to developing reliable space reactor power systems

NASA Technical Reports Server (NTRS)

Mondt, Jack F.; Shinbrot, Charles H.

1991-01-01

During Phase II, the Engineering Development Phase, the SP-100 Project has defined and is pursuing a new approach to developing reliable power systems. The approach to developing such a system during the early technology phase is described along with some preliminary examples to help explain the approach. Developing reliable components to meet space reactor power system requirements is based on a top-down systems approach which includes a point design based on a detailed technical specification of a 100-kW power system. The SP-100 system requirements implicitly recognize the challenge of achieving a high system reliability for a ten-year lifetime, while at the same time using technologies that require very significant development efforts. A low-cost method for assessing reliability, based on an understanding of fundamental failure mechanisms and design margins for specific failure mechanisms, is being developed as part of the SP-100 Program.

Brief: Multizone subsea completions in the Dai Hung field, Vietnam

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

Lay, K.R.

1996-04-01

The early production phase of the Dai Hung field development involved drilling and completion of five subsea wells. Owing to the complex nature of the reservoirs, selective multizone completions were installed for effective reservoir data acquisition and reservoir management. Downhole completion designs used equipment that was primarily of existing proven design, and downhole equipment was installed in a single trip. Ongoing reservoir management will be aided by use of a subsea wireline system to facilitate data acquisition.

The use of analytical models in human-computer interface design

NASA Technical Reports Server (NTRS)

Gugerty, Leo

1993-01-01

Recently, a large number of human-computer interface (HCI) researchers have investigated building analytical models of the user, which are often implemented as computer models. These models simulate the cognitive processes and task knowledge of the user in ways that allow a researcher or designer to estimate various aspects of an interface's usability, such as when user errors are likely to occur. This information can lead to design improvements. Analytical models can supplement design guidelines by providing designers rigorous ways of analyzing the information-processing requirements of specific tasks (i.e., task analysis). These models offer the potential of improving early designs and replacing some of the early phases of usability testing, thus reducing the cost of interface design. This paper describes some of the many analytical models that are currently being developed and evaluates the usefulness of analytical models for human-computer interface design. This paper will focus on computational, analytical models, such as the GOMS model, rather than less formal, verbal models, because the more exact predictions and task descriptions of computational models may be useful to designers. The paper also discusses some of the practical requirements for using analytical models in complex design organizations such as NASA.

Science with the space-based interferometer eLISA. II: gravitational waves from cosmological phase transitions

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

Caprini, Chiara, E-mail: chiara.caprini@cea.fr; Hindmarsh, Mark; Huber, Stephan

We investigate the potential for the eLISA space-based interferometer to detect the stochastic gravitational wave background produced by strong first-order cosmological phase transitions. We discuss the resulting contributions from bubble collisions, magnetohydrodynamic turbulence, and sound waves to the stochastic background, and estimate the total corresponding signal predicted in gravitational waves. The projected sensitivity of eLISA to cosmological phase transitions is computed in a model-independent way for various detector designs and configurations. By applying these results to several specific models, we demonstrate that eLISA is able to probe many well-motivated scenarios beyond the Standard Model of particle physics predicting strong first-ordermore » cosmological phase transitions in the early Universe.« less

Development of Carbon Dioxide Removal Systems for Advanced Exploration Systems 2016-2017

NASA Technical Reports Server (NTRS)

Knox, James C.; Peters, Warren; Cmarik, Gregory E.; Watson, David; Coker, Robert; Miller, Lee

2017-01-01

A long-term goal for NASA is to enable crewed missions to Mars: first to the vicinity of Mars, and then to the Mars surface. These missions present new challenges for all aspects of spacecraft design in comparison with the International Space Station, as resupply is unavailable in the transit phase, and early return is not possible. Additionally, mass, power, and volume must be minimized for all phases to reduce propulsion needs. In this paper we describe current and planned developments in the area of carbon dioxide removal to support future crewed Mars missions. Activities are also described that apply to both the resolution of anomalies observed in the ISS CDRA and the design of life support systems for future missions.

Identification of genetic variants predictive of early onset pancreatic cancer through a population science analysis of functional genomic datasets

PubMed Central

Chen, Jinyun; Wu, Xifeng; Huang, Yujing; Chen, Wei; Brand, Randall E.; Killary, Ann M.; Sen, Subrata; Frazier, Marsha L.

2016-01-01

Biomarkers are critically needed for the early detection of pancreatic cancer (PC) are urgently needed. Our purpose was to identify a panel of genetic variants that, combined, can predict increased risk for early-onset PC and thereby identify individuals who should begin screening at an early age. Previously, we identified genes using a functional genomic approach that were aberrantly expressed in early pathways to PC tumorigenesis. We now report the discovery of single nucleotide polymorphisms (SNPs) in these genes associated with early age at diagnosis of PC using a two-phase study design. In silico and bioinformatics tools were used to examine functional relevance of the identified SNPs. Eight SNPs were consistently associated with age at diagnosis in the discovery phase, validation phase and pooled analysis. Further analysis of the joint effects of these 8 SNPs showed that, compared to participants carrying none of these unfavorable genotypes (median age at PC diagnosis 70 years), those carrying 1–2, 3–4, or 5 or more unfavorable genotypes had median ages at diagnosis of 64, 63, and 62 years, respectively (P = 3.0E–04). A gene-dosage effect was observed, with age at diagnosis inversely related to number of unfavorable genotypes (Ptrend = 1.0E–04). Using bioinformatics tools, we found that all of the 8 SNPs were predicted to play functional roles in the disruption of transcription factor and/or enhancer binding sites and most of them were expression quantitative trait loci (eQTL) of the target genes. The panel of genetic markers identified may serve as susceptibility markers for earlier PC diagnosis. PMID:27486767

Space Station Furnace Facility. Volume 1: Requirements definition and conceptual design study, executive summary

NASA Technical Reports Server (NTRS)

1992-01-01

The Space Station Freedom Furnace (SSFF) Study was awarded on June 2, 1989, to Teledyne Brown Engineering (TBE) to define an advanced facility for materials research in the microgravity environment of Space Station Freedom (SSF). The SSFF will be designed for research in the solidification of metals and alloys, the crystal growth of electronic and electro-optical materials, and research in glasses and ceramics. The SSFF is one of the first 'facility' class payloads planned by the Microgravity Science and Applications Division (MSAD) of the Office of Space Science and Applications of NASA Headquarters. This facility is planned for early deployment during man-tended operations of the SSF with continuing operations through the Permanently Manned Configuration (PMC). The SSFF will be built around a general 'Core' facility which provides common support functions not provided by SSF, common subsystems which are best centralized, and common subsystems which are best distributed with each experiment module. The intent of the facility approach is to reduce the overall cost associated with implementing and operating a variety of experiments. This is achieved by reducing the launch mass and simplifying the hardware development and qualification processes associated with each experiment. The Core will remain on orbit and will require only periodic maintenance and upgrading while new Furnace Modules, samples, and consumables are developed, qualified, and transported to the SSF. The SSFF Study was divided into two phases: phase 1, a definition study phase, and phase 2, a design and development phase. The definition phase 1 is addressed. Phase 1 was divided into two parts. In the first part, the basic part of the effort, covered the preliminary definition and assessment of requirements; conceptual design of the SSFF; fabrication of mockups; and the preparation for and support of the Conceptual Design Review (CoDR). The second part, the option part, covered requirements update and documentation; refinement of the selected conceptual design through additional trades and analyses; design, fabrication, and test of the Development Model; and design, fabrication, and test of the Interrack Demonstration Unit; and support of the requirements definition review (RDR). The purpose of part 2 was to prove concept feasibility.

Kepler: NASA's First Mission Capable of Finding Earth-Size Planets

NASA Technical Reports Server (NTRS)

Borucki, William J.

2009-01-01

Kepler, a NASA Discovery mission, is a spaceborne telescope designed to search a nearby region of our galaxy for Earth-size planets orbiting in the habitable zone of stars like our sun. The habitable zone is that region around a start where the temperature permits water to be liquid on the surface of a planet. Liquid water is considered essential forth existence of life. Mission Phases: Six mission phases have been defined to describe the different periods of activity during Kepler's mission. These are: launch; commissioning; early science operations, science operations: and decommissioning

Early Formulation Model-centric Engineering on NASA's Europa Mission Concept Study

NASA Technical Reports Server (NTRS)

Bayer, Todd; Chung, Seung; Cole, Bjorn; Cooke, Brian; Dekens, Frank; Delp, Chris; Gontijo, Ivair; Lewis, Kari; Moshir, Mehrdad; Rasmussen, Robert;

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

Levy, E.; Mullens, M.; Rath, P.

The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective envelope designs that can be effectively integrated into the plant production process while meeting the thermal requirements of the 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing new envelope technologies. This work is part of a multi-phase effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three methods for building high performance walls. Phase 2 focused on developing viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysismore » of the three selected options. An industry advisory committee helped narrow the research focus to perfecting a stud wall design with exterior continuous insulation (CI). Phase 3, completed in two stages, continued the design development effort, exploring and evaluating a range or methods for applying CI to factory built homes. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing. During this phase, a home was built with CI, evaluated, and placed in service. The experience of building a mock up wall section with CI and then constructing on line a prototype home resolved important concerns about how to integrate the material into the production process. First steps were taken toward finding least expensive approaches for incorporating CI in standard factory building practices and a preliminary assessment suggested that even at this early stage the technology is attractive when viewed from a life cycle cost perspective.« less

Multizone subsea completions in the Dai Hung field, Vietnam

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

Lay, K.R.

1996-09-01

The early production phase of the Dai Hung field development resulted in the drilling and completion of five subsea wells. Because of the complex nature of the reservoirs, selective multizone completions were installed for effective reservoir data acquisition and reservoir management. The downhole completion designs used equipment that was primarily of existing proven design and downhole equipment installation was successfully achieved in a single trip. Ongoing reservoir management will be aided by the use of a subsea wireline system to facilitate data acquisition.

Using historical perspective in designing discovery learning on Integral for undergraduate students

NASA Astrophysics Data System (ADS)

Abadi; Fiangga, S.

2018-01-01

In the course of Integral Calculus, to be able to calculate an integral of a given function is becoming the main idea in the teaching beside the ability in implementing the application of integral. The students tend to be unable to understand the conceptual idea of what is integration actually. One of the promising perspectives that can be used to invite students to discover the idea of integral is the History and Pedagogy Mathematics (HPM). The method of exhaustion and indivisible appear in the discussion on the early history of area measurement. This paper study will discuss the designed learning activities based on the method of exhaustion and indivisible in providing the undergraduate student’s discovery materials for integral using design research. The designed learning activities were conducted into design experiment that consists of three phases, i.e., preliminary, design experimental, and teaching experiment. The teaching experiment phase was conducted in two cycles for refinement purpose. The finding suggests that the implementation of the method of exhaustion and indivisible enable students to reinvent the idea of integral by using the concept of derivative.

Emerging Use of Early Health Technology Assessment in Medical Product Development: A Scoping Review of the Literature.

PubMed

IJzerman, Maarten J; Koffijberg, Hendrik; Fenwick, Elisabeth; Krahn, Murray

2017-07-01

Early health technology assessment is increasingly being used to support health economic evidence development during early stages of clinical research. Such early models can be used to inform research and development about the design and management of new medical technologies to mitigate the risks, perceived by industry and the public sector, associated with market access and reimbursement. Over the past 25 years it has been suggested that health economic evaluation in the early stages may benefit the development and diffusion of medical products. Early health technology assessment has been suggested in the context of iterative economic evaluation alongside phase I and II clinical research to inform clinical trial design, market access, and pricing. In addition, performing early health technology assessment was also proposed at an even earlier stage for managing technology portfolios. This scoping review suggests a generally accepted definition of early health technology assessment to be "all methods used to inform industry and other stakeholders about the potential value of new medical products in development, including methods to quantify and manage uncertainty". The present review also aimed to identify recent published empirical studies employing an early-stage assessment of a medical product. With most included studies carried out to support a market launch, the dominant methodology was early health economic modeling. Further methodological development is required, in particular, by combining systems engineering and health economics to manage uncertainty in medical product portfolios.

HIV/AIDS in Early Childhood Day-Care Settings. Final Report. Phase I.

ERIC Educational Resources Information Center

McKinney, David D., Ed.; And Others

A feasibility study regarding the training and information needs of preschool and day care administrators, staff, and teachers regarding HIV/AIDS was conducted. This study also examined the issues associated with the presence of HIV-positive children in preschool and day care settings and the need for designing a program to help preschools and day…

Multi-mission telecom analysis tool

NASA Technical Reports Server (NTRS)

Hanks, D.; Kordon, M.; Baker, J.

2002-01-01

In the early formulation phase of a mission it is critically important to have fast, easy to use, easy to integrate space vehicle subsystem analysis tools so that engineers can rapidly perform trade studies not only by themselves but in coordination with other subsystem engineers as well. The Multi-Mission Telecom Analysis Tool (MMTAT) is designed for just this purpose.

An Analysis of Excellent Early Educational Practices: Preliminary Report.

ERIC Educational Resources Information Center

White, Burton L.

This document reports the first phase of a longitudinal research project designed to produce information on how to raise children so their basic abilities may develop optimally during the first six years of life. Although this Preschool Project has been in operation five years, the study is not yet completed because statements about the effects of…

Towards more accurate life cycle risk management through integration of DDP and PRA

NASA Technical Reports Server (NTRS)

Cornford, Steven L.; Paulos, Todd; Meshkat, Leila; Feather, Martin

2003-01-01

The focus of this paper is on the integration of PRA and DDP. The intent is twofold: to extend risk-based decision though more of the lifecycle, and to lead to improved risk modeling (hence better informed decision making) wherever it is applied, most especially in the early phases as designs begin to mature.

Performance assessment of the antenna setup for the ITER plasma position reflectometry in-vessel systems.

PubMed

Varela, P; Belo, J H; Quental, P B

2016-11-01

The design of the in-vessel antennas for the ITER plasma position reflectometry diagnostic is very challenging due to the need to cope both with the space restrictions inside the vacuum vessel and with the high mechanical and thermal loads during ITER operation. Here, we present the work carried out to assess and optimise the design of the antenna. We show that the blanket modules surrounding the antenna strongly modify its characteristics and need to be considered from the early phases of the design. We also show that it is possible to optimise the antenna performance, within the design restrictions.

A synopsis of test results and knowledge gained from the Phase-0 CSI evolutionary model

NASA Technical Reports Server (NTRS)

Belvin, W. Keith; Elliott, Kenny B.; Horta, Lucas G.

1993-01-01

The Phase-0 CSI Evolutionary Model (CEM) is a testbed for the study of space platform global line-of-sight (LOS) pointing. Now that the tests have been completed, a summary of hardware and closed-loop test experiences is necessary to insure a timely dissemination of the knowledge gained. The testbed is described and modeling experiences are presented followed by a summary of the research performed by various investigators. Some early lessons on implementing the closed-loop controllers are described with particular emphasis on real-time computing requirements. A summary of closed-loop studies and a synopsis of test results are presented. Plans for evolving the CEM from phase 0 to phases 1 and 2 are also described. Subsequently, a summary of knowledge gained from the design and testing of the Phase-0 CEM is made.

Modified Toxicity Probability Interval Design: A Safer and More Reliable Method Than the 3 + 3 Design for Practical Phase I Trials

PubMed Central

Ji, Yuan; Wang, Sue-Jane

2013-01-01

The 3 + 3 design is the most common choice among clinicians for phase I dose-escalation oncology trials. In recent reviews, more than 95% of phase I trials have been based on the 3 + 3 design. Given that it is intuitive and its implementation does not require a computer program, clinicians can conduct 3 + 3 dose escalations in practice with virtually no logistic cost, and trial protocols based on the 3 + 3 design pass institutional review board and biostatistics reviews quickly. However, the performance of the 3 + 3 design has rarely been compared with model-based designs in simulation studies with matched sample sizes. In the vast majority of statistical literature, the 3 + 3 design has been shown to be inferior in identifying true maximum-tolerated doses (MTDs), although the sample size required by the 3 + 3 design is often orders-of-magnitude smaller than model-based designs. In this article, through comparative simulation studies with matched sample sizes, we demonstrate that the 3 + 3 design has higher risks of exposing patients to toxic doses above the MTD than the modified toxicity probability interval (mTPI) design, a newly developed adaptive method. In addition, compared with the mTPI design, the 3 + 3 design does not yield higher probabilities in identifying the correct MTD, even when the sample size is matched. Given that the mTPI design is equally transparent, costless to implement with free software, and more flexible in practical situations, we highly encourage its adoption in early dose-escalation studies whenever the 3 + 3 design is also considered. We provide free software to allow direct comparisons of the 3 + 3 design with other model-based designs in simulation studies with matched sample sizes. PMID:23569307

Detection of Objects Hidden in Highly Scattering Media Using Time-Gated Imaging Methods

NASA Technical Reports Server (NTRS)

Galland, Pierre A.; Wang, L.; Liang, X.; Ho, P. P.; Alfano, R. R.

2000-01-01

Non-intrusive and non-invasive optical imaging techniques has generated great interest among researchers for their potential applications to biological study, device characterization, surface defect detection, and jet fuel dynamics. Non-linear optical parametric amplification gate (NLOPG) has been used to detect back-scattered images of objects hidden in diluted Intralipid solutions. To directly detect objects hidden in highly scattering media, the diffusive component of light needs to be sorted out from early arrived ballistic and snake photons. In an optical imaging system, images are collected in transmission or back-scattered geometry. The early arrival photons in the transmission approach, always carry the direct information of the hidden object embedded in the turbid medium. In the back-scattered approach, the result is not so forth coming. In the presence of a scattering host, the first arrival photons in back-scattered approach will be directly photons from the host material. In the presentation, NLOPG was applied to acquire time resolved back-scattered images under the phase matching condition. A time-gated amplified signal was obtained through this NLOPG process. The system's gain was approximately 100 times. The time-gate was achieved through phase matching condition where only coherent photons retain their phase. As a result, the diffusive photons, which were the primary contributor to the background, were removed. With a large dynamic range and high resolution, time-gated early light imaging has the potential for improving rocket/aircraft design by determining jets shape and particle sizes. Refinements to these techniques may enable drop size measurements in the highly scattering, optically dense region of multi-element rocket injectors. These types of measurements should greatly enhance the design of stable, and higher performing rocket engines.

Development and application of a biorelevant dissolution method using USP apparatus 4 in early phase formulation development.

PubMed

Fang, Jiang B; Robertson, Vivian K; Rawat, Archana; Flick, Tawnya; Tang, Zhe J; Cauchon, Nina S; McElvain, James S

2010-10-04

Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.

The space station freedom flight telerobotic servicer. The design and evolution of a dexterous space robot

NASA Astrophysics Data System (ADS)

McCain, Harry G.; Andary, James F.; Hewitt, Dennis R.; Haley, Dennis C.

The Flight Telerobotic Servicer (FTS) Project at the Goddard Space Flight Center is developing an advanced telerobotic system to assist in and reduce crew extravehicular activity (EVA) for Space Station Freedom (SSF). The FTS will provide a telerobotic capability to the Freedom Station in the early assembly phases of the program and will be employed for assembly, maintenance, and inspection applications throughout the lifetime of the space station. Appropriately configured elements of the FTS will also be employed for robotic manipulation in remote satellite servicing applications and possibly the Lunar/Mars Program. In mid-1989, the FTS entered the flight system design and implementation phase (Phase C/D) of development with the signing of the FTS prime contract with Martin Marietta Astronautics Group in Denver, Colorado. The basic FTS design is now established and can be reported on in some detail. This paper will describe the FTS flight system design and the rationale for the specific design approaches and component selections. The current state of space technology and the general nature of the FTS task dictate that the FTS be designed with sophisticated teleoperation capabilities for its initial primary operating mode. However, there are technologies, such as advanced computer vision and autonomous planning techniques currently in research and advanced development phases which would greatly enhance the FTS capabilities to perform autonomously in less structured work environments. Therefore, a specific requirement on the initial FTS design is that it has the capability to evolve as new technology becomes available. This paper will describe the FTS design approach for evolution to more autonomous capabilities. Some specific task applications of the FTS and partial automation approaches of these tasks will also be discussed in this paper.

The Space Station Freedom Flight Telerobotic Servicer: the design and evolution of a dexterous space robot.

PubMed

McCain, H G; Andary, J F; Hewitt, D R; Haley, D C

1991-01-01

The Flight Telerobotic Servicer (FTS) Project at the Goddard Space Flight Center is developing an advanced telerobotic system to assist in and reduce crew extravehicular activity (EVA) for Space Station) Freedom (SSF). The FTS will provide a telerobotic capability to the Freedom Station in the early assembly phases of the program and will be employed for assembly, maintenance, and inspection applications throughout the lifetime of the space station. Appropriately configured elements of the FTS will also be employed for robotic manipulation in remote satellite servicing applications and possibly the Lunar/Mars Program. In mid-1989, the FTS entered the flight system design and implementation phase (Phase C/D) of development with the signing of the FTS prime contract with Martin Marietta Astronautics Group in Denver, Colorado. The basic FTS design is now established and can be reported on in some detail. This paper will describe the FTS flight system design and the rationale for the specific design approaches and component selections. The current state of space technology and the nature of the FTS task dictate that the FTS be designed with sophisticated teleoperation capabilities for its initial primary operating mode. However, there are technologies, such as advanced computer vision and autonomous planning techniques currently in research and advanced development phases which would greatly enhance the FTS capabilities to perform autonomously in less structured work environments. Therefore, a specific requirement on the initial FTS design is that it has the capability to evolve as new technology becomes available. This paper will describe the FTS design approach for evolution to more autonomous capabilities. Some specific task applications of the FTS and partial automation approaches of these tasks will also be discussed in this paper.

The Space Station Freedom Flight Telerobotic Servicer: the design and evolution of a dexterous space robot

NASA Technical Reports Server (NTRS)

McCain, H. G.; Andary, J. F.; Hewitt, D. R.; Haley, D. C.

1991-01-01

The Flight Telerobotic Servicer (FTS) Project at the Goddard Space Flight Center is developing an advanced telerobotic system to assist in and reduce crew extravehicular activity (EVA) for Space Station) Freedom (SSF). The FTS will provide a telerobotic capability to the Freedom Station in the early assembly phases of the program and will be employed for assembly, maintenance, and inspection applications throughout the lifetime of the space station. Appropriately configured elements of the FTS will also be employed for robotic manipulation in remote satellite servicing applications and possibly the Lunar/Mars Program. In mid-1989, the FTS entered the flight system design and implementation phase (Phase C/D) of development with the signing of the FTS prime contract with Martin Marietta Astronautics Group in Denver, Colorado. The basic FTS design is now established and can be reported on in some detail. This paper will describe the FTS flight system design and the rationale for the specific design approaches and component selections. The current state of space technology and the nature of the FTS task dictate that the FTS be designed with sophisticated teleoperation capabilities for its initial primary operating mode. However, there are technologies, such as advanced computer vision and autonomous planning techniques currently in research and advanced development phases which would greatly enhance the FTS capabilities to perform autonomously in less structured work environments. Therefore, a specific requirement on the initial FTS design is that it has the capability to evolve as new technology becomes available. This paper will describe the FTS design approach for evolution to more autonomous capabilities. Some specific task applications of the FTS and partial automation approaches of these tasks will also be discussed in this paper.

A new design approach to achieve a minimum impulse limit cycle in the presence of significant measurement uncertainties

NASA Technical Reports Server (NTRS)

Martin, M. W.; Kubiak, E. T.

1982-01-01

A new design was developed for the Space Shuttle Transition Phase Digital Autopilot to reduce the impact of large measurement uncertainties in the rate signal during attitude control. The signal source, which was dictated by early computer constraints, is characterized by large quantization, noise, bias, and transport lag which produce a measurement uncertainty larger than the minimum impulse rate change. To ensure convergence to a minimum impulse limit cycle, the design employed bias and transport lag compensation and a switching logic with hysteresis, rate deadzone, and 'walking' switching line. The design background, the rate measurement uncertainties, and the design solution are documented.

Ambient Assisted Living spaces validation by services and devices simulation.

PubMed

Fernández-Llatas, Carlos; Mocholí, Juan Bautista; Sala, Pilar; Naranjo, Juan Carlos; Pileggi, Salvatore F; Guillén, Sergio; Traver, Vicente

2011-01-01

The design of Ambient Assisted Living (AAL) products is a very demanding challenge. AAL products creation is a complex iterative process which must accomplish exhaustive prerequisites about accessibility and usability. In this process the early detection of errors is crucial to create cost-effective systems. Computer-assisted tools can suppose a vital help to usability designers in order to avoid design errors. Specifically computer simulation of products in AAL environments can be used in all the design phases to support the validation. In this paper, a computer simulation tool for supporting usability designers in the creation of innovative AAL products is presented. This application will benefit their work saving time and improving the final system functionality.

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model

PubMed Central

Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

2016-01-01

The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet–fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of sublethal tubular cell injury. PMID:26752420

Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

PubMed Central

Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

2016-01-01

Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, p<0.0001), but was not associated with the therapeutic misconception. (Spearman r=−0.075, p=0.329). Dispositional optimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (p<0.0001) were independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

Dispositional optimism and therapeutic expectations in early-phase oncology trials.

PubMed

Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

2016-04-15

Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early-phase oncology research. © 2016 American Cancer Society.

WISPER: Wirless Space Power Experiment

NASA Technical Reports Server (NTRS)

Hawkins, Joseph

1993-01-01

The 1993 Advanced Design Project at the University of Alaska Fairbanks was to design a spacecraft as a technology demonstration of wireless power transmission (WPT). With cost effectiveness as a design constraint, a micro-satellite in low earth orbit (LEO) was chosen for the mission. Existing and near term technologies were analyzed and selected for the project. In addition to the conceptual design of the payload, support systems, and structure, the analysis included attention to safety, environmental impact, cost, and schedule for construction and operation. Wireless power beaming is not a new concept. Experimental demonstrations and study efforts have continued since the early 1960's. With the latest progress in transmitter and receiver technology, the next natural step is to beam power from earth to space. This proposed flight demonstration will advance the science of power beaming and prove the viability of various applications of WPT in space. Two methods of power beaming will be examined during the two separate phases of the spacecraft life. The first phase will demonstrate the technology and examine the theory of microwave power transmission at a high frequency. Special aspects of the first phase will include a highly accurate attitude control system and a 14 m inflatable parabolic antenna. The second phase will investigate the utilization of high intensity laser power using modified photovoltaic arrays. Special instrumentation on the spacecraft will measure the conversion efficiency from the received microwave or laser power to direct current power.

Stressful events and coping related to acute and sub-acute whiplash-associated disorders.

PubMed

Pettersson, Susanne; Bring, Annika; Åsenlöf, Pernilla

2017-03-01

Purpose To describe daily stressors affecting and coping strategies employed by individuals with whiplash-associated disorders (WAD) immediately to one month (acute) and three to four months (sub-acute) after injury events using a daily coping assessment. Levels of pain, anxiety, depressed mood and activity are also compared between phases. Method A descriptive prospective design with a content analysis approach was used. Participants completed daily coping assessments for one week during both acute and sub-acute phases. Main measure was whiplash-associated disorders-daily coping assessment (WAD-DCA). Results Nine participants used words describing recovery in the sub-acute phase; 31 described stressful events during both phases. Most frequently reported stressors were related to "symptoms", "emotions" and "occupations/studies". These were equally reported during both phases. Cognitive coping strategies were employed more often during the sub-acute phase (p = 0.008). The only behavioral strategy that increased in prevalence over time was the "relaxed" strategy (p = 0.001). Anxiety levels declined over time (p = 0.022). Conclusion The reported stressors were largely uniform across both acute and sub-acute phases; however, the use of cognitive coping strategies increased over time. The WAD-DCA captures individual stressors and coping strategies employed during a vulnerable phase of rehabilitation and can thus provide information that is useful to clinical practice. Implications for rehabilitation The WAD-DCA provides valuable information for clinical practice when employed during early phases of whiplash-associated disorder development. Reported stressors during the acute and sub-acute phases are essentially the same, whereas cognitive coping strategies grow in prevalence over time. Tailored treatments in early phases of whip-lash associated disorders may benefit from strategies aimed at matching patient-specific stressors with contextually adapted coping strategies.

Longitudinal design considerations to optimize power to detect variances and covariances among rates of change: Simulation results based on actual longitudinal studies

PubMed Central

Rast, Philippe; Hofer, Scott M.

2014-01-01

We investigated the power to detect variances and covariances in rates of change in the context of existing longitudinal studies using linear bivariate growth curve models. Power was estimated by means of Monte Carlo simulations. Our findings show that typical longitudinal study designs have substantial power to detect both variances and covariances among rates of change in a variety of cognitive, physical functioning, and mental health outcomes. We performed simulations to investigate the interplay among number and spacing of occasions, total duration of the study, effect size, and error variance on power and required sample size. The relation between growth rate reliability (GRR) and effect size to the sample size required to detect power ≥ .80 was non-linear, with rapidly decreasing sample sizes needed as GRR increases. The results presented here stand in contrast to previous simulation results and recommendations (Hertzog, Lindenberger, Ghisletta, & von Oertzen, 2006; Hertzog, von Oertzen, Ghisletta, & Lindenberger, 2008; von Oertzen, Ghisletta, & Lindenberger, 2010), which are limited due to confounds between study length and number of waves, error variance with GCR, and parameter values which are largely out of bounds of actual study values. Power to detect change is generally low in the early phases (i.e. first years) of longitudinal studies but can substantially increase if the design is optimized. We recommend additional assessments, including embedded intensive measurement designs, to improve power in the early phases of long-term longitudinal studies. PMID:24219544

Early Phase Contingency Trajectory Design for the Failure of the First Lunar Orbit Insertion Maneuver: Direct Recovery Options

NASA Astrophysics Data System (ADS)

Song, Young-Joo; Bae, Jonghee; Kim, Young-Rok; Kim, Bang-Yeop

2017-12-01

To ensure the successful launch of the Korea pathfinder lunar orbiter (KPLO) mission, the Korea Aerospace Research Institute (KARI) is now performing extensive trajectory design and analysis studies. From the trajectory design perspective, it is crucial to prepare contingency trajectory options for the failure of the first lunar brake or the failure of the first lunar orbit insertion (LOI) maneuver. As part of the early phase trajectory design and analysis activities, the required time of flight (TOF) and associated delta-V magnitudes for each recovery maneuver (RM) to recover the KPLO mission trajectory are analyzed. There are two typical trajectory recovery options, direct recovery and low energy recovery. The current work is focused on the direct recovery option. Results indicate that a quicker execution of the first RM after the failure of the first LOI plays a significant role in saving the magnitudes of the RMs. Under the conditions of the extremely tight delta-V budget that is currently allocated for the KPLO mission, it is found that the recovery of the KPLO without altering the originally planned mission orbit (a 100 km circular orbit) cannot be achieved via direct recovery options. However, feasible recovery options are suggested within the boundaries of the currently planned delta-V budget. By changing the shape and orientation of the recovered final mission orbit, it is expected that the KPLO mission may partially pursue its scientific mission after successful recovery, though it will be limited.

Practical Communication Guidance to Improve Phase I Informed Consent Conversations and Decision-Making in Pediatric Oncology

PubMed Central

Johnson, Liza-Marie; Leek, Angela C.; Drotar, Dennis; Noll, Robert B.; Rheingold, Susan R.; Kodish, Eric D.; Baker, Justin N.

2015-01-01

Background It can be difficult to explain pediatric Phase I oncology trials to families of children with refractory cancer. Parents may misunderstand the information presented to them, and physicians may assume that certain topics are covered in the informed consent document and need not be discussed. Communication models can help to ensure effective discussions. Methods Suggestions for improving the informed consent process were first solicited from Phase I study clinicians via questionnaire. Eight parents who had enrolled their child on a Phase I pediatric oncology trial were recruited for an advisory group designed to assess the clinicians’ suggestions and make additional recommendations for improving informed consent for pediatric Phase I trials. Results A Phase I Communication Model was designed to incorporate the suggestions of clinicians and families. It focuses on education of parents/families about Phase I trials at specific time points during a child’s illness, but specifically at the point of relapse. We also present an informative Phase I fact sheet that can be distributed to families. Conclusions Families who will be offered information about a Phase I clinical trial can first receive a standardized fact sheet explaining the general purpose of these early-phase clinical trials. Parental understanding may be further enhanced when oncologists address key themes, beginning at diagnosis and continuing through important decision points during the child’s illness. This model should be prospectively evaluated. PMID:25873253

The creation and early implementation of a high speed fiber optic network for a university health sciences center.

PubMed Central

Schueler, J. D.; Mitchell, J. A.; Forbes, S. M.; Neely, R. C.; Goodman, R. J.; Branson, D. K.

1991-01-01

In late 1989 the University of Missouri Health Sciences Center began the process of creating an extensive fiber optic network throughout its facilities, with the intent to provide networked computer access to anyone in the Center desiring such access, regardless of geographic location or organizational affiliation. A committee representing all disciplines within the Center produced and, in conjunction with independent consultants, approved a comprehensive design for the network. Installation of network backbone components commenced in the second half of 1990 and was completed in early 1991. As the network entered its initial phases of operation, the first realities of this important new resource began to manifest themselves as enhanced functional capacity in the Health Sciences Center. This paper describes the development of the network, with emphasis on its design criteria, installation, early operation, and management. Also included are discussions on its organizational impact and its evolving significance as a medical community resource. PMID:1807660

35t Prototype Detector for Experiment at Long Base Line Neutrino Facility (ELBNF) Far Detector

NASA Astrophysics Data System (ADS)

Santucci, Gabriel; Elbnf Collaboration

2015-04-01

The 35ton prototype detector is a Liquid Argon Time Projection Chamber (LAr TPC) utilizing a membrane cryostat. It serves as a prototype for testing technology proposed for the ELBNF far detector. The construction of the prototype is an essential part of the ELBNF project due to the large amount of new technologies introduced for the far detector. In early 2014, it was shown that the membrane cryostat technology was able to reach and maintain the required LAr purity and an electron lifetime of 2.5 ms was achieved. The goals for the next phase include the installation of a fully functional TPC using the novel designs for the ELBNF far detector as much as possible. This includes the installation of the cold electronics, scintillation photon detectors and multiple Anode Plane Arrays with wrapped wires. In this talk I will review the status of the 35t prototype detector and describe what has been accomplished during 2014 and early 2015, including the commissioning phase and the early stages of data taking from cosmic-rays.

A Bayesian pick-the-winner design in a randomized phase II clinical trial.

PubMed

Chen, Dung-Tsa; Huang, Po-Yu; Lin, Hui-Yi; Chiappori, Alberto A; Gabrilovich, Dmitry I; Haura, Eric B; Antonia, Scott J; Gray, Jhanelle E

2017-10-24

Many phase II clinical trials evaluate unique experimental drugs/combinations through multi-arm design to expedite the screening process (early termination of ineffective drugs) and to identify the most effective drug (pick the winner) to warrant a phase III trial. Various statistical approaches have been developed for the pick-the-winner design but have been criticized for lack of objective comparison among the drug agents. We developed a Bayesian pick-the-winner design by integrating a Bayesian posterior probability with Simon two-stage design in a randomized two-arm clinical trial. The Bayesian posterior probability, as the rule to pick the winner, is defined as probability of the response rate in one arm higher than in the other arm. The posterior probability aims to determine the winner when both arms pass the second stage of the Simon two-stage design. When both arms are competitive (i.e., both passing the second stage), the Bayesian posterior probability performs better to correctly identify the winner compared with the Fisher exact test in the simulation study. In comparison to a standard two-arm randomized design, the Bayesian pick-the-winner design has a higher power to determine a clear winner. In application to two studies, the approach is able to perform statistical comparison of two treatment arms and provides a winner probability (Bayesian posterior probability) to statistically justify the winning arm. We developed an integrated design that utilizes Bayesian posterior probability, Simon two-stage design, and randomization into a unique setting. It gives objective comparisons between the arms to determine the winner.

Simple uncertainty propagation for early design phase aircraft sizing

NASA Astrophysics Data System (ADS)

Lenz, Annelise

Many designers and systems analysts are aware of the uncertainty inherent in their aircraft sizing studies; however, few incorporate methods to address and quantify this uncertainty. Many aircraft design studies use semi-empirical predictors based on a historical database and contain uncertainty -- a portion of which can be measured and quantified. In cases where historical information is not available, surrogate models built from higher-fidelity analyses often provide predictors for design studies where the computational cost of directly using the high-fidelity analyses is prohibitive. These surrogate models contain uncertainty, some of which is quantifiable. However, rather than quantifying this uncertainty, many designers merely include a safety factor or design margin in the constraints to account for the variability between the predicted and actual results. This can become problematic if a designer does not estimate the amount of variability correctly, which then can result in either an "over-designed" or "under-designed" aircraft. "Under-designed" and some "over-designed" aircraft will likely require design changes late in the process and will ultimately require more time and money to create; other "over-designed" aircraft concepts may not require design changes, but could end up being more costly than necessary. Including and propagating uncertainty early in the design phase so designers can quantify some of the errors in the predictors could help mitigate the extent of this additional cost. The method proposed here seeks to provide a systematic approach for characterizing a portion of the uncertainties that designers are aware of and propagating it throughout the design process in a procedure that is easy to understand and implement. Using Monte Carlo simulations that sample from quantified distributions will allow a systems analyst to use a carpet plot-like approach to make statements like: "The aircraft is 'P'% likely to weigh 'X' lbs or less, given the uncertainties quantified" without requiring the systems analyst to have substantial knowledge of probabilistic methods. A semi-empirical sizing study of a small single-engine aircraft serves as an example of an initial version of this simple uncertainty propagation. The same approach is also applied to a variable-fidelity concept study using a NASA-developed transonic Hybrid Wing Body aircraft.

On Using Commercial Off-the-Shelf (COTS) Electronic Products in Space

NASA Technical Reports Server (NTRS)

Culpepper, William X.

2002-01-01

NASA's Johnson Space Center (JSC) has utilized COTS products in its programs since the early 1990's. Recently it has become evident that, of all failure modes possible, radiation will probably dominate; sometimes to the point of driving system architecture. It is now imperative that radiation susceptibility be addressed when writing the system requirements. Susceptibility assessment, e.g. testing, must begin early in the design phase to establish performance and continue through the hardware qualification program to prove satisfaction of the original requirements(s). Examples of requirements, testing, and architecture versus failure rate will be given.

Diagnostics Tools Identify Faults Prior to Failure

NASA Technical Reports Server (NTRS)

2013-01-01

Through the SBIR program, Rochester, New York-based Impact Technologies LLC collaborated with Ames Research Center to commercialize the Center s Hybrid Diagnostic Engine, or HyDE, software. The fault detecting program is now incorporated into a software suite that identifies potential faults early in the design phase of systems ranging from printers to vehicles and robots, saving time and money.

The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort.

PubMed

Korten, Insa; Kieninger, Elisabeth; Yammine, Sophie; Regamey, Nicolas; Nyilas, Sylvia; Ramsey, Kathryn; Casaulta, Carmen; Latzin, Philipp; For The Scild Study Group

2018-04-26

The Swiss Cystic Fibrosis Infant Lung Development (SCILD) cohort is a prospective birth cohort study investigating the initiating events of cystic fibrosis lung disease during infancy, and their influence on the trajectory of disease progression throughout early childhood. Infants with cystic fibrosis are recruited throughout Switzerland after diagnosis by new-born screening. It is the first European population-based prospective cohort study of infants with cystic fibrosis taking advantage of a nationwide new-born screening programme. The study was established in 2011 and recruitment is ongoing. The cohort study is currently divided into three study phases (phase 1: diagnosis to age 1 year; phase 2: age 1 to 3 years; and phase 3: age 3 to 6 years). Study participants have weekly telephone interviews, weekly anterior nasal swab collection and two study visits in the first year of life. They also complete follow-up study visits at 3 and 6 years of age. Data for this study are derived from questionnaires, lung function measurements, telephone interviews, nasal swab material and magnetic resonance imaging. To date, 70 infants have been recruited into the study and 56 have completed phase 1, including a baseline study visit at 6 weeks of age, weekly surveillance and a study visit at one year of age. More than 2500 data points on respiratory health and almost 2000 nasal samples have been collected. Phases 2 and 3 will commence in 2018. The dataset of the SCILD cohort combines lung function data, the collection of environmental and sociodemographic factors, documentation of respiratory symptoms, and microbiological analyses. The design not only allows tracking of the cystic fibrosis lung disease independent of clinical status, but also surveillance of early disease prior to severe clinical symptoms. This cohort profile provides details on the study design and summarizes the first published results of the SCILD cohort.

Designing a community-based lay health advisor training curriculum to address cancer health disparities.

PubMed

Gwede, Clement K; Ashley, Atalie A; McGinnis, Kara; Montiel-Ishino, F Alejandro; Standifer, Maisha; Baldwin, Julie; Williams, Coni; Sneed, Kevin B; Wathington, Deanna; Dash-Pitts, Lolita; Green, B Lee

2013-05-01

Racial and ethnic minorities have disproportionately higher cancer incidence and mortality than their White counterparts. In response to this inequity in cancer prevention and care, community-based lay health advisors (LHAs) may be suited to deliver effective, culturally relevant, quality cancer education, prevention/screening, and early detection services for underserved populations. APPROACH AND STRATEGIES: Consistent with key tenets of community-based participatory research (CBPR), this project engaged community partners to develop and implement a unique LHA training curriculum to address cancer health disparities among medically underserved communities in a tricounty area. Seven phases of curriculum development went into designing a final seven-module LHA curriculum. In keeping with principles of CBPR and community engagement, academic-community partners and LHAs themselves were involved at all phases to ensure the needs of academic and community partners were mutually addressed in development and implementation of the LHA program. Community-based LHA programs for outreach, education, and promotion of cancer screening and early detection, are ideal for addressing cancer health disparities in access and quality care. When community-based LHAs are appropriately recruited, trained, and located in communities, they provide unique opportunities to link, bridge, and facilitate quality cancer education, services, and research.

Governing nanobiotechnology: lessons from agricultural biotechnology regulation

NASA Astrophysics Data System (ADS)

Johnson, Robbin S.

2011-04-01

This article uses lessons from biotechnology to help inform the design of oversight for nanobiotechnology. Those lessons suggest the following: first, oversight needs to be broadly defined, encompassing not just regulatory findings around safety and efficacy, but also public understanding and acceptance of the technology and its products. Second, the intensity of scrutiny and review should reflect not just risks but also perceptions of risk. Finally, a global marketplace argues for uniform standards or commercially practical solutions to differences in standards. One way of designing oversight to achieve these purposes is to think about it in three phases—precaution, prudence, and promotion. Precaution comes early in the technology or product's development and reflects real and perceived uncertainties. Prudence governs when risks and hazards have been identified, containment approaches established, and benefits broadly defined. Transparency and public participation rise to the fore. The promotional phase moves toward shaping public understanding and acceptance and involves marketing issues rather than safety ones. This flexible, three-phase approach to oversight would have avoided some of the early regulatory problems with agricultural biotechnology. It also would have led to a more risk-adjusted pathway to regulatory approval. Furthermore, it would avoid some of the arbitrary, disruptive marketing issues that have arisen.

Environmental, health, and safety issues of fuel cells in transportation. Volume 1: Phosphoric acid fuel-cell buses

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

Ring, S

1994-12-01

The U.S. Department of Energy (DOE) chartered the Phosphoric Acid Fuel-Cell (PAFC) Bus Program to demonstrate the feasibility of fuel cells in heavy-duty transportation systems. As part of this program, PAFC- powered buses are being built to meet transit industry design and performance standards. Test-bed bus-1 (TBB-1) was designed in 1993 and integrated in March 1994. TBB-2 and TBB-3 are under construction and should be integrated in early 1995. In 1987 Phase I of the program began with the development and testing of two conceptual system designs- liquid- and air-cooled systems. The liquid-cooled PAFC system was chosen to continue, throughmore » a competitive award, into Phase H, beginning in 1991. Three hybrid buses, which combine fuel-cell and battery technologies, were designed during Phase III. After completing Phase II, DOE plans a comprehensive performance testing program (Phase HI) to verify that the buses meet stringent transit industry requirements. The Phase III study will evaluate the PAFC bus and compare it to a conventional diesel bus. This NREL study assesses the environmental, health, and safety (EH&S) issues that may affect the commercialization of the PAFC bus. Because safety is a critical factor for consumer acceptance of new transportation-based technologies the study focuses on these issues. The study examines health and safety together because they are integrally related. In addition, this report briefly discusses two environmental issues that are of concern to the Environmental Protection Agency (EPA). The first issue involves a surge battery used by the PAFC bus that contains hazardous constituents. The second issue concerns the regulated air emissions produced during operation of the PAFC bus.« less

TITLE: Environmental, health, and safety issues offuel cells in transportation. Volume 1: Phosphoricacid fuel-cell buses

NASA Astrophysics Data System (ADS)

Ring, Shan

1994-12-01

The U.S. Department of Energy (DOE) chartered the Phosphoric Acid Fuel-Cell (PAFC) Bus Program to demonstrate the feasibility of fuel cells in heavy-duty transportation systems. As part of this program, PAFC- powered buses are being built to meet transit industry design and performance standards. Test-bed bus-1 (TBB-1) was designed in 1993 and integrated in March 1994. TBB-2 and TBB-3 are under construction and should be integrated in early 1995. In 1987 Phase 1 of the program began with the development and testing of two conceptual system designs- liquid- and air-cooled systems. The liquid-cooled PAFC system was chosen to continue, through a competitive award, into Phase H, beginning in 1991. Three hybrid buses, which combine fuel-cell and battery technologies, were designed during Phase 3. After completing Phase 2, DOE plans a comprehensive performance testing program (Phase H1) to verify that the buses meet stringent transit industry requirements. The Phase 3 study will evaluate the PAFC bus and compare it to a conventional diesel bus. This NREL study assesses the environmental, health, and safety (EH&S) issues that may affect the commercialization of the PAFC bus. Because safety is a critical factor for consumer acceptance of new transportation-based technologies the study focuses on these issues. The study examines health and safety together because they are integrally related. In addition, this report briefly discusses two environmental issues that are of concern to the Environmental Protection Agency (EPA). The first issue involves a surge battery used by the PAFC bus that contains hazardous constituents. The second issue concerns the regulated air emissions produced during operation of the PAFC bus.

TRAVELLERS: a school-based early intervention programme helping young people manage and process change, loss and transition. Pilot phase findings.

PubMed

Dickinson, Pauline; Coggan, Carolyn; Bennett, Sara

2003-06-01

This paper outlines the conceptual background and findings from the pilot phase of TRAVELLERS--an early intervention programme designed to enhance protective factors for young people experiencing change, loss and transition events and early signs of emotional distress. The pilot study aimed to determine whether TRAVELLERS was a feasible, acceptable and promising intervention for young people within secondary schools in Aotearoa/New Zealand. The conceptual origins of the TRAVELLERS programme are described in terms of: adolescent mental health concerns; emerging mental health promotion theory and practice; and prevention and early intervention models. The key elements of the TRAVELLERS programme are described. The programme was piloted in two secondary schools, one rural and one urban with 34 participants (females n = 24, males n = 10). Evaluation methods included: review of programme materials; identification of potential selection tools appropriate to Year 9 students; analysis of selection questionnaire; and conduct of feedback from participants, facilitators and parents/caregivers. The TRAVELLERS programme provides a means of identifying and selecting young people who may benefit from participating in an early intervention programme. The programme has achieved a statistically significant reduction in participants' distress (p < 0.01). Young people were overwhelmingly enthusiastic about most aspects of TRAVELLERS. School personnel reported that TRAVELLERS was an appropriate and acceptable programme to the school. Targeted interventions provided within a supportive school environment can contribute to enhancing protective factors such as personal and interpersonal coping strategies, increased help-seeking behaviour, and young people feeling more positive about themselves and their lives. The pilot programme has been amended and prepared for a two year trial phase in 10 secondary schools during 2002-2003.

Guidance, Navigation and Control (GN&C): Best Practices for Human-Rated Spacecraft Systems

NASA Technical Reports Server (NTRS)

Lebsock, Ken; West, John

2008-01-01

In 2007 the NESC completed an in-depth assessment to identify, define and document engineering considerations for the Design Development Test and Evaluation (DDT&E) of human-rated spacecraft systems. This study had been requested by the Astronaut Office at JSC to help them to better understand what is required to ensure safe, robust, and reliable human-rated spacecraft systems. The 22 GN&C engineering Best Practices described in this paper are a condensed version of what appears in the NESC Technical Report. These Best Practices cover a broad range from fundamental system architectural considerations to more specific aspects (e.g., stability margin recommendations) of GN&C system design and development. 15 of the Best Practices address the early phases of a GN&C System development project and the remaining 7 deal with the later phases. Some of these Best Practices will cross-over between both phases. We recognize that this set of GN&C Best Practices will not be universally applicable to all projects and mission applications.

Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

PubMed

Matić, Katarina; Gereš, Natko; Gerlach, Josefina; Prskalo-Čule, Diana; Zadravec Vrbanc, Tihana; Lovretić, Vanja; Librenjak, Dina; Vuk Pisk, Sandra; Ivezić, Ena; Šimunović Filipčić, Ivona; Jeleč, Vjekoslav; Filipčić, Igor

2018-06-01

There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

Knowledge exchange in the UK CLAHRCs.

PubMed

Racko, Girts

2018-04-09

Purpose The purpose of this paper is to examine how knowledge exchange between academics and clinicians in Collaborations for Leadership in Applied Health Research and Care (CLAHRCs) is influenced by their social position based on their symbolic and social capitals, that is, their personal professional status and connections to high-status professional peers, knowledge brokers, and unfamiliar professional peers. Design/methodology/approach Using an online survey, the author triangulates the cross-sectional measurement of the effects of academic and clinicians' social position in the initial and later phases of CLAHRCs with the longitudinal measurement of these effects over a two-year period. Findings First, academics and clinicians with a higher personal professional status are more likely to develop joint networks and decision making both in the early and later phases of a CLAHRC. Second, academics and clinicians who are more connected to higher status occupational peers are more likely to develop joint networks in the early phase of a knowledge exchange partnership but are less likely to become engaged in joint networks over time. Third, involvement of knowledge brokers in the networks of academics and clinicians is likely to facilitate their inter-professional networking only in the later partnership phase. Practical implications Academics and clinicians' capitals have a distinctive influence on knowledge exchange in the early and later phases of CLAHRCs and on a change in knowledge exchange over a two-year period. Originality/value Prior research on CLAHRCs has examined how knowledge exchange between academics and clinicians can be encouraged by the creation of shared governance mechanisms. The author advances this research by highlighting the role of their social position in facilitating knowledge exchange.

The Application of the Human Engineering Modeling and Performance Laboratory for Space Vehicle Ground Processing Tasks at Kennedy Space Center

NASA Technical Reports Server (NTRS)

Woodbury, Sarah K.

2008-01-01

The introduction of United Space Alliance's Human Engineering Modeling and Performance Laboratory began in early 2007 in an attempt to address the problematic workspace design issues that the Space Shuttle has imposed on technicians performing maintenance and inspection operations. The Space Shuttle was not expected to require the extensive maintenance it undergoes between flights. As a result, extensive, costly resources have been expended on workarounds and modifications to accommodate ground processing personnel. Consideration of basic human factors principles for design of maintenance is essential during the design phase of future space vehicles, facilities, and equipment. Simulation will be needed to test and validate designs before implementation.

Selecting promising treatments in randomized Phase II cancer trials with an active control.

PubMed

Cheung, Ying Kuen

2009-01-01

The primary objective of Phase II cancer trials is to evaluate the potential efficacy of a new regimen in terms of its antitumor activity in a given type of cancer. Due to advances in oncology therapeutics and heterogeneity in the patient population, such evaluation can be interpreted objectively only in the presence of a prospective control group of an active standard treatment. This paper deals with the design problem of Phase II selection trials in which several experimental regimens are compared to an active control, with an objective to identify an experimental arm that is more effective than the control or to declare futility if no such treatment exists. Conducting a multi-arm randomized selection trial is a useful strategy to prioritize experimental treatments for further testing when many candidates are available, but the sample size required in such a trial with an active control could raise feasibility concerns. In this study, we extend the sequential probability ratio test for normal observations to the multi-arm selection setting. The proposed methods, allowing frequent interim monitoring, offer high likelihood of early trial termination, and as such enhance enrollment feasibility. The termination and selection criteria have closed form solutions and are easy to compute with respect to any given set of error constraints. The proposed methods are applied to design a selection trial in which combinations of sorafenib and erlotinib are compared to a control group in patients with non-small-cell lung cancer using a continuous endpoint of change in tumor size. The operating characteristics of the proposed methods are compared to that of a single-stage design via simulations: The sample size requirement is reduced substantially and is feasible at an early stage of drug development.

The Space Station Freedom Flight Telerobotic Servicer - The design and evolution of a dexterous space robot

NASA Technical Reports Server (NTRS)

Mccain, Harry G.; Andary, James F.; Hewitt, Dennis R.; Haley, Dennis C.

1990-01-01

The Flight Telerobotic Servicer (FTS) will provide a telerobotic capability to the Space Station in the early assembly phases of the program and will be used for assembly, maintenance, and inspection throughout the lifetime of the Station. Here, the FTS design approach to the development of autonomous capabilities is discussed. The FTS telerobotic workstations for the Shuttle and Space Station, and facility for on-orbit storage are examined. The rationale of the FTS with regard to ease of operation, operational versatility, maintainability, safety, and control is discussed.

Small-Molecule Inhibitors of the MDM2–p53 Protein–Protein Interaction (MDM2 Inhibitors) in Clinical Trials for Cancer Treatment

PubMed Central

2015-01-01

Design of small-molecule inhibitors (MDM2 inhibitors) to block the MDM2–p53 protein–protein interaction has been pursued as a new cancer therapeutic strategy. In recent years, potent, selective, and efficacious MDM2 inhibitors have been successfully obtained and seven such compounds have been advanced into early phase clinical trials for the treatment of human cancers. Here, we review the design, synthesis, properties, preclinical, and clinical studies of these clinical-stage MDM2 inhibitors. PMID:25396320

Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

PubMed Central

Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

2015-01-01

Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

Early Validation of Failure Detection, Isolation, and Recovery Design Using Heterogeneous Modelling and Simulation

NASA Astrophysics Data System (ADS)

van der Plas, Peter; Guerriero, Suzanne; Cristiano, Leorato; Rugina, Ana

2012-08-01

Modelling and simulation can support a number of use cases across the spacecraft development life-cycle. Given the increasing complexity of space missions, the observed general trend is for a more extensive usage of simulation already in the early phases. A major perceived advantage is that modelling and simulation can enable the validation of critical aspects of the spacecraft design before the actual development is started, as such reducing the risk in later phases.Failure Detection, Isolation, and Recovery (FDIR) is one of the areas with a high potential to benefit from early modelling and simulation. With the increasing level of required spacecraft autonomy, FDIR specifications can grow in such a way that the traditional document-based review process soon becomes inadequate.This paper shows that FDIR modelling and simulation in a system context can provide a powerful tool to support the FDIR verification process. It is highlighted that FDIR modelling at this early stage requires heterogeneous modelling tools and languages, in order to provide an adequate functional description of the different components (i.e. FDIR functions, environment, equipment, etc.) to be modelled.For this reason, an FDIR simulation framework is proposed in this paper. This framework is based on a number of tools already available in the Avionics Systems Laboratory at ESTEC, which are the Avionics Test Bench Functional Engineering Simulator (ATB FES), Matlab/Simulink, TASTE, and Real Time Developer Studio (RTDS).The paper then discusses the application of the proposed simulation framework to a real case-study, i.e. the FDIR modelling of a satellite in support of actual ESA mission. Challenges and benefits of the approach are described. Finally, lessons learned and the generality of the proposed approach are discussed.

Composable Framework Support for Software-FMEA Through Model Execution

NASA Astrophysics Data System (ADS)

Kocsis, Imre; Patricia, Andras; Brancati, Francesco; Rossi, Francesco

2016-08-01

Performing Failure Modes and Effect Analysis (FMEA) during software architecture design is becoming a basic requirement in an increasing number of domains; however, due to the lack of standardized early design phase model execution, classic SW-FMEA approaches carry significant risks and are human effort-intensive even in processes that use Model-Driven Engineering.Recently, modelling languages with standardized executable semantics have emerged. Building on earlier results, this paper describes framework support for generating executable error propagation models from such models during software architecture design. The approach carries the promise of increased precision, decreased risk and more automated execution for SW-FMEA during dependability- critical system development.

Lunar base launch and landing facilities conceptual design

NASA Technical Reports Server (NTRS)

Phillips, Paul G.; Simonds, Charles H.; Stump, William R.

1992-01-01

The purpose of this study was to perform a first look at the requirements for launch and landing facilities for early lunar bases and to prepared conceptual designs for some of these facilities. The emphasis of the study is on the facilities needed from the first manned landing until permanent occupancy, the Phase 2 lunar base. Factors including surface characteristics, navigation system, engine blast effects, and expected surface operations are used to develop landing pad designs, and definitions fo various other elements of the launch and landing facilities. Finally, the dependence of the use of these elements and the evolution of the facilities are established.

Circadian Phase-Shifting Effects of Bright Light, Exercise, and Bright Light + Exercise.

PubMed

Youngstedt, Shawn D; Kline, Christopher E; Elliott, Jeffrey A; Zielinski, Mark R; Devlin, Tina M; Moore, Teresa A

2016-02-26

Limited research has compared the circadian phase-shifting effects of bright light and exercise and additive effects of these stimuli. The aim of this study was to compare the phase-delaying effects of late night bright light, late night exercise, and late evening bright light followed by early morning exercise. In a within-subjects, counterbalanced design, 6 young adults completed each of three 2.5-day protocols. Participants followed a 3-h ultra-short sleep-wake cycle, involving wakefulness in dim light for 2h, followed by attempted sleep in darkness for 1 h, repeated throughout each protocol. On night 2 of each protocol, participants received either (1) bright light alone (5,000 lux) from 2210-2340 h, (2) treadmill exercise alone from 2210-2340 h, or (3) bright light (2210-2340 h) followed by exercise from 0410-0540 h. Urine was collected every 90 min. Shifts in the 6-sulphatoxymelatonin (aMT6s) cosine acrophase from baseline to post-treatment were compared between treatments. Analyses revealed a significant additive phase-delaying effect of bright light + exercise (80.8 ± 11.6 [SD] min) compared with exercise alone (47.3 ± 21.6 min), and a similar phase delay following bright light alone (56.6 ± 15.2 min) and exercise alone administered for the same duration and at the same time of night. Thus, the data suggest that late night bright light followed by early morning exercise can have an additive circadian phase-shifting effect.

Adaptive Clinical Trials: Advantages and Disadvantages of Various Adaptive Design Elements.

PubMed

Korn, Edward L; Freidlin, Boris

2017-06-01

There is a wide range of adaptive elements of clinical trial design (some old and some new), with differing advantages and disadvantages. Classical interim monitoring, which adapts the design based on early evidence of superiority or futility of a treatment arm, has long been known to be extremely useful. A more recent application of interim monitoring is in the use of phase II/III designs, which can be very effective (especially in the setting of multiple experimental treatments and a reliable intermediate end point) but do have the cost of having to commit earlier to the phase III question than if separate phase II and phase III trials were performed. Outcome-adaptive randomization is an older technique that has recently regained attention; it increases trial complexity and duration without offering substantial benefits to the patients in the trial. The use of adaptive trials with biomarkers is new and has great potential for efficiently identifying patients who will be helped most by specific treatments. Master protocols in which trial arms and treatment questions are added to an ongoing trial can be especially efficient in the biomarker setting, where patients are screened for entry into different subtrials based on evolving knowledge about targeted therapies. A discussion of three recent adaptive clinical trials (BATTLE-2, I-SPY 2, and FOCUS4) highlights the issues. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

A Planetary Protection Strategy for the Mars Aerial Regional-Scale Environmental Survey (ARES) Mission Concept

NASA Technical Reports Server (NTRS)

Kuhl, Christopher A.

2008-01-01

The Aerial Regional-scale Environmental Survey (ARES) is a Mars exploration mission concept designed to send an airplane to fly through the lower atmosphere of Mars, with the goal of taking scientific measurements of the atmosphere, surface, and subsurface phenomenon. ARES was first proposed to the Mars Scout program in December 2002 for a 2007 launch opportunity and was selected to proceed with a Phase A study, step-2 proposal which was submitted in May 2003. ARES was not selected for the Scout mission, but efforts continued on risk reduction of the atmospheric flight system in preparation for the next Mars Scout opportunity in 2006. The ARES concept was again proposed in July 2006 to the Mars Scout program but was not selected to proceed into Phase A. This document describes the Planetary Protection strategy that was developed in ARES Pre Phase-A activities to help identify, early in the design process, certain hardware, assemblies, and/or subsystems that will require unique design considerations based on constraints imposed by Planetary Protection requirements. Had ARES been selected as an exploration project, information in this document would make up the ARES Project Planetary Protection Plan.

An Integrated Approach to Functional Engineering: An Engineering Database for Harness, Avionics and Software

NASA Astrophysics Data System (ADS)

Piras, Annamaria; Malucchi, Giovanni

2012-08-01

In the design and development phase of a new program one of the critical aspects is the integration of all the functional requirements of the system and the control of the overall consistency between the identified needs on one side and the available resources on the other side, especially when both the required needs and available resources are not yet consolidated, but they are evolving as the program maturity increases.The Integrated Engineering Harness Avionics and Software database (IDEHAS) is a tool that has been developed to support this process in the frame of the Avionics and Software disciplines through the different phases of the program. The tool is in fact designed to allow an incremental build up of the avionics and software systems, from the description of the high level architectural data (available in the early stages of the program) to the definition of the pin to pin connectivity information (typically consolidated in the design finalization stages) and finally to the construction and validation of the detailed telemetry parameters and commands to be used in the test phases and in the Mission Control Centre. The key feature of this approach and of the associated tool is that it allows the definition and the maintenance / update of all these data in a single, consistent environment.On one side a system level and concurrent approach requires the feasibility to easily integrate and update the best data available since the early stages of a program in order to improve confidence in the consistency and to control the design information.On the other side, the amount of information of different typologies and the cross-relationships among the data imply highly consolidated structures requiring lot of checks to guarantee the data content consistency with negative effects on simplicity and flexibility and often limiting the attention to special needs and to the interfaces with other disciplines.

Patient-centred screening for primary immunodeficiency: a multi-stage diagnostic protocol designed for non-immunologists

PubMed Central

de Vries, E

2006-01-01

Efficient early identification of primary immunodeficiency disease (PID) is important for prognosis, but is not an easy task for non-immunologists. The Clinical Working Party of the European Society for Immunodeficiencies (ESID) has composed a multi-stage diagnostic protocol that is based on expert opinion, in order to increase the awareness of PID among doctors working in different fields. The protocol starts from the clinical presentation of the patient; immunological skills are not needed for its use. The multi-stage design allows cost-effective screening for PID within the large pool of potential cases in all hospitals in the early phases, while more expensive tests are reserved for definitive classification in collaboration with an immunologist at a later stage. Although many PIDs present in childhood, others may present at any age. The protocols presented here are therefore aimed at both adult physicians and paediatricians. While designed for use throughout Europe, there will be national differences which may make modification of this generic algorithm necessary. PMID:16879238

Viking lander spacecraft battery

NASA Technical Reports Server (NTRS)

Newell, D. R.

1976-01-01

The Viking Lander was the first spacecraft to fly a sterilized nickel-cadmium battery on a mission to explore the surface of a planet. The significant results of the battery development program from its inception through the design, manufacture, and test of the flight batteries which were flown on the two Lander spacecraft are documented. The flight performance during the early phase of the mission is also presented.

Expert Systems on Multiprocessor Architectures. Phase 1

DTIC Science & Technology

1988-08-01

great rate) as early experience indicates what alternative aspect of system operation should have been monitored in any given completed run. The... system operation should have been monitored in any given completed run. The design goals that emerged then were (1) that the simulation system should...ORGANIZATION 6b OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION Stanford University (If applicable) Knowledge Systems Laboratory Rome Air Development

Viking Lander spacecraft battery. Final report

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

Newell, D.R.

1976-09-01

The Viking Lander was the first spacecraft to fly a sterilized nickel--cadmium battery on a mission to explore the surface of a planet. The significant results of the battery development program from its inception through the design, manufacture, and test of the flight batteries which were flown on the two Lander spacecraft are documented. The flight performance during the early phase of the mission is also presented.

Methods and costs associated with outfitting light aircraft for remote sensing applications

NASA Technical Reports Server (NTRS)

Rhodes, O. L.; Zetka, E. F.

1973-01-01

This document was designed to provide the potential user of a light aircraft remote sensor platform/data gathering system with general information on aircraft definition, implementation complexity, costs, scheduling and operational factors involved in this type of activity. Most of the subject material was developed from actual situations and problem areas encountered during the build-up cycle and early phases of flight operations.

Dawn Orbit Determination Team: Trajectory and Gravity Prediction Performance During Vesta Science Phases

NASA Technical Reports Server (NTRS)

Kennedy, Brian; Abrahamson, Matt; Ardito, Alessandro; Han, Dongsuk; Haw, Robert; Mastrodemos, Nicholas; Nandi, Sumita; Park, Ryan; Rush, Brian; Vaughan, Andrew

2013-01-01

The Dawn spacecraft was launched on September 27th, 2007. Its mission is to consecutively rendezvous with and observe the two largest bodies in the asteroid belt, Vesta and Ceres. It has already completed over a year's worth of direct observations of Vesta (spanning from early 2011 through late 2012) and is currently on a cruise trajectory to Ceres, where it will begin scientific observations in mid-2015. Achieving this data collection required careful planning and execution from all spacecraft teams. Dawn's Orbit Determination (OD) team was tasked with accurately predicting the trajectory of the Dawn spacecraft during the Vesta science phases, and also determining the parameters of Vesta to support future science orbit design. The future orbits included the upcoming science phase orbits as well as the transfer orbits between science phases. In all, five science phases were executed at Vesta, and this paper will describe some of the OD team contributions to the planning and execution of those phases.

Hearing the signal of dark sectors with gravitational wave detectors

NASA Astrophysics Data System (ADS)

Jaeckel, Joerg; Khoze, Valentin V.; Spannowsky, Michael

2016-11-01

Motivated by advanced LIGO (aLIGO)'s recent discovery of gravitational waves, we discuss signatures of new physics that could be seen at ground- and space-based interferometers. We show that a first-order phase transition in a dark sector would lead to a detectable gravitational wave signal at future experiments, if the phase transition has occurred at temperatures few orders of magnitude higher than the electroweak scale. The source of gravitational waves in this case is associated with the dynamics of expanding and colliding bubbles in the early universe. At the same time we point out that topological defects, such as dark sector domain walls, may generate a detectable signal already at aLIGO. Both bubble and domain-wall scenarios are sourced by semiclassical configurations of a dark new physics sector. In the first case, the gravitational wave signal originates from bubble wall collisions and subsequent turbulence in hot plasma in the early universe, while the second case corresponds to domain walls passing through the interferometer at present and is not related to gravitational waves. We find that aLIGO at its current sensitivity can detect smoking-gun signatures from domain-wall interactions, while future proposed experiments including the fifth phase of aLIGO at design sensitivity can probe dark sector phase transitions.

Premenstrual symptoms are associated with psychological and physical symptoms in early pregnancy.

PubMed

Winkel, Susanne; Einsle, Franziska; Wittchen, Hans-Ulrich; Martini, Julia

2013-04-01

The reproductive life of women is characterised by a number of distinct reproductive events and phases (e.g. premenstrual phase, peripartum, perimenopause). The hormonal transitions during these phases are often associated with both psychological and physical symptoms. Associations between these reproductive phases have been shown by numerous studies. However, the relationship between symptoms during the premenstrual phase and during early pregnancy has received little attention thus far, although early pregnancy is a time of dramatic hormonal as well as physical adaptation. Findings are based on a prospective longitudinal study with N = 306 pregnant women (MARI study). Three hundred five women that had menstrual bleeding in the year before pregnancy rated the severity of psychological and physical symptoms during premenstrual phases in the year preceding pregnancy. Besides this, they rated the severity of the same symptoms during early pregnancy (weeks 10 to 12 of gestation). The overall severity of premenstrual symptoms was significantly associated with the overall severity of early pregnancy symptoms (b = 0.4, 95% CI = 0.3-0.5; p < 0.001). The overall severity of early pregnancy symptoms was best predicted by the severity of premenstrual irritability. The best predictor for a particular symptom in early pregnancy mostly was the corresponding premenstrual symptom. The associations between premenstrual and early pregnancy symptoms support the reproductive hormone sensitivity hypothesis that some women are prone to repeatedly experience specific psychological and physical symptoms during different reproductive phases. The findings further imply that the nature of symptoms might be rather consistent between different reproductive phases.

The steroidogenic response and corpus luteum expression of the steroidogenic acute regulatory protein after human chorionic gonadotropin administration at different times in the human luteal phase.

PubMed

Kohen, Paulina; Castro, Olga; Palomino, Alberto; Muñoz, Alex; Christenson, Lane K; Sierralta, Walter; Carvallo, Pilar; Strauss, Jerome F; Devoto, Luigi

2003-07-01

This study was designed 1) to assess corpus luteum (CL) steroidogenesis in response to exogenous human chorionic gonadotropin (hCG) at different times during the luteal phase, 2) to examine the effect of hCG on steroidogenic acute regulatory protein (StAR) expression within the CL, 3) to correlate StAR expression and luteal steroidogenic responses to hCG, and 4) to determine whether endogenous LH regulates ovarian steroidogenesis in the early luteal phase. Blood was collected before and after hCG treatment for steroid and hCGbeta determinations. CL were obtained at the time of surgery to assess StAR gene and protein expression. During the early luteal phase various women received the GnRH antagonist for 24-48 h; some of them also received hCG 24 h after the GnRH antagonist. A slight steroidogenic response to hCG was observed in early luteal phase; 17alpha-hydroxyprogesterone, but not progesterone (P4), levels were significantly increased 8 h post-hCG, indicating a differential response by the granulosa and theca-lutein cells. The 1.6- and 4.4-kb StAR transcripts and the 37-kDa preprotein and 30-kDa mature StAR protein did not change post-hCG administration in early luteal phase CL. In contrast, the StAR 4.4- and 1.6-kb transcripts diminished significantly (P < 0.05) after the antagonist treatment. Immunohistochemical staining for StAR protein was weak, particularly in granulosa-lutein cells. Treatment with hCG restored StAR mRNA and protein and plasma P4 levels within 24 h in antagonist-treated women. hCG stimulated the highest plasma concentrations of P4 and estradiol in the midluteal phase, indicating its greatest steroidogenic capacity. Midluteal tissue StAR gene and protein expression increased by 1.6- and 1.4-fold after 24 h of hCG treatment, respectively. Administration of hCG resulted in the greatest increment in plasma P4 (4-fold) and 17alpha-hydroxyprogesterone (3-fold) levels over baseline in the late luteal phase. This was associated with an increase in StAR mRNA (3.5-fold) and protein (1.8-fold). Collectively, these data indicate that 1) the hCG-stimulated steroidogenic response is dependent on the age of the CL; 2) the early luteal phase CL is relatively insensitive to exogenous hCG in the presence of normal pituitary gonadotropin support, but becomes responsive when the latter is withdrawn; 3) the hCG-stimulated steroidogenic response in the mid- and late luteal phase is correlated with increased StAR mRNA and protein abundance; and 4) there are differential responses of small and large luteal cells to hCG stimulation that depend upon the age of the CL.

Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update.

PubMed

Bautista, Francisco; Fioravantti, Victoria; de Rojas, Teresa; Carceller, Fernando; Madero, Luis; Lassaletta, Alvaro; Moreno, Lucas

2017-11-01

Survival rates for patients with medulloblastoma have improved in the last decades but for those who relapse outcome is dismal and new approaches are needed. Emerging drugs have been tested in the last two decades within the context of phase I/II trials. In parallel, advances in genetic profiling have permitted to identify key molecular alterations for which new strategies are being developed. We performed a systematic review focused on the design and outcome of early-phase trials evaluating new agents in patients with relapsed medulloblastoma. PubMed, clinicaltrials.gov, and references from selected studies were screened to identify phase I/II studies with reported results between 2000 and 2015 including patients with medulloblastoma aged <18 years. A total of 718 studies were reviewed and 78 satisfied eligibility criteria. Of those, 69% were phase I; 31% phase II. Half evaluated conventional chemotherapeutics and 35% targeted agents. Overall, 662 patients with medulloblastoma/primitive neuroectodermal tumors were included. The study designs and the response assessments were heterogeneous, limiting the comparisons among trials and the correct identification of active drugs. Median (range) objective response rate (ORR) for patients with medulloblastoma in phase I/II studies was 0% (0-100) and 6.5% (0-50), respectively. Temozolomide containing regimens had a median ORR of 16.5% (0-100). Smoothened inhibitors trials had a median ORR of 8% (3-8). Novel drugs have shown limited activity against relapsed medulloblastoma. Temozolomide might serve as backbone for new combinations. Novel and more homogenous trial designs might facilitate the development of new drugs. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Design of rapid hardening engineered cementitious composites for sustainable construction

NASA Astrophysics Data System (ADS)

Marushchak, Uliana; Sanytsky, Myroslav; Sydor, Nazar

2017-12-01

This paper deals with design of environmentally friendly Rapid Hardening Engineered Cementitious Composite (RHECC) nanomodified with ultrafine mineral additives, polycarboxylate ether based superplasticizer, calcium hydrosilicate nanoparticles and dispersal reinforced by fibers. The incremental coefficient of surface activity was proposed in order to estimation of ultrafine supplementary materials (fly ash, methakaolin, microsilica) efficiency. A characterization of RHECC's compressive and flexural properties at different ages is reported in this paper. Early compressive strength of ECC is 45-50 MPa, standard strength - 84-95 MPa and parameter Rc2/Rc28 - 65-70%. The microstructure of the cement matrix and RHECC was investigated. The use of ultrafine mineral supplementary materials provides reinforcement of structure on micro- and nanoscale level (cementing matrix) due to formation of sub-microreinforcing hydrate phase as AFt- and C-S-H phases in unclinker part of cement matrix, resulting in the phenomena of "self-reinforcement" on the microstructure level. Designed RHECC may be regarded as lower brittle since the crack resistance coefficient is higher comparison to conventional fine grain concrete.

PRA in Design: Increasing Confidence in Pre-Operational Assessments of Risks (Results of a Joint NASA/NRC Workshop)

NASA Technical Reports Server (NTRS)

Youngblood, Robert; Dezfuli, Homayoon; Siu, Nathan

2010-01-01

In late 2009, the National Aeronautics and Space Administration (NASA) and the U.S. Nuclear Regulatory Commission (NRC) jointly organized a workshop to discuss technical issues associated with application of risk assessments to early phases of system design. The workshop, which was coordinated by the Idaho National Laboratory, involved invited presentations from a number of PRA experts in the aerospace and nuclear fields and subsequent discussion to address the following questions: (a) What technical issues limit decision-makers' confidence in PRA results, especially at a pre-operational phase of the system life cycle? (b) What is being done to address these issues'? (c) What more can be done ? The workshop resulted in participant observations and suggestions on several technical issues, including the pursuit of non-traditional approaches to risk assessment and the verification and validation of risk models. The workshop participants also identified several important non-technical issues, including risk communication with decision makers, and the integration of PRA into the overall design process.

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

Flanigan, Tom; Pybus, Craig; Roy, Sonya

This report summarizes the results of the Pre-Front End Engineering Design (pre-FEED) phase of a proposed advanced oxy-combustion power generation plant to repower the existing 200 MWe Unit 4 at Ameren Energy Resources’ (AER) Meredosia Power Plant. AER has formed an alliance with Air Liquide Process and Construction, Inc. (ALPC) and Babcock & Wilcox Power Generation Group (B&W PGG) for the design, construction, and testing of the facility, and has contracted with URS Corporation (URS) for preliminary design and Owner’s engineering services. The Project employs oxy-combustion technology – combustion of coal with nearly pure oxygen and recycled flue gas (insteadmore » of air) – to capture approximately 90% of the flue gas CO2 for transport and sequestration by another Project. Plant capacity and configuration has been developed based on the B&W PGG-ALPC cool recycle process firing high-sulfur bituminous coal fuel, assuming baseload plant operation to maximize existing steam turbine capability, with limited consideration for plant redundancy and performance optimization in order to keep plant costs as low as practical. Activities and preliminary results from the pre-FEED phase addressed in this report include the following: Overall plant thermal performance; Equipment sizing and system configuration; Plant operation and control philosophy; Plant emissions and effluents; CO 2 production and recovery characteristics; Project cost estimate and economic evaluation; Integrated project engineering and construction schedule; Project risk and opportunity assessment; Development of Project permitting strategy and requirements During the Phase 2 of the Project, additional design details will be developed and the Phase 1 work products updated to support actual construction and operation of the facility in Phase 3. Additional information will be provided early in Phase 2 to support Ameren-Environmental in finalizing the appropriate permitting strategies and permit applications. Additional performance and reliability enhancements will also be evaluated in Phase 2 to try to improve overall project economics.« less

Supersonic Aerodynamic Design Improvements of an Arrow-Wing HSCT Configuration Using Nonlinear Point Design Methods

NASA Technical Reports Server (NTRS)

Unger, Eric R.; Hager, James O.; Agrawal, Shreekant

1999-01-01

This paper is a discussion of the supersonic nonlinear point design optimization efforts at McDonnell Douglas Aerospace under the High-Speed Research (HSR) program. The baseline for these optimization efforts has been the M2.4-7A configuration which represents an arrow-wing technology for the High-Speed Civil Transport (HSCT). Optimization work on this configuration began in early 1994 and continued into 1996. Initial work focused on optimization of the wing camber and twist on a wing/body configuration and reductions of 3.5 drag counts (Euler) were realized. The next phase of the optimization effort included fuselage camber along with the wing and a drag reduction of 5.0 counts was achieved. Including the effects of the nacelles and diverters into the optimization problem became the next focus where a reduction of 6.6 counts (Euler W/B/N/D) was eventually realized. The final two phases of the effort included a large set of constraints designed to make the final optimized configuration more realistic and they were successful albeit with a loss of performance.

Application of Design of Experiments and Surrogate Modeling within the NASA Advanced Concepts Office, Earth-to-Orbit Design Process

NASA Technical Reports Server (NTRS)

Zwack, Mathew R.; Dees, Patrick D.; Holt, James B.

2016-01-01

Decisions made during early conceptual design have a large impact upon the expected life-cycle cost (LCC) of a new program. It is widely accepted that up to 80% of such cost is committed during these early design phases [1]. Therefore, to help minimize LCC, decisions made during conceptual design must be based upon as much information as possible. To aid in the decision making for new launch vehicle programs, the Advanced Concepts Office (ACO) at NASA Marshall Space Flight Center (MSFC) provides rapid turnaround pre-phase A and phase A concept definition studies. The ACO team utilizes a proven set of tools to provide customers with a full vehicle mass breakdown to tertiary subsystems, preliminary structural sizing based upon worst-case flight loads, and trajectory optimization to quantify integrated vehicle performance for a given mission [2]. Although the team provides rapid turnaround for single vehicle concepts, the scope of the trade space can be limited due to analyst availability and the manpower requirements for manual execution of the analysis tools. In order to enable exploration of a broader design space, the ACO team has implemented an advanced design methods (ADM) based approach. This approach applies the concepts of design of experiments (DOE) and surrogate modeling to more exhaustively explore the trade space and provide the customer with additional design information to inform decision making. This paper will first discuss the automation of the ACO tool set, which represents a majority of the development effort. In order to fit a surrogate model within tolerable error bounds a number of DOE cases are needed. This number will scale with the number of variable parameters desired and the complexity of the system's response to those variables. For all but the smallest design spaces, the number of cases required cannot be produced within an acceptable timeframe using a manual process. Therefore, automation of the tools was a key enabler for the successful application of an ADM approach to an ACO design study. Following the overview of the tool set automation, an example problem will be given to illustrate the implementation of the ADM approach. The example problem will first cover the inclusion of ground rules and assumptions (GR&A) for a study. The GR&A are very important to the study as they determine the constraints within which a trade study can be conducted. These trades must ultimately reconcile with the customer's desired output and any anticipated "what if" questions.

Conceptual Design Optimization of an Augmented Stability Aircraft Incorporating Dynamic Response and Actuator Constraints

NASA Technical Reports Server (NTRS)

Welstead, Jason; Crouse, Gilbert L., Jr.

2014-01-01

Empirical sizing guidelines such as tail volume coefficients have long been used in the early aircraft design phases for sizing stabilizers, resulting in conservatively stable aircraft. While successful, this results in increased empty weight, reduced performance, and greater procurement and operational cost relative to an aircraft with optimally sized surfaces. Including flight dynamics in the conceptual design process allows the design to move away from empirical methods while implementing modern control techniques. A challenge of flight dynamics and control is the numerous design variables, which are changing fluidly throughout the conceptual design process, required to evaluate the system response to some disturbance. This research focuses on addressing that challenge not by implementing higher order tools, such as computational fluid dynamics, but instead by linking the lower order tools typically used within the conceptual design process so each discipline feeds into the other. In thisresearch, flight dynamics and control was incorporated into the conceptual design process along with the traditional disciplines of vehicle sizing, weight estimation, aerodynamics, and performance. For the controller, a linear quadratic regulator structure with constant gains has been specified to reduce the user input. Coupling all the disciplines in the conceptual design phase allows the aircraft designer to explore larger design spaces where stabilizers are sized according to dynamic response constraints rather than historical static margin and volume coefficient guidelines.

National Institutes of Health Update: Translating Basic Behavioral Science into New Pediatric Obesity Interventions.

PubMed

Czajkowski, Susan M

2016-06-01

Pediatric obesity increases the risk of later-life obesity and chronic diseases. Basic research to better understand factors associated with excessive weight gain in early life and studies translating research findings into preventive and therapeutic strategies are essential to our ability to better prevent and treat childhood obesity. This overview describes several National Institutes of Health efforts designed to stimulate basic and translational research in childhood obesity prevention and treatment. These examples demonstrate the value of research in early phase translational pediatric obesity research and highlight some promising directions for this important area of research. Published by Elsevier Inc.

Deployable bamboo structure project: A building life-cycle report

NASA Astrophysics Data System (ADS)

Firdaus, Adrian; Prastyatama, Budianastas; Sagara, Altho; Wirabuana, Revian N.

2017-11-01

Bamboo is considered as a sustainable material in the world of construction, and it is vastly available in Indonesia. The general utilization of the material is increasingly frequent, however, its usage as a deployable structure-a recently-developed use of bamboo, is still untapped. This paper presents a report on a deployable bamboo structure project, covering the entire building life-cycle phase. The cycle encompasses the designing; fabrication; transportation; construction; operation and maintenance; as well as a plan for future re-use. The building is made of a configuration of the structural module, each being a folding set of bars which could be reduced in size to fit into vehicles for easy transportation. Each structural module was made of Gigantochloa apus bamboo. The fabrication, transportation, and construction phase require by a minimum of three workers. The fabrication and construction phase require three hours and fifteen minutes respectively. The building is utilized as cafeteria stands, the operation and maintenance phase started since early March 2017. The maintenance plan is scheduled on a monthly basis, focusing on the inspection of the locking mechanism element and the entire structural integrity. The building is designed to allow disassembly process so that it is reusable in the future.

Multipath noise reduction spread spectrum signals

NASA Technical Reports Server (NTRS)

Meehan, Thomas K. (Inventor)

1994-01-01

The concepts of early-prompt delay tracking, multipath correction of early-prompt delay tracking from correlation shape, and carrier phase multipath correction are addressed. In early-prompt delay tracking, since multipath is always delayed with respect to the direct signals, the system derives phase and pseudorange observables from earlier correlation lags. In multipath correction of early-prompt delay tracking from correlation shape, the system looks for relative variations of amplitude across the code correlation function that do not match the predicted multipath-free code cross-correlation shape. The system then uses deviations from the multipath-free shape to infer the magnitude of multipath, and to generate corrections pseudorange observables. In carrier phase multipath correction, the system looks for variations of phase among plural early and prompt lags. The system uses the measured phase variations, along with the general principle that the multipath errors are larger for later lags, to infer the presence of multipath, and to generate corrections for carrier-phase observables.

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

Levy, E.; Mullens, M.; Rath, P.

The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective envelope designs that can be effectively integrated into the plant production process while meeting the thermal requirements of the 2012 IECC standards. This work is part of a multiphase effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three methods for building high performance walls. Phase 2 focused on developing viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped narrow the research focus to perfecting a stud wall designmore » with exterior continuous insulation (CI). This report describes Phase 3, which was completed in two stages and continued the design development effort, exploring and evaluating a range or methods for applying CI to factory built homes. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing. During this phase, a home was built with CI, evaluated, and placed in service. The experience of building a mock up wall section with CI and then constructing on line a prototype home resolved important concerns about how to integrate the material into the production process. First steps were taken toward finding least expensive approaches for incorporating CI in standard factory building practices and a preliminary assessment suggested that even at this early stage the technology is attractive when viewed from a life cycle cost perspective.« less

Linear Proof Mass Actuator

NASA Technical Reports Server (NTRS)

Holloway, Sidney E., III

1994-01-01

This paper describes the mechanical design, analysis, fabrication, testing, and lessons learned by developing a uniquely designed spaceflight-like actuator. The linear proof mass actuator (LPMA) was designed to attach to both a large space structure and a ground test model without modification. Previous designs lacked the power to perform in a terrestrial environment while other designs failed to produce the desired accelerations or frequency range for spaceflight applications. Thus, the design for a unique actuator was conceived and developed at NASA Langley Research Center. The basic design consists of four large mechanical parts (mass, upper housing, lower housing, and center support) and numerous smaller supporting components including an accelerometer, encoder, and four drive motors. Fabrication personnel were included early in the design phase of the LPMA as part of an integrated manufacturing process to alleviate potential difficulties in machining an already challenging design. Operating testing of the LPMA demonstrated that the actuator is capable of various types of load functions.

Linear Proof Mass Actuator

NASA Technical Reports Server (NTRS)

Holloway, S. E., III

1995-01-01

This paper describes the mechanical design, analysis, fabrication, testing, and lessons learned by developing a uniquely designed spaceflight-like actuator. The Linear Proof Mass Actuator (LPMA) was designed to attach to both a large space structure and a ground test model without modification. Previous designs lacked the power to perform in a terrestrial environment while other designs failed to produce the desired accelerations or frequency range for spaceflight applications. Thus, the design for a unique actuator was conceived and developed at NASA Langley Research Center. The basic design consists of four large mechanical parts (Mass, Upper Housing, Lower Housing, and Center Support) and numerous smaller supporting components including an accelerometer, encoder, and four drive motors. Fabrication personnel were included early in the design phase of the LPMA as part of an integrated manufacturing process to alleviate potential difficulties in machining an already challenging design. Operational testing of the LPMA demonstrated that the actuator is capable of various types of load functions.

Early detection of sporadic pancreatic cancer: strategic map for innovation--a white paper.

PubMed

Kenner, Barbara J; Chari, Suresh T; Cleeter, Deborah F; Go, Vay Liang W

2015-07-01

Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer.

Early Detection of Sporadic Pancreatic Cancer

PubMed Central

Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

2015-01-01

Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

Designing "Real-World" trials to meet the needs of health policy makers at marketing authorization.

PubMed

Calvert, Melanie; Wood, John; Freemantle, Nick

2011-07-01

There is increasing interest in conducting "Real-World" trials that go beyond traditional assessment of efficacy and safety to examine market access and value for money questions before marketing authorization of a new pharmaceutical product or health technology. This commentary uses practical examples to demonstrate how high-quality evidence of the cost-effectiveness of an intervention may be gained earlier in the development process. Issues surrounding the design and analysis of "Real-World" trials to demonstrate relative cost-effectiveness early in the life of new technologies are discussed. The modification of traditional phase III trial designs, de novo trial designs, the combination of trial-based and epidemiological data, and the use of simulation model-based approaches to address reimbursement questions are described. Modest changes to a phase III trial protocol and case report form may be undertaken at the design stage to provide valid estimates of health care use and the benefits accrued; however, phase III designs often preclude "real-life" practice. Relatively small de novo trials may be used to address adherence to therapy or patient preference, although simply designed studies with active comparators enrolling large numbers of patients may provide evidence on long-term safety and rare adverse events. Practical examples demonstrate that it is possible to provide high-quality evidence of the cost-effectiveness of an intervention earlier in the development process. Payers and decision makers should preferentially adopt treatments with such evidence than treatments for which evidence is lacking or of lower quality. Copyright © 2011 Elsevier Inc. All rights reserved.

Resting Heart Rate Predicts Depression and Cognition Early after Ischemic Stroke: A Pilot Study.

PubMed

Tessier, Arnaud; Sibon, Igor; Poli, Mathilde; Audiffren, Michel; Allard, Michèle; Pfeuty, Micha

2017-10-01

Early detection of poststroke depression (PSD) and cognitive impairment (PSCI) remains challenging. It is well documented that the function of autonomic nervous system is associated with depression and cognition. However, their relationship has never been investigated in the early poststroke phase. This pilot study aimed at determining whether resting heart rate (HR) parameters measured in early poststroke phase (1) are associated with early-phase measures of depression and cognition and (2) could be used as new tools for early objective prediction of PSD or PSCI, which could be applicable to patients unable to answer usual questionnaires. Fifty-four patients with first-ever ischemic stroke, without cardiac arrhythmia, were assessed for resting HR and heart rate variability (HRV) within the first week after stroke and for depression and cognition during the first week and at 3 months after stroke. Multiple regression analyses controlled for age, gender, and stroke severity revealed that higher HR, lower HRV, and higher sympathovagal balance (low-frequency/high-frequency ratio of HRV) were associated with higher severity of depressive symptoms within the first week after stroke. Furthermore, higher sympathovagal balance in early phase predicted higher severity of depressive symptoms at the 3-month follow-up, whereas higher HR and lower HRV in early phase predicted lower global cognitive functioning at the 3-month follow-up. Resting HR measurements obtained in early poststroke phase could serve as an objective tool, applicable to patients unable to complete questionnaires, to help in the early prediction of PSD and PSCI. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Advanced Structural Optimization Under Consideration of Cost Tracking

NASA Astrophysics Data System (ADS)

Zell, D.; Link, T.; Bickelmaier, S.; Albinger, J.; Weikert, S.; Cremaschi, F.; Wiegand, A.

2014-06-01

In order to improve the design process of launcher configurations in the early development phase, the software Multidisciplinary Optimization (MDO) was developed. The tool combines different efficient software tools such as Optimal Design Investigations (ODIN) for structural optimizations, Aerospace Trajectory Optimization Software (ASTOS) for trajectory and vehicle design optimization for a defined payload and mission.The present paper focuses to the integration and validation of ODIN. ODIN enables the user to optimize typical axis-symmetric structures by means of sizing the stiffening designs concerning strength and stability while minimizing the structural mass. In addition a fully automatic finite element model (FEM) generator module creates ready-to-run FEM models of a complete stage or launcher assembly.Cost tracking respectively future improvements concerning cost optimization are indicated.

Dose-finding designs for trials of molecularly targeted agents and immunotherapies

PubMed Central

Chiuzan, Cody; Shtaynberger, Jonathan; Manji, Gulam A.; Duong, Jimmy K.; Schwartz, Gary K.; Ivanova, Anastasia; Lee, Shing M.

2017-01-01

Recently, there has been a surge of early phase trials of molecularly targeted agents (MTAs) and immunotherapies. These new therapies have different toxicity profiles compared to cytotoxic therapies. MTAs can benefit from new trial designs that allow inclusion of low-grade toxicities, late-onset toxicities, addition of an efficacy endpoint, and flexibility in the specification of a target toxicity probability. To study the degree of adoption of these methods, we conducted a Web of Science search of articles published between 2008 and 2014 that describe phase 1 oncology trials. Trials were categorized based on the dose-finding design used and the type of drug studied. Out of 1,712 dose-finding trials that met our criteria, 1,591 (92.9%) utilized a rule-based design, and 92 (5.4%; range 2.3% in 2009 to 9.7% in 2014) utilized a model-based or novel design. Over half of the trials tested an MTA or immunotherapy. Among the MTA and immunotherapy trials, 5.8% used model-based methods, compared to 3.9% and 8.3% of the chemotherapy or radiotherapy trials, respectively. While the percentage of trials using novel dose-finding designs has tripled since 2007, only 7.1% of trials use novel designs. PMID:28166468

Logistical challenges and design considerations for studies using acute anterior cruciate ligament injury as a potential model for early posttraumatic osteoarthritis.

PubMed

Lattermann, Christian; Jacobs, Cale A; Bunnell, Mary Proffitt; Jochimsen, Kate N; Abt, John P; Reinke, Emily K; Gammon, Lee G; Huebner, Janet L; Kraus, Virginia B; Spindler, Kurt P

2017-03-01

Anterior cruciate ligament (ACL) injuries are common and lead to posttraumatic osteoarthritis (PTOA) in a high percentage of patients. Research has been ineffective in identifying successful treatment options for people suffering from symptomatic PTOA resulting in a shift of focus toward the young, ACL injured patients at risk of developing PTOA. Randomized clinical trials examining the very early phase after ACL injury are ideal to study this population; however, these trials face significant challenges regarding recruitment as well as reproducibility of patient-reported outcomes (PROs) and inflammatory and/or chondrodegenerative biomarkers associated with early PTOA. The aim of this work was to develop an approach to allow for early recruitment into an RCT for early treatment following ACL injury and to analyze the variability of commonly used measures and biomarkers at various time points after injury. This paper reports the study design and data related to the first month of treatment for the placebo group of an ongoing 2-year clinical trial to evaluate the effect of an early intra-articular intervention after ACL injury. The results of this study suggest that acute ACL injury results in early changes of both inflammatory and chondrodegenerative biomarkers. These results also provide vital information for researchers to consider when developing future protocols, both related to the logistics of early patient enrollment as well as the appropriate timing of biomarker and patient-reported outcome collection. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:641-650, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Definition of technology development missions for early Space Station satellite servicing. Volume 2: Technical

NASA Technical Reports Server (NTRS)

Cable, D. A.; Diewald, C. A.; Hills, T. C.; Parmentier, T. J.; Spencer, R. A.; Stone, G. E.

1984-01-01

Volume 2 contains the Technical Report of the approach and results of the Phase 2 study. The phase 2 servicing study was initiated in June 1983, and is being reported in this document. The scope of the contract was to: (1) define in detail five selected technology development missions (TDM); (2) conduct a design requirement analysis to refine definitions of satellite servicing requirements at the space station; and (3) develop a technology plan that would identify and schedule prerequisite precursor technology development, associated. STS flight experiments and space station experiments needed to provide onorbit validation of the evolving technology.

A status of the Turbine Technology Team activities

NASA Technical Reports Server (NTRS)

Griffin, Lisa W.

1992-01-01

The recent activities of the Turbine Technology Team of the Consortium for Computational Fluid Dynamics (CFD) Application in Propulsion Technology is presented. The team consists of members from the government, industry, and universities. The goal of this team is to demonstrate the benefits to the turbine design process attainable through the application of CFD. This goal is to be achieved by enhancing and validating turbine design tools for improved loading and flowfield definition and loss prediction, and transferring the advanced technology to the turbine design process. In order to demonstrate the advantages of using CFD early in the design phase, the Space Transportation Main Engine (STME) turbines for the National Launch System (NLS) were chosen on which to focus the team's efforts. The Turbine Team activities run parallel to the STME design work.

Sustainable Design Approach: A case study of BIM use

NASA Astrophysics Data System (ADS)

Abdelhameed, Wael

2017-11-01

Achieving sustainable design in areas such as energy-efficient design depends largely on the accuracy of the analysis performed after the design is completed with all its components and material details. There are different analysis approaches and methods that predict relevant values and metrics such as U value, energy use and energy savings. Although certain differences in the accuracy of these approaches and methods have been recorded, this research paper does not focus on such matter, where determining the reason for discrepancies between those approaches and methods is difficult, because all error sources act simultaneously. The research paper rather introduces an approach through which BIM, building information modelling, can be utilised during the initial phases of the designing process, by analysing the values and metrics of sustainable design before going into the design details of a building. Managing all of the project drawings in a single file, BIM -building information modelling- is well known as one digital platform that offers a multidisciplinary detailed design -AEC model (Barison and Santos, 2010, Welle et.al., 2011). The paper presents in general BIM use in the early phases of the design process, in order to achieve certain required areas of sustainable design. The paper proceeds to introduce BIM use in specific areas such as site selection, wind velocity and building orientation, in terms of reaching the farther possible sustainable solution. In the initial phases of designing, material details and building components are not fully specified or selected yet. The designer usually focuses on zoning, topology, circulations, and other design requirements. The proposed approach employs the strategies and analysis of BIM use during those initial design phases in order to have the analysis and results of each solution or alternative design. The stakeholders and designers would have a better effective decision making process with a full clarity of each alternative's consequences. The architect would settle down and proceed in the alternative design of the best sustainable analysis. In later design stages, using the sustainable types of materials such as insulation, cladding, etc., and applying sustainable building components such as doors, windows, etc. would add more improvements and enhancements in reaching better values and metrics. The paper describes the methodology of this design approach through BIM strategies adopted in design creation. Case studies of architectural designs are used to highlight the details and benefits of this proposed approach.

Continued Water-Based Phase Change Material Heat Exchanger Development

NASA Technical Reports Server (NTRS)

Hansen, Scott W.; Sheth, Rubik B.; Poynot, Joe; Giglio, Tony; Ungar, Gene K.

2015-01-01

In a cyclical heat load environment such as low Lunar orbit, a spacecraft's radiators are not sized to meet the full heat rejection demands. Traditionally, a supplemental heat rejection device (SHReD) such as an evaporator or sublimator is used to act as a "topper" to meet the additional heat rejection demands. Utilizing a Phase Change Material (PCM) heat exchanger (HX) as a SHReD provides an attractive alternative to evaporators and sublimators as PCM HX's do not use a consumable, thereby leading to reduced launch mass and volume requirements. In continued pursuit of water PCM HX development two full-scale, Orion sized water-based PCM HX's were constructed by Mezzo Technologies. These HX's were designed by applying prior research on freeze front propagation to a full-scale design. Design options considered included bladder restraint and clamping mechanisms, bladder manufacturing, tube patterns, fill/drain methods, manifold dimensions, weight optimization, and midplate designs. Two units, Units A and B, were constructed and differed only in their midplate design. Both units failed multiple times during testing. This report highlights learning outcomes from these tests and are applied to a final sub-scale PCM HX which is slated to be tested on the ISS in early 2017.

Control system design for the MOD-5A 7.3 mW wind turbine generator

NASA Technical Reports Server (NTRS)

Barton, Robert S.; Hosp, Theodore J.; Schanzenbach, George P.

1995-01-01

This paper provides descriptions of the requirements analysis, hardware development and software development phases of the Control System design for the MOD-5A 7.3 mW Wind Turbine Generator. The system, designed by General Electric Company, Advanced Energy Programs Department, under contract DEN 3-153 with NASA Lewis Research Center and DOE, provides real time regulation of rotor speed by control of both generator torque and rotor torque. A variable speed generator system is used to provide both airgap torque control and reactive power control. The wind rotor is designed with segmented ailerons which are positioned to control blade torque. The central component of the control system, selected early in the design process, is a programmable controller used for sequencing, alarm monitoring, communication, and real time control. Development of requirements for use of aileron controlled blades and a variable speed generator required an analytical simulation that combined drivetrain, tower and blade elastic modes with wind disturbances and control behavior. An orderly two phase plan was used for controller software development. A microcomputer based turbine simulator was used to facilitate hardware and software integration and test.

A Framework for Performing V&V within Reuse-Based Software Engineering

NASA Technical Reports Server (NTRS)

Addy, Edward A.

1996-01-01

Verification and validation (V&V) is performed during application development for many systems, especially safety-critical and mission-critical systems. The V&V process is intended to discover errors, especially errors related to critical processing, as early as possible during the development process. Early discovery is important in order to minimize the cost and other impacts of correcting these errors. In order to provide early detection of errors, V&V is conducted in parallel with system development, often beginning with the concept phase. In reuse-based software engineering, however, decisions on the requirements, design and even implementation of domain assets can be made prior to beginning development of a specific system. In this case, V&V must be performed during domain engineering in order to have an impact on system development. This paper describes a framework for performing V&V within architecture-centric, reuse-based software engineering. This framework includes the activities of traditional application-level V&V, and extends these activities into domain engineering and into the transition between domain engineering and application engineering. The framework includes descriptions of the types of activities to be performed during each of the life-cycle phases, and provides motivation for the activities.

Cost-engineering modeling to support rapid concept development of an advanced infrared satellite system

NASA Astrophysics Data System (ADS)

Bell, Kevin D.; Dafesh, Philip A.; Hsu, L. A.; Tsuda, A. S.

1995-12-01

Current architectural and design trade techniques often carry unaffordable alternatives late into the decision process. Early decisions made during the concept exploration and development (CE&D) phase will drive the cost of a program more than any other phase of development; thus, designers must be able to assess both the performance and cost impacts of their early choices. The Space Based Infrared System (SBIRS) cost engineering model (CEM) described in this paper is an end-to-end process integrating engineering and cost expertise through commonly available spreadsheet software, allowing for concurrent design engineering and cost estimation to identify and balance system drives to reduce acquisition costs. The automated interconnectivity between subsystem models using spreadsheet software allows for the quick and consistent assessment of the system design impacts and relative cost impacts due to requirement changes. It is different from most CEM efforts attempted in the past as it incorporates more detailed spacecraft and sensor payload models, and has been applied to determine the cost drivers for an advanced infrared satellite system acquisition. The CEM is comprised of integrated detailed engineering and cost estimating relationships describing performance, design, and cost parameters. Detailed models have been developed to evaluate design parameters for the spacecraft bus and sensor; both step-starer and scanner sensor types incorporate models of focal plane array, optics, processing, thermal, communications, and mission performance. The current CEM effort has provided visibility to requirements, design, and cost drivers for system architects and decision makers to determine the configuration of an infrared satellite architecture that meets essential requirements cost effectively. In general, the methodology described in this paper consists of process building blocks that can be tailored to the needs of many applications. Descriptions of the spacecraft and payload subsystem models provide insight into The Aerospace Corporation expertise and scope of the SBIRS concept development effort.

Area/latency optimized early output asynchronous full adders and relative-timed ripple carry adders.

PubMed

Balasubramanian, P; Yamashita, S

2016-01-01

This article presents two area/latency optimized gate level asynchronous full adder designs which correspond to early output logic. The proposed full adders are constructed using the delay-insensitive dual-rail code and adhere to the four-phase return-to-zero handshaking. For an asynchronous ripple carry adder (RCA) constructed using the proposed early output full adders, the relative-timing assumption becomes necessary and the inherent advantages of the relative-timed RCA are: (1) computation with valid inputs, i.e., forward latency is data-dependent, and (2) computation with spacer inputs involves a bare minimum constant reverse latency of just one full adder delay, thus resulting in the optimal cycle time. With respect to different 32-bit RCA implementations, and in comparison with the optimized strong-indication, weak-indication, and early output full adder designs, one of the proposed early output full adders achieves respective reductions in latency by 67.8, 12.3 and 6.1 %, while the other proposed early output full adder achieves corresponding reductions in area by 32.6, 24.6 and 6.9 %, with practically no power penalty. Further, the proposed early output full adders based asynchronous RCAs enable minimum reductions in cycle time by 83.4, 15, and 8.8 % when considering carry-propagation over the entire RCA width of 32-bits, and maximum reductions in cycle time by 97.5, 27.4, and 22.4 % for the consideration of a typical carry chain length of 4 full adder stages, when compared to the least of the cycle time estimates of various strong-indication, weak-indication, and early output asynchronous RCAs of similar size. All the asynchronous full adders and RCAs were realized using standard cells in a semi-custom design fashion based on a 32/28 nm CMOS process technology.

Phase III Early Restoration Meeting | NOAA Gulf Spill Restoration

Science.gov Websites

Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Phase III Early Restoration Meeting - Corpus Christi, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Phase III Early Restoration Meeting - Pensacola, FL (rescheduled) | NOAA

Science.gov Websites

Restoration Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Circulation and Purification in the LUX-ZEPLIN System Test

NASA Astrophysics Data System (ADS)

Alsum, Shaun; Lz Collaboration

2016-03-01

LZ is a dark-matter direct detection experiment whose detector is a two-phase TPC using approximately seven tons of active xenon as its scintillator. The xenon must have few electronegative impurities to ensure sufficient electron transport through the drift region. The LZ purification system is being prototyped in the LZ system test, a test platform located at SLAC using about 100kg of Xenon, which consists of gas circulation through a SAES getter. We utilize a dual-phase and a gas-phase heat exchanger to reduce needed cooling power. To achieve this circulation we employ an all metal seal triple diaphragm pump, also prototyped in the System Test. This talk will present early results from the system test as well as some baseline LZ designs. The LUX-ZEPLIN dark matter direct detection experiment.

Navigation and Guidance for Low-Thrust Trajectories, LOTNAV

NASA Astrophysics Data System (ADS)

Cano, J. L.; Bello, M.; Rodriguez-Canabal, J.

A number of interplanetary low-thrust missions have already been flown by many space agencies. Examples of already flown missions based on the use of electric propulsion are Deep Space 1, Hayabusa and SMART-1. Many others are already in the assessment phase or in the development phase itself. In such perspective, it is required by the space agencies the procurement and utilisation of assessment tools for fast prototyping in the areas of mission design and navigation. The Low-Thrust Interplanetary Navigation Tool, which is the subject of this paper, allows the mission analyst performing such type of quick assessment studies for the early phases in the development of low-thrust missions. A number of test cases on low-thrust missions are also presented along with the utilities composing the LOTNAV tool.

Structural analysis at aircraft conceptual design stage

NASA Astrophysics Data System (ADS)

Mansouri, Reza

In the past 50 years, computers have helped by augmenting human efforts with tremendous pace. The aircraft industry is not an exception. Aircraft industry is more than ever dependent on computing because of a high level of complexity and the increasing need for excellence to survive a highly competitive marketplace. Designers choose computers to perform almost every analysis task. But while doing so, existing effective, accurate and easy to use classical analytical methods are often forgotten, which can be very useful especially in the early phases of the aircraft design where concept generation and evaluation demands physical visibility of design parameters to make decisions [39, 2004]. Structural analysis methods have been used by human beings since the very early civilization. Centuries before computers were invented; the pyramids were designed and constructed by Egyptians around 2000 B.C, the Parthenon was built by the Greeks, around 240 B.C, Dujiangyan was built by the Chinese. Persepolis, Hagia Sophia, Taj Mahal, Eiffel tower are only few more examples of historical buildings, bridges and monuments that were constructed before we had any advancement made in computer aided engineering. Aircraft industry is no exception either. In the first half of the 20th century, engineers used classical method and designed civil transport aircraft such as Ford Tri Motor (1926), Lockheed Vega (1927), Lockheed 9 Orion (1931), Douglas DC-3 (1935), Douglas DC-4/C-54 Skymaster (1938), Boeing 307 (1938) and Boeing 314 Clipper (1939) and managed to become airborne without difficulty. Evidencing, while advanced numerical methods such as the finite element analysis is one of the most effective structural analysis methods; classical structural analysis methods can also be as useful especially during the early phase of a fixed wing aircraft design where major decisions are made and concept generation and evaluation demands physical visibility of design parameters to make decisions. Considering the strength and limitations of both methodologies, the question to be answered in this thesis is: How valuable and compatible are the classical analytical methods in today's conceptual design environment? And can these methods complement each other? To answer these questions, this thesis investigates the pros and cons of classical analytical structural analysis methods during the conceptual design stage through the following objectives: Illustrate structural design methodology of these methods within the framework of Aerospace Vehicle Design (AVD) lab's design lifecycle. Demonstrate the effectiveness of moment distribution method through four case studies. This will be done by considering and evaluating the strength and limitation of these methods. In order to objectively quantify the limitation and capabilities of the analytical method at the conceptual design stage, each case study becomes more complex than the one before.

Optimal surveillance strategy for invasive species management when surveys stop after detection.

PubMed

Guillera-Arroita, Gurutzeta; Hauser, Cindy E; McCarthy, Michael A

2014-05-01

Invasive species are a cause for concern in natural and economic systems and require both monitoring and management. There is a trade-off between the amount of resources spent on surveying for the species and conducting early management of occupied sites, and the resources that are ultimately spent in delayed management at sites where the species was present but undetected. Previous work addressed this optimal resource allocation problem assuming that surveys continue despite detection until the initially planned survey effort is consumed. However, a more realistic scenario is often that surveys stop after detection (i.e., follow a "removal" sampling design) and then management begins. Such an approach will indicate a different optimal survey design and can be expected to be more efficient. We analyze this case and compare the expected efficiency of invasive species management programs under both survey methods. We also evaluate the impact of mis-specifying the type of sampling approach during the program design phase. We derive analytical expressions that optimize resource allocation between monitoring and management in surveillance programs when surveys stop after detection. We do this under a scenario of unconstrained resources and scenarios where survey budget is constrained. The efficiency of surveillance programs is greater if a "removal survey" design is used, with larger gains obtained when savings from early detection are high, occupancy is high, and survey costs are not much lower than early management costs at a site. Designing a surveillance program disregarding that surveys stop after detection can result in an efficiency loss. Our results help guide the design of future surveillance programs for invasive species. Addressing program design within a decision-theoretic framework can lead to a better use of available resources. We show how species prevalence, its detectability, and the benefits derived from early detection can be considered.

Enlisted Personnel Individualized Career System (EPICS) Test and Evaluation

DTIC Science & Technology

1984-01-01

The EPICS program, which was developed using an integrated personnel systems approach ( IPSA ), delays formal school training until after personnel have...received shipboard on-job training complemented by job performance aids (3PAs). Early phases of the program, which involved developing the IPSA EPICS...detailed description of the conception and development of the EPICS IPSA model, the execution of the front-end job design analyses, 3PA and instructional

Designing a Community-Based Lay Health Advisor Training Curriculum to Address Cancer Health Disparities

PubMed Central

Gwede, Clement K.; Ashley, Atalie A.; McGinnis, Kara; Montiel-Ishino, F. Alejandro; Standifer, Maisha; Baldwin, Julie; Williams, Coni; Sneed, Kevin B.; Wathington, Deanna; Dash-Pitts, Lolita; Green, B. Lee

2012-01-01

Introduction Racial and ethnic minorities have disproportionately higher cancer incidence and mortality than their White counterparts. In response to this inequity in cancer prevention and care, community-based lay health advisors (LHAs) may be suited to deliver effective, culturally relevant, quality cancer education, prevention/screening, and early detection services for underserved populations. Approach and Strategies Consistent with key tenets of community-based participatory research (CBPR), this project engaged community partners to develop and implement a unique LHA training curriculum to address cancer health disparities among medically underserved communities in a tricounty area. Seven phases of curriculum development went into designing a final seven-module LHA curriculum. In keeping with principles of CBPR and community engagement, academic–community partners and LHAs themselves were involved at all phases to ensure the needs of academic and community partners were mutually addressed in development and implementation of the LHA program. Discussion and Conclusions Community-based LHA programs for outreach, education, and promotion of cancer screening and early detection, are ideal for addressing cancer health disparities in access and quality care. When community-based LHAs are appropriately recruited, trained, and located in communities, they provide unique opportunities to link, bridge, and facilitate quality cancer education, services, and research. PMID:22982709

[The design of a nationwide cohort study in Germany : the pretest studies of the German National Cohort (GNC)].

PubMed

Ahrens, W; Greiser, H; Linseisen, J; Kluttig, A; Schipf, S; Schmidt, B; Günther, K

2014-11-01

The German National Cohort (GNC) is the largest population-based cohort study in Germany. Beginning in 2014, a total of 200,000 women and men aged 20-69 years will be examined in 18 study centers. The aim of the study is to investigate the etiology of chronic diseases in relation to lifestyle, genetic, socioeconomic, and environmental factors and to develop appropriate methods for early diagnosis and prevention of diseases such as cardiovascular and respiratory diseases, cancer, diabetes, neurodegenerative/psychiatric diseases, as well as musculoskeletal and infectious diseases. Pretest studies (phase 1 and 2) were conducted to select methods, instruments, and procedures for the main study, to develop standard operating procedures, and to design and test the examination program according to acceptance, expected duration, and feasibility. The pretest studies included testing of interviews, questionnaires, anthropometric measurements, several medical examinations, and the collection of biosamples. In addition, the logistic, technical, and personnel infrastructure for the main study could be established including the study centers, the central infrastructure for data management, processes to coordinate the study, and data protection and quality management concepts. The examination program for the main phase of the GNC was designed and optimized based on the results of the pretest studies. The GNC is a population-based, highly standardized and excellently phenotyped cohort that will be the basis for new strategies for risk assessment and identification, early diagnosis, and prevention of multifactorial diseases.

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

Protocol for the systematic review of the reporting of transoral robotic surgery.

PubMed

Main, Barry G; Blencowe, Natalie S; Howes, Noah; Cousins, Sian; Avery, Kerry N L; Gormley, Alexander; Radford, Phil; Elliott, Daisy; Byrne, Benjamin; Wilson, Nicholas; Hinchliffe, Robert; Blazeby, Jane M

2018-01-23

Transoral robotic surgery (TORS) has been adopted in some parts of the world as an innovative approach to the resection of oropharyngeal tumours. The development, details and outcomes of early-to-later phase evaluation of this technique and the quality of evidence to support its adoption into practice have hitherto not been summarised. The aim of this review is to identify and summarise the early and later phase studies of, and evidence for, TORS and to understand how early phase studies report intervention development, governance procedures and selection and reporting of outcomes to optimise methods for using the Idea, Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework for surgical innovation that informs evidence-based practice. The protocol has been written in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist. Electronic searches in OVID SP versions of Medline and EMBASE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews from the start of indexing to 30 April 2017 will identify studies reporting TORS. At least two independent researchers will identify studies for inclusion. Two researchers will extract data from each paper. Studies will be categorised into IDEAL stages of study design from 'pre-IDEAL' to randomised controlled trials (stage 3). Data will be collected about the (1) novel intervention and criteria for modification, (2) governance arrangements and patient information provision, (3) outcome domains selected and reported and (4) quality of study design, conduct and reporting. Descriptive statistics and a narrative synthesis will be presented. The results of this systematic review will be presented at relevant conferences. The methods will be used to inform future reviews exploring other novel surgical innovations. The findings will be published in a peer-reviewed journal. This study does not require ethical approval. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Understanding cost growth during operations of planetary missions: An explanation of changes

NASA Astrophysics Data System (ADS)

McNeill, J. F.; Chapman, E. L.; Sklar, M. E.

In the development of project cost estimates for interplanetary missions, considerable focus is generally given to the development of cost estimates for the development of ground, flight, and launch systems, i.e., Phases B, C, and D. Depending on the project team, efforts expended to develop cost estimates for operations (Phase E) may be relatively less rigorous than that devoted to estimates for ground and flight systems development. Furthermore, the project team may be challenged to develop a solid estimate of operations cost in the early stages of mission development, e.g., Concept Study Report or Systems Requirement Review (CSR/SRR), Preliminary Design Review (PDR), as mission specific peculiarities that impact cost may not be well understood. In addition, a methodology generally used to develop Phase E cost is engineering build-up, also known as “ grass roots” . Phase E can include cost and schedule risks that are not anticipated at the time of the major milestone reviews prior to launch. If not incorporated into the engineering build-up cost method for Phase E, this may translate into an estimation of the complexity of operations and overall cost estimates that are not mature and at worse, insufficient. As a result, projects may find themselves with thin reserves during cruise and on-orbit operations or project overruns prior to the end of mission. This paper examines a set of interplanetary missions in an effort to better understand the reasons for cost and staffing growth in Phase E. The method used in the study is discussed as well as the major findings summarized as the Phase E Explanation of Change (EoC). Research for the study entailed the review of project materials, including Estimates at Completion (EAC) for Phase E and staffing profiles, major project milestone reviews, e.g., CSR, PDR, Critical Design Review (CDR), the interviewing of select project and mission management, and review of Phase E replan materials. From this work, a detai- ed picture is constructed of why cost grew during the operations phase, even to the level of specific events in the life of the missions. As a next step, the Phase E EoC results were gleaned and synthesized to produce leading indicators, i.e., what may be identifiable signs of cost and staffing growth that may be present as early as PDR or CDR. Both a qualitative and quantitative approach was used to determine leading indicators. These leading indicators will be reviewed and a practical method for their use will be discussed.

Manned space flight nuclear system safety. Volume 6: Space base nuclear system safety plan

NASA Technical Reports Server (NTRS)

1972-01-01

A qualitative identification of the steps required to assure the incorporation of radiological system safety principles and objectives into all phases of a manned space base program are presented. Specific areas of emphasis include: (1) radiological program management, (2) nuclear system safety plan implementation, (3) impact on program, and (4) summary of the key operation and design guidelines and requirements. The plan clearly indicates the necessity of considering and implementing radiological system safety recommendations as early as possible in the development cycle to assure maximum safety and minimize the impact on design and mission plans.

Cassini Attitude Control Flight Software: from Development to In-Flight Operation

NASA Technical Reports Server (NTRS)

Brown, Jay

2008-01-01

The Cassini Attitude and Articulation Control Subsystem (AACS) Flight Software (FSW) has achieved its intended design goals by successfully guiding and controlling the Cassini-Huygens planetary mission to Saturn and its moons. This paper describes an overview of AACS FSW details from early design, development, implementation, and test to its fruition of operating and maintaining spacecraft control over an eleven year prime mission. Starting from phases of FSW development, topics expand to FSW development methodology, achievements utilizing in-flight autonomy, and summarize lessons learned during flight operations which can be useful to FSW in current and future spacecraft missions.

Engineering the Lidar In-space Technology Experiment

NASA Technical Reports Server (NTRS)

Couch, Richard H.; Moore, Chris L.

1992-01-01

The Lidar In-space Technology Experiment (LITE) is being developed by NASA for flight on the Space Shuttle in early 1994. A discussion of the NASA four-phase design process is followed by a short history of the experiment heritage. The instrument is then described at the subsystem level from an engineering point of view, with special emphasis on the laser and the receiver. Some aspects of designing for the space environment are discussed, as well as the importance of contamination control, and product assurance. Finally, the instrument integration and test process is described and the current status of the instrument development is given.

Statistical Methods for Rapid Aerothermal Analysis and Design Technology: Validation

NASA Technical Reports Server (NTRS)

DePriest, Douglas; Morgan, Carolyn

2003-01-01

The cost and safety goals for NASA s next generation of reusable launch vehicle (RLV) will require that rapid high-fidelity aerothermodynamic design tools be used early in the design cycle. To meet these requirements, it is desirable to identify adequate statistical models that quantify and improve the accuracy, extend the applicability, and enable combined analyses using existing prediction tools. The initial research work focused on establishing suitable candidate models for these purposes. The second phase is focused on assessing the performance of these models to accurately predict the heat rate for a given candidate data set. This validation work compared models and methods that may be useful in predicting the heat rate.

Promising developments in neuropsychological approaches for the detection of preclinical Alzheimer's disease: a selective review.

PubMed

Rentz, Dorene M; Parra Rodriguez, Mario A; Amariglio, Rebecca; Stern, Yaakov; Sperling, Reisa; Ferris, Steven

2013-01-01

Recently published guidelines suggest that the most opportune time to treat individuals with Alzheimer's disease is during the preclinical phase of the disease. This is a phase when individuals are defined as clinically normal but exhibit evidence of amyloidosis, neurodegeneration and subtle cognitive/behavioral decline. While our standard cognitive tests are useful for detecting cognitive decline at the stage of mild cognitive impairment, they were not designed for detecting the subtle cognitive variations associated with this biomarker stage of preclinical Alzheimer's disease. However, neuropsychologists are attempting to meet this challenge by designing newer cognitive measures and questionnaires derived from translational efforts in neuroimaging, cognitive neuroscience and clinical/experimental neuropsychology. This review is a selective summary of several novel, potentially promising, approaches that are being explored for detecting early cognitive evidence of preclinical Alzheimer's disease in presymptomatic individuals.

Development of Carbon Dioxide Removal Systems for Advanced Exploration Systems 2015-2016

NASA Technical Reports Server (NTRS)

Knox, James C.; Coker, Robert; Howard, David; Peters, Warren; Watson, David; Cmarik, Gregory; Miller, Lee A.

2016-01-01

A long-term goal for NASA is to enable crewed missions to Mars: first to the vicinity of Mars, and then to the Mars surface. These missions present new challenges for all aspects of spacecraft design in comparison with the International Space Station, as resupply is unavailable in the transit phase, and early return is not possible. Additionally, mass, power, and volume must be minimized for all phases to reduce propulsion needs. Mass reduction is particularly crucial for Mars surface landing and liftoff due to the challenges inherent in these operations for even much smaller payloads. In this paper we describe current and planned developments in the area of carbon dioxide removal to support future crewed Mars missions. Activities are also described that apply to both the resolution of anomalies observed in the ISS CDRA and the design of life support systems for future missions.

Development of Carbon Dioxide Removal Systems for Advanced Exploration Systems 2014-2015

NASA Technical Reports Server (NTRS)

Knox, James C.; Coker, Robert; Huff, Timothy L.; Gatens, Robyn; Miller, Lee A.; Stanley, Christine

2015-01-01

A long-term goal for NASA is to enable crewed missions to Mars: first to the vicinity of Mars, and then to the Mars surface. These missions present new challenges for all aspects of spacecraft design in comparison with the International Space Station, as resupply is unavailable in the transit phase, and early return is not possible. Additionally, mass, power, and volume must be minimized for all phases to reduce propulsion needs. Mass reduction is particularly crucial for Mars surface landing and liftoff due to the challenges inherent in these operations for even much smaller payloads. In this paper we describe current and planned developments in the area of carbon dioxide removal to support future crewed Mars missions. Activities are also described that apply to both the resolution of anomalies observed in the ISS CDRA and the design of life support systems for future missions.

Phase III Early Restoration Meeting - Lake Charles, LA | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News early restoration planning for Phase III and future early restoration plans. Open House: 5:30pm Public

Computational Methods to Assess the Production Potential of Bio-Based Chemicals.

PubMed

Campodonico, Miguel A; Sukumara, Sumesh; Feist, Adam M; Herrgård, Markus J

2018-01-01

Elevated costs and long implementation times of bio-based processes for producing chemicals represent a bottleneck for moving to a bio-based economy. A prospective analysis able to elucidate economically and technically feasible product targets at early research phases is mandatory. Computational tools can be implemented to explore the biological and technical spectrum of feasibility, while constraining the operational space for desired chemicals. In this chapter, two different computational tools for assessing potential for bio-based production of chemicals from different perspectives are described in detail. The first tool is GEM-Path: an algorithm to compute all structurally possible pathways from one target molecule to the host metabolome. The second tool is a framework for Modeling Sustainable Industrial Chemicals production (MuSIC), which integrates modeling approaches for cellular metabolism, bioreactor design, upstream/downstream processes, and economic impact assessment. Integrating GEM-Path and MuSIC will play a vital role in supporting early phases of research efforts and guide the policy makers with decisions, as we progress toward planning a sustainable chemical industry.

Heritage and Advanced Technology Systems Engineering Lessons Learned from NASA Space Missions

NASA Technical Reports Server (NTRS)

Barley, Bryan; Newhouse, Marilyn; Bacskay, Allen

2010-01-01

Use of heritage and new technology is necessary/enabling to implementing small, low cost missions, yet overruns decrease the ability to sustain future mission flight rates The majority of the cost growth drivers seen in the D&NF study were embedded early during formulation phase and later realized during the development and I&T phases Cost drivers can be avoided or significantly decreased by project management and SE emphasis on early identification of risks and realistic analyses SE processes that emphasize an assessment of technology within the mission system to identify technical issues in the design or operational use of the technology. Realistic assessment of new and heritage spacecraft technology assumptions , identification of risks and mitigation strategies. Realistic estimates of effort required to inherit existing or qualify new technology, identification of risks to estimates and develop mitigation strategies. Allocation of project reserves for risk-based mitigation strategies of each individual area of heritage or new technology. Careful tailoring of inheritance processes to ensure due diligence.

Circadian Phase-Shifting Effects of Bright Light, Exercise, and Bright Light + Exercise

PubMed Central

Kline, Christopher E.; Elliott, Jeffrey A.; Zielinski, Mark R.; Devlin, Tina M.; Moore, Teresa A.

2016-01-01

Limited research has compared the circadian phase-shifting effects of bright light and exercise and additive effects of these stimuli. The aim of this study was to compare the phase-delaying effects of late night bright light, late night exercise, and late evening bright light followed by early morning exercise. In a within-subjects, counterbalanced design, 6 young adults completed each of three 2.5-day protocols. Participants followed a 3-h ultra-short sleep-wake cycle, involving wakefulness in dim light for 2h, followed by attempted sleep in darkness for 1 h, repeated throughout each protocol. On night 2 of each protocol, participants received either (1) bright light alone (5,000 lux) from 2210–2340 h, (2) treadmill exercise alone from 2210–2340 h, or (3) bright light (2210–2340 h) followed by exercise from 0410–0540 h. Urine was collected every 90 min. Shifts in the 6-sulphatoxymelatonin (aMT6s) cosine acrophase from baseline to post-treatment were compared between treatments. Analyses revealed a significant additive phase-delaying effect of bright light + exercise (80.8 ± 11.6 [SD] min) compared with exercise alone (47.3 ± 21.6 min), and a similar phase delay following bright light alone (56.6 ± 15.2 min) and exercise alone administered for the same duration and at the same time of night. Thus, the data suggest that late night bright light followed by early morning exercise can have an additive circadian phase-shifting effect. PMID:27103935

Parasitic Reactions in Nanosized Silicon Anodes for Lithium-Ion Batteries

DOE PAGES

Gao, Han; Xiao, Lisong; Plumel, Ingo; ...

2017-02-08

When designing nano-Si electrodes for lithium-ion batteries, the detrimental effect of the c-Li 15Si 4 phase formed upon full lithiation is often a concern. In this study, Si nanoparticles with controlled particle sizes and morphology were synthesized and parasitic reactions of the metastable c-Li 15Si 4 phase with the non-aqueous electrolyte was investigated. The use of smaller Si nanoparticles (~ 60 nm) and the addition of fluoroethylene carbonate additive played decisive roles in the parasitic reactions such that the c-Li 15Si 4 phase could disappear at the end of lithiation. This suppression of c-Li 15Si 4 improved cycle life ofmore » the nano-Si electrodes but with a little loss of specific capacity. Also the characteristic c-Li 15Si 4 peak in the dQ/dV plots can be used as an early-stage indicator to cell capacity fade during cycling. Lastly, our findings can contribute to the design guidelines of Si electrodes and allow us to quantify another factor to the performance of the Si electrodes.« less

Fatigue and Oxidative Stress in Children Undergoing Leukemia Treatment.

PubMed

Rodgers, Cheryl; Sanborn, Chelse; Taylor, Olga; Gundy, Patricia; Pasvogel, Alice; Moore, Ida M Ki; Hockenberry, Marilyn J

2016-10-01

Fatigue is a frequent and distressing symptom in children undergoing leukemia treatment; however, little is known about factors influencing this symptom. Antioxidants such as glutathione can decrease symptom severity in adult oncology patients, but no study has evaluated antioxidants' effects on symptoms in pediatric oncology patients. This study describes fatigue patterns and associations of fatigue with antioxidants represented by reduced glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio among children receiving leukemia treatment. A repeated measures design assessed fatigue and antioxidants among 38 children from two large U.S. cancer centers. Fatigue was assessed among school-age children and by parent proxy among young children. Antioxidants (GSH and GSH/GSSG ratio) were assessed from cerebrospinal fluid at four phases during leukemia treatment. Young children had a steady decline of fatigue from the end of induction treatment through the continuation phase of treatment, but no significant changes were noted among the school-age children. Mean antioxidant scores varied slightly over time; however, the GSH/GSSG ratios in these children were significantly lower than the normal ratio. Mean GSH/GSSG ratios significantly correlated to fatigue scores of the school-age children during early phases of treatment. Children with low mean GSH/GSSG ratios demonstrated oxidative stress. The low ratios noted early in therapy were significantly correlated with higher fatigue scores during induction and postinduction treatment phases. This finding suggests that increased oxidative stress during the more intensive phases of therapy may explain the experience of fatigue children report. © The Author(s) 2016.

Real-time dynamic modelling for the design of a cluster-randomized phase 3 Ebola vaccine trial in Sierra Leone.

PubMed

Camacho, A; Eggo, R M; Goeyvaerts, N; Vandebosch, A; Mogg, R; Funk, S; Kucharski, A J; Watson, C H; Vangeneugden, T; Edmunds, W J

2017-01-23

Declining incidence and spatial heterogeneity complicated the design of phase 3 Ebola vaccine trials during the tail of the 2013-16 Ebola virus disease (EVD) epidemic in West Africa. Mathematical models can provide forecasts of expected incidence through time and can account for both vaccine efficacy in participants and effectiveness in populations. Determining expected disease incidence was critical to calculating power and determining trial sample size. In real-time, we fitted, forecasted, and simulated a proposed phase 3 cluster-randomized vaccine trial for a prime-boost EVD vaccine in three candidate regions in Sierra Leone. The aim was to forecast trial feasibility in these areas through time and guide study design planning. EVD incidence was highly variable during the epidemic, especially in the declining phase. Delays in trial start date were expected to greatly reduce the ability to discern an effect, particularly as a trial with an effective vaccine would cause the epidemic to go extinct more quickly in the vaccine arm. Real-time updates of the model allowed decision-makers to determine how trial feasibility changed with time. This analysis was useful for vaccine trial planning because we simulated effectiveness as well as efficacy, which is possible with a dynamic transmission model. It contributed to decisions on choice of trial location and feasibility of the trial. Transmission models should be utilised as early as possible in the design process to provide mechanistic estimates of expected incidence, with which decisions about sample size, location, timing, and feasibility can be determined. Copyright © 2016. Published by Elsevier Ltd.

Unveiling changes in the landscape of patient populations in cancer early drug development

PubMed Central

Hierro, Cinta; Azaro, Analía; Argilés, Guillem; Elez, Elena; Gómez, Patricia; Carles, Joan; Rodon, Jordi

2017-01-01

The introduction of new Molecularly Targeted Agents (MTA) has changed the landscape in Early Drug Development (EDD) over the last two decades, leading to an improvement in clinical trial design. Previous Phase 1 (Ph1) studies with cytotoxics focused on safety objectives, only recruiting heavily pre-treated cancer patients, have been left behind. In this review, we will illustrate the slow although unstoppable change that has increasingly been observed in those populations candidate to participate in EDD trials with the advent of MTA. As more evidence regarding oncogene addiction becomes available, molecular-biomarker driven selection has been implemented among Molecularly-Selected Population (MSP) studies. New Window-Of-Opportunity (WOO) and Phase 0 (Ph0) studies have been developed in order to assess whether a MTA produces the hypothetical proposed biological effect. The rising need of getting early pharmacokinetics and pharmacodynamics data has led to the conduction of Healthy Volunteer (HV) studies, in part favoured for the particular and different toxicity profile of these MTA. However, several challenges will need to be addressed in order to boost the implementation of these new clinical trial designs in the forthcoming years. Among the problems to overcome, we would highlight a better coordination effort between centers for ensuring adequate patient accrual among small patient populations and a deepening into the ethics implied in enrolling patients in studies with no therapeutic intent. However, these tribulations will be certainly compensated by the possibility of opening a new horizon of treatment for diseases with dismal prognosis. PMID:27835915

Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

PubMed

Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

2008-01-01

The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.

Transcriptomic responses to wounding: meta-analysis of gene expression microarray data.

PubMed

Sass, Piotr Andrzej; Dąbrowski, Michał; Charzyńska, Agata; Sachadyn, Paweł

2017-11-07

A vast amount of microarray data on transcriptomic response to injury has been collected so far. We designed the analysis in order to identify the genes displaying significant changes in expression after wounding in different organisms and tissues. This meta-analysis is the first study to compare gene expression profiles in response to wounding in as different tissues as heart, liver, skin, bones, and spinal cord, and species, including rat, mouse and human. We collected available microarray transcriptomic profiles obtained from different tissue injury experiments and selected the genes showing a minimum twofold change in expression in response to wounding in prevailing number of experiments for each of five wound healing stages we distinguished: haemostasis & early inflammation, inflammation, early repair, late repair and remodelling. During the initial phases after wounding, haemostasis & early inflammation and inflammation, the transcriptomic responses showed little consistency between different tissues and experiments. For the later phases, wound repair and remodelling, we identified a number of genes displaying similar transcriptional responses in all examined tissues. As revealed by ontological analyses, activation of certain pathways was rather specific for selected phases of wound healing, such as e.g. responses to vitamin D pronounced during inflammation. Conversely, we observed induction of genes encoding inflammatory agents and extracellular matrix proteins in all wound healing phases. Further, we selected several genes differentially upregulated throughout different stages of wound response, including established factors of wound healing in addition to those previously unreported  in this context such as PTPRC and AQP4. We found that transcriptomic responses to wounding showed similar traits in a diverse selection of tissues including skin, muscles, internal organs and nervous system. Notably, we distinguished transcriptional induction of inflammatory genes not only in the initial response to wounding, but also later, during wound repair and tissue remodelling.

Southern Impact Testing Alliance (SITA)

NASA Technical Reports Server (NTRS)

Hubbs, Whitney; Roebuck, Brian; Zwiener, Mark; Wells, Brian

2009-01-01

Efforts to form this Alliance began in 2008 to showcase the impact testing capabilities within the southern United States. Impact testing customers can utilize SITA partner capabilities to provide supporting data during all program phases-materials/component/ flight hardware design, development, and qualification. This approach would allow programs to reduce risk by providing low cost testing during early development to flush out possible problems before moving on to larger scale1 higher cost testing. Various SITA partners would participate in impact testing depending on program phase-materials characterization, component/subsystem characterization, full-scale system testing for qualification. SITA partners would collaborate with the customer to develop an integrated test approach during early program phases. Modeling and analysis validation can start with small-scale testing to ensure a level of confidence for the next step large or full-scale conclusive test shots. Impact Testing Facility (ITF) was established and began its research in spacecraft debris shielding in the early 1960's and played a malor role in the International Space Station debris shield development. As a result of return to flight testing after the loss of STS-107 (Columbia) MSFC ITF realized the need to expand their capabilities beyond meteoroid and space debris impact testing. MSFC partnered with the Department of Defense and academic institutions as collaborative efforts to gain and share knowledge that would benefit the Space Agency as well as the DoD. MSFC ITF current capabilities include: Hypervelocity impact testing, ballistic impact testing, and environmental impact testing.

Systems-Oriented Workplace Learning Experiences for Early Learners: Three Models.

PubMed

O'Brien, Bridget C; Bachhuber, Melissa R; Teherani, Arianne; Iker, Theresa M; Batt, Joanne; O'Sullivan, Patricia S

2017-05-01

Early workplace learning experiences may be effective for learning systems-based practice. This study explores systems-oriented workplace learning experiences (SOWLEs) for early learners to suggest a framework for their development. The authors used a two-phase qualitative case study design. In Phase 1 (spring 2014), they prepared case write-ups based on transcribed interviews from 10 SOWLE leaders at the authors' institution and, through comparative analysis of cases, identified three SOWLE models. In Phase 2 (summer 2014), studying seven 8-week SOWLE pilots, the authors used interview and observational data collected from the seven participating medical students, two pharmacy students, and site leaders to construct case write-ups of each pilot and to verify and elaborate the models. In Model 1, students performed specific patient care activities that addressed a system gap. Some site leaders helped students connect the activities to larger systems problems and potential improvements. In Model 2, students participated in predetermined systems improvement (SI) projects, gaining experience in the improvement process. Site leaders had experience in SI and often had significant roles in the projects. In Model 3, students worked with key stakeholders to develop a project and conduct a small test of change. They experienced most elements of an improvement cycle. Site leaders often had experience with SI and knew how to guide and support students' learning. Each model could offer systems-oriented learning opportunities provided that key elements are in place including site leaders facile in SI concepts and able to guide students in SOWLE activities.

Army-NASA aircrew/aircraft integration program: Phase 4 A(3)I Man-Machine Integration Design and Analysis System (MIDAS) software detailed design document

NASA Technical Reports Server (NTRS)

Banda, Carolyn; Bushnell, David; Chen, Scott; Chiu, Alex; Constantine, Betsy; Murray, Jerry; Neukom, Christian; Prevost, Michael; Shankar, Renuka; Staveland, Lowell

1991-01-01

The Man-Machine Integration Design and Analysis System (MIDAS) is an integrated suite of software components that constitutes a prototype workstation to aid designers in applying human factors principles to the design of complex human-machine systems. MIDAS is intended to be used at the very early stages of conceptual design to provide an environment wherein designers can use computational representations of the crew station and operator, instead of hardware simulators and man-in-the-loop studies, to discover problems and ask 'what if' questions regarding the projected mission, equipment, and environment. This document is the Software Product Specification for MIDAS. Introductory descriptions of the processing requirements, hardware/software environment, structure, I/O, and control are given in the main body of the document for the overall MIDAS system, with detailed discussion of the individual modules included in Annexes A-J.

Portfolio management in early stage drug discovery - a traveler's guide through uncharted territory.

PubMed

Betz, Ulrich A K

2011-07-01

Portfolio management in drug development has become a best practice in the pharmaceutical industry. By contrast, early on in the value chain - the discovery phase - portfolio management is still in its infancy. Nevertheless, owing to the attrition of R&D projects from phase to phase and the cost of capital involved, these early phases of drug discovery play a significant part for the overall cost of bringing new, innovative drugs to the market. This paper describes various approaches to manage a portfolio of projects in early-stage drug discovery and provides crucial factors that determine the success of such an approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

Combination of Light and Melatonin Time Cues for Phase Advancing the Human Circadian Clock

PubMed Central

Burke, Tina M.; Markwald, Rachel R.; Chinoy, Evan D.; Snider, Jesse A.; Bessman, Sara C.; Jung, Christopher M.; Wright, Kenneth P.

2013-01-01

Study Objectives: Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure. Design: Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m2)-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m2)-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time. Setting: Sleep and chronobiology laboratory environment free of time cues. Participants: Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD). Results: Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances. Conclusion: Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders. Citation: Burke TM; Markwald RR; Chinoy ED; Snider JA; Bessman SC; Jung CM; Wright Jr KP. Combination of light and melatonin time cues for phase advancing the human circadian clock. SLEEP 2013;36(11):1617-1624. PMID:24179293

Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-12-1-0138 TITLE: Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT PRINCIPAL INVESTIGATOR...NUMBER W81XWH-12-1-0138 Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...method for early detection of amyloid plaque in Alzheimer’s disease , with three Specific Aims: #1 Develop and optimize an x-ray PCCT to explore the

A Pooled Analysis of the Phase 3 REVIVE Trials: Randomized, Double-blind Studies to EValuate the Safety and Efficacy of Iclaprim Versus Vancomycin for trEatment of Acute Bacterial Skin and Skin Structure Infections.

PubMed

Huang, David B; Corey, G Ralph; Holland, Thomas L; Lodise, Thomas; O'Riordan, William; Wilcox, Mark H; File, Thomas M; Dryden, Matthew; Balser, Barbara; Desplats, Eve; Torres, Antoni

2018-05-18

Iclaprim, a diaminopyrimidine antibiotic, was compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) in two studies (REVIVE-1 and REVIVE-2). We explored the efficacy and tolerability of iclaprim in a pooled analysis of results from both studies. REVIVE-1 and REVIVE-2 were Phase 3, double-blind, randomized (1:1), multicenter, active-controlled, non-inferiority (margin of 10%) trials, each designed to enroll 600 patients a piece with ABSSSI. The studies used identical study protocols. Iclaprim 80 mg and vancomycin 15 mg/kg were administered IV every 12 hours for 5-14 days. The primary endpoint was a ≥20% reduction from baseline in lesion size (early clinical response [ECR]) at the early time point (48 to 72 hours after the start of study drug) in the intent-to-treat population. In REVIVE-1, ECR at the early time point was 80.9% with iclaprim vs. 81.0% with vancomycin (treatment difference, -0.13%; 95% confidence interval, -6.42% to 6.17%). In REVIVE-2, ECR was 78.3% with iclaprim vs. 76.7% with vancomycin (treatment difference: 1.58%, 95% CI: -5.10% to 8.26%). The pooled ECR was 79.6% with iclaprim vs. 78.8% with vancomycin (treatment difference: 0.75%, 95% CI: -3.84 to 5.35%). Iclaprim and vancomycin were comparable for the incidence of mostly mild adverse events, except for a higher incidence of elevated serum creatinine with vancomycin (n=7) compared with iclaprim (n=0). Iclaprim achieved noninferiority compared with vancomycin for early clinical response at the early time point and secondary endpoints with a similar safety profile in two Phase 3 studies for the treatment of ABSSSI suspected or confirmed to be caused by Gram-positive pathogens. NCT02600611 and NCT02607618. Copyright © 2018. Published by Elsevier B.V.

Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular Endothelial Cells of Type 2 Diabetic Rats

PubMed Central

Song, Zhenqiang; Li, Jing; Li, Chunshen

2016-01-01

In the study, type 2 diabetic rat model was established using streptozotocin (STZ) combined with a high-fat diet, and the rats were divided into control and diabetic groups. Diabetic groups were further divided into nonintervening, simvastatin, Didang Decoction (DDD) early-phase intervening, DDD mid-phase intervening, and DDD late-phase intervening groups. The expression level of MLCK was detected using Western Blot analysis, and the levels of cyclic adenosine monophosphate (cAMP), protein kinase C (PKC), and protein kinase A (PKA) were examined using Real Time PCR. Under the electron microscope, the cells in the early-DDD-intervention group and the simvastatin group were significantly more continuous and compact than those in the diabetic group. Compared with the control group, the expression of cAMP-1 and PKA was decreased in all diabetic groups, whereas the expression of MLCK and PKC was increased in early- and mid-phase DDD-intervening groups (P < 0.05); compared with the late-phase DDD-intervening group, the expression of cAMP-1 and PKA was higher, but the level of MLCK and PKC was lower in early-phase DDD-intervening group (P < 0.05). In conclusion, the early use of DDD improves the permeability of vascular endothelial cells by regulating the MLCK signaling pathway. PMID:27703477

SETL for Internet Data Processing

DTIC Science & Technology

2000-01-01

early phase in the evolution of most large software systems, especially those featuring novel designs [135, 173, 66, 70, 71 ]. Second, SETL’s strong...into SETL/E [66, 61], a revision of SETL that was extended with a process creation operator and renamed ProSet [ 71 ] to signify its role in prototyping...set-oriented languages having intrinsic persistence features [60, 64, 67, 70, 71 , 62] that sought to spare the programmer the trouble of coding data

Early Program Development

NASA Image and Video Library

1970-01-01

In 1970, NASA initiated Phase A contracts to study alternate Space Shuttle designs in addition to the two-stage fully-reusable Space Shuttle system already under development. A number of alternate systems were developed to ensure the development of the optimum earth-to-orbit system, including the Stage-and-a-half Chemical Interorbital Shuttle, shown here. The concept would utilize a reusable marned spacecraft with an onboard propulsion system attached to an expendable fuel tank to provide supplementary propellants.

Installation Restoration Program. Phase 1 - Records Search, Homestead AFB, Florida

DTIC Science & Technology

1983-08-01

con- ducted on a weekly basis. Since the early 1970’s, water and Aqueous . Film Forming Foam ( AFFF ) have been the main extinguishing agents used. Fuels...were occasionally disposed of at the site. Typically, water and AFFF were used as fire extinguishing agents. The site received a HARM score of 66. This...project activities include designs for Owens-Corning Fiberglas; 36,000 gpm neutralization facilities for FC Corporation; wastewater reclamation facilities

Conceptual Design of Simulation Models in an Early Development Phase of Lunar Spacecraft Simulator Using SMP2 Standard

NASA Astrophysics Data System (ADS)

Lee, Hoon Hee; Koo, Cheol Hea; Moon, Sung Tae; Han, Sang Hyuck; Ju, Gwang Hyeok

2013-08-01

The conceptual study for Korean lunar orbiter/lander prototype has been performed in Korea Aerospace Research Institute (KARI). Across diverse space programs around European countries, a variety of simulation application has been developed using SMP2 (Simulation Modelling Platform) standard related to portability and reuse of simulation models by various model users. KARI has not only first-hand experience of a development of SMP compatible simulation environment but also an ongoing study to apply the SMP2 development process of simulation model to a simulator development project for lunar missions. KARI has tried to extend the coverage of the development domain based on SMP2 standard across the whole simulation model life-cycle from software design to its validation through a lunar exploration project. Figure. 1 shows a snapshot from a visualization tool for the simulation of lunar lander motion. In reality, a demonstrator prototype on the right-hand side of image was made and tested in 2012. In an early phase of simulator development prior to a kick-off start in the near future, targeted hardware to be modelled has been investigated and indentified at the end of 2012. The architectural breakdown of the lunar simulator at system level was performed and the architecture with a hierarchical tree of models from the system to parts at lower level has been established. Finally, SMP Documents such as Catalogue, Assembly, Schedule and so on were converted using a XML(eXtensible Mark-up Language) converter. To obtain benefits of the suggested approaches and design mechanisms in SMP2 standard as far as possible, the object-oriented and component-based design concepts were strictly chosen throughout a whole model development process.

The Australian SKA Pathfinder: operations management and user engagement

NASA Astrophysics Data System (ADS)

Harvey-Smith, Lisa

2016-07-01

This paper describes the science operations model for the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. ASKAP is a radio interferometer currently being commissioned in Western Australia. It will be operated by a dedicated team of observatory staff with the support of telescope monitoring, control and scheduling software. These tools, as well as the proposal tools and data archive will enable the telescope to operate with little direct input from the astronomy user. The paper also discusses how close engagement with the telescope user community has been maintained throughout the ASKAP construction and commissioning phase, leading to positive outcomes including early input into the design of telescope systems and a vibrant early science program.

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

PubMed

Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C; Dworkin, Robert H; Katz, Nathaniel P; Kehlet, Henrik; Ballantyne, Jane C; Burke, Laurie B; Carragee, Eugene; Cowan, Penney; Croll, Scott; Dionne, Raymond A; Farrar, John T; Gilron, Ian; Gordon, Debra B; Iyengar, Smriti; Jay, Gary W; Kalso, Eija A; Kerns, Robert D; McDermott, Michael P; Raja, Srinivasa N; Rappaport, Bob A; Rauschkolb, Christine; Royal, Mike A; Segerdahl, Märta; Stauffer, Joseph W; Todd, Knox H; Vanhove, Geertrui F; Wallace, Mark S; West, Christine; White, Richard E; Wu, Christopher

2016-02-01

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.

Liver Full Reference Set Application: David Lubman - Univ of Michigan (2011) — EDRN Public Portal

Cancer.gov

In this work we will perform the next step in the biomarker development and validation. This step will be the Phase 2 validation of glycoproteins that have passed Phase 1 blinded validation using ELISA kits based on target glycoproteins selected based on our previous work. This will be done in a large Phase 2 sample set obtained in a multicenter study funded by the EDRN. The assays will be performed in our research lab located in the Center for Cancer Proteomics in the University of Michigan Medical Center. This study will include patients in whom serum was stored for future validation and includes samples from early HCC (n = 158), advanced cases (n=214) and cirrhotic controls (n = 417). These samples will be supplied by the EDRN (per Dr. Jo Ann Rinaudo) and will be analyzed in a blinded fashion by Dr. Feng from the Fred Hutchinson Cancer Center. This phase 2 study was designed to have above 90% power at one-sided 5% type-I error for comparing the joint sensitivity and specificity for differentiating early stage HCC from cirrhotic patients between AFP and a new marker. Sample sizes of 200 for early stage HCC and 400 for cirrhotics were required to achieve the stated power (14). We will select our candidates for this larger phase validation set based on the results of previous work. These will include HGF and CD14 and the results of these assays will be used to evaluate the performance of each of these markers and combinations of HGF and CD14 and AFP and HGF. It is expected that each assay will be repeated three times for each marker and will also be performed for AFP as the standard for comparison. 250 uL of each sample is requested for analysis.

Career Planning and Development for Early-Career Scientists

EPA Science Inventory

Early career development can be looked at as being of two major phases. The first phase is the formal educational process leading to an awarded degree, postdoctoral training, and potentially formal certification in a scientific discipline. The second phase is the informal educa...

Space Mission Concept Development Using Concept Maturity Levels

NASA Technical Reports Server (NTRS)

Wessen, Randii R.; Borden, Chester; Ziemer, John; Kwok, Johnny

2013-01-01

Over the past five years, pre-project formulation experts at the Jet Propulsion Laboratory (JPL) has developed and implemented a method for measuring and communicating the maturity of space mission concepts. Mission concept development teams use this method, and associated tools, prior to concepts entering their Formulation Phases (Phase A/B). The organizing structure is Concept Maturity Level (CML), which is a classification system for characterizing the various levels of a concept's maturity. The key strength of CMLs is the ability to evolve mission concepts guided by an incremental set of assessment needs. The CML definitions have been expanded into a matrix form to identify the breadth and depth of analysis needed for a concept to reach a specific level of maturity. This matrix enables improved assessment and communication by addressing the fundamental dimensions (e.g., science objectives, mission design, technical risk, project organization, cost, export compliance, etc.) associated with mission concept evolution. JPL's collaborative engineering, dedicated concept development, and proposal teams all use these and other CML-appropriate design tools to advance their mission concept designs. This paper focuses on mission concept's early Pre-Phase A represented by CMLs 1- 4. The scope was limited due to the fact that CMLs 5 and 6 are already well defined based on the requirements documented in specific Announcement of Opportunities (AO) and Concept Study Report (CSR) guidelines, respectively, for competitive missions; and by NASA's Procedural Requirements NPR 7120.5E document for Projects in their Formulation Phase.

Operations and support cost modeling using Markov chains

NASA Technical Reports Server (NTRS)

Unal, Resit

1989-01-01

Systems for future missions will be selected with life cycle costs (LCC) as a primary evaluation criterion. This reflects the current realization that only systems which are considered affordable will be built in the future due to the national budget constaints. Such an environment calls for innovative cost modeling techniques which address all of the phases a space system goes through during its life cycle, namely: design and development, fabrication, operations and support; and retirement. A significant portion of the LCC for reusable systems are generated during the operations and support phase (OS). Typically, OS costs can account for 60 to 80 percent of the total LCC. Clearly, OS costs are wholly determined or at least strongly influenced by decisions made during the design and development phases of the project. As a result OS costs need to be considered and estimated early in the conceptual phase. To be effective, an OS cost estimating model needs to account for actual instead of ideal processes by associating cost elements with probabilities. One approach that may be suitable for OS cost modeling is the use of the Markov Chain Process. Markov chains are an important method of probabilistic analysis for operations research analysts but they are rarely used for life cycle cost analysis. This research effort evaluates the use of Markov Chains in LCC analysis by developing OS cost model for a hypothetical reusable space transportation vehicle (HSTV) and suggests further uses of the Markov Chain process as a design-aid tool.

Solar glint suppression in compact planetary ultraviolet spectrographs

NASA Astrophysics Data System (ADS)

Davis, Michael W.; Cook, Jason C.; Grava, Cesare; Greathouse, Thomas K.; Gladstone, G. Randall; Retherford, Kurt D.

2015-08-01

Solar glint suppression is an important consideration in the design of compact photon-counting ultraviolet spectrographs. Southwest Research Institute developed the Lyman Alpha Mapping Project for the Lunar Reconnaissance Orbiter (launch in 2009), and the Ultraviolet Spectrograph on Juno (Juno-UVS, launch in 2011). Both of these compact spectrographs revealed minor solar glints in flight that did not appear in pre-launch analyses. These glints only appeared when their respective spacecraft were operating outside primary science mission parameters. Post-facto scattered light analysis verifies the geometries at which these glints occurred and why they were not caught during ground testing or nominal mission operations. The limitations of standard baffle design at near-grazing angles are discussed, as well as the importance of including surface scatter properties in standard stray light analyses when determining solar keep-out efficiency. In particular, the scattered light analysis of these two instruments shows that standard "one bounce" assumptions in baffle design are not always enough to prevent scattered sunlight from reaching the instrument focal plane. Future builds, such as JUICE-UVS, will implement improved scattered and stray light modeling early in the design phase to enhance capabilities in extended mission science phases, as well as optimize solar keep out volume.

Early intervention for psychosis

PubMed Central

Marshall, Max; Rathbone, John

2014-01-01

Background Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness). Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia. Objectives To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field. Selection criteria We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. Data collection and analysis We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). Main results Studies were diverse, mostly small, undertaken by pioneering researchers and with many methodological limitations (18 RCTs, total n=1808). Mostly, meta-analyses were inappropriate. For the six studies addressing prevention of psychosis for people with prodromal symptoms, olanzapine seemed of little benefit (n=60, 1 RCT, RR conversion to psychosis 0.58 CI 0.3 to 1.2), and cognitive behavioural therapy (CBT) equally so (n=60, 1 RCT, RR conversion to psychosis 0.50 CI 0.2 to 1.7). A risperidone plus CBT plus specialised team did have benefit over specialist team alone at six months (n=59, 1 RCT, RR conversion to psychosis 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20), but this was not seen by 12 months (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). Omega 3 fatty acids (EPA) had advantage over placebo (n=76, 1 RCT, RR transition to psychosis 0.13 CI 0.02 to 1.0, NNT 6 CI 5 to 96). We know of no replications of this finding. The remaining trials aimed to improve outcome in first-episode psychosis. Phase-specific CBT for suicidality seemed to have little effect, but the single study was small (n=56, 1 RCT, RR suicide 0.81 CI 0.05 to 12.26). Family therapy plus a specialised team in the Netherlands did not clearly affect relapse (n=76, RR 1.05 CI 0.4 to 3.0), but without the specialised team in China it may (n=83, 1 RCT, RR admitted to hospital 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The largest and highest quality study compared specialised team with standard care. Leaving the study early was reduced (n=547, 1 RCT, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) and compliance with treatment improved (n=507, RR stopped treatment 0.20 CI 0.1 to 0.4, NNT 9 CI 8 to 12). The mean number of days spent in hospital at one year were not significantly different (n=507, WMD, −1.39 CI −2.8 to 0.1), neither were data for ‘Not hospitalised’ by five years (n=547, RR 1.05 CI 0.90 to 1.2). There were no significant differences in numbers ‘not living independently’ by one year (n=507, RR 0.55 CI 0.3 to 1.2). At five years significantly fewer participants in the treatment group were ‘not living independently’ (n=547, RR 0.42 CI 0.21 to 0.8, NNT 19 CI 14 to 62). When phase-specific treatment (CBT) was compared with befriending no significant differences emerged in the number of participants being hospitalised over the 12 months (n=62, 1 RCT, RR 1.08 CI 0.59 to 1.99). Phase-specific treatment E-EPA oils suggested no benefit (n=80, 1 RCT, RR no response 0.90 CI 0.6 to 1.4) as did phase-specific treatment brief intervention (n=106, 1 RCT, RR admission 0.86 CI 0.4 to 1.7). Phase-specific ACE found no benefit but participants given vocational intervention were more likely to be employed (n=41, 1 RCT, RR 0.39 CI 0.21 to 0.7, NNT 2 CI 2 to 4). Phase-specific cannabis and psychosis therapy did not show benefit (n=47, RR cannabis use 1.30 CI 0.8 to 2.2) and crisis assessment did not reduce hospitalisation (n=98, RR 0.85 CI 0.6 to 1.3). Weight was unaffected by early behavioural intervention. Authors’ conclusions There is emerging, but as yet inconclusive evidence, to suggest that people in the prodrome of psychosis can be helped by some interventions. There is some support for specialised early intervention services, but further trials would be desirable, and there is a question of whether gains are maintained. There is some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials. PMID:21678345

Practical Application of PRA as an Integrated Design Tool for Space Systems

NASA Technical Reports Server (NTRS)

Kalia, Prince; Shi, Ying; Pair, Robin; Quaney, Virginia; Uhlenbrock, John

2013-01-01

This paper presents the application of the first comprehensive Probabilistic Risk Assessment (PRA) during the design phase of a joint NASA/NOAA weather satellite program, Geostationary Operational Environmental Satellite Series R (GOES-R). GOES-R is the next generation weather satellite primarily to help understand the weather and help save human lives. PRA has been used at NASA for Human Space Flight for many years. PRA was initially adopted and implemented in the operational phase of manned space flight programs and more recently for the next generation human space systems. Since its first use at NASA, PRA has become recognized throughout the Agency as a method of assessing complex mission risks as part of an overall approach to assuring safety and mission success throughout project lifecycles. PRA is now included as a requirement during the design phase of both NASA next generation manned space vehicles as well as for high priority robotic missions. The influence of PRA on GOES-R design and operation concepts are discussed in detail. The GOES-R PRA is unique at NASA for its early implementation. It also represents a pioneering effort to integrate risks from both Spacecraft (SC) and Ground Segment (GS) to fully assess the probability of achieving mission objectives. PRA analysts were actively involved in system engineering and design engineering to ensure that a comprehensive set of technical risks were correctly identified and properly understood from a design and operations perspective. The analysis included an assessment of SC hardware and software, SC fault management system, GS hardware and software, common cause failures, human error, natural hazards, solar weather and infrastructure (such as network and telecommunications failures, fire). PRA findings directly resulted in design changes to reduce SC risk from micro-meteoroids. PRA results also led to design changes in several SC subsystems, e.g. propulsion, guidance, navigation and control (GNC), communications, mechanisms, and command and data handling (C&DH). The fault tree approach assisted in the development of the fault management system design. Human error analysis, which examined human response to failure, indicated areas where automation could reduce the overall probability of gaps in operation by half. In addition, the PRA brought to light many potential root causes of system disruptions, including earthquakes, inclement weather, solar storms, blackouts and other extreme conditions not considered in the typical reliability and availability analyses. Ultimately the PRA served to identify potential failures that, when mitigated, resulted in a more robust design, as well as to influence the program's concept of operations. The early and active integration of PRA with system and design engineering provided a well-managed approach for risk assessment that increased reliability and availability, optimized lifecyc1e costs, and unified the SC and GS developments.

An early start to STEM education among year 1 primary students through project-based inquiry learning in the context of a magnet

NASA Astrophysics Data System (ADS)

Safiee, N.; Jusoh, Z. M.; Noor, A. M. H. M.; Tek, O. E.; Salleh, S. M.

2018-01-01

For the needs of the 21st century, the Government of Malaysia has conceptualized the Malaysia Education Blueprint 2013-2025 which embodies 11 strategic and operational shifts. In Shift 1, it is emphasized that the quality of Science, Technology, Engineering, and Mathematics (STEM) Education will be enhanced. This study employed the mixed-method approach using the “one-group pre-test and post-test design”. Accordingly, this paper describes the pedagogical practice of Project-based Inquiry Learning (PIL) which promotes STEM Education among Year 1 students in the move to progress in tandem with Shift 1. Specifically, using the context of a magnet which has been stipulated in the Primary School Standard Curriculum, Year 1 students experienced the STEM Education through the STEM Pedagogy in which they raised questions upon the presentation of a relevant stimulus (Inquiry Phase), explored the ways in which a train carriage or coach could be assembled by means of recycled materials and magnets (Exploration Phase), designed a train carriage (Design Phase), and ultimately reflected on their inventions (Reflection Phase). The cognitive and affective impacts through the use of this Project-based Inquiry Learning are presented. Implications for the teaching and learning of science are discussed within the context of STEM Education.

A Validation of Object-Oriented Design Metrics

NASA Technical Reports Server (NTRS)

Basili, Victor R.; Briand, Lionel; Melo, Walcelio L.

1995-01-01

This paper presents the results of a study conducted at the University of Maryland in which we experimentally investigated the suite of Object-Oriented (00) design metrics introduced by [Chidamber and Kemerer, 1994]. In order to do this, we assessed these metrics as predictors of fault-prone classes. This study is complementary to [Lieand Henry, 1993] where the same suite of metrics had been used to assess frequencies of maintenance changes to classes. To perform our validation accurately, we collected data on the development of eight medium-sized information management systems based on identical requirements. All eight projects were developed using a sequential life cycle model, a well-known 00 analysis/design method and the C++ programming language. Based on experimental results, the advantages and drawbacks of these 00 metrics are discussed and suggestions for improvement are provided. Several of Chidamber and Kemerer's 00 metrics appear to be adequate to predict class fault-proneness during the early phases of the life-cycle. We also showed that they are, on our data set, better predictors than "traditional" code metrics, which can only be collected at a later phase of the software development processes.

Decision Support System Requirements Definition for Human Extravehicular Activity Based on Cognitive Work Analysis

PubMed Central

Miller, Matthew James; McGuire, Kerry M.; Feigh, Karen M.

2016-01-01

The design and adoption of decision support systems within complex work domains is a challenge for cognitive systems engineering (CSE) practitioners, particularly at the onset of project development. This article presents an example of applying CSE techniques to derive design requirements compatible with traditional systems engineering to guide decision support system development. Specifically, it demonstrates the requirements derivation process based on cognitive work analysis for a subset of human spaceflight operations known as extravehicular activity. The results are presented in two phases. First, a work domain analysis revealed a comprehensive set of work functions and constraints that exist in the extravehicular activity work domain. Second, a control task analysis was performed on a subset of the work functions identified by the work domain analysis to articulate the translation of subject matter states of knowledge to high-level decision support system requirements. This work emphasizes an incremental requirements specification process as a critical component of CSE analyses to better situate CSE perspectives within the early phases of traditional systems engineering design. PMID:28491008

Cost estimating methods for advanced space systems

NASA Technical Reports Server (NTRS)

Cyr, Kelley

1994-01-01

NASA is responsible for developing much of the nation's future space technology. Cost estimates for new programs are required early in the planning process so that decisions can be made accurately. Because of the long lead times required to develop space hardware, the cost estimates are frequently required 10 to 15 years before the program delivers hardware. The system design in conceptual phases of a program is usually only vaguely defined and the technology used is so often state-of-the-art or beyond. These factors combine to make cost estimating for conceptual programs very challenging. This paper describes an effort to develop parametric cost estimating methods for space systems in the conceptual design phase. The approach is to identify variables that drive cost such as weight, quantity, development culture, design inheritance and time. The nature of the relationships between the driver variables and cost will be discussed. In particular, the relationship between weight and cost will be examined in detail. A theoretical model of cost will be developed and tested statistically against a historical database of major research and development projects.

Decision Support System Requirements Definition for Human Extravehicular Activity Based on Cognitive Work Analysis.

PubMed

Miller, Matthew James; McGuire, Kerry M; Feigh, Karen M

2017-06-01

The design and adoption of decision support systems within complex work domains is a challenge for cognitive systems engineering (CSE) practitioners, particularly at the onset of project development. This article presents an example of applying CSE techniques to derive design requirements compatible with traditional systems engineering to guide decision support system development. Specifically, it demonstrates the requirements derivation process based on cognitive work analysis for a subset of human spaceflight operations known as extravehicular activity . The results are presented in two phases. First, a work domain analysis revealed a comprehensive set of work functions and constraints that exist in the extravehicular activity work domain. Second, a control task analysis was performed on a subset of the work functions identified by the work domain analysis to articulate the translation of subject matter states of knowledge to high-level decision support system requirements. This work emphasizes an incremental requirements specification process as a critical component of CSE analyses to better situate CSE perspectives within the early phases of traditional systems engineering design.

Structure of interphase chromosomes in the nuclei of Drosophila cells.

PubMed

Banfalvi, Gaspar

2006-10-01

Fluorescent images of interphase chromatin structures and chromosome structures isolated from reversibly permeable Drosophila cells were analyzed. Decondensed chromatin in early S phase (2.0-2.5 C-value) consisted of a veil-like fibrillary network. Fibrillar chromatin formed rodlets later in the early S phase (2.5-2.75 C). Drosophila chromosomes contain several smaller subunits called rodlets. Fibrillar chromatin turned to chromatin ribbon and the early mid-S-phase globular chromosomes (2.75-3.0 C), then to opened fibrous globular forms later in the mid-S-phase (3.0-3.25 C), to late-S-phase supercoiled ribbons (3.25-3.5 C), end-S-phase elongated prechromosomes (3.5-3.75 C), bent and linear chromosomes (3.75-4.0 C). Early-S phase chromatin fibrils in the nuclei of Drosophila cells are thinner than the veil-like structures in mammalian cells. The connectivity of chromosomes shows linear arrangement (3, 1, 2, 4), with larger chromosomes (1 and 2) inside and smaller chromosomes (3, 4) at the two ends in the chromosomal chain.

Early visual processing is enhanced in the midluteal phase of the menstrual cycle.

PubMed

Lusk, Bethany R; Carr, Andrea R; Ranson, Valerie A; Bryant, Richard A; Felmingham, Kim L

2015-12-01

Event-related potential (ERP) studies have revealed an early attentional bias in processing unpleasant emotional images in women. Recent neuroimaging data suggests there are significant differences in cortical emotional processing according to menstrual phase. This study examined the impact of menstrual phase on visual emotional processing in women compared to men. ERPs were recorded from 28 early follicular women, 29 midluteal women, and 27 men while they completed a passive viewing task of neutral and low- and high- arousing pleasant and unpleasant images. There was a significant effect of menstrual phase in early visual processing, as midluteal women displayed significantly greater P1 amplitude at occipital regions to all visual images compared to men. Both midluteal and early follicular women displayed larger N1 amplitudes than men (although this only reached significance for the midluteal group) to the visual images. No sex or menstrual phase differences were apparent in later N2, P3, or LPP. A condition effect demonstrated greater P3 and LPP amplitude to highly-arousing unpleasant images relative to all other stimuli conditions. These results indicate that women have greater early automatic visual processing compared to men, and suggests that this effect is particularly strong in women in the midluteal phase at the earliest stage of visual attention processing. Our findings highlight the importance of considering menstrual phase when examining sex differences in the cortical processing of visual stimuli. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of Sensor Technology to Detect Fall Risk and Prevent Falls in Acute Care.

PubMed

Potter, Patricia; Allen, Kelly; Costantinou, Eileen; Klinkenberg, William Dean; Malen, Jill; Norris, Traci; O'Connor, Elizabeth; Roney, Wilhemina; Tymkew, Heidi Hahn; Wolf, Laurie

2017-08-01

Sensor technology that dynamically identifies hospitalized patients' fall risk and detects and alerts nurses of high-risk patients' early exits out of bed has potential for reducing fall rates and preventing patient harm. During Phase 1 (August 2014-January 2015) of a previously reported performance improvement project, an innovative depth sensor was evaluated on two inpatient medical units to study fall characteristics. In Phase 2 (April 2015-January 2016), a combined depth and bed sensor system designed to assign patient fall probability, detect patient bed exits, and subsequently prevent falls was evaluated. Fall detection depth sensors remained in place on two medicine units; bed sensors used to detect patient bed exits were added on only one of the medicine units. Fall rates and fall with injury rates were evaluated on both units. During Phase 2, the designated evaluation unit had 14 falls, for a fall rate of 2.22 per 1,000 patient-days-a 54.1% reduction compared with the Phase 1 fall rate. The difference in rates from Phase 1 to Phase 2 was statistically significant (z = 2.20; p = 0.0297). The comparison medicine unit had 30 falls-a fall rate of 4.69 per 1,000 patient-days, representing a 57.9% increase as compared with Phase 1. A fall detection sensor system affords a level of surveillance that standard fall alert systems do not have. Fall prevention remains a complex issue, but sensor technology is a viable fall prevention option. Copyright © 2017 The Joint Commission. Published by Elsevier Inc. All rights reserved.

Differential Response Pattern of Oropharyngeal Pressure by Bolus and Dry Swallows.

PubMed

Hasegawa, Mana; Kurose, Masayuki; Okamoto, Keiichiro; Yamada, Yoshiaki; Tsujimura, Takanori; Inoue, Makoto; Sato, Taisuke; Narumi, Takatsune; Fujii, Noritaka; Yamamura, Kensuke

2018-02-01

The aim of this study was to determine if bolus and dry swallow showed similar pressure changes in the oropharynx using our newly developed device. A unique character of it includes that baropressure can be measured with the sensor being placed in the balloon and can assess the swallowing mechanics in terms of pressure changes in the oropharynx with less influences of direct contacts of boluses and oropharyngeal structures during swallow indirectly. Fifteen healthy subjects swallowed saliva (dry), 15 ml of water, 45 ml of water, and 15 ml of two different types of food in terms of viscosity (potage soup-type and mayonnaise-type foods). Suprahyoid muscle activity was recorded simultaneously. Three parameters, area under the curve (AUC), peak amplitude, and duration of pressure, were analyzed from each swallow. Almost all of the bolus swallowing events had biphasic baropressure responses consisting of an early phase and late phase (99%), whereas 90% of the saliva swallowing events had a single phase. AUC, peak, and duration displayed greater effects during the late phase than during the early phase. Baropressure of the early phase, but not of the late phase, significantly increased with increasing volume; however, small but significant viscosity effects on pressure were seen during both phases. Peak pressure of the late phase was preceded by maximum muscle activity, whereas that of the early phase was seen when muscle activity displayed a peak response. These findings indicated that our device with the ability to measure baropressure has the potential to provide additional parameter to assess the swallow physiology, and biphasic baropressure responses in the early and late phases could reflect functional aspects of the swallowing reflexes.

Designing using Lego and Uno-Stacko: A Playful Architecture for an Integrated Kindergarten and Elementary School

NASA Astrophysics Data System (ADS)

Muthmainnah, K.; Aryanti, T.; Ardiansyah, A.

2017-03-01

The integrated kindergarten and elementary school is a public educational facility used for early age and elementary education. Designated for children at 4-12 years of age, the design should meet the standards and requirements, while considering children’s needs in their development phase. This paper discusses the design of an integrated kindergarten and elementary school using the playful theme. Design was explored using LEGO and UNO-STACKO to create spaces that accommodate material exploration for children. The design takes the play concept as a medium of child’s learning in order to improve their ability and awareness of the surrounding environment. The design translates the playful theme into imaginary dimension, constructive-deconstructive shapes, and glide circulations concept. The spatial pattern is applied by considering children’s behavior in the designated ages to trigger their creativity improvement. The design is expected to serve as a model of an integrated kindergarten and elementary school architecture.

The Triangle of the Space Launch System Operations

NASA Astrophysics Data System (ADS)

Fayolle, Eric

2010-09-01

Firemen know it as “fire triangle”, mathematicians know it as “golden triangle”, sailormen know it as “Bermuda triangle”, politicians know it as “Weimar triangle”… This article aims to present a new aspect of that shape geometry in the space launch system world: “the triangle of the space launch system operations”. This triangle is composed of these three following topics, which have to be taken into account for any space launch system operation processing: design, safety and operational use. Design performance is of course taking into account since the early preliminary phase of a system development. This design performance is matured all along the development phases, thanks to consecutives iterations in order to respect the financial and timing constraints imposed to the development of the system. This process leads to a detailed and precise design to assess the required performance. Then, the operational use phase brings its batch of constraints during the use of the system. This phase is conducted by specific procedures for each operation. Each procedure has sequences for each sub-system, which have to be conducted in a very precise chronological way. These procedures can be processed by automatic way or manual way, with the necessity or not of the implication of operators, and in a determined environment. Safeguard aims to verify the respect of the specific constraints imposed to guarantee the safety of persons and property, the protection of public health and the environment. Safeguard has to be taken into account above the operational constraints of any space operation, without forgetting the highest safety level for the operators of the space operation, and of course without damaging the facilities or without disturbing the external environment. All space operations are the result of a “win-win” compromise between these three topics. Contrary to the fire triangle where one of the topics has to be suppressed in order to avoid the combustion, no topics at all should be suppressed in the triangle of the space launch system operations. Indeed, if safeguard is not considered since the beginning of the development phase, this development will not take into account safeguard constraints. Then, the operational phase will become very difficult because unavailable, to respect safety rules required for the operational use phase of the system. Taking into account safeguard constraints in late project phases will conduct to very high operational constraints, sometimes quite disturbing for the operator, even blocking to be able to consider the operational use phase as mature and optimized. On the contrary, if design performance is not taken into account in order to favor safeguard aspect in the operational use phase, system design will not be optimized, what will lead to high planning and timing impacts. The examples detailed in this article show the compromise for what each designer should confront with during the development of any system dealing with the safety of persons and property, the protection of public health and the environment.

Potential subjects' responses to an ethics questionnaire in a phase I study of deep brain stimulation in early Parkinson's disease.

PubMed

Finder, Stuart G; Bliton, Mark J; Gill, Chandler E; Davis, Thomas L; Konrad, Peter E; Charles, P David

2012-01-01

Central to ethically justified clinical trial design is the need for an informed consent process responsive to how potential subjects actually comprehend study participation, especially study goals, risks, and potential benefits. This will be particularly challenging when studying deep brain stimulation and whether it impedes symptom progression in Parkinson's disease, since potential subjects will be Parkinson's patients for whom deep brain stimulation will likely have therapeutic value in the future as their disease progresses. As part of an expanded informed consent process for a pilot Phase I study of deep brain stimulation in early stage Parkinson's disease, an ethics questionnaire composed of 13 open-ended questions was distributed to potential subjects. The questionnaire was designed to guide potential subjects in thinking about their potential participation. While the purpose of the study (safety and tolerability) was extensively presented during the informed consent process, in returned responses 70 percent focused on effectiveness and 91 percent included personal benefit as poten- tial benefit from enrolling. However, 91 percent also indicated helping other Parkinson's patients as motivation when considering whether or not to enroll. This combination of responses highlights two issues to which investigators need to pay close attention in future trial designs: (1) how, and in what ways, informed consent processes reinforce potential subjects' preconceived understandings of benefit, and (2) that potential subjects see themselves as part of a community of Parkinson's sufferers with responsibilities extending beyond self-interest. More importantly, it invites speculation that a different paradigm for informed consent may be needed.

Numerical experiments on the impact of spring north pacific SSTA on NPO and unusually cool summers in Northeast China

NASA Astrophysics Data System (ADS)

Lian, Yi; Zhao, Bin; Shen, Baizhu; Li, Shangfeng; Liu, Gang

2014-11-01

A set of numerical experiments designed to analyze the oceanic forcing in spring show that the combined forcing of cold (warm) El Niño (La Niña) phases in the Niño4 region and sea surface temperature anomalies (SSTA) in the westerly drifts region would result in abnormally enhanced NorthEast Cold Vortex (NECV) activities in early summer. In spring, the central equatorial Pacific El Niño phase and westerly drift SSTA forcing would lead to the retreat of non-adiabatic waves, inducing elliptic low-frequency anomalies of tropical air flows. This would enhance the anomalous cyclone-anticyclone-cyclone-anticyclone low-frequency wave train that propagates from the tropics to the extratropics and further to the mid-high latitudes, constituting a major physical mechanism that contributes to the early summer circulation anomalies in the subtropics and in the North Pacific mid-high latitudes. The central equatorial Pacific La Niña forcing in the spring would, on the one hand, induce teleconnection anomalies of high pressure from the Sea of Okhotsk to the Sea of Japan in early summer, and on the other hand indirectly trigger a positive low-frequency East Asia-Pacific teleconnection (EAP) wave train in the lower troposphere.

Analysis of Drug Development Paradigms for Immune Checkpoint Inhibitors.

PubMed

Jardim, Denis L; de Melo Gagliato, Débora; Giles, Francis J; Kurzrock, Razelle

2018-04-15

Immune checkpoint inhibitors have unique toxicities and response kinetics compared with cytotoxic and gene-targeted anticancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the FDA website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared with that found in later trials leading to regulatory approvals of the same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a variety of cancer types. All checkpoint inhibitors received a priority review status and access to at least two additional FDA special access programs, more often breakthrough therapy designation and accelerated approval. Median clinical development time (investigational new drug application to approval) was 60.77 months [avelumab had the shortest timeline (52.33 months)]. Response rates during early phase I trials (median = 16%) are higher than for phase I trials of other agents (with the exception of gene-targeted agents tested with a biomarker). Doses approved were usually not identical to doses recommended on phase I trials. Approximately 50% of types of immune-related and 43% of types of clinically relevant toxicities from later trials were identified in early-phase trials. Even so, treatment-related mortality remains exceedingly low in later studies (0.33% of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors appear to be reasonably predicted from the dose-finding portion of phase I trials, indicating that the fast-track development of these agents is safe and justified. Clin Cancer Res; 24(8); 1785-94. ©2017 AACR . ©2017 American Association for Cancer Research.

Design and approach of the Living Organ Video Educated Donors (LOVED) program to promote living kidney donation in African Americans.

PubMed

Sieverdes, John C; Price, Matthew; Ruggiero, Kenneth J; Baliga, Prabhakar K; Chavin, Kenneth D; Brunner-Jackson, Brenda; Patel, Sachin; Treiber, Frank A

2017-10-01

To describe the rationale, methodology, design, and interventional approach of a mobile health education program designed for African Americans with end stage renal disease (ESRD) to increase knowledge and self-efficacy to approach others about their need for a living donor kidney transplant (LDKT). The Living Organ Video Educated Donors (LOVED) program is a theory-guided iterative designed, mixed methods study incorporating three phases: 1) a formative evaluation using focus groups to develop program content and approach; 2) a 2-month proof of concept trial (n=27) to primarily investigate acceptability, tolerability and investigate increases of LDKT knowledge and self-efficacy; and 3) a 6-month, 2-arm, 60-person feasibility randomized control trial (RCT) to primarily investigate increases in LDKT knowledge and self-efficacy, and secondarily, to increase the number of living donor inquiries, medical evaluations, and LDKTs. The 8-week LOVED program includes an interactive web-based app delivered on 10″ tablet computer incorporating weekly interactive video education modules, weekly group video chat sessions with an African American navigator who has had LDKT and other group interactions for support and improve strategies to promote their need for a kidney. Phase 1 and 2 have been completed and the program is currently enrolling for the feasibility RCT. Phase 2 experienced 100% retention rates with 91% adherence completing the video modules and 88% minimum adherence to the video chat sessions. We are in the early stages of an RCT to evaluate the LOVED program; to date, we have found high tolerability reported from Phase 2. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a Low Cost 10kW Tubular SOFC Power System

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

Bessette, Norman; Litka, Anthony; Rawson, Jolyon

The DOE program funded from 2003 through early 2013 has brought the Acumentrics SOFC program from an early stage R&D program to an entry level commercial product offering. The development work started as one of the main core teams under the DOE Solid State Energy Conversion Alliance (SECA) program administered by the National Energy Technology Laboratory (NETL) of the DOE. During the first phase of the program, lasting approximately 3-4 years, a 5kW machine was designed, manufactured and tested against the specification developed by NETL. This unit was also shipped to NETL for independent verification testing which validated all ofmore » the results achieved while in the laboratory at Acumentrics. The Acumentrics unit passed all criteria established from operational stability, efficiency, and cost projections. Passing of the SECA Phase I test allowed the program to move into Phase II of the program. During this phase, the overall objective was to further refine the unit meeting a higher level of performance stability as well as further cost reductions. During the first year of this new phase, the NETL SECA program was refocused towards larger size units and operation on coal gasification due to the severe rise in natural gas prices and refocus on the US supply of indigenous coal. At this point, the program was shifted to the U.S. DOE’s Energy Efficiency and Renewable Energy (EERE) division located in Golden, Colorado. With this shift, the focus remained on smaller power units operational on gaseous fuels for a variety of applications including micro combined heat and power (mCHP). To achieve this goal, further enhancements in power, life expectancy and reductions in cost were necessary. The past 5 years have achieved these goals with machines that can now achieve over 40% electrical efficiency and field units that have now operated for close to a year and a half with minimal maintenance. The following report details not only the first phase while under the SECA program and the key achievements but also the results while under EERE’s leadership and the transition to an early commercial product offering.« less

Commissioning and Early Operation for the NSLS-II Booster RF System

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

Marques, C.; Cupolo, J.; Davila, P.

2015-05-03

The National Synchrotron Light Source II (NSLS-II) at Brookhaven National Laboratory (BNL) is a third generation 3GeV, 500mA synchrotron light source. We discuss the booster synchrotron RF system responsible for providing power to accelerate an electron beam from 200MeV to 3GeV. The RF system design and construction are complete and is currently in the operational phase of the NSLS-II project. Preliminary operational data is also discussed.

Coarse pointing mechanism assembly for satellite interlink experiment

NASA Technical Reports Server (NTRS)

Maeusli, P. A.; Ivorra, M. T.; Gass, V.; Berthoud, J. F.

1996-01-01

Since 1975, MECANEX S.A. has been manufacturing components for solar array drives and mechanisms used in space applications. In 1991, work was started in an early phase C (Engineering Model) on a Coarse Pointing Mechanism Assembly (CPMA) for the Semiconductor-laser Inter-satellite Link EXperiment (SILEX). This paper deals with the history, the evolution, and the lessons learned from taking over a pre-design in 1991 to the delivery of last flight models (FM 5 & 6) in 1995.

A Designer Fluid For Aluminum Phase Change Devices: Aluminum Inorganic Aqueous Solutions (IAS) Chemistry and Experiments. Volume 2

DTIC Science & Technology

2016-11-17

magnitude larger than necessary. Adding more permanganate into the solution can produce a thicker coating . Manganese oxide has a thermal conductivity ...void before sealing both ends. For terrestrial heat pipes, copper is the most commonly used casing material due to its high thermal conductivity ... thermal conductivity ; however, these were early results and the tubes that were obtained from the Chinese manufacturer appeared to be of inconsistent

Evaluation and Numerical Simulation of Tsunami for Coastal Nuclear Power Plants of India

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

Sharma, Pavan K.; Singh, R.K.; Ghosh, A.K.

2006-07-01

Recent tsunami generated on December 26, 2004 due to Sumatra earthquake of magnitude 9.3 resulted in inundation at the various coastal sites of India. The site selection and design of Indian nuclear power plants demand the evaluation of run up and the structural barriers for the coastal plants: Besides it is also desirable to evaluate the early warning system for tsunami-genic earthquakes. The tsunamis originate from submarine faults, underwater volcanic activities, sub-aerial landslides impinging on the sea and submarine landslides. In case of a submarine earthquake-induced tsunami the wave is generated in the fluid domain due to displacement of themore » seabed. There are three phases of tsunami: generation, propagation, and run-up. Reactor Safety Division (RSD) of Bhabha Atomic Research Centre (BARC), Trombay has initiated computational simulation for all the three phases of tsunami source generation, its propagation and finally run up evaluation for the protection of public life, property and various industrial infrastructures located on the coastal regions of India. These studies could be effectively utilized for design and implementation of early warning system for coastal region of the country apart from catering to the needs of Indian nuclear installations. This paper presents some results of tsunami waves based on different analytical/numerical approaches with shallow water wave theory. (authors)« less

Verification and Validation of Digitally Upgraded Control Rooms

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

Boring, Ronald; Lau, Nathan

2015-09-01

As nuclear power plants undertake main control room modernization, a challenge is the lack of a clearly defined human factors process to follow. Verification and validation (V&V) as applied in the nuclear power community has tended to involve efforts such as integrated system validation, which comes at the tail end of the design stage. To fill in guidance gaps and create a step-by-step process for control room modernization, we have developed the Guideline for Operational Nuclear Usability and Knowledge Elicitation (GONUKE). This approach builds on best practices in the software industry, which prescribe an iterative user-centered approach featuring multiple cyclesmore » of design and evaluation. Nuclear regulatory guidance for control room design emphasizes summative evaluation—which occurs after the design is complete. In the GONUKE approach, evaluation is also performed at the formative stage of design—early in the design cycle using mockups and prototypes for evaluation. The evaluation may involve expert review (e.g., software heuristic evaluation at the formative stage and design verification against human factors standards like NUREG-0700 at the summative stage). The evaluation may also involve user testing (e.g., usability testing at the formative stage and integrated system validation at the summative stage). An additional, often overlooked component of evaluation is knowledge elicitation, which captures operator insights into the system. In this report we outline these evaluation types across design phases that support the overall modernization process. The objective is to provide industry-suitable guidance for steps to be taken in support of the design and evaluation of a new human-machine interface (HMI) in the control room. We suggest the value of early-stage V&V and highlight how this early-stage V&V can help improve the design process for control room modernization. We argue that there is a need to overcome two shortcomings of V&V in current practice—the propensity for late-stage V&V and the use of increasingly complex psychological assessment measures for V&V.« less

Towards early inclusion of children in tuberculosis drugs trials: a consensus statement.

PubMed

Nachman, Sharon; Ahmed, Amina; Amanullah, Farhana; Becerra, Mercedes C; Botgros, Radu; Brigden, Grania; Browning, Renee; Gardiner, Elizabeth; Hafner, Richard; Hesseling, Anneke; How, Cleotilde; Jean-Philippe, Patrick; Lessem, Erica; Makhene, Mamodikoe; Mbelle, Nontombi; Marais, Ben; McIlleron, Helen; McNeeley, David F; Mendel, Carl; Murray, Stephen; Navarro, Eileen; Anyalechi, E Gloria; Porcalla, Ariel R; Powell, Clydette; Powell, Mair; Rigaud, Mona; Rouzier, Vanessa; Samson, Pearl; Schaaf, H Simon; Shah, Seema; Starke, Jeff; Swaminathan, Soumya; Wobudeya, Eric; Worrell, Carol

2015-06-01

Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained. Copyright © 2015 Elsevier Ltd. All rights reserved.

Translation failure and medical reversal: Two sides to the same coin.

PubMed

Prasad, Vinay

2016-01-01

Translation failure occurs when the results of preclinical, observational and/or early phase studies fail to predict the results of well done (i.e. appropriately controlled, adequately powered, and properly conducted) phase III or randomised clinical trials. Some failures occur when promising basic science findings fail to replicate in human studies, while others happen when promising uncontrolled trial data show an exaggerated effect that vanishes in the setting of a randomised trial. Medical reversals occur when the results of preclinical, observational and/or early phase studies fail to predict the results of subsequent randomized clinical trials, but the practice has already gained widespread acceptance. Oncologic examples include bevacizumab and the use of autologous stem cell transplant in metastatic breast cancer. In a well-intentioned effort to reduce the rate of translation failure, oncologists must be careful that changes to regulatory processes and clinical trial design do not actually work to increase the approval of ineffective compounds. By trying to cure translation failure, we should be careful to avoid medical reversal. The rise of surrogate end-points and role of hard-wired bias in oncology trials suggest that we may be currently ignoring the simple fact that translation failure and medical reversal are two sides to the same coin. Published by Elsevier Ltd.

The hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the evaluation of hepatic fibrosis and early liver cirrhosis in a rat model: an experimental study.

PubMed

Ma, Chunmei; Liu, Ailian; Wang, Yuanyuan; Geng, Xiaoling; Hao, Li; Song, Qingwei; Sun, Bo; Wang, Heqing; Zhao, Gang

2014-07-17

To evaluate the hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the early diagnosis of hepatic fibrosis and cirrhosis and assessment of liver function in a rat model. In 2 groups of SD rats, liver fibrosis was induced in experimental animals by repetitive carbon tetrachloride injections, while the control group received saline injections. Five experimental rats and 2 control rats were randomly selected at weeks 4, 8, 12. One week after carbon tetrachloride administration, MRI (FIRM T1WI) scan was performed. Gd-EOB-DTPA (0.08mL) was injected into the rat's tail vein and hepatocyte phase images were obtained after 20min. The pre-enhanced phase and hepatocyte phase signal intensities (SI) were measured, and the relative contrast enhancement index (RCEI) was calculated. ANOVA analysis (LSD) of RCEI values in controls (n=6), hepatic fibrosis (n=7), and histopathologically-determined early cirrhosis group (n=6) was performed. RECI values showed a decreasing trend in the control group, hepatic fibrosis and early cirrhosis groups (1.11±0.43, 0.96±0.22, and 0.57±0.33, respectively). While the difference between the control and early cirrhosis groups was statistically significant (p=0.013), there was no significant difference in the hepatic fibrosis group vs the control (p=0.416) and the hepatic fibrosis group vs the early cirrhosis group (p=0.054). Hepatocyte phase RCEI values obtained with Gd-EOB-DTPA-enhanced MRI scan indicate liver injury in hepatic fibrosis and early cirrhosis. RCEI values are helpful for early diagnosis of liver cirrhosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Presumed Symbolic Use of Diurnal Raptors by Neanderthals

PubMed Central

Morin, Eugène; Laroulandie, Véronique

2012-01-01

In Africa and western Eurasia, occurrences of burials and utilized ocher fragments during the late Middle and early Late Pleistocene are often considered evidence for the emergence of symbolically-mediated behavior. Perhaps less controversial for the study of human cognitive evolution are finds of marine shell beads and complex designs on organic and mineral artifacts in early modern human (EMH) assemblages conservatively dated to ≈100–60 kilo-years (ka) ago. Here we show that, in France, Neanderthals used skeletal parts of large diurnal raptors presumably for symbolic purposes at Combe-Grenal in a layer dated to marine isotope stage (MIS) 5b (≈90 ka) and at Les Fieux in stratigraphic units dated to the early/middle phase of MIS 3 (60–40 ka). The presence of similar objects in other Middle Paleolithic contexts in France and Italy suggest that raptors were used as means of symbolic expression by Neanderthals in these regions. PMID:22403717

Presumed symbolic use of diurnal raptors by Neanderthals.

PubMed

Morin, Eugène; Laroulandie, Véronique

2012-01-01

In Africa and western Eurasia, occurrences of burials and utilized ocher fragments during the late Middle and early Late Pleistocene are often considered evidence for the emergence of symbolically-mediated behavior. Perhaps less controversial for the study of human cognitive evolution are finds of marine shell beads and complex designs on organic and mineral artifacts in early modern human (EMH) assemblages conservatively dated to ≈ 100-60 kilo-years (ka) ago. Here we show that, in France, Neanderthals used skeletal parts of large diurnal raptors presumably for symbolic purposes at Combe-Grenal in a layer dated to marine isotope stage (MIS) 5b (≈ 90 ka) and at Les Fieux in stratigraphic units dated to the early/middle phase of MIS 3 (60-40 ka). The presence of similar objects in other Middle Paleolithic contexts in France and Italy suggest that raptors were used as means of symbolic expression by Neanderthals in these regions.

Planning and Estimation of Operations Support Requirements

NASA Technical Reports Server (NTRS)

Newhouse, Marilyn E.; Barley, Bryan; Bacskay, Allen; Clardy, Dennon

2010-01-01

Life Cycle Cost (LCC) estimates during the proposal and early design phases, as well as project replans during the development phase, are heavily focused on hardware development schedules and costs. Operations (phase E) costs are typically small compared to the spacecraft development and test costs. This, combined with the long lead time for realizing operations costs, can lead to de-emphasizing estimation of operations support requirements during proposal, early design, and replan cost exercises. The Discovery and New Frontiers (D&NF) programs comprise small, cost-capped missions supporting scientific exploration of the solar system. Any LCC growth can directly impact the programs' ability to fund new missions, and even moderate yearly underestimates of the operations costs can present significant LCC impacts for deep space missions with long operational durations. The National Aeronautics and Space Administration (NASA) D&NF Program Office at Marshall Space Flight Center (MSFC) recently studied cost overruns and schedule delays for 5 missions. The goal was to identify the underlying causes for the overruns and delays, and to develop practical mitigations to assist the D&NF projects in identifying potential risks and controlling the associated impacts to proposed mission costs and schedules. The study found that 4 out of the 5 missions studied had significant overruns at or after launch due to underestimation of the complexity and supporting requirements for operations activities; the fifth mission had not launched at the time of the mission. The drivers behind these overruns include overly optimistic assumptions regarding the savings resulting from the use of heritage technology, late development of operations requirements, inadequate planning for sustaining engineering and the special requirements of long duration missions (e.g., knowledge retention and hardware/software refresh), and delayed completion of ground system development work. This paper updates the D&NF LCC study, looking at the operations (phase E) cost drivers in more detail and extending the study to include 2 additional missions and identifies areas for increased emphasis by project management in order to improve the fidelity of operations estimates.

Study design and early result of a phase I study of SABR for early-stage glottic cancer.

PubMed

Yu, Tosol; Wee, Chan Woo; Choi, Noorie; Wu, Hong-Gyun; Kang, Hyun-Cheol; Park, Jong Min; Kim, Jung-In; Kim, Jin Ho; Kwon, Tack-Kyun; Chung, Eun-Jae

2018-05-14

Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Human Factors in the Design of the Crew Exploration Vehicle (CEV)

NASA Technical Reports Server (NTRS)

Whitmore, Mihriban; Byrne, Vicky; Holden, Kritina

2007-01-01

NASA s Space Exploration vision for humans to venture to the moon and beyond provides interesting human factors opportunities and challenges. The Human Engineering group at NASA has been involved in the initial phases of development of the Crew Exploration Vehicle (CEV), Orion. Getting involved at the ground level, Human Factors engineers are beginning to influence design; this involvement is expected to continue throughout the development lifecycle. The information presented here describes what has been done to date, what is currently going on, and what is expected in the future. During Phase 1, prior to the contract award to Lockheed Martin, the Human Engineering group was involved in generating requirements, conducting preliminary task analyses based on interviews with subject matter experts in all vehicle systems areas, and developing preliminary concepts of operations based on the task analysis results. In addition, some early evaluations to look at CEV net habitable volume were also conducted. The program is currently in Phase 2, which is broken down into design cycles, including System Readiness Review, Preliminary Design Review, and Critical Design Review. Currently, there are ongoing Human Engineering Technical Interchange Meetings being held with both NASA and Lockheed Martin in order to establish processes, desired products, and schedules. Multiple design trades and quick-look evaluations (e.g. display device layout and external window size) are also in progress. Future Human Engineering activities include requirement verification assessments and crew/stakeholder evaluations of increasing fidelity. During actual flights of the CEV, the Human Engineering group is expected to be involved in in-situ testing and lessons learned reporting, in order to benefit human space flight beyond the initial CEV program.

Figure-ground organization in different phases of the perceptual alternation phenomenon.

PubMed

Tuccio, M T

1995-12-01

Two experiments on figure-ground organization were designed to examine whether the regions of an ambiguous stimulus perceived as "figure" vary as a function of regional area and experience with the stimulus. In Exp. 1 the perceived duration of each interpretation was recorded during continuous viewing for 10 subjects who had been trained until both percepts appeared with statistical regularity (stationary phase). In Exp. 2 the first interpretation reported by 172 naive observers after a few seconds of pattern exposure was recorded. The well-known tendency to interpret smaller regions as figure was noted in Exp. 2 whereas the results of Exp. 1 suggested equal probability of the percepts. Over-all results suggest that alternation is learned during the transient or "early" phase of perception, with some stimulus features and cultural factors influencing the figure-ground organization. During the stationary or late phase of perception the subject is well practiced and the alternating of interpretations becomes largely automatic.

A Digital App to Aid Detection, Monitoring, and Management of Dyslexia in Young Children (DIMMAND): Protocol for a Digital Health and Education Solution.

PubMed

Sood, Mariam R; Toornstra, Annet; Sereno, Martin I; Boland, Mark; Filaretti, Daniele; Sood, Anuj

2018-05-17

Dyslexia, a specific learning difficulty and a disability as defined in the Equality Act 2010, is a lifelong condition that affects a child from the start of education. Dyslexia is characterized by difficulties in language processing (reading, spelling, and writing) which do not correspond with the child's general intellectual abilities. Although dyslexia cannot be cured, there is a consensus that interventions are more effective and have greater impact the earlier they are administered. Effective interventions start with diagnosis. Currently, formal diagnosis requires an assessment by a dyslexia specialist or educational psychologist. These assessments are expensive and are not easy for a non-specialist teacher or parent to interpret. Consequently, formal assessments are normally performed at a much later age, when interventions are less likely to be effective. Combining the latest in scientific research, expertise of dyslexia practitioners and real-time interactivity facilitated by digital technologies, we aim to provide a cost-effective and convenient solution that focuses on early dyslexia detection and management. We discuss the rationale and protocol for the design and development of a digital health solution aimed at improving the early detection, monitoring and management of dyslexia (DIMMAND) in young children (4-8 years). The primary objective is to create a game-based digital solution aimed at children, parents, and teachers that firstly assesses, then monitors and manages progress in a convenient, cost-effective and private environment. The proposed solution will be designed and developed in phases. In the initial phase, the full functional specification of the games that constitute the app will be designed, together with the overall architecture of the solution. Prototype proof-of-concept implementation for few of these games, and commercialization strategies will also be developed. The follow-on phases will see the design implemented into a validated solution. In the initial phase, we worked closely with dyslexia specialists, adult dyslexics, teachers of special-needs children, parents of dyslexic children, and senior dyslexia representatives for large organizations. These interactions provided insights into the range of language difficulties faced by dyslexics, which solutions are used by teachers and professionals, and an overall understanding of the market. We comprehensively defined the ethical, privacy, and data security issues. The detailed design spec of the games, the methodology to be followed to interpret the results, and flow diagrams illustrating how the game screens will be presented was completed. As proof of concept, a few reading, visual, and auditory games were developed and successfully tested by stakeholders on different digital devices. The stakeholders provided regular feedback and confirmed the viability of our game-based solution. DIMMAND has the potential to provide significant positive health care and economic impact. It is expected to reduce intervention costs, improve dyslexia detection at an early age and aid self-management. RR1-10.2196/9583. ©Mariam R Sood, Annet Toornstra, Martin I Sereno, Mark Boland, Daniele Filaretti, Anuj Sood. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 17.05.2018.

Interactions of non-detergent sulfobetaines with early folding intermediates facilitate in vitro protein renaturation.

PubMed

Vuillard, L; Rabilloud, T; Goldberg, M E

1998-08-15

Non-detergent sulfobetaines (NDSB) are a family of solubilizing and stabilizing agents for proteins. In a previous study [Goldberg, M. E., Expert-Bezancon, N., Vuillard, L. & Rabilloud, T. (1996) Folding & Design 1, 21-27] we showed that the amount of active protein recovered in in vitro folding experiments could be significantly increased by some NDSBS. In this work we investigated the mechanisms by which these molecules facilitate protein renaturation. Stopped-flow and manual-mixing fluorescence and enzyme activity measurements were used to compare the kinetics of protein folding in the presence and absence of N-phenyl-methyl-N,N-dimethylammonium-propane-sulfonate (NDSB 256). Hen lysozyme and the beta2 subunit of Escherichia coli tryptophan synthase were chosen as model systems since their folding pathways had been previously investigated in detail. It is shown that, massive aggregation of tryptophan synthase occurs within less than 2.5 s after dilution in the renaturation buffer, but can be prevented by NDSB 256; only very early folding phases (such as the formation of a loosely packed hydrophobic core able to bind 8-anilino-1-naphthalenesulphonic acid, and the initial burying of tryptophan 177) are significantly altered by NDSB 256; none of the later phases is affected. Furthermore, NDSB 256 did not significantly affect any of the kinetic phases observed during the refolding of denatured lysozyme retaining intact disulphide bonds. This shows that NDSB 256 only interferes with very early steps in the folding process and acts by limiting the abortive interactions that could lead to the formation of inactive aggregates.

An advanced design of non-radioactive image capturing and management system for applications in non-invasive skin disorder diagnosis

NASA Astrophysics Data System (ADS)

Liu, Carol Y. B.; Luk, David C. K.; Zhou, Kany S. Y.; So, Bryan M. K.; Louie, Derek C. H.

2015-03-01

Due to the increasing incidences of malignant melanoma, there is a rising demand for assistive technologies for its early diagnosis and improving the survival rate. The commonly used visual screening method is with limited accuracy as the early phase of melanoma shares many clinical features with an atypical nevus, while conventional dermoscopes are not user-friendly in terms of setup time and operations. Therefore, the development of an intelligent and handy system to assist the accurate screening and long-term monitoring of melanocytic skin lesions is crucial for early diagnosis and prevention of melanoma. In this paper, an advanced design of non-invasive and non-radioactive dermoscopy system was reported. Computer-aided simulations were conducted for optimizing the optical design and uniform illumination distribution. Functional prototype and the software system were further developed, which could enable image capturing at 10x amplified and general modes, convenient data transmission, analysis of dermoscopic features (e.g., asymmetry, border irregularity, color, diameter and dermoscopic structure) for assisting the early detection of melanoma, extract patient information (e.g. code, lesion location) and integrate with dermoscopic images, thus further support long term monitoring of diagnostic analysis results. A clinical trial study was further conducted on 185 Chinese children (0-18 years old). The results showed that for all subjects, skin conditions diagnosed based on the developed system accurately confirmed the diagnoses by conventional clinical procedures. Besides, clinical analysis on dermoscopic features and a potential standard approach by the developed system to support identifying specific melanocytic patterns for dermoscopic examination in Chinese children were also reported.

Examining social-cognitive predictors of parenting skills among mothers with preschool and early elementary school-aged children

PubMed Central

Norouzi, Saiideh; Moghaddam, Mohammad Hossein Baghiani; Morowatisharifabad, Mohammad Ali; Norouzi, Ali; Jafari, Ali Reza; Fallahzadeh, Hossein

2015-01-01

Context: Identification of parenting skills determinants among mothers is an ongoing field of research. Aims: The aim of this study was to identify the social cognitive predictors of parenting skills among mothers. Settings and Design: Previous studies have demonstrated the health action process approach (HAPA) as a credible frame for predicting behavior, but the number of studies considering the predictive value of parenting skills determinants among mothers is rare. Subjects and Methods: An 8 months prospective design was applied. Participants were mothers with preschool and early elementary school-aged children. At the 1st time, 120 participants completed self-report questionnaires regarding their risk perception, outcome expectancies, task self-efficacy, and intentions toward parenting skills. At the 2nd time, they returned a follow-up questionnaire, which measured planning, coping self-efficacy, and recovery self-efficacy and finally, 8 months later as the 3rd time, parenting skills were measured. Path analysis was used for analysis. Results: Path analysis indicated that, in the motivational phase, there was no relationship between parenting skills intention and risk perception, outcome expectancies, and task self-efficacy. Furthermore, no relationship was found between parenting skills intention and planning. In the volitional phase, coping self-efficacy, recovery self-efficacy, and planning were statistically significant predictors of parenting skills. Conclusion: The results of this study confirm that volitional phase of the HAPA model is useful in determining parenting skills. However, the role motivational variables seem to be unimportant in performing these behaviors. It was concluded that everybody intended to apply parenting skills, in nature, and intervention strategies should be focused on turning intentions into behavior. PMID:27462638

A phase II clinical trial of a dental health education program delivered by aboriginal health workers to prevent early childhood caries

PubMed Central

2012-01-01

Background Early Childhood Caries (ECC) is a widespread problem in Australian Aboriginal communities causing severe pain and sepsis. In addition dental services are difficult to access for many Aboriginal children and trying to obtain care can be stressful for the parents. The control of dental caries has been identified as a key indictor in the reduction of Indigenous disadvantage. Thus, there is a need for new approaches to prevent ECC, which reflect the cultural norms of Aboriginal communities. Methods/Design This is a Phase II single arm trial designed to gather information on the effectiveness of a dental health education program for Aboriginal children aged 6 months, followed over 2 years. The program will deliver advice from Aboriginal Health Workers on tooth brushing, diet and the use of fluoride toothpaste to Aboriginal families. Six waves of data collection will be conducted to enable estimates of change in parental knowledge and their views on the acceptability of the program. The Aboriginal Health Workers will also be interviewed to record their views on the acceptability and program feasibility. Clinical data on the child participants will be recorded when they are 30 months old and compared with a reference population of similar children when the study began. Latent variable modeling will be used to interpret the intervention effects on disease outcome. Discussion The research project will identify barriers to the implementation of a family centered Aboriginal oral health strategy, as well as the development of evidence to assist in the planning of a Phase III cluster randomized study. Trial registration ACTRN12612000712808 PMID:22909327

Improving the luteal phase after ovarian stimulation: reviewing new options.

PubMed

Yding Andersen, C; Vilbour Andersen, K

2014-05-01

The human chorionic gonadotrophin (HCG) trigger used for final follicular maturation in connection with assisted reproduction treatment combines ovulation induction and early luteal-phase stimulation of the corpora lutea. The use of a gonadotrophin-releasing hormone agonist (GnRHa) for final follicular maturation has, however, for the first time allowed a separation of the ovulatory signal from the early luteal-phase support. This has generated new information that may improve the currently employed luteal-phase support. Thus, combined results from a number of randomized controlled trials using the GnRHa trigger suggest an association between the reproductive outcome after IVF treatment and the mid-luteal-phase serum progesterone concentration. It appears that a minimum mid-luteal progesterone threshold of approximately 80-100 nmol/l exists, which, when surpassed, results in reduced early pregnancy loss and an increased live birth rate. Further, the trade off between the HCG bolus and the subsequent risk of ovarian hyperstimulation syndrome has resulted in a trend to reduce the HCG bolus from 10,000 IU to 6500-5000 IU, which augments the HCG/LH deficiency during the early/mid-luteal phase. The mid-luteal HCG/LH shortage results in an altered progesterone profile, showing the highest concentration during the early luteal phase, contrasting with the mid-luteal peak seen in the natural menstrual cycle. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

MOS 2.0: Modeling the Next Revolutionary Mission Operations System

NASA Technical Reports Server (NTRS)

Delp, Christopher L.; Bindschadler, Duane; Wollaeger, Ryan; Carrion, Carlos; McCullar, Michelle; Jackson, Maddalena; Sarrel, Marc; Anderson, Louise; Lam, Doris

2011-01-01

Designed and implemented in the 1980's, the Advanced Multi-Mission Operations System (AMMOS) was a breakthrough for deep-space NASA missions, enabling significant reductions in the cost and risk of implementing ground systems. By designing a framework for use across multiple missions and adaptability to specific mission needs, AMMOS developers created a set of applications that have operated dozens of deep-space robotic missions over the past 30 years. We seek to leverage advances in technology and practice of architecting and systems engineering, using model-based approaches to update the AMMOS. We therefore revisit fundamental aspects of the AMMOS, resulting in a major update to the Mission Operations System (MOS): MOS 2.0. This update will ensure that the MOS can support an increasing range of mission types, (such as orbiters, landers, rovers, penetrators and balloons), and that the operations systems for deep-space robotic missions can reap the benefits of an iterative multi-mission framework.12 This paper reports on the first phase of this major update. Here we describe the methods and formal semantics used to address MOS 2.0 architecture and some early results. Early benefits of this approach include improved stakeholder input and buy-in, the ability to articulate and focus effort on key, system-wide principles, and efficiency gains obtained by use of well-architected design patterns and the use of models to improve the quality of documentation and decrease the effort required to produce and maintain it. We find that such methods facilitate reasoning, simulation, analysis on the system design in terms of design impacts, generation of products (e.g., project-review and software-delivery products), and use of formal process descriptions to enable goal-based operations. This initial phase yields a forward-looking and principled MOS 2.0 architectural vision, which considers both the mission-specific context and long-term system sustainability.

Engineering Changes in Product Design - A Review

NASA Astrophysics Data System (ADS)

Karthik, K.; Janardhan Reddy, K., Dr

2016-09-01

Changes are fundamental to product development. Engineering changes are unavoidable and can arise at any phase of the product life cycle. The consideration of market requirements, customer/user feedbacks, manufacturing constraints, design innovations etc., turning them into viable products can be accomplished when product change is managed properly. In the early design cycle, informal changes are accepted. However, changes become formal when its complexity and cost increases, and as product matures. To maximize the market shares, manufacturers have to effectively and efficiently manage engineering changes by means of Configuration Control. The paper gives a broad overview about ‘Engineering Change Management’ (ECM) through configuration management and its implications in product design. The aim is to give an idea and understanding about the engineering changes in product design scenario to the new researchers. This paper elaborates the significant aspect of managing the engineering changes and the importance of ECM in a product life cycle.

Hydration kinetics and morphology of cement pastes with pozzolanic volcanic ash studied via synchrotron-based techniques

DOE PAGES

Kupwade-Patil, Kunal; Chin, Stephanie; Ilavsky, Jan; ...

2017-10-13

Here, this study investigates the early ages of hydration behavior when basaltic volcanic ash was used as a partial substitute to ordinary Portland cement using ultra-small-angle X-ray scattering and wide-angle X-ray scattering (WAXS). The mix design consisted of 10, 30 and 50% substitution of Portland cement with two different-sized volcanic ashes. The data showed that substitution of volcanic ash above 30% results in excess unreacted volcanic ash, rather than additional pozzolanic reactions along longer length scales. WAXS studies revealed that addition of finely ground volcanic ash facilitated calcium-silicate-hydrate related phases, whereas inclusion of coarser volcanic ash caused domination by calcium-aluminum-silicate-hydratemore » and unreacted MgO phases, suggesting some volcanic ash remained unreacted throughout the hydration process. Addition of more than 30% volcanic ash leads to coarser morphology along with decreased surface area and higher intensity of scattering at early-age hydration. This suggests an abrupt dissolution indicated by changes in surface area due to the retarding gel formation that can have implication on early-age setting influencing the mechanical properties of the resulting cementitious matrix. The findings from this work show that the concentration of volcanic ash influences the specific surface area and morphology of hydration products during the early age of hydration. Therefore, natural pozzolanic volcanic ashes can be a viable substitute to Portland cement by providing environmental benefits in terms of lower-carbon footprint along with long-term durability.« less

Hydration kinetics and morphology of cement pastes with pozzolanic volcanic ash studied via synchrotron-based techniques

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

Kupwade-Patil, Kunal; Chin, Stephanie; Ilavsky, Jan

Here, this study investigates the early ages of hydration behavior when basaltic volcanic ash was used as a partial substitute to ordinary Portland cement using ultra-small-angle X-ray scattering and wide-angle X-ray scattering (WAXS). The mix design consisted of 10, 30 and 50% substitution of Portland cement with two different-sized volcanic ashes. The data showed that substitution of volcanic ash above 30% results in excess unreacted volcanic ash, rather than additional pozzolanic reactions along longer length scales. WAXS studies revealed that addition of finely ground volcanic ash facilitated calcium-silicate-hydrate related phases, whereas inclusion of coarser volcanic ash caused domination by calcium-aluminum-silicate-hydratemore » and unreacted MgO phases, suggesting some volcanic ash remained unreacted throughout the hydration process. Addition of more than 30% volcanic ash leads to coarser morphology along with decreased surface area and higher intensity of scattering at early-age hydration. This suggests an abrupt dissolution indicated by changes in surface area due to the retarding gel formation that can have implication on early-age setting influencing the mechanical properties of the resulting cementitious matrix. The findings from this work show that the concentration of volcanic ash influences the specific surface area and morphology of hydration products during the early age of hydration. Therefore, natural pozzolanic volcanic ashes can be a viable substitute to Portland cement by providing environmental benefits in terms of lower-carbon footprint along with long-term durability.« less

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex.

PubMed

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants.

Developmental Changes in Sensory-Evoked Optical Intrinsic Signals in the Rat Barrel Cortex

PubMed Central

Sintsov, Mikhail; Suchkov, Dmitrii; Khazipov, Rustem; Minlebaev, Marat

2017-01-01

Optical Intrinsic Signal imaging (OISi) is a powerful technique for optical brain studies. OIS mainly reflects the hemodynamic response (HR) and metabolism, but it may also involve changes in tissue light scattering (LS) caused by transient cellular swelling in the active tissue. Here, we explored the developmental features of sensory-evoked OIS in the rat barrel cortex during the first 3 months after birth. Multispectral OISi revealed that two temporally distinct components contribute to the neonatal OIS: an early phase of LS followed by a late phase of HR. The contribution of LS to the early response was also evidenced by an increase in light transmission through the active barrel. The early OIS phase correlated in time and amplitude with the sensory-evoked electrophysiological response. Application of the Modified Beer-Lambert Law (MBLL) to the OIS data revealed that HR during the early phase involved only a slight decrease in blood oxygenation without any change in blood volume. In contrast, HR during the late phase manifested an adult-like increase in blood volume and oxygenation. During development, the peak time of the delayed HR progressively shortened with age, nearly reaching the stimulus onset and overlapping with the early LS phase by the fourth postnatal week. Thus, LS contributes to the sensory-evoked OIS in the barrel cortex of rats at all ages, and it dominates the early OIS phase in neonatal rats due to delayed HR. Our results are also consistent with the delayed blood oxygen level dependent (BOLD) signal in human preterm infants. PMID:29311827

ELISA, a demonstrator environment for information systems architecture design

NASA Technical Reports Server (NTRS)

Panem, Chantal

1994-01-01

This paper describes an approach of reusability of software engineering technology in the area of ground space system design. System engineers have lots of needs similar to software developers: sharing of a common data base, capitalization of knowledge, definition of a common design process, communication between different technical domains. Moreover system designers need to simulate dynamically their system as early as possible. Software development environments, methods and tools now become operational and widely used. Their architecture is based on a unique object base, a set of common management services and they host a family of tools for each life cycle activity. In late '92, CNES decided to develop a demonstrative software environment supporting some system activities. The design of ground space data processing systems was chosen as the application domain. ELISA (Integrated Software Environment for Architectures Specification) was specified as a 'demonstrator', i.e. a sufficient basis for demonstrations, evaluation and future operational enhancements. A process with three phases was implemented: system requirements definition, design of system architectures models, and selection of physical architectures. Each phase is composed of several activities that can be performed in parallel, with the provision of Commercial Off the Shelves Tools. ELISA has been delivered to CNES in January 94, currently used for demonstrations and evaluations on real projects (e.g. SPOT4 Satellite Control Center). It is on the way of new evolutions.

Overview of the Photovoltaic Manufacturing Technology (PVMaT) project

NASA Astrophysics Data System (ADS)

Witt, C. E.; Mitchell, R. L.; Mooney, G. D.

1993-08-01

The Photovoltaic Manufacturing Technology (PVMaT) project is a historic government/industry photovoltaic (PV) manufacturing R&D partnership composed of joint efforts between the federal government (through the US Department of Energy) and members of the US PV industry. The project's ultimate goal is to ensure that the US industry retains and extends its world leadership role in the manufacture and commercial development of PV components and systems. PVMaT is designed to do this by helping the US PV industry improve manufacturing processes, accelerate manufacturing cost reductions for PV modules, improve commercial product performance, and lay the groundwork for a substantial scale-up of US-based PV manufacturing capacities. Phase 1 of the project, the problem identification phase, was completed in early 1991. Phase 2, the problem solution phase, which addresses process-specific problems of specific manufacturers, is now underway with an expected duration of 5 years. Phase 3 addresses R&D problems that are relatively common to a number of PV companies or the PV industry as a whole. These 'generic' problem areas are being addressed through a teamed research approach.

The Lemur Conjecture

NASA Astrophysics Data System (ADS)

Lanzagorta, Marco; Jitrik, Oliverio; Uhlmann, Jeffrey; Venegas-Andraca, Salvador E.

2017-05-01

In previous research we designed an interferometric quantum seismograph that uses entangled photon states to enhance sensitivity in an optomechanic device. However, a spatially-distributed array of such sensors, with each sensor measuring only nm-vibrations, may not provide sufficient sensitivity for the prediction of major earthquakes because it fails to exploit potentially critical phase information. We conjecture that relative phase information can explain the anecdotal observations that animals such as lemurs exhibit sensitivity to impending earthquakes earlier than can be done confidently with traditional seismic technology. More specifically, we propose that lemurs use their limbs as ground motion sensors and that relative phase differences are fused in the brain in a manner similar to a phased-array or synthetic-aperture radar. In this paper we will describe a lemur-inspired quantum sensor network for early warning of earthquakes. The system uses 4 interferometric quantum seismographs (e.g., analogous to a lemurs limbs) and then conducts phase and data fusion of the seismic information. Although we discuss a quantum-based technology, the principles described can also be applied to classical sensor arrays

Early Childhood Technology Integrated Instructional System (EC-TIIS) Phase 1: A Final Report

ERIC Educational Resources Information Center

Hutinger, Patricia; Robinson, Linda; Schneider, Carol

2004-01-01

The Early Childhood Technology Integrated Instructional System (EC-TIIS), a Steppingstones of Technology Innovation Phase 1--Development project, was developed by the Center for Best Practices in Early Childhood (the Center) at Western Illinois University as an online instructional system. EC-TIIS' ultimate goal was to improve technology services…

Bayesian enhancement two-stage design for single-arm phase II clinical trials with binary and time-to-event endpoints.

PubMed

Shi, Haolun; Yin, Guosheng

2018-02-21

Simon's two-stage design is one of the most commonly used methods in phase II clinical trials with binary endpoints. The design tests the null hypothesis that the response rate is less than an uninteresting level, versus the alternative hypothesis that the response rate is greater than a desirable target level. From a Bayesian perspective, we compute the posterior probabilities of the null and alternative hypotheses given that a promising result is declared in Simon's design. Our study reveals that because the frequentist hypothesis testing framework places its focus on the null hypothesis, a potentially efficacious treatment identified by rejecting the null under Simon's design could have only less than 10% posterior probability of attaining the desirable target level. Due to the indifference region between the null and alternative, rejecting the null does not necessarily mean that the drug achieves the desirable response level. To clarify such ambiguity, we propose a Bayesian enhancement two-stage (BET) design, which guarantees a high posterior probability of the response rate reaching the target level, while allowing for early termination and sample size saving in case that the drug's response rate is smaller than the clinically uninteresting level. Moreover, the BET design can be naturally adapted to accommodate survival endpoints. We conduct extensive simulation studies to examine the empirical performance of our design and present two trial examples as applications. © 2018, The International Biometric Society.

Importance of Requirements Analysis & Traceability to Improve Software Quality and Reduce Cost and Risk

NASA Technical Reports Server (NTRS)

Kapoor, Manju M.; Mehta, Manju

2010-01-01

The goal of this paper is to emphasize the importance of developing complete and unambiguous requirements early in the project cycle (prior to Preliminary Design Phase). Having a complete set of requirements early in the project cycle allows sufficient time to generate a traceability matrix. Requirements traceability and analysis are the key elements in improving verification and validation process, and thus overall software quality. Traceability can be most beneficial when the system changes. If changes are made to high-level requirements it implies that low-level requirements need to be modified. Traceability ensures that requirements are appropriately and efficiently verified at various levels whereas analysis ensures that a rightly interpreted set of requirements is produced.

Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update.

PubMed

Grunberg, Steven M; Osoba, David; Hesketh, Paul J; Gralla, Richard J; Borjeson, Sussanne; Rapoport, Bernardo L; du Bois, Andreas; Tonato, Maurizio

2005-02-01

Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.

78 FR 5816 - Guidance for Industry on Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

.... The guidance provides recommendations on when and how genomic principles should be considered and... recommendations on when and how genomic principles should be considered and applied in early-phase clinical... the larger, later adequate, and well-controlled trials (phase 3) that are needed to support marketing...

Review of hardware cost estimation methods, models and tools applied to early phases of space mission planning

NASA Astrophysics Data System (ADS)

Trivailo, O.; Sippel, M.; Şekercioğlu, Y. A.

2012-08-01

The primary purpose of this paper is to review currently existing cost estimation methods, models, tools and resources applicable to the space sector. While key space sector methods are outlined, a specific focus is placed on hardware cost estimation on a system level, particularly for early mission phases during which specifications and requirements are not yet crystallised, and information is limited. For the space industry, cost engineering within the systems engineering framework is an integral discipline. The cost of any space program now constitutes a stringent design criterion, which must be considered and carefully controlled during the entire program life cycle. A first step to any program budget is a representative cost estimate which usually hinges on a particular estimation approach, or methodology. Therefore appropriate selection of specific cost models, methods and tools is paramount, a difficult task given the highly variable nature, scope as well as scientific and technical requirements applicable to each program. Numerous methods, models and tools exist. However new ways are needed to address very early, pre-Phase 0 cost estimation during the initial program research and establishment phase when system specifications are limited, but the available research budget needs to be established and defined. Due to their specificity, for vehicles such as reusable launchers with a manned capability, a lack of historical data implies that using either the classic heuristic approach such as parametric cost estimation based on underlying CERs, or the analogy approach, is therefore, by definition, limited. This review identifies prominent cost estimation models applied to the space sector, and their underlying cost driving parameters and factors. Strengths, weaknesses, and suitability to specific mission types and classes are also highlighted. Current approaches which strategically amalgamate various cost estimation strategies both for formulation and validation of an estimate, and techniques and/or methods to attain representative and justifiable cost estimates are consequently discussed. Ultimately, the aim of the paper is to establish a baseline for development of a non-commercial, low cost, transparent cost estimation methodology to be applied during very early program research phases at a complete vehicle system level, for largely unprecedented manned launch vehicles in the future. This paper takes the first step to achieving this through the identification, analysis and understanding of established, existing techniques, models, tools and resources relevant within the space sector.

The NASA probe-class mission concept, CETUS (Cosmic Evolution Through Ultraviolet Spectroscopy)

NASA Astrophysics Data System (ADS)

Heap, Sara; Danchi, William; Burge, James; Dodson, Kelly; Hull, Anthony; Kendrick, Steven; McCandliss, Stephan; Mehle, Gregory; Purves, Lloyd; Sheikh, David; Valente, Martin; Woodruff, Robert A.

2017-09-01

We report on the early phases of a NASA-sponsored study of CETUS (Cosmic Evolution Through Ultraviolet Spectroscopy), a Probe-class mission concept. By definition, the full lifecycle cost of a Probe mission is greater than 400M (i.e. Explorer missions) and less than 1.00B ("Flagship" missions). The animating idea behind our study is that CETUS can help answer fundamental questions about galaxy evolution by carrying out a massive UV imaging and spectroscopic survey of galaxies and combining its findings with data obtained by other survey telescopes of the 2020's. The CETUS mission concept comprises a 1.5-m wide-field telescope and three scientific instruments: a near-UV multi-object slit spectrograph with a micro-shutter array as the slit device; a near-UV and far-UV camera with angular resolution of 0.42" (near-UV) or 0.55" (far-UV); and a near-UV or far-UV single-object spectrograph aimed at providing access to the UV after Hubble is gone. We describe the scientific rationale for CETUS and the telescope and instruments in their early design phase.

Failsafe automation of Phase II clinical trial interim monitoring for stopping rules.

PubMed

Day, Roger S

2010-02-01

In Phase II clinical trials in cancer, preventing the treatment of patients on a study when current data demonstrate that the treatment is insufficiently active or too toxic has obvious benefits, both in protecting patients and in reducing sponsor costs. Considerable efforts have gone into experimental designs for Phase II clinical trials with flexible sample size, usually implemented by early stopping rules. The intended benefits will not ensue, however, if the design is not followed. Despite the best intentions, failures can occur for many reasons. The main goal is to develop an automated system for interim monitoring, as a backup system supplementing the protocol team, to ensure that patients are protected. A secondary goal is to stimulate timely recording of patient assessments. We developed key concepts and performance needs, then designed, implemented, and deployed a software solution embedded in the clinical trials database system. The system has been in place since October 2007. One clinical trial tripped the automated monitor, resulting in e-mails that initiated statistician/investigator review in timely fashion. Several essential contributing activities still require human intervention, institutional policy decisions, and institutional commitment of resources. We believe that implementing the concepts presented here will provide greater assurance that interim monitoring plans are followed and that patients are protected from inadequate response or excessive toxicity. This approach may also facilitate wider acceptance and quicker implementation of new interim monitoring algorithms.

Greenhouse gas emissions of alternative pavement designs: framework development and illustrative application.

PubMed

Liu, Xiaoyu; Cui, Qingbin; Schwartz, Charles

2014-01-01

Pavement rehabilitation is carbon intensive and the choice of pavement type is a critical factor in controlling greenhouse gas (GHG) emissions. The existing body of knowledge is not able to support decision-making on pavement choice due to a lack of consensus on the system boundaries, the functional units and the estimation periods. Excessive data requirements further inhibit the generalization of the existing methodologies for design evaluation at the early planning stage. This study proposes a practical life-cycle GHG estimation approach, which is arguably effective to benchmark pavement emissions given project bid tabulation. A set of case studies conducted for this study suggest that recycled asphalt pavement (e.g., foam stabilized base (FSB), and warm mix asphalt (WMA)) would prevent up to 50% of GHGs from the initial construction phase. However, from a life-cycle perspective, pavement emissions are dictated largely by the traffic characteristics and the analysis period for the use phase. The benefits from using recycled materials (e.g., FSB) are likely to diminish if the recycled products do not perform as well as those properly proportioned with less recycled materials, or if the recycled materials are locally unavailable. When the AADT reaches 10,000, use phase releases more than 97% of the life cycle emissions and the emissions difference among alternative designs will be within 1%. Copyright © 2013 Elsevier Ltd. All rights reserved.

Can a quality improvement project impact maternal and child health outcomes at scale in northern Ghana?

PubMed

Singh, Kavita; Brodish, Paul; Speizer, Ilene; Barker, Pierre; Amenga-Etego, Issac; Dasoberi, Ireneous; Kanyoke, Ernest; Boadu, Eric A; Yabang, Elma; Sodzi-Tettey, Sodzi

2016-06-16

Quality improvement (QI) interventions are becoming more common in low- and middle-income countries, yet few studies have presented impact evaluations of these approaches. In this paper, we present an impact evaluation of a scale-up phase of 'Project Fives Alive!', a QI intervention in Ghana that aims to improve maternal and child health outcomes. 'Project Fives Alive!' employed a QI methodology to recognize barriers to care-seeking and care provision at the facility level and then to identify, test and implement simple and low-cost local solutions that address the barriers. A quasi-experimental design, multivariable interrupted time series analysis, with data coming from 744 health facilities and controlling for potential confounding factors, was used to study the effect of the project. The key independent variables were the change categories (interventions implemented) and implementation phase - Wave 2a (early phase) versus Wave 2b (later phase). The outcomes studied were early antenatal care (ANC), skilled delivery, facility-level under-five mortality and attendance of underweight infants at child welfare clinics. We stratified the analysis by facility type, namely health posts, health centres and hospitals. Several of the specific change categories were significantly associated with improved outcomes. For example, three of five change categories (early ANC, four or more ANC visits and skilled delivery/immediate postnatal care (PNC)) for health posts and two of five change categories (health education and triage) for hospitals were associated with increased skilled delivery. These change categories were associated with increases in skilled delivery varying from 28% to 58%. PNC changes for health posts and health centres were associated with greater attendance of underweight infants at child welfare clinics. The triage change category was associated with increased early antenatal care in hospitals. Intensity, the number of change categories tested, was associated with increased skilled delivery in health centres and reduced under-five mortality in hospitals. Using an innovative evaluation technique we determined that 'Project Fives Alive!' demonstrated impact at scale for the outcomes studied. The QI approach used by this project should be considered by other low- and middle-income countries in their efforts to improve maternal and child health.

Technical Guidance from the International Safety Framework for Nuclear Power Source Applications in Outer Space for Design and Development Phases

NASA Astrophysics Data System (ADS)

Summerer, Leopold

2014-08-01

In 2009, the International Safety Framework for Nuclear Power Source Applications in Outer Space [1] has been adopted, following a multi-year process that involved all major space faring nations in the frame of the International Atomic Energy Agency and the UN Committee on the Peaceful Uses of Outer Space. The safety framework reflects an international consensus on best practices. After the older 1992 Principles Relevant to the Use of Nuclear Power Sources in Outer Space, it is the second document at UN level dedicated entirely to space nuclear power sources.This paper analyses aspects of the safety framework relevant for the design and development phases of space nuclear power sources. While early publications have started analysing the legal aspects of the safety framework, its technical guidance has not yet been subject to scholarly articles. The present paper therefore focuses on the technical guidance provided in the safety framework, in an attempt to assist engineers and practitioners to benefit from these.

MESA - A new approach to low cost scientific spacecraft

NASA Astrophysics Data System (ADS)

Keyes, G. W.; Case, C. M.

1982-09-01

Today, the greatest obstacle to science and exploration in space is its cost. The present investigation is concerned with approaches for reducing this cost. Trends in the scientific spacecraft market are examined, and a description is presented for the MESA space platform concept. The cost drivers are considered, taking into account planning, technical aspects, and business factors. It is pointed out that the primary function of the MESA concept is to provide a satellite system at the lowest possible price. In order to reach this goal an attempt is made to benefit from all of the considered cost drivers. It is to be tried to work with the customer early in the mission analysis stage in order to assist in finding the right compromise between mission cost and return. A three phase contractual arrangement is recommended for MESA platforms. The phases are related to mission feasibility, specification definition, and design and development. Modular kit design promotes flexibility at low cost.

WFIRST: Project Overview and Status

NASA Astrophysics Data System (ADS)

Kruk, Jeffrey; WFIRST Formulation Science Working Group, WFIRST Project Team

2018-01-01

The Wide-Field InfraRed Survey Telescope (WFIRST) will be the next Astrophysics flagship mission to follow JWST. The observatory payload consists of a Hubble-size telescope aperture with a wide-field NIR instrument and a coronagraph operating at visible wavelengths and employing state-of-the-art wavefront sensing and control. The Wide-field instrument is optimized for large area NIR imaging and spectroscopic surveys, with performance requirements driven by programs to study cosmology and exoplanet detection via gravitational microlensing. All data will be public immediately, and a substantial guest observer program will be supported.The WFIRST Project is presently in Phase A, with a transition to Phase B expected in early to mid 2018. Candidate observing programs are under detailed study in order to inform the mission design, but the actual science investigations will not be selected until much closer to launch. We will present an overview of the present mission design and expected performance, a summary of Project status, and plans for selecting the observing programs.

Simulation and Analysis of Three-Phase Rectifiers for Aerospace Power Applications

NASA Technical Reports Server (NTRS)

Truong, Long V.; Birchenough, Arthur G.

2004-01-01

Due to the nature of planned planetary missions, fairly large advanced power systems are required for the spacecraft. These future high power spacecrafts are expected to use dynamic power conversion systems incorporating high speed alternators as three-phase AC electrical power source. One of the early design considerations in such systems is the type of rectification to be used with the AC source for DC user loads. This paper address the issues involved with two different rectification methods, namely the conventional six and twelve pulses. Two circuit configurations which involved parallel combinations of the six and twelve-pulse rectifiers were selected for the simulation. The rectifier s input and output power waveforms will be thoroughly examined through simulations. The effects of the parasitic load for power balancing and filter components for reducing the ripple voltage at the DC loads are also included in the analysis. Details of the simulation circuits, simulation results, and design examples for reducing risk from damaging of spacecraft engines will be presented and discussed.

CLB5-dependent activation of late replication origins in S. cerevisiae.

PubMed

Donaldson, A D; Raghuraman, M K; Friedman, K L; Cross, F R; Brewer, B J; Fangman, W L

1998-08-01

Replication origins in chromosomes are activated at specific times during the S phase. We show that the B-type cyclins are required for proper execution of this temporal program. clb5 cells activate early origins but not late origins, explaining the previously described long clb5 S phase. Origin firing appears normal in cIb6 mutants. In clb5 clb6 double mutant cells, the late origin firing defect is suppressed, accounting for the normal duration of the phase despite its delayed onset. Therefore, Clb5p promotes the timely activation of early and late origins, but Clb6p can activate only early origins. In clb5 clb6 mutants, the other B-type cyclins (Clb1-4p) promote an S phase during which both early and late replication origins fire.

Insights into intermediate phases of human intestinal fluids visualized by atomic force microscopy and cryo-transmission electron microscopy ex vivo.

PubMed

Müllertz, Anette; Fatouros, Dimitrios G; Smith, James R; Vertzoni, Maria; Reppas, Christos

2012-02-06

The current work aims to study at the ultrastructural level the morphological development of colloidal intermediate phases of human intestinal fluids (HIFs) produced during lipid digestion. HIFs were aspirated near the ligament of Treitz early (30 min), Aspirate(early), and 1 h, Aspirate(1h)(ave,comp), after the administration of a heterogeneous liquid meal into the antrum. The composition of the sample aspirated 1 h after meal administration was similar to the average lumenal composition 1 h after meal administration (Aspirate(1h)(ave,comp)). The colloidal structures of individual aspirates and supernatants of aspirates after ultracentrifugation (micellar phase) were characterized by means of atomic force microscopy (AFM) and cryogenic transmission electron microscopy (Cryo-TEM). AFM revealed domain-like structures in Aspirate(early) and both vesicles and large aggregates Aspirate(1h)(ave,comp). Rough surfaces and domains varying in size were frequently present in the micellar phase of both Aspirate(early) and Aspirate(1h)(ave,comp). Cryo-TEM revealed an abundance of spherical micelles and occasionally presented worm-like micelles coexisting with faceted and less defined vesicles in Aspirate(early) and Aspirate(1h)(ave,comp). In Aspirate(1h)(ave,comp) oil droplets were visualized with bilayers closely located to their surface suggesting lipolytic product phases accumulated on the surface of the oil droplet. In the micellar phase of Aspirate(early), Cryo-TEM revealed the presence of spherical micelles, small vesicles, membrane fragments, oil droplets and plate-like structures. In the micellar phase of Aspirate(1h)(ave,comp) the only difference was the absence of oil droplets. Visualization studies previously performed with biorelevant media revealed structural features with many similarities as presented in the current investigation. The impression of the complexity and diversion of these phases has been reinforced with the excessive variation of structural features visualized ex vivo in the current study offering insights at the ultrastuctural level of intermediate phases which impact drug solubilization.

Investor Outlook: Significance of the Positive LCA2 Gene Therapy Phase III Results.

PubMed

Schimmer, Joshua; Breazzano, Steven

2015-12-01

Spark Therapeutics recently reported positive phase III results for SPK-RPE65 targeting the treatment of visual impairment caused by RPE65 gene mutations (often referred to as Leber congenital amaurosis type 2, or LCA2, but may include other retinal disorders), marking an important inflection point for the field of gene therapy. The results highlight the ability to successfully design and execute a randomized trial of a gene therapy and also reinforce the potentially predictive nature of early preclinical and clinical data. The results are expected to pave the way for the first approved gene therapy product in the United States and should sustain investor interest and confidence in gene therapy for many approaches, including retina targeting and beyond.

Adaptive clinical trial designs for European marketing authorization: a survey of scientific advice letters from the European Medicines Agency.

PubMed

Elsäßer, Amelie; Regnstrom, Jan; Vetter, Thorsten; Koenig, Franz; Hemmings, Robert James; Greco, Martina; Papaluca-Amati, Marisa; Posch, Martin

2014-10-02

Since the first methodological publications on adaptive study design approaches in the 1990s, the application of these approaches in drug development has raised increasing interest among academia, industry and regulators. The European Medicines Agency (EMA) as well as the Food and Drug Administration (FDA) have published guidance documents addressing the potentials and limitations of adaptive designs in the regulatory context. Since there is limited experience in the implementation and interpretation of adaptive clinical trials, early interaction with regulators is recommended. The EMA offers such interactions through scientific advice and protocol assistance procedures. We performed a text search of scientific advice letters issued between 1 January 2007 and 8 May 2012 that contained relevant key terms. Letters containing questions related to adaptive clinical trials in phases II or III were selected for further analysis. From the selected letters, important characteristics of the proposed design and its context in the drug development program, as well as the responses of the Committee for Human Medicinal Products (CHMP)/Scientific Advice Working Party (SAWP), were extracted and categorized. For 41 more recent procedures (1 January 2009 to 8 May 2012), additional details of the trial design and the CHMP/SAWP responses were assessed. In addition, case studies are presented as examples. Over a range of 5½ years, 59 scientific advices were identified that address adaptive study designs in phase II and phase III clinical trials. Almost all were proposed as confirmatory phase III or phase II/III studies. The most frequently proposed adaptation was sample size reassessment, followed by dropping of treatment arms and population enrichment. While 12 (20%) of the 59 proposals for an adaptive clinical trial were not accepted, the great majority of proposals were accepted (15, 25%) or conditionally accepted (32, 54%). In the more recent 41 procedures, the most frequent concerns raised by CHMP/SAWP were insufficient justifications of the adaptation strategy, type I error rate control and bias. For the majority of proposed adaptive clinical trials, an overall positive opinion was given albeit with critical comments. Type I error rate control, bias and the justification of the design are common issues raised by the CHMP/SAWP.

Design knowledge capture for a corporate memory facility

NASA Technical Reports Server (NTRS)

Boose, John H.; Shema, David B.; Bradshaw, Jeffrey M.

1990-01-01

Currently, much of the information regarding decision alternatives and trade-offs made in the course of a major program development effort is not represented or retained in a way that permits computer-based reasoning over the life cycle of the program. The loss of this information results in problems in tracing design alternatives to requirements, in assessing the impact of change in requirements, and in configuration management. To address these problems, the problem was studied of building an intelligent, active corporate memory facility which would provide for the capture of the requirements and standards of a program, analyze the design alternatives and trade-offs made over the program's lifetime, and examine relationships between requirements and design trade-offs. Early phases of the work have concentrated on design knowledge capture for the Space Station Freedom. Tools are demonstrated and extended which helps automate and document engineering trade studies, and another tool is being developed to help designers interactively explore design alternatives and constraints.

Microwave Power Transmission System Studies. Volume 1: Executive Summary

NASA Technical Reports Server (NTRS)

Maynard, O. E.; Brown, W. C.; Edwards, A.; Meltz, G.; Haley, J. T.; Howell, J. M.; Nathan, A.

1975-01-01

A study of microwave power generation, transmission, reception and control was conducted as a part of a program to demonstrate the feasibility of power transmission from geosynchronous orbit. A summary is presented of results concerning design approaches, estimated costs (ROM), critical technology, associated ground and orbital test programs with emphasis on dc to rf conversion, transmitting antenna, phase control, mechanical systems, flight operations, ground power receiving-rectifying antenna with systems analysis, and evaluation. Recommendations for early further in-depth studies complementing the technology program are included.

Genesis of a flexible turning center

NASA Astrophysics Data System (ADS)

Sanclemente, Paul; French, Robert D.

GE - Aircraft Engines has designed, built, and is operating a flexible turning center for jet engine hardware. Although the plant is in the forefront of manufacturing technology development, it was intended from the start to be a production facility. So while there was much to learn from being involved in all phases of the project, meeting production schedules was, and is, key to its success. This paper reviews the early history of the project and ends with a view of its recent production status.

Early Childhood Settings in 15 Countries: What Are Their Structural Characteristics? The IEA Preprimary Project, Phase 2.

ERIC Educational Resources Information Center

Olmsted, Patricia P., Ed.; Montie, Jeanne, Ed.

This is the second of four monographs reporting the findings of Phase 2 of the International Association for the Evaluation of Educational Achievement (IEA) Preprimary Project, which presents data on the physical characteristics of children's early childhood settings. Early childhood settings were documented in the following 15 countries: (1)…

Insights into early stage of antibiotic development in small- and medium-sized enterprises: a survey of targets, costs, and durations.

PubMed

Årdal, Christine; Baraldi, Enrico; Theuretzbacher, Ursula; Outterson, Kevin; Plahte, Jens; Ciabuschi, Francesco; Røttingen, John-Arne

2018-01-01

Antibiotic innovation has dwindled to dangerously low levels in the past 30 years. Since resistance continues to evolve, this innovation deficit can have perilous consequences on patients. A number of new incentives have been suggested to stimulate greater antibacterial drug innovation. To design effective solutions, a greater understanding is needed of actual antibiotic discovery and development costs and timelines. Small and medium-sized enterprises (SMEs) undertake most discovery and early phase development for antibiotics and other drugs. This paper attempts to gather a better understanding of SMEs' targets, costs, and durations related to discovery and early phase development of antibacterial therapies. DRIVE-AB, a project focused on developing new economic incentives to stimulate antibacterial innovation, held a European stakeholder meeting in February 2015. All SMEs invited to this meeting ( n  = 44) were subsequently sent a survey to gather more data regarding their areas of activity, completed and expected development costs and timelines, and business models. Twenty-five companies responded to the survey. Respondents were primarily small companies each focusing on developing 1 to 3 new antibiotics, focused on pathogens of public health importance. Most have not yet completed any clinical trials. They have reported ranges of discovery and development out-of-pocket costs that appear to be less expensive than other studies of general pharmaceutical research and development (R&D) costs. The duration ranges reported for completing each phase of R&D are highly variable when compared to previously published general pharmaceutical innovation average durations. However, our sample population is small and may not be fully representative of all relevant antibiotic SMEs. The data collected by this study provide important insights and estimates about R&D in European SMEs focusing on antibiotics, which can be combined with other data to design incentives to stimulate antibacterial innovation. The variation implies that costs and durations are difficult to generalize due to the unique characteristics of each antibiotic project and depend on individual business strategies and circumstances.

Phase distribution of spliceosomal introns: implications for intron origin

PubMed Central

Nguyen, Hung D; Yoshihama, Maki; Kenmochi, Naoya

2006-01-01

Background The origin of spliceosomal introns is the central subject of the introns-early versus introns-late debate. The distribution of intron phases is non-uniform, with an excess of phase-0 introns. Introns-early explains this by speculating that a fraction of present-day introns were present between minigenes in the progenote and therefore must lie in phase-0. In contrast, introns-late predicts that the nonuniformity of intron phase distribution reflects the nonrandomness of intron insertions. Results In this paper, we tested the two theories using analyses of intron phase distribution. We inferred the evolution of intron phase distribution from a dataset of 684 gene orthologs from seven eukaryotes using a maximum likelihood method. We also tested whether the observed intron phase distributions from 10 eukaryotes can be explained by intron insertions on a genome-wide scale. In contrast to the prediction of introns-early, the inferred evolution of intron phase distribution showed that the proportion of phase-0 introns increased over evolution. Consistent with introns-late, the observed intron phase distributions matched those predicted by an intron insertion model quite well. Conclusion Our results strongly support the introns-late hypothesis of the origin of spliceosomal introns. PMID:16959043

Developing calculus textbook model that supported with GeoGebra to enhancing students’ mathematical problem solving and mathematical representation

NASA Astrophysics Data System (ADS)

Dewi, N. R.; Arini, F. Y.

2018-03-01

The main purpose of this research is developing and produces a Calculus textbook model that supported with GeoGebra. This book was designed to enhancing students’ mathematical problem solving and mathematical representation. There were three stages in this research i.e. define, design, and develop. The textbooks consisted of 6 chapters which each chapter contains introduction, core materials and include examples and exercises. The textbook developed phase begins with the early stages of designed the book (draft 1) which then validated by experts. Revision of draft 1 produced draft 2. The data were analyzed with descriptive statistics. The analysis showed that the Calculus textbook model that supported with GeoGebra, valid and fill up the criteria of practicality.

The Impact of Housing on the Characteristics of Ceramic Pressure Sensors—An Issue of Design for Manufacturability

PubMed Central

Santo Zarnik, Marina; Belavic, Darko; Novak, Franc

2015-01-01

An exploratory study of the impact of housing on the characteristics of a low-temperature co-fired ceramic (LTCC) pressure sensor is presented. The ceramic sensor structure is sealed in a plastic housing. This may have non-negligible effect on the final characteristics and should be considered in the early design phase. The manufacturability issue mainly concerning the selection of available housing and the most appropriate materials was considered with respect to different requirements for low and high pressure ranges of operation. Numerical predictions showed the trends and helped reveal the critical design parameters. Proper selection of the adhesive material remains an essential issue. Curing of the epoxy adhesive may introduce non-negligible residual stresses, which considerably influence the sensor’s characteristics. PMID:26694386

Liquid hydrogen turbopump ALS advanced development program. Volume 1: Hot fire unit

NASA Technical Reports Server (NTRS)

Lindley, Bruce

1990-01-01

The interface criteria for the Turbopump Test article (TPA) and the Component Test Facility located at NASA, Stennis Space Center is defined by this interface Control Document (ICD). TPA ICD Volume 2 is submitted for the Cold Gas Drive Turbopump Test Article, which is generally similar but incorporates certain changes, particularly in fluid requirements and in instrumentation needs. For the purposes of this ICD, the test article consists of the Hot Fire Drive Turbopump mounted on its test cart, readied for installation in the component test facility. It should be emphasized that the LH2 turbopump program is still in its early concept design phase. Design of the turbopump, test cart, and spools are subject to revisions until successful conclusion of the Detail Design Review (DDR).

Collaborating with human factors when designing an electronic textbook

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

Ratner, J.A.; Zadoks, R.I.; Attaway, S.W.

The development of on-line engineering textbooks presents new challenges to authors to effectively integrate text and tools in an electronic environment. By incorporating human factors principles of interface design and cognitive psychology early in the design process, a team at Sandia National Laboratories was able to make the end product more usable and shorten the prototyping and editing phases. A critical issue was simultaneous development of paper and on-line versions of the textbook. In addition, interface consistency presented difficulties with distinct goals and limitations for each media. Many of these problems were resolved swiftly with human factors input using templates,more » style guides and iterative usability testing of both paper and on-line versions. Writing style continuity was also problematic with numerous authors contributing to the text.« less

Combination of light and melatonin time cues for phase advancing the human circadian clock.

PubMed

Burke, Tina M; Markwald, Rachel R; Chinoy, Evan D; Snider, Jesse A; Bessman, Sara C; Jung, Christopher M; Wright, Kenneth P

2013-11-01

Photic and non-photic stimuli have been shown to shift the phase of the human circadian clock. We examined how photic and non-photic time cues may be combined by the human circadian system by assessing the phase advancing effects of one evening dose of exogenous melatonin, alone and in combination with one session of morning bright light exposure. Randomized placebo-controlled double-blind circadian protocol. The effects of four conditions, dim light (∼1.9 lux, ∼0.6 Watts/m(2))-placebo, dim light-melatonin (5 mg), bright light (∼3000 lux, ∼7 Watts/m(2))-placebo, and bright light-melatonin on circadian phase was assessed by the change in the salivary dim light melatonin onset (DLMO) prior to and following treatment under constant routine conditions. Melatonin or placebo was administered 5.75 h prior to habitual bedtime and 3 h of bright light exposure started 1 h prior to habitual wake time. Sleep and chronobiology laboratory environment free of time cues. Thirty-six healthy participants (18 females) aged 22 ± 4 y (mean ± SD). Morning bright light combined with early evening exogenous melatonin induced a greater phase advance of the DLMO than either treatment alone. Bright light alone and melatonin alone induced similar phase advances. Information from light and melatonin appear to be combined by the human circadian clock. The ability to combine circadian time cues has important implications for understanding fundamental physiological principles of the human circadian timing system. Knowledge of such principles is important for designing effective countermeasures for phase-shifting the human circadian clock to adapt to jet lag, shift work, and for designing effective treatments for circadian sleep-wakefulness disorders.

EVA Suit R and D for Performance Optimization

NASA Technical Reports Server (NTRS)

Cowley, Matthew S.; Harvill, Lauren; Benson, Elizabeth; Rajulu, Sudhakar

2014-01-01

Designing a planetary suit is very complex and often requires difficult trade-offs between performance, cost, mass, and system complexity. To verify that new suit designs meet requirements, full prototypes must be built and tested with human subjects. However, numerous design iterations will occur before the hardware meets those requirements. Traditional draw-prototype-test paradigms for R&D are prohibitively expensive with today's shrinking Government budgets. Personnel at NASA are developing modern simulation techniques which focus on human-centric designs by creating virtual prototype simulations and fully adjustable physical prototypes of suit hardware. During the R&D design phase, these easily modifiable representations of an EVA suit's hard components will allow designers to think creatively and exhaust design possibilities before they build and test working prototypes with human subjects. It allows scientists to comprehensively benchmark current suit capabilities and limitations for existing suit sizes and sizes that do not exist. This is extremely advantageous and enables comprehensive design down-selections to be made early in the design process, enables the use of human performance as design criteria, and enables designs to target specific populations

Practitioners' Experiences of Personal Ownership and Autonomy in Their Support for Young Children's Thinking

ERIC Educational Resources Information Center

Robson, Sue; Fumoto, Hiroko

2009-01-01

This article reports the third phase of the Froebel Research Fellowship Project: "The Voice of the Child: ownership and autonomy in early learning". Building on the first and second phases of this study, this phase examined early years practitioners' experiences of supporting young children's thinking in relation to the personal…

PRA and Conceptual Design

NASA Technical Reports Server (NTRS)

DeMott, Diana; Fuqua, Bryan; Wilson, Paul

2013-01-01

Once a project obtains approval, decision makers have to consider a variety of alternative paths for completing the project and meeting the project objectives. How decisions are made involves a variety of elements including: cost, experience, current technology, ideologies, politics, future needs and desires, capabilities, manpower, timing, available information, and for many ventures management needs to assess the elements of risk versus reward. The use of high level Probabilistic Risk Assessment (PRA) Models during conceptual design phases provides management with additional information during the decision making process regarding the risk potential for proposed operations and design prototypes. The methodology can be used as a tool to: 1) allow trade studies to compare alternatives based on risk, 2) determine which elements (equipment, process or operational parameters) drives the risk, and 3) provide information to mitigate or eliminate risks early in the conceptual design to lower costs. Creating system models using conceptual design proposals and generic key systems based on what is known today can provide an understanding of the magnitudes of proposed systems and operational risks and facilitates trade study comparisons early in the decision making process. Identifying the "best" way to achieve the desired results is difficult, and generally occurs based on limited information. PRA provides a tool for decision makers to explore how some decisions will affect risk before the project is committed to that path, which can ultimately save time and money.

Miniaturized Water Flow and Level Monitoring System for Flood Disaster Early Warning

NASA Astrophysics Data System (ADS)

Ifedapo Abdullahi, Salami; Hadi Habaebi, Mohamed; Surya Gunawan, Teddy; Rafiqul Islam, MD

2017-11-01

This study presents the performance of a prototype miniaturised water flow and water level monitoring sensor designed towards supporting flood disaster early warning systems. The design involved selection of sensors, coding to control the system mechanism, and automatic data logging and storage. During the design phase, the apparatus was constructed where all the components were assembled using locally sourced items. Subsequently, under controlled laboratory environment, the system was tested by running water through the inlet during which the flow rate and rising water levels are automatically recorded and stored in a database via Microsoft Excel using Coolterm software. The system is simulated such that the water level readings measured in centimeters is output in meters using a multiplicative of 10. A total number of 80 readings were analyzed to evaluate the performance of the system. The result shows that the system is sensitive to water level rise and yielded accurate measurement of water level. But, the flow rate fluctuates due to the manual water supply that produced inconsistent flow. It was also observed that the flow sensor has a duty cycle of 50% of operating time under normal condition which implies that the performance of the flow sensor is optimal.

A Community-Based Intervention to Prevent Obesity Beginning at Birth among American Indian Children: Study Design and Rationale for the PTOTS study

PubMed Central

Karanja, Njeri; Aickin, Mikel; Lutz, Tam; Mist, Scott; Jobe, Jared B.; Maupomé, Gerardo; Ritenbaugh, Cheryl

2012-01-01

Eating and physical activity behaviors associated with adult obesity have early antecedents, yet few studies have focused on obesity prevention interventions targeting very young children. Efforts to prevent obesity beginning at birth seem particularly important in populations at risk for early-onset obesity. National estimates indicate that American Indian (AI) children have higher rates of overweight and obesity than children of other races/ethnicities. The Prevention of Toddler Obesity and Teeth Health Study (PTOTS) is a community-partnered randomized controlled trial designed to prevent obesity beginning at birth in AI children. PTOTS was developed to test the effectiveness of a multi-component intervention designed to: promote breastfeeding, reduce sugar-sweetened beverage consumption, appropriately time the introduction of healthy solid foods, and counsel parents to reduce sedentary lifestyles in their children. A birth cohort of 577 children from five AI tribes is randomized by tribe to either the intervention (three tribes) or the comparison condition (two tribes). The strengths and weaknesses of PTOTS include a focus on a critical growth phase, placement in the community, and intervention at many levels, using a variety of approaches. PMID:23001689

Achieving the Proper Balance Between Crew and Public Safety

NASA Technical Reports Server (NTRS)

Gowan, John; Rosati, Paul; Silvestri, Ray; Stahl, Ben; Wilde, Paul

2011-01-01

A paramount objective of all human-rated launch and reentry vehicle developers is to ensure that the risks to both the crew onboard and the public are minimized within reasonable cost, schedule, and technical constraints. Past experience has shown that proper attention to range safety requirements necessary to ensure public safety must be given early in the design phase to avoid additional operational complexities or threats to the safety of people onboard. This paper will outline the policy considerations, technical issues, and operational impacts regarding launch and reentry vehicle failure scenarios where crew and public safety are intertwined and thus addressed optimally in an integrated manner. Historical examples and lessons learned from both the Space Shuttle and Constellation Programs will be presented. Using these examples as context, the paper will discuss some operational, design, and analysis approaches to mitigate and balance the risks to people onboard and in the public. Manned vehicle perspectives from the FAA and Air Force organizations that oversee public safety will also be summarized. Finally, the paper will emphasize the need to factor policy, operational, and analysis considerations into the early design trades of new vehicles to help ensure that both crew and public safety are maximized to the greatest extent possible.

Evaluation of the influence of dominance rules for the assembly line design problem under consideration of product design alternatives

NASA Astrophysics Data System (ADS)

Oesterle, Jonathan; Lionel, Amodeo

2018-06-01

The current competitive situation increases the importance of realistically estimating product costs during the early phases of product and assembly line planning projects. In this article, several multi-objective algorithms using difference dominance rules are proposed to solve the problem associated with the selection of the most effective combination of product and assembly lines. The list of developed algorithms includes variants of ant colony algorithms, evolutionary algorithms and imperialist competitive algorithms. The performance of each algorithm and dominance rule is analysed by five multi-objective quality indicators and fifty problem instances. The algorithms and dominance rules are ranked using a non-parametric statistical test.

Getting nano tattoos right - a checklist of legal and ethical hurdles for an emerging nanomedical technology.

PubMed

Bennett, Michael G; Naranja, R John

2013-08-01

The nano tattoo represents a nascent technology designed to be implanted in the skin to provide continuous and reliable glucose detection for diabetics. Its potential benefits are compelling not only for its ability to prevent diabetic complications and decrease related social costs, but also for its ease of use and relative patient-user comfort. This Note aims to articulate a checklist of fundamental intellectual property, bioethical and system design issues that are appropriately considered in the pre-clinical, pre-commercialization phase of nano tattoo development. Early and regular consideration of these factors can increase the odds of a societally beneficial dissemination of this device by engaging relevant researcher, medical, patient-user and patient-advocate communities concerned with its appropriate application, as well as policymaking communities focused on effectively managing diabetes-related healthcare costs. The checklist of factors includes fundamental issues and is generally applicable to nanomedical inventions. This paper presents a comprehensive list of fundamental intellectual property, bioethical, and system design issues to be considered in the pre-commercialization phase of nanomedicine development, through the specific example of nano tattoo development. Nano tattoo is designed to be implanted in the skin to provide reliable glucose monitoring for diabetics, enabling enhanced prevention of complications and decreased socioeconomic costs. Copyright © 2013 Elsevier Inc. All rights reserved.

Experimental demonstration of a two-phase population extinction hazard

PubMed Central

Drake, John M.; Shapiro, Jeff; Griffen, Blaine D.

2011-01-01

Population extinction is a fundamental biological process with applications to ecology, epidemiology, immunology, conservation biology and genetics. Although a monotonic relationship between initial population size and mean extinction time is predicted by virtually all theoretical models, attempts at empirical demonstration have been equivocal. We suggest that this anomaly is best explained with reference to the transient properties of ensembles of populations. Specifically, we submit that under experimental conditions, many populations escape their initially vulnerable state to reach quasi-stationarity, where effects of initial conditions are erased. Thus, extinction of populations initialized far from quasi-stationarity may be exposed to a two-phase extinction hazard. An empirical prediction of this theory is that the fit Cox proportional hazards regression model for the observed survival time distribution of a group of populations will be shown to violate the proportional hazards assumption early in the experiment, but not at later times. We report results of two experiments with the cladoceran zooplankton Daphnia magna designed to exhibit this phenomenon. In one experiment, habitat size was also varied. Statistical analysis showed that in one of these experiments a transformation occurred so that very early in the experiment there existed a transient phase during which the extinction hazard was primarily owing to the initial population size, and that this was gradually replaced by a more stable quasi-stationary phase. In the second experiment, only habitat size unambiguously displayed an effect. Analysis of data pooled from both experiments suggests that the overall extinction time distribution in this system results from the mixture of extinctions during the initial rapid phase, during which the effects of initial population size can be considerable, and a longer quasi-stationary phase, during which only habitat size has an effect. These are the first results, to our knowledge, of a two-phase population extinction process. PMID:21429907

Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates

PubMed Central

Vohs, Jenifer L.; Hummer, Tom A.; Yung, Matthew G.; Francis, Michael M.; Lysaker, Paul H.; Breier, Alan

2015-01-01

Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID:26132568

Safety assessment in plant layout design using indexing approach: implementing inherent safety perspective. Part 1 - guideword applicability and method description.

PubMed

Tugnoli, Alessandro; Khan, Faisal; Amyotte, Paul; Cozzani, Valerio

2008-12-15

Layout planning plays a key role in the inherent safety performance of process plants since this design feature controls the possibility of accidental chain-events and the magnitude of possible consequences. A lack of suitable methods to promote the effective implementation of inherent safety in layout design calls for the development of new techniques and methods. In the present paper, a safety assessment approach suitable for layout design in the critical early phase is proposed. The concept of inherent safety is implemented within this safety assessment; the approach is based on an integrated assessment of inherent safety guideword applicability within the constraints typically present in layout design. Application of these guidewords is evaluated along with unit hazards and control devices to quantitatively map the safety performance of different layout options. Moreover, the economic aspects related to safety and inherent safety are evaluated by the method. Specific sub-indices are developed within the integrated safety assessment system to analyze and quantify the hazard related to domino effects. The proposed approach is quick in application, auditable and shares a common framework applicable in other phases of the design lifecycle (e.g. process design). The present work is divided in two parts: Part 1 (current paper) presents the application of inherent safety guidelines in layout design and the index method for safety assessment; Part 2 (accompanying paper) describes the domino hazard sub-index and demonstrates the proposed approach with a case study, thus evidencing the introduction of inherent safety features in layout design.

Cdc7 is required throughout the yeast S phase to activate replication origins.

PubMed

Donaldson, A D; Fangman, W L; Brewer, B J

1998-02-15

The long-standing conclusion that the Cdc7 kinase of Saccharomyces cerevisiae is required only to trigger S phase has been challenged by recent data that suggests it acts directly on individual replication origins. We tested the possibility that early- and late-activated origins have different requirements for Cdc7 activity. Cells carrying a cdc7(ts) allele were first arrested in G1 at the cdc7 block by incubation at 37 degrees C, and then were allowed to enter S phase by brief incubation at 23 degrees C. During the S phase, after return to 37 degrees C, early-firing replication origins were activated, but late origins failed to fire. Similarly, a plasmid with a late-activated origin was defective in replication. As a consequence of the origin activation defect, duplication of chromosomal sequences that are normally replicated from late origins was greatly delayed. Early-replicating regions of the genome duplicated at approximately their normal time. The requirements of early and late origins for Cdc7 appear to be temporally rather than quantitatively different, as reducing overall levels of Cdc7 by growth at semi-permissive temperature reduced activation at early and late origins approximately equally. Our results show that Cdc7 activates early and late origins separately, with late origins requiring the activity later in S phase to permit replication initiation.

Elastomeric Thermal Insulation Design Considerations in Long, Aluminized Solid Rocket Motors

NASA Technical Reports Server (NTRS)

Martin, Heath T.

2017-01-01

An all-new sounding rocket was designed at NASA's Marshall Space Flight Center that featured an aft finocyl, aluminized solid propellant grain and silica-filled ethylene-propylene-diene monomer (SFEPDM) internal insulation. Upon the initial static firing of the first of this new design, the solid rocket motor (SRM) case failed thermally just upstream of the aft closure early in the burn time. Subsequent fluid modeling indicated that the high-velocity combustion-product jets emanating from the fin-slots in the propellant grain were likely inducing a strongly swirling flow, thus substantially increasing the severity of the convective environment on the exposed portion of the SFEPDM insulation in this region. The aft portion of the fin-slots in another of the motors were filled with propellant to eliminate the possibility of both direct jet impingement on the exposed SFEPDM and the appearance of strongly swirling flow in the aft region of the motor. When static-fired, this motor's case still failed in the same axial location, and, though somewhat later than for the first static firing, still in less than 1/3rd of the desired burn duration. These results indicate that the extreme material decomposition rates of the SFEPDM in this application are not due to gas-phase convection or shear but rather to interactions with burning aluminum or alumina slag. Further comparisons with between SFEPDM performance in this design and that in other hot-fire tests provide insight into the mechanisms of SFEPDM decomposition in SRM aft domes that can guide the upcoming redesign effort, as well as other future SRM designs. These data also highlight the current limitations of modeling elastomeric insulators solely with diffusion-controlled, gas-phase thermochemistry in SRM regions with significant viscous shear and/or condense-phase impingement or flow.

Framing the conversation: use of PRECIS-2 ratings to advance understanding of pragmatic trial design domains.

PubMed

Lipman, Paula Darby; Loudon, Kirsty; Dluzak, Leanora; Moloney, Rachael; Messner, Donna; Stoney, Catherine M

2017-11-10

There continues to be debate about what constitutes a pragmatic trial and how it is distinguished from more traditional explanatory trials. The NIH Pragmatic Trials Collaborative Project, which includes five trials and a coordinating unit, has adopted the Pragmatic-Explanatory Continuum Indicator Summary (PRECIS-2) instrument. The purpose of the study was to collect PRECIS-2 ratings at two points in time to assess whether the tool was sensitive to change in trial design, and to explore with investigators the rationale for rating shifts. A mixed-methods design included sequential collection and analysis of quantitative data (PRECIS-2 ratings) and qualitative data. Ratings were collected at two annual, in-person project meetings, and subsequent interviews conducted with investigators were recorded, transcribed, and coded using NVivo 11 Pro for Windows. Rating shifts were coded as either (1) actual change (reflects a change in procedure or protocol), (2) primarily a rating shift reflecting rater variability, or (3) themes that reflect important concepts about the tool and/or pragmatic trial design. Based on PRECIS-2 ratings, each trial was highly pragmatic at the planning phase and remained so 1 year later in the early phases of trial implementation. Over half of the 45 paired ratings for the nine PRECIS-2 domains indicated a rating change from Time 1 to Time 2 (N = 24, 53%). Of the 24 rating changes, only three represented a true change in the design of the trial. Analysis of rationales for rating shifts identified critical themes associated with the tool or pragmatic trial design more generally. Each trial contributed one or more relevant comments, with Eligibility, Flexibility of Adherence, and Follow-up each accounting for more than one. PRECIS-2 has proved useful for "framing the conversation" about trial design among members of the Pragmatic Trials Collaborative Project. Our findings suggest that design elements assessed by the PRECIS-2 tool may represent mostly stable decisions. Overall, there has been a positive response to using PRECIS-2 to guide conversations around trial design, and the project's focus on the use of the tool by this group of early adopters has provided valuable feedback to inform future trainings on the tool.

Aircraft conceptual design - an adaptable parametric sizing methodology

NASA Astrophysics Data System (ADS)

Coleman, Gary John, Jr.

Aerospace is a maturing industry with successful and refined baselines which work well for traditional baseline missions, markets and technologies. However, when new markets (space tourism) or new constrains (environmental) or new technologies (composite, natural laminar flow) emerge, the conventional solution is not necessarily best for the new situation. Which begs the question "how does a design team quickly screen and compare novel solutions to conventional solutions for new aerospace challenges?" The answer is rapid and flexible conceptual design Parametric Sizing. In the product design life-cycle, parametric sizing is the first step in screening the total vehicle in terms of mission, configuration and technology to quickly assess first order design and mission sensitivities. During this phase, various missions and technologies are assessed. During this phase, the designer is identifying design solutions of concepts and configurations to meet combinations of mission and technology. This research undertaking contributes the state-of-the-art in aircraft parametric sizing through (1) development of a dedicated conceptual design process and disciplinary methods library, (2) development of a novel and robust parametric sizing process based on 'best-practice' approaches found in the process and disciplinary methods library, and (3) application of the parametric sizing process to a variety of design missions (transonic, supersonic and hypersonic transports), different configurations (tail-aft, blended wing body, strut-braced wing, hypersonic blended bodies, etc.), and different technologies (composite, natural laminar flow, thrust vectored control, etc.), in order to demonstrate the robustness of the methodology and unearth first-order design sensitivities to current and future aerospace design problems. This research undertaking demonstrates the importance of this early design step in selecting the correct combination of mission, technologies and configuration to meet current aerospace challenges. Overarching goal is to avoid the reoccurring situation of optimizing an already ill-fated solution.

Supporting universal prevention programs: a two-phased coaching model.

PubMed

Becker, Kimberly D; Darney, Dana; Domitrovich, Celene; Keperling, Jennifer Pitchford; Ialongo, Nicholas S

2013-06-01

Schools are adopting evidence-based programs designed to enhance students' emotional and behavioral competencies at increasing rates (Hemmeter et al. in Early Child Res Q 26:96-109, 2011). At the same time, teachers express the need for increased support surrounding implementation of these evidence-based programs (Carter and Van Norman in Early Child Educ 38:279-288, 2010). Ongoing professional development in the form of coaching may enhance teacher skills and implementation (Noell et al. in School Psychol Rev 34:87-106, 2005; Stormont et al. 2012). There exists a need for a coaching model that can be applied to a variety of teacher skill levels and one that guides coach decision-making about how best to support teachers. This article provides a detailed account of a two-phased coaching model with empirical support developed and tested with coaches and teachers in urban schools (Becker et al. 2013). In the initial universal coaching phase, all teachers receive the same coaching elements regardless of their skill level. Then, in the tailored coaching phase, coaching varies according to the strengths and needs of each teacher. Specifically, more intensive coaching strategies are used only with teachers who need additional coaching supports, whereas other teachers receive just enough support to consolidate and maintain their strong implementation. Examples of how coaches used the two-phased coaching model when working with teachers who were implementing two universal prevention programs (i.e., the PATHS curriculum and PAX Good Behavior Game [PAX GBG]) provide illustrations of the application of this model. The potential reach of this coaching model extends to other school-based programs as well as other settings in which coaches partner with interventionists to implement evidence-based programs.

Understanding the experience of "burnout" in first-episode psychosis carers.

PubMed

Onwumere, Juliana; Sirykaite, Sandra; Schulz, Joerg; Man, Emma; James, Gareth; Afsharzadegan, Roya; Khan, Sanna; Harvey, Raythe; Souray, Jonathan; Raune, David

2018-05-01

The first onset of psychosis can exert a significant negative impact on the functioning and positive wellbeing of family carers. Carer reports of "burnout" have recently been recorded in early psychosis carers, though the literature is scarce detailing our understanding of how burnout relates to the primary experience of caregiving. The current study investigated reports of burnout and its relationship with beliefs about caregiving and wellbeing in a large group of early psychosis carers who were routinely assessed within an early intervention team. Using a cross-sectional design, 169 early psychosis carers completed the Maslach Burnout Inventory alongside measures of caregiving experiences, affect and wellbeing. The mean illness length for patients with psychosis was 18 months. Their mean age was 24.4 years and most was male (65%). The majority of carer participants were parental caregivers and living with their relative with psychosis. Across the three key burnout dimensions, 58% of the sample reported high levels of emotional exhaustion; 31% endorsed high levels of depersonalization; and 43% reported low levels personal accomplishment. The most severe level of burnout, reflecting elevated rates across all three dimensions, was observed in 16% of the sample. Carer burnout was positively associated with negative caregiving experiences (i.e. burden), poor affect, and reduced levels of positive wellbeing and perception of being in good health. Reports by early psychosis carers of exhaustion, feeling inadequate and expressing negativity towards the relative they care for is not uncommon and are closely associated with their overall negative appraisals of caregiving. The results underscore the importance of developing targeted interventions during the early phase, which are designed to reduce the development and entrenchment of burnout responses in carers, but to also mitigate its negative sequelae. Copyright © 2018. Published by Elsevier Inc.

Automatic extraction and visualization of object-oriented software design metrics

NASA Astrophysics Data System (ADS)

Lakshminarayana, Anuradha; Newman, Timothy S.; Li, Wei; Talburt, John

2000-02-01

Software visualization is a graphical representation of software characteristics and behavior. Certain modes of software visualization can be useful in isolating problems and identifying unanticipated behavior. In this paper we present a new approach to aid understanding of object- oriented software through 3D visualization of software metrics that can be extracted from the design phase of software development. The focus of the paper is a metric extraction method and a new collection of glyphs for multi- dimensional metric visualization. Our approach utilize the extensibility interface of a popular CASE tool to access and automatically extract the metrics from Unified Modeling Language class diagrams. Following the extraction of the design metrics, 3D visualization of these metrics are generated for each class in the design, utilizing intuitively meaningful 3D glyphs that are representative of the ensemble of metrics. Extraction and visualization of design metrics can aid software developers in the early study and understanding of design complexity.

Chronology and pyroclastic stratigraphy of the May 18, 1980, eruption of Mount St. Helens, Washington

NASA Technical Reports Server (NTRS)

Criswell, C. William

1987-01-01

The eruption of Mount St. Helens on May 18, 1980 can be subdivided into six phases: the paroxysmal phase I, the early Plinian phase II, the early ash flow phase III, the climactic phase IV, the late ash flow phase V, and phase VI, the activity of which consisted of a low-energy ash plume. These phases are correlated with stratigraphic subunits of ash-fall tephra and pyroclastic flow deposits. Sustained vertical discharge of phase II produced evolved dacite with high S/Cl ratios. Ash flow activity of phase III is attributed to decreases in gas content, indicated by reduced S/Cl ratios and increased clast density of the less evolved gray pumice. Climactic events are attributed to vent clearing and exhaustion of the evolved dacite.

High Level Analysis, Design and Validation of Distributed Mobile Systems with CoreASM

NASA Astrophysics Data System (ADS)

Farahbod, R.; Glässer, U.; Jackson, P. J.; Vajihollahi, M.

System design is a creative activity calling for abstract models that facilitate reasoning about the key system attributes (desired requirements and resulting properties) so as to ensure these attributes are properly established prior to actually building a system. We explore here the practical side of using the abstract state machine (ASM) formalism in combination with the CoreASM open source tool environment for high-level design and experimental validation of complex distributed systems. Emphasizing the early phases of the design process, a guiding principle is to support freedom of experimentation by minimizing the need for encoding. CoreASM has been developed and tested building on a broad scope of applications, spanning computational criminology, maritime surveillance and situation analysis. We critically reexamine here the CoreASM project in light of three different application scenarios.

Ethical considerations of neuro-oncology trial design in the era of precision medicine.

PubMed

Gupta, Saksham; Smith, Timothy R; Broekman, Marike L

2017-08-01

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

Timing of the endometrial biopsy may be critical for the accurate diagnosis of luteal phase deficiency.

PubMed

Castelbaum, A J; Wheeler, J; Coutifaris, C B; Mastroianni, L; Lessey, B A

1994-03-01

To determine the optimal time to perform the endometrial biopsy for the detection of "out-of-phase" endometrium. Two endometrial biopsies were performed during a single menstrual cycle in each subject. The patient's chronological day was determined by counting forward from the midcycle LH surge, as assessed by urinary LH detection. The "early" biopsy was done on day LH + 7.4 +/- 0.8, and the "late" biopsy on day LH + 11.6 +/- 0.7. Each biopsy was independently read by two pathologists and was considered out of phase if the histologic date was > or = 3 days delayed compared with the chronological date. Infertility practice of an academic teaching hospital. Thirty-three ovulatory women seeking evaluation for infertility. Number of patients with out-of-phase endometrium detected by the early versus the late biopsy. There was a significantly greater detection rate for out-of-phase endometrium using the early biopsy (12.1% to 18.2% incidence depending on the observer) compared with the later biopsy (6.1% to 9.1% incidence). A majority of the early out-of-phase biopsies corrected by the time of the later biopsy. Our findings indicate that an endometrial biopsy performed in the midluteal phase may detect a greater number of women with delayed endometrial maturation during the temporal window of embryo implantation. The observation that most of the women with out-of-phase midluteal biopsies had normal late luteal endometrium may represent a cryptic form of luteal phase deficiency.

Phase III Early Restoration Meeting - Galveston, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Phase III Early Restoration Meeting - Port Arthur, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Phase III Early Restoration Meeting - Panama City, FL | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Definition of technology development missions for early Space Station satellite servicing. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1984-01-01

The Executive Summary volume 1, includes an overview of both phases of the Definition of Technology Development Missions for Early Space Station Satellite Servicing. The primary purpose of Phase 1 of the Marshall Space Flight Center (MSFC) Satellite Servicing Phase 1 study was to establish requirements for demonstrating the capability of performing satellite servicing activities on a permanently manned Space Station in the early 1990s. The scope of Phase 1 included TDM definition, outlining of servicing objectives, derivation of initial Space Station servicing support requirements, and generation of the associated programmatic schedules and cost. The purpose of phase 2 of the satellite servicing study was to expand and refine the overall understanding of how best to use the manned space station as a test bed for demonstration of satellite servicing capabilities.

EUFEMED London Conference 2017: Exploratory Medicines Development: Innovation and Risk Management.

PubMed

Van Bortel, Luc; Sourgens, Hildegard; Breithaupt-Grögler, Kerstin; Caplain, Henri; Donazzolo, Yves; Klingmann, Ingrid; Hammond, Michael; Hardman, Timothy C; Stringer, Steffan; de Hoon, Jan

2017-01-01

The first formal conference of the EUropean Federation for Exploratory MEdicines Development (EUFEMED) held in London was the result of a collaborative effort of its founding associations: the Association for Applied Human Pharmacology (AGAH; Germany), the Association for Human Pharmacology in the Pharmaceutical Industry (AHPPI; UK), the Belgian Association of Phase-I Units (BAPU; Belgium), and Club Phase-I (France). The conference focused on innovation and risk management in early clinical drug development. Among other innovations, immunotherapy in oncology and inflammatory diseases were discussed as well as the importance of adaptive trial designs in early clinical drug development. Consideration was given to assessing and mitigating risk in early clinical drug development, and included a preconference workshop. Different measures to minimize risks in healthy volunteers and patients in first-in-human trials were discussed in addition to the importance of non-clinical data, the need for reliable biomarkers, improved communication on adverse events (AEs) and well-trained study sites with ready access to intensive care units and clinical specialists. The need for a European-wide system for prevention of over-volunteering was also discussed. The conference provided opportunity to discuss these developments and concerns and the changing regulatory environment with stakeholders from academia, industry, and regulatory agencies including the European Medicines Agency (EMA). Presentations given by invited speakers are published on http://www.eufemed.eu/london-conference-2017/.

Knee flexion with quadriceps cocontraction: A new therapeutic exercise for the early stage of ACL rehabilitation.

PubMed

Biscarini, Andrea; Contemori, Samuele; Busti, Daniele; Botti, Fabio M; Pettorossi, Vito E

2016-12-08

Quadriceps strengthening exercises designed for the early phase of anterior cruciate ligament (ACL) rehabilitation should limit the anterior tibial translation developed by quadriceps contraction near full knee extension, in order to avoid excessive strain on the healing tissue. We hypothesize that knee-flexion exercises with simultaneous voluntary contraction of quadriceps (voluntary quadriceps cocontraction) can yield considerable levels of quadriceps activation while preventing the tibia from translating forward relative to the femur. Electromyographic activity in quadriceps and hamstring muscles was measured in 20 healthy males during isometric knee-flexion exercises executed near full knee extension with maximal voluntary effort of quadriceps cocontraction and external resistance (R) ranging from 0% to 60% of the 1-repetition maximum (1RM). Biomechanical modeling was applied to derive the shear (anterior/posterior) tibiofemoral force developed in each exercise condition. Isometric knee-flexion exercises with small external resistance (R=10% 1RM) and maximal voluntary effort of quadriceps cocontraction yielded a net posterior (ACL-unloading) tibial pull (P=0.005) and levels of activation of 32%, 50%, and 45% of maximum voluntary isometric contraction, for the rectus femoris, vastus medialis, and vastus lateralis, respectively. This exercise might potentially rank as one of the most appropriate quadriceps strengthening interventions in the early phase of ACL rehabilitation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Design definition of the Laser Atmospheric Wind Sounder (LAWS), phase 2. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1992-01-01

The LAWS phase 1 and phase 2 studies have been completed on schedule and have led to significant advances in CO2 laser development. The Phase 2 Design Definition Study has shown that a large scanning mirror/high pulse energy laser LAWS Instrument is feasible and within the existing technology. The capability to monitor wind velocities with backscatter ratios of 10(exp 11) m(exp -1) SR(exp -1) is feasible. The weight budget allocated for the baseline LAWS is adequate, and sufficient reserves exist with the potential downsized configuration. With the possible decrease in available power from the baseline of 2.2 kW guideline, power and shot management is critical for the baseline configuration (15 to 20 J). This is particularly true during the 100 day occultation period each year. With the downsized configurations (5 to 7 J), power management is still necessary during the occultation but is primarily limited to shot management over the polar regions. The breadboard effort has produced significant laser advances for a tight 18 month schedule and the minimum budgets available from NASA, Lockheed, and TDS. Using the NASA funds and Lockheed and TDS fixed assets budgets, the breadboard was designed, fabricated, and brought on-line with first laser light within 16 months after ATP. First laser beam was obtained on 21 April 1992 at a 5 J power level. Tests since then have been conducted at sustained, repetitive pulse levels of over 7 J and 20 Hz. This is an increase of over two or three times greater than any system previously developed from this type laser. Increased power levels and additional life tests will be accomplished in the next LAWS phase. The Lockheed LAWS design will operate in the gravity gradient mode on-orbit, and all possible instrument vibration and jitter modes have been considered. Adequate pointing stability and control is state-of-the-art technology for the critical time periods, frequency rates, and control responses required by LAWS. Lockheed recommends a 6-1/2 year phase C/D program for LAWS to provide adequate feedback from the engineering unit and the qualification unit to the final flight unit. Assuming a one year period for LAWS integration to the spacecraft, followed by a six-month period for launch vehicle integration, LAWS could be successfully developed and launched in eight years. Our baseline design or downsized design can be accommodated by either the Atlas 2AS or the Delta launch vehicles. Lockheed's recommendation is that, based on the successful phase 2 design study and breadboard program, a follow-on 18 month extended breadboard testing program and additional system engineering studies, primarily in interfacing with a to be defined platform, be initiated. This should be immediately followed by the phase C/D program, leading to a LAWS launch in late 2001 or early 2002.

Design innovations and baseline findings in a long-term Parkinson’s trial: NET-PD LS-1

PubMed Central

2012-01-01

Background Based on the pre-clinical and the results of a phase 2 futility study, creatine was selected for an efficacy trial in Parkinson’s disease (PD). We present the design rationale and a description of the study cohort at baseline. Methods A randomized, multicenter, double-blind, parallel group, placebo controlled Phase 3 study of creatine (10 gm daily) in participants with early, treated PD, the Long-term Study – 1 (LS-1) is being conducted by the NINDS Exploratory Trials in Parkinson’s Disease (NET-PD) network. The study utilizes a global statistical test (GST) encompassing multiple clinical rating scales to provide a multidimensional assessment of disease progression. Results A total of 1,741 PD participants from 45 sites in the U.S. and Canada were randomized 1:1 to either 10-gm creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. Conclusions LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care. PMID:23079770

The ethics of HIV "cure" research: what can we learn from consent forms?

PubMed

Henderson, Gail E

2015-01-01

The advent of HIV "cure" research has generated enormous attention, but also concern about its potential to engender false hope, leading to overestimation of benefits and underestimation of risks, and about recruiting relatively healthy participants to studies with uncertain or serious risks. Currently, little is known about potential ethical problems in the ways that informed consent for HIV cure research is described to potential participants. As a first step to address this question, early phase, HIV "cure" research consent forms were analyzed to assess how study aims and potential risks and benefits are presented. Thirteen consent forms from a diverse group of clinical studies were selected to represent the major categories of cure research, including 11 interventional (gene transfer, vaccine intensification, treatment interruption, and latency reversing) and two observational. Consent forms were coded using seven categories, abstracting data on study purpose and design, participant selection criteria, presentation of risks and benefits of participation, and potential return of research results. Findings demonstrate variation and deficiencies that merit attention, but that can largely be addressed by turning to existing guidance about early phase research and specific study designs from other research contexts. The most challenging of these is ensuring that clear, specific, and consistent language is used to describe study aims, risks, benefits, and possible return of results. Informed consent for HIV "cure" research represents an opportunity to apply relevant existing guidance, measure the effectiveness of its application, and develop standardized best-practice policies for consent forms and processes.

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

PubMed Central

Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

2011-01-01

Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P < .001). The difference in change in scores between the groups was not significant (P = .16). With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004) and in the placebo group by 15% (P = .05). The change in scores was similar in the groups (P = .83). Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

James Webb Space Telescope: Supporting Multiple Ground System Transitions in One Year

NASA Technical Reports Server (NTRS)

Detter, Ryan; Fatig, Curtis; Steck, Jane

2004-01-01

Ideas, requirements, and concepts developed during the very early phases of the mission design often conflict with the reality of a situation once the prime contractors are awarded. This happened for the James Webb Space Telescope (JWST) as well. The high level requirement of a common real-time ground system for both the Integration and Test (I&T), as well as the Operation phase of the mission is meant to reduce the cost and time needed later in the mission development for re-certification of databases, command and control systems, scripts, display pages, etc. In the case of JWST, the early Phase A flight software development needed a real-time ground system and database prior to the spacecraft prime contractor being selected. To compound the situation, the very low level requirements for the real-time ground system were not well defined. These two situations caused the initial real-time ground system to be switched out for a system that was previously used by the Bight software development team. To meet the high-!evel requirement, a third ground system was selected based on the prime spacecraft contractor needs and JWST Project decisions. The JWST ground system team has responded to each of these changes successfully. The lessons learned from each transition have not only made each transition smoother, but have also resolved issues earlier in the mission development than what would normally occur.

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

Uncertainty Requirement Analysis for the Orbit, Attitude, and Burn Performance of the 1st Lunar Orbit Insertion Maneuver

NASA Astrophysics Data System (ADS)

Song, Young-Joo; Bae, Jonghee; Kim, Young-Rok; Kim, Bang-Yeop

2016-12-01

In this study, the uncertainty requirements for orbit, attitude, and burn performance were estimated and analyzed for the execution of the 1st lunar orbit insertion (LOI) maneuver of the Korea Pathfinder Lunar Orbiter (KPLO) mission. During the early design phase of the system, associate analysis is an essential design factor as the 1st LOI maneuver is the largest burn that utilizes the onboard propulsion system; the success of the lunar capture is directly affected by the performance achieved. For the analysis, the spacecraft is assumed to have already approached the periselene with a hyperbolic arrival trajectory around the moon. In addition, diverse arrival conditions and mission constraints were considered, such as varying periselene approach velocity, altitude, and orbital period of the capture orbit after execution of the 1st LOI maneuver. The current analysis assumed an impulsive LOI maneuver, and two-body equations of motion were adapted to simplify the problem for a preliminary analysis. Monte Carlo simulations were performed for the statistical analysis to analyze diverse uncertainties that might arise at the moment when the maneuver is executed. As a result, three major requirements were analyzed and estimated for the early design phase. First, the minimum requirements were estimated for the burn performance to be captured around the moon. Second, the requirements for orbit, attitude, and maneuver burn performances were simultaneously estimated and analyzed to maintain the 1st elliptical orbit achieved around the moon within the specified orbital period. Finally, the dispersion requirements on the B-plane aiming at target points to meet the target insertion goal were analyzed and can be utilized as reference target guidelines for a mid-course correction (MCC) maneuver during the transfer. More detailed system requirements for the KPLO mission, particularly for the spacecraft bus itself and for the flight dynamics subsystem at the ground control center, are expected to be prepared and established based on the current results, including a contingency trajectory design plan.

New Round of Studies Begin in Phase 0/I/II Cancer Prevention Clinical Trials Program | Division of Cancer Prevention

Cancer.gov

The NCI Division of Cancer Prevention’s Phase 0/I/II Cancer Prevention Clinical Trials Program, also known as the Consortia for Early Phase Prevention Trials, is beginning a new round of studies in the effort toward systematic early clinical development of promising preventive agents for people at increased risk of developing cancer. |

Intermediate Experimental Vehicle (IXV): Avionics and Software of the ESA Reentry Demonstrator

NASA Astrophysics Data System (ADS)

Malucchi, Giovanni; Dussy, Stephane; Camuffo, Fabrizio

2012-08-01

The IXV project is conceived as a technology platform that would perform the step forward with respect to the Atmospheric Reentry Demonstrator (ARD), by increasing the system maneuverability and verifying the critical technology performances against a wider re- entry corridor.The main objective is to design, develop and to perform an in-flight verification of an autonomous lifting and aerodynamically controlled (by a combined use of thrusters and aerodynamic surfaces) reentry system.The project also includes the verification and experimentation of a set of critical reentry technologies and disciplines:Thermal Protection System (TPS), for verification and characterization of thermal protection technologies in representative operational environment;Aerodynamics - Aerthermodynamics (AED-A TD), for understanding and validation of aerodynamics and aerothermodyamics phenomena with improvement of design tools;Guidance, Navigation and Control (GNC), for verification of guidance, navigation and control techniques in representative operational environment (i.e. reentry from Low Earth Orbit);Flight dynamics, to update and validate the vehicle model during actual flight, focused on stability and control derivatives.The above activities are being performed through the implementation of a strict system design-to-cost approach with a proto-flight model development philosophy.In 2008 and 2009, the IXV project activities reached the successful completion of the project Phase-B, including the System PDR, and early project Phase-C.In 2010, following a re-organization of the industrial consortium, the IXV project successfully completed a design consolidation leading to an optimization of the technical baseline including the GNC, avionics (i.e. power, data handling, radio frequency and telemetry), measurement sensors, hot and cold composite structures, thermal protections and control, with significant improvements of the main system budgets.The project has successfully closed the System CDR during 2011 and it is currently running the Phase-D with the target to be launched with Vega from Kourou in 2014The paper will provide an overview of the IXV design and mission objectives in the frame of the atmospheric reentry overall activities, focusing on the avionics and software architecture and design.

Innovative strategies for early clinical R&D.

PubMed

Butz, Robert F; Morelli, Gaetano

2008-01-01

Developments in translational medicine and regulatory initiatives associated with the FDA's Critical Path Initiative are creating new opportunities for innovation in early clinical R&D. The introduction of the exploratory IND process allows small, 'phase 0' clinical trials to be conducted prior to traditional phase I trials - sometimes requiring considerably less chemistry, manufacturing and controls, or preclinical support. Phase 0 clinical trials involving subtherapeutic, yet pharmacologically active, dose levels can provide an early demonstration of clinical proof of concept; such demonstration is of particular importance to small pharmaceutical and early-stage biotechnology companies. However, these opportunities for rapid entry into the clinic must be balanced by a consideration of the unique risks associated with first-in-human clinical trials, and by accounting for public concerns regarding drug safety in general. This feature review discusses how innovative clinical strategies can be used effectively in early drug development.

Physicomechanical, In Vitro and In Vivo Performance of 3D Printed Doped Tricalcium Phosphate Scaffolds for Bone Tissue Engineering and Drug Delivery

NASA Astrophysics Data System (ADS)

Tarafder, Solaiman

Although tricalcium phosphate (TCP) is widely used in bone tissue engineering, the strength degradation kinetics is not well controlled. This study focuses on the underlying mechanism of strength degradation kinetics by incorporating trace elements in TCP. The objective of this research is to modify the mechanical properties of TCP to achieve the desired degradation rate for the specific need, and improve the in vivo bioactivity for early wound healing by incorporating trace elements such as strontium (Sr2+), magnesium (Mg2+) and silicon (Si4+) as dopants. The hypothesis of this research is that the presence of different trace elements in TCP will influence its phase stability, microstructure, mechanical strength, and both in vitro and in vivo bioactivity. Direct three dimensional printing (3DP) was used to fabricate designed interconnected macroporous pure and doped TCP scaffolds. Microwave sintering as opposed to conventional sintering was also used for better densification and higher mechanical strength. A maximum compressive strength of 10.95 +/- 1.28 MPa and 12.01 +/- 1.56 MPa were achieved for pure and Sr2+-Mg2+ doped TCP scaffolds with 500 microm designed pores (˜400 microm after sintering) sintered in microwave furnace, respectively. Substitution of Mg2+ and Sr2+ into calcium (Ca2+) sites of TCP crystal lattice contributed to phase stability and controlled gradual degradation. On the other hand, Si4+ substitution into phosphorous (P5+) sites destabilized the crystal structure and accelerated degradation of TCP. Interconnected macroporous beta-TCP scaffolds facilitated in vivo guided bone tissue regeneration through infiltration of cells and extracellular matrix into the designed pores. Presence of Sr2+, Mg2+ and Si4+ into beta-TCP induced increased in vivo early bone formation and better bone remodeling through increased extracellular matrix production such as, collagen and osteocalcin, when tested in rat and rabbit distal femur model. The presence of Si4+ along with Mg 2+ induced increased new blood vessel formation. Our results exhibited that Sr2+, Mg2+ and Si4+ doped 3DP TCP scaffolds have strong potential in bone tissue engineering applications for early wound healing.

Management of high risk metastatic prostate cancer: the case for novel therapies.

PubMed

Brand, Timothy C; Tolcher, Anthony W

2006-12-01

We reviewed the results of preliminary studies of select novel agents for metastatic prostate cancer and discuss the potential benefit of these agents for earlier stage disease, eg biochemically recurrent prostate cancer with high risk features. Available data on select investigational immunotherapies as well as endothelin-A receptor antagonists and survivin inhibitors were obtained and reviewed through PubMed searches, conference proceedings and unpublished proprietary information, when available. A large number of promising agents are in varying stages of development. Phase III results have been reported for the endothelin-A receptor antagonist atrasentan. Several immunotherapies are currently in phase II/III trials, namely the GM-CSF transduced tumor cell vaccine GVAX, the prostatic acid phosphatase loaded dendritic cell vaccine Provenge and the prostate specific antigen expressing poxvirus vaccine PROSTVAC-VF. Another immunotherapy, the prostate specific membrane antigen immunoconjugate MLN2704 (Millennium Pharmaceuticals, Cambridge, Massachusetts), is in phase I/II study. The first clinical inhibitors of survivin are in early phase I studies. Several of these agents, including atrasentan, have shown statistically significant but modest effects in the advanced disease setting in which they have been studied. Clinical trial design with these novel therapies presents particular challenges since most of these agents may induce disease stabilization rather than disease regression. There is a risk of false-negative results and failure to recognize a potentially efficacious agent if these cytostatic agents are studied only in men with advanced, heavily pretreated disease in whom life expectancy is measured in months. We advocate the early referral and enrollment of men with high risk prostate cancer in clinical trials.

Social regulation of maternal traits in nest-founding bumble bee (Bombus terrestris) queens.

PubMed

Woodard, S Hollis; Bloch, Guy; Band, Mark R; Robinson, Gene E

2013-09-15

During the nest-founding phase of the bumble bee colony cycle, queens undergo striking changes in maternal care behavior. Early in the founding phase, prior to the emergence of workers in the nest, queens are reproductive and also provision and feed their offspring. However, later in the founding phase, queens reduce their feeding of larvae and become specialized on reproduction. This transition is synchronized with the emergence of workers in the colony, who assume the task of feeding their siblings. Using a social manipulation experiment with the bumble bee Bombus terrestris, we tested the hypothesis that workers regulate the transition from feeding brood to specialization on reproduction in nest-founding bumble bee queens. Consistent with this hypothesis, we found that early-stage nest-founding queens with workers prematurely added to their nests reduce their brood-feeding behavior and increase egg laying, and likewise, late-stage nest-founding queens increase their brood-feeding behavior and decrease egg-laying when workers are removed from their nests. Further, brood-feeding and egg-laying behaviors were negatively correlated. We used Agilent microarrays designed from B. terrestris brain expressed sequenced tags (ESTs) to explore a second hypothesis, that workers alter brain gene expression in nest-founding queens. We found evidence that brain gene expression in nest-founding queens is altered by the presence of workers, with the effect being much stronger in late-stage founding queens. This study provides new insights into how the transition from feeding brood to specialization on reproduction in queen bumble bees is regulated during the nest initiation phase of the colony cycle.

tkLayout: a design tool for innovative silicon tracking detectors

NASA Astrophysics Data System (ADS)

Bianchi, G.

2014-03-01

A new CMS tracker is scheduled to become operational for the LHC Phase 2 upgrade in the early 2020's. tkLayout is a software package developed to create 3d models for the design of the CMS tracker and to evaluate its fundamental performance figures. The new tracker will have to cope with much higher luminosity conditions, resulting in increased track density, harsher radiation exposure and, especially, much higher data acquisition bandwidth, such that equipping the tracker with triggering capabilities is envisaged. The design of an innovative detector involves deciding on an architecture offering the best trade-off among many figures of merit, such as tracking resolution, power dissipation, bandwidth, cost and so on. Quantitatively evaluating these figures of merit as early as possible in the design phase is of capital importance and it is best done with the aid of software models. tkLayout is a flexible modeling tool: new performance estimates and support for different detector geometries can be quickly added, thanks to its modular structure. Besides, the software executes very quickly (about two minutes), so that many possible architectural variations can be rapidly modeled and compared, to help in the choice of a viable detector layout and then to optimize it. A tracker geometry is generated from simple configuration files, defining the module types, layout and materials. Support structures are automatically added and services routed to provide a realistic tracker description. The tracker geometries thus generated can be exported to the standard CMS simulation framework (CMSSW) for full Monte Carlo studies. tkLayout has proven essential in giving guidance to CMS in studying different detector layouts and exploring the feasibility of innovative solutions for tracking detectors, in terms of design, performance and projected costs. This tool has been one of the keys to making important design decisions for over five years now and has also enabled project engineers and simulation experts to focus their efforts on other important or specific issues. Even if tkLayout was designed for the CMS tracker upgrade project, its flexibility makes it experiment-agnostic, so that it could be easily adapted to model other tracking detectors. The technology behind tkLayout is presented, as well as some of the results obtained in the context of the CMS silicon tracker design studies.

Fluctuation-driven electroweak phase transition. [in early universe

NASA Technical Reports Server (NTRS)

Gleiser, Marcelo; Kolb, Edward W.

1992-01-01

We examine the dynamics of the electroweak phase transition in the early Universe. For Higgs masses in the range 46 less than or = M sub H less than or = 150 GeV and top quark masses less than 200 GeV, regions of symmetric and asymmetric vacuum coexist to below the critical temperature, with thermal equilibrium between the two phases maintained by fluctuations of both phases. We propose that the transition to the asymmetric vacuum is completed by percolation of these subcritical fluctuations. Our results are relevant to scenarios of baryogenesis that invoke a weakly first-order phase transition at the electroweak scale.

Taking the brakes off the learning curve.

PubMed

Gheysen, Freja; Lasne, Gabriel; Pélégrini-Issac, Mélanie; Albouy, Genevieve; Meunier, Sabine; Benali, Habib; Doyon, Julien; Popa, Traian

2017-03-01

Motor learning is characterized by patterns of cerebello-striato-cortical activations shifting in time, yet the early dynamic and function of these activations remains unclear. Five groups of subjects underwent either continuous or intermittent theta-burst stimulation of one cerebellar hemisphere, or no stimulation just before learning a new motor sequence during fMRI scanning. We identified three phases during initial learning: one rapid, one slow, and one quasi-asymptotic performance phase. These phases were not changed by left cerebellar stimulation. Right cerebellar inhibition, however, accelerated learning and enhanced brain activation in critical motor learning-related areas during the first phase, continuing with reduced brain activation but high-performance in late phase. Right cerebellar excitation did not affect the early learning process, but slowed learning significantly in late phase, along with increased brain activation. We conclude that the right cerebellum is a key factor coordinating other neuronal loops in the early acquisition of an explicit motor sequential skill. Hum Brain Mapp 38:1676-1691, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A late wake time phase delays the human dim light melatonin rhythm.

PubMed

Burgess, Helen J; Eastman, Charmane I

2006-03-13

Short sleep/dark durations, due to late bedtimes or early wake times or both, are common in modern society. We have previously shown that a series of days with a late bedtime phase delays the human dim light melatonin rhythm, as compared to a series of days with an early bedtime, despite a fixed wake time. Here we compared the effect of an early versus late wake time with a fixed bedtime on the human dim light melatonin rhythm. Fourteen healthy subjects experienced 2 weeks of short 6h nights with an early wake time fixed at their habitual weekday wake time and 2 weeks of long 9 h nights with a wake time that occurred 3h later than the early wake time, in counterbalanced order. We found that after 2 weeks with the late wake time, the dim light melatonin onset delayed by 2.4 h and the dim light melatonin offset delayed by 2.6 h (both p < 0.001), as compared to after 2 weeks with the early wake time. These results highlight the substantial influence that wake time, likely via the associated morning light exposure, has on the timing of the human circadian clock. Furthermore, the results suggest that when people truncate their sleep by waking early their circadian clocks phase advance and when people wake late their circadian clocks phase delay.

IMPLEMENTATION OF THE SEISMIC DESIGN CRITERIA OF DOE-STD-1189-2008 APPENDIX A [FULL PAPER

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

OMBERG SK

2008-05-14

This paper describes the approach taken by two Fluor Hanford projects for implementing of the seismic design criteria from DOE-STD-1189-2008, Appendix A. The existing seismic design criteria and the new seismic design criteria is described, and an assessment of the primary differences provided. The gaps within the new system of seismic design criteria, which necessitate conduct of portions of work to the existing technical standards pending availability of applicable industry standards, is discussed. Two Hanford Site projects currently in the Control Decision (CD)-1 phase of design have developed an approach to implementation of the new criteria. Calculations have been performedmore » to determine the seismic design category for one project, based on information available in early CD-1. The potential effects of DOE-STD-1189-2008, Appendix A seismic design criteria on the process of project alternatives analysis is discussed. Present of this work is expected to benefit others in the DOE Complex that may be implementing DOE-STD-1189-2008.« less

Medicinal chemistry inspired fragment-based drug discovery.

PubMed

Lanter, James; Zhang, Xuqing; Sui, Zhihua

2011-01-01

Lead generation can be a very challenging phase of the drug discovery process. The two principal methods for this stage of research are blind screening and rational design. Among the rational or semirational design approaches, fragment-based drug discovery (FBDD) has emerged as a useful tool for the generation of lead structures. It is particularly powerful as a complement to high-throughput screening approaches when the latter failed to yield viable hits for further development. Engagement of medicinal chemists early in the process can accelerate the progression of FBDD efforts by incorporating drug-friendly properties in the earliest stages of the design process. Medium-chain acyl-CoA synthetase 2b and ketohexokinase are chosen as examples to illustrate the importance of close collaboration of medicinal chemists, crystallography, and modeling. Copyright © 2011 Elsevier Inc. All rights reserved.

A Multi-Encoding Approach for LTL Symbolic Satisfiability Checking

NASA Technical Reports Server (NTRS)

Rozier, Kristin Y.; Vardi, Moshe Y.

2011-01-01

Formal behavioral specifications written early in the system-design process and communicated across all design phases have been shown to increase the efficiency, consistency, and quality of the system under development. To prevent introducing design or verification errors, it is crucial to test specifications for satisfiability. Our focus here is on specifications expressed in linear temporal logic (LTL). We introduce a novel encoding of symbolic transition-based Buchi automata and a novel, "sloppy," transition encoding, both of which result in improved scalability. We also define novel BDD variable orders based on tree decomposition of formula parse trees. We describe and extensively test a new multi-encoding approach utilizing these novel encoding techniques to create 30 encoding variations. We show that our novel encodings translate to significant, sometimes exponential, improvement over the current standard encoding for symbolic LTL satisfiability checking.

Phase in Optical Image Processing

NASA Astrophysics Data System (ADS)

Naughton, Thomas J.

2010-04-01

The use of phase has a long standing history in optical image processing, with early milestones being in the field of pattern recognition, such as VanderLugt's practical construction technique for matched filters, and (implicitly) Goodman's joint Fourier transform correlator. In recent years, the flexibility afforded by phase-only spatial light modulators and digital holography, for example, has enabled many processing techniques based on the explicit encoding and decoding of phase. One application area concerns efficient numerical computations. Pushing phase measurement to its physical limits, designs employing the physical properties of phase have ranged from the sensible to the wonderful, in some cases making computationally easy problems easier to solve and in other cases addressing mathematics' most challenging computationally hard problems. Another application area is optical image encryption, in which, typically, a phase mask modulates the fractional Fourier transformed coefficients of a perturbed input image, and the phase of the inverse transform is then sensed as the encrypted image. The inherent linearity that makes the system so elegant mitigates against its use as an effective encryption technique, but we show how a combination of optical and digital techniques can restore confidence in that security. We conclude with the concept of digital hologram image processing, and applications of same that are uniquely suited to optical implementation, where the processing, recognition, or encryption step operates on full field information, such as that emanating from a coherently illuminated real-world three-dimensional object.

Contribution of economic evaluation to decision making in early phases of product development: a methodological and empirical review.

PubMed

Hartz, Susanne; John, Jürgen

2008-01-01

Economic evaluation as an integral part of health technology assessment is today mostly applied to established technologies. Evaluating healthcare innovations in their early states of development has recently attracted attention. Although it offers several benefits, it also holds methodological challenges. The aim of our study was to investigate the possible contributions of economic evaluation to industry's decision making early in product development and to confront the results with the actual use of early data in economic assessments. We conducted a literature research to detect methodological contributions as well as economic evaluations that used data from early phases of product development. Economic analysis can be beneficially used in early phases of product development for various purposes including early market assessment, R&D portfolio management, and first estimations of pricing and reimbursement scenarios. Analytical tools available for these purposes have been identified. Numerous empirical works were detected, but most do not disclose any concrete decision context and could not be directly matched with the suggested applications. Industry can benefit from starting economic evaluation early in product development in several ways. Empirical evidence suggests that there is still potential left unused.

NASA Collaborative Design Processes

NASA Technical Reports Server (NTRS)

Jones, Davey

2017-01-01

This is Block 1, the first evolution of the world's most powerful and versatile rocket, the Space Launch System, built to return humans to the area around the moon. Eventually, larger and even more powerful and capable configurations will take astronauts and cargo to Mars. On the sides of the rocket are the twin solid rocket boosters that provide more than 75 percent during liftoff and burn for about two minutes, after which they are jettisoned, lightening the load for the rest of the space flight. Four RS-25 main engines provide thrust for the first stage of the rocket. These are the world's most reliable rocket engines. The core stage is the main body of the rocket and houses the fuel for the RS-25 engines, liquid hydrogen and liquid oxygen, and the avionics, or "brain" of the rocket. The core stage is all new and being manufactured at NASA's "rocket factory," Michoud Assembly Facility near New Orleans. The Launch Vehicle Stage Adapter, or LVSA, connects the core stage to the Interim Cryogenic Propulsion Stage. The Interim Cryogenic Propulsion Stage, or ICPS, uses one RL-10 rocket engine and will propel the Orion spacecraft on its deep-space journey after first-stage separation. Finally, the Orion human-rated spacecraft sits atop the massive Saturn V-sized launch vehicle. Managed out of Johnson Space Center in Houston, Orion is the first spacecraft in history capable of taking humans to multiple destinations within deep space. 2) Each element of the SLS utilizes collaborative design processes to achieve the incredible goal of sending human into deep space. Early phases are focused on feasibility and requirements development. Later phases are focused on detailed design, testing, and operations. There are 4 basic phases typically found in each phase of development.

Development of an above-knee prosthesis equipped with a microcomputer-controlled knee joint: first test results.

PubMed

Aeyels, B; Peeraer, L; Vander Sloten, J; Van der Perre, G

1992-05-01

The shortcomings of conventional above-knee prostheses are due to their lack of adaptive control. Implementation of a microcomputer controlling the knee joint in a passive way has been suggested to enhance the patient's gait comfort, safety and cosmesis. This approach was used in the design of a new prosthetic system for the above-knee amputee, and tested on one patient. The knee joint of a conventional, modular prosthesis was replaced by a knee joint mechanism, equipped with a controllable brake on the knee joint axis. Sensors and a microcomputer were added, keeping the system self-contained. The modularity of the design permits the use of an alternative, external, PC-based control unit, emulating the self-contained one, and offering extended data monitoring and storage facilities. For both units an operating environment was written, including sensor/actuator interfacing and the implementation of a real-time interrupt, executing the control algorithm. A double finite state approach was used in the design of the control algorithm. On a higher level, the mode identification algorithm reveals the patient's intent. Within a specific mode (lower level), the relevant mode control algorithm looks for the current phase within the gait cycle. Within a particular phase, a specific simple control action with the brake replaces normal knee muscle activity. Tests were carried out with one prosthetic patient using a basic control algorithm for level walking, allowing controlled knee flexion during stance phase. The technical feasibility of such a concept is illustrated by the test results, even though only flexion during early stance phase was controlled during the trials.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV/AIDS Clinical Trials

MedlinePlus

... Participants Studies with Female Participants What's this? Age Group: What's this? Child (birth-17) Adult (18-65) Senior (66+) Phase: What's this? Early Phase 1 Phase 1 Phase 2 Phase 3 Phase 4 Funded By: What's this? NIH Other U.S. Federal ...

Menstrual phase-related differences in the pulsatility index on the central retinal artery suggest an oestrogen vasodilatation effect that antagonizes with progesterone.

PubMed

Viana, Luiz Carlos; Faria, Marcos; Pettersen, Heverton; Sampaio, Marcos; Geber, Selmo

2011-03-01

The actual effect of steroid hormones on cerebral microcirculation is still controversial. Therefore, the aim of our study was to investigate vascular flow variations in the central retinal artery that may exist during the ovulatory menstrual cycle. A total of 34 healthy women were included in this observational, longitudinal, and prospective study. All participants were submitted to dopplerfluxometric evaluation of the eyes in order to study the pulsatility index (PI) of the central retinal arteries, during four phases of the menstrual cycle: early follicular, mid follicular, periovulatory, and mid luteal phases. Subjects' ages ranged from 14 to 47 years old (mean: 29.7 ± 10.1) and PI did not differ among age groups. The PI of the central retinal artery was different among the four phases of the menstrual cycle. PI showed a significant decrease from early follicular phase (1.72) to mid follicular phase (1.57) (p = 0.037), and was similar during periovulatory phase (1.56) and significantly increased in mid luteal phase (1.70). After that it returned to the values observed in the early follicular phase. Our results suggest the existence of an oestrogen vasodilatation effect on the central retinal artery that is menstrual phase-related and antagonized by progesterone.

White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

PubMed

Cookey, Jacob; Bernier, Denise; Tibbo, Philip G

2014-07-01

The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.

Transcription-dependent induction of G1 phase during the zebra fish midblastula transition.

PubMed

Zamir, E; Kam, Z; Yarden, A

1997-02-01

The early development of the zebra fish (Danio rerio) embryo is characterized by a series of rapid and synchronous cell cycles with no detectable transcription. This period is followed by the midblastula transition (MBT), during which the cell cycle gradually lengthens, cell synchrony is lost, and zygotic transcription is initially detected. In this work, we examined the changes in the pattern of the cell cycle during MBT in zebra fish and whether these changes are dependent on the initiation of zygotic transcription. To characterize the pattern of the early zebra fish cell cycles, the embryonic DNA content was determined by flow cytometric analysis. We found that G1 phase is below detection levels during the first 10 cleavages and can be initially detected at the onset of MBT. Inhibition of zygotic transcription, by microinjection of actinomycin D, abolished the appearance of G1 phase at MBT. Premature activation of zygotic transcription, by microinjection of nonspecific DNA, induced G1 phase before the onset of MBT, while coinjection of actinomycin D and nonspecific DNA abolished this early appearance of G1 phase. We therefore suggest that during the early development of the zebra fish embryo, G1 phase appears at the onset of MBT and that the activation of transcription at MBT is essential and sufficient for the G1-phase induction.

The neutron star interior composition explorer (NICER): mission definition

NASA Astrophysics Data System (ADS)

Arzoumanian, Z.; Gendreau, K. C.; Baker, C. L.; Cazeau, T.; Hestnes, P.; Kellogg, J. W.; Kenyon, S. J.; Kozon, R. P.; Liu, K.-C.; Manthripragada, S. S.; Markwardt, C. B.; Mitchell, A. L.; Mitchell, J. W.; Monroe, C. A.; Okajima, T.; Pollard, S. E.; Powers, D. F.; Savadkin, B. J.; Winternitz, L. B.; Chen, P. T.; Wright, M. R.; Foster, R.; Prigozhin, G.; Remillard, R.; Doty, J.

2014-07-01

Over a 10-month period during 2013 and early 2014, development of the Neutron star Interior Composition Explorer (NICER) mission [1] proceeded through Phase B, Mission Definition. An external attached payload on the International Space Station (ISS), NICER is scheduled to launch in 2016 for an 18-month baseline mission. Its prime scientific focus is an in-depth investigation of neutron stars—objects that compress up to two Solar masses into a volume the size of a city—accomplished through observations in 0.2-12 keV X-rays, the electromagnetic band into which the stars radiate significant fractions of their thermal, magnetic, and rotational energy stores. Additionally, NICER enables the Station Explorer for X-ray Timing and Navigation Technology (SEXTANT) demonstration of spacecraft navigation using pulsars as beacons. During Phase B, substantive refinements were made to the mission-level requirements, concept of operations, and payload and instrument design. Fabrication and testing of engineering-model components improved the fidelity of the anticipated scientific performance of NICER's X-ray Timing Instrument (XTI), as well as of the payload's pointing system, which enables tracking of science targets from the ISS platform. We briefly summarize advances in the mission's formulation that, together with strong programmatic performance in project management, culminated in NICER's confirmation by NASA into Phase C, Design and Development, in March 2014.

Early 20th Century Arctic Warming Intensified by Pacific and Atlantic Multidecadal Variability

NASA Astrophysics Data System (ADS)

Tokinaga, H.; Xie, S. P.; Mukougawa, H.

2017-12-01

We investigate the influence of Pacific and Atlantic multidecadal variability on the Arctic temperature, with a particular focus on the early 20th century Arctic warming. Arctic surface air temperature increased rapidly over the early 20th century, at rates comparable to those of recent decades despite much weaker greenhouse gas forcing than at present. We find that the concurrent phase shift of Pacific and Atlantic multidecadal variability is the major driver for the early 20th century Arctic warming. Atmospheric model simulations reproduce the early Arctic warming when the interdecadal variability of sea surface temperature (SST) is properly prescribed. The early Arctic warming is associated with the cold-to-warm phase shifts of Atlantic and Pacific multidecadal variability modes, a SST pattern reminiscent of the positive phase of the Pacific decadal and Atlantic multidecadal oscillations. The extratropical North Atlantic and North Pacific SST warming strengthens surface westerly winds over northern Eurasia, intensifying the warming there. The equatorial Pacific warming deepens the Aleutian low, advecting warm air to the North American Arctic. Coupled ocean-atmosphere simulations support the constructive intensification of Arctic warming by a concurrent, cold-to-warm phase shift of the Pacific and Atlantic multidecadal variability. Our results aid attributing the historical Arctic warming and thereby constrain the amplified warming projected for this important region.

Embedded I&C for Extreme Environments

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

Kisner, Roger A.

2016-04-01

This project uses embedded instrumentation and control (I&C) technologies to demonstrate potential performance gains of nuclear power plant components in extreme environments. Extreme environments include high temperature, radiation, high pressure, high vibration, and high EMI conditions. For extreme environments, performance gains arise from moment-to-moment sensing of local variables and immediate application of local feedback control. Planning for embedding I&C during early system design phases contrasts with the traditional, serial design approach that incorporates minimal I&C after mechanical and electrical design is complete. The demonstration application involves the development and control of a novel, proof-of-concept motor/pump design. The motor and pumpmore » combination operate within the fluid environment, eliminating the need for rotating seals. Actively controlled magnetic bearings also replace failure-prone mechanical contact bearings that typically suspend rotating components. Such as design has the potential to significantly enhance the reliability and life of the pumping system and would not be possible without embedded I&C.« less

Management and integration of engineering and construction activities: Lessons learned from the AP1000{sup R} nuclear power plant China project

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

McCullough, M. C.; Ebeling-Koning, D.; Evans, M. C.

2012-07-01

The lessons learned during the early phase of design engineering and construction activities for the AP1000 China Project can be applied to any project involving multiple disciplines and multiple organizations. Implementation of a first-of-a-kind design to directly support construction activities utilizing resources assigned to design development and design delivery creates challenges with prioritization of activities, successful closure of issues, and communication between site organizations and the home office. To ensure successful implementation, teams were assigned and developed to directly support construction activities including prioritization of activities, site communication and ensuring closure of site emergent issues. By developing these teams, themore » organization is better suited to meet the demands of the construction schedule while continuing with design evolution of a standard plant and engineering delivery for multiple projects. For a successful project, proper resource utilization and prioritization are key for overcoming obstacles and ensuring success of the engineering organization. (authors)« less

Trophic or full nutritional support?

PubMed

Arabi, Yaseen M; Al-Dorzi, Hasan M

2018-06-04

Full nutritional support during the acute phase of critical illness has traditionally been recommended to reduce catabolism and prevent malnutrition. Approaches to achieve full nutrition include early initiation of nutritional support, targeting full nutritional requirement as soon as possible and initiation of supplemental parenteral nutrition when enteral nutrition does not reach the target. Existing evidence supports early enteral nutrition over delayed enteral nutrition or early parenteral nutrition. Recent randomized controlled trials have demonstrated that permissive underfeeding or trophic feeding is associated with similar outcomes compared with full feeding in the acute phase of critical illness. In patients with refeeding syndrome, patients with high nutritional risk and patients with shock, early enteral nutrition targeting full nutritional targets may be associated with worse outcomes compared with less aggressive enteral nutrition strategy. A two-phase approach for nutritional support may more appropriately account for the physiologic changes during critical illness than one-phase approach. Further evidence is awaited for the optimal protein amount during critical illness and for feeding patients at high nutritional risk or with acute gastrointestinal injury.

Anaphase-promoting complex/cyclosome-CDH1-mediated proteolysis of the forkhead box M1 transcription factor is critical for regulated entry into S phase.

PubMed

Park, Hyun Jung; Costa, Robert H; Lau, Lester F; Tyner, Angela L; Raychaudhuri, Pradip

2008-09-01

The forkhead box M1 (FoxM1) transcription factor is overexpressed in many cancers, and in mouse models it is required for tumor progression. FoxM1 activates expression of the cell cycle genes required for both S and M phase progression. Here we demonstrate that FoxM1 is degraded in late mitosis and early G(1) phase by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. FoxM1 interacts with the APC/C complex and its adaptor, Cdh1. Expression of Cdh1 stimulated degradation of the FoxM1 protein, and depletion of Cdh1 resulted in stabilization of the FoxM1 protein in late mitosis and in early G(1) phase of the cell cycle. Cdh1 has been implicated in regulating S phase entry. We show that codepletion of FoxM1 inhibits early S phase entry observed in Cdh1-depleted cells. The N-terminal region of FoxM1 contains both destruction box (D box) and KEN box sequences that are required for targeting by Cdh1. Mutation of either the D box sequence or the KEN box sequence stabilized FoxM1 and blocked Cdh1-induced proteolysis. Cells expressing a nondegradable form of FoxM1 entered S phase rapidly following release from M phase arrest. Together, our observations show that FoxM1 is one of the targets of Cdh1 in late M or early G(1) phase and that its proteolysis is important for regulated entry into S phase.

PAPER: The Precision Array To Probe The Epoch Of Reionization

NASA Astrophysics Data System (ADS)

Backer, Donald C.; Parsons, A.; Bradley, R.; Parashare, C.; Gugliucci, N.; Mastrantonio, E.; Herne, D.; Lynch, M.; Wright, M.; Werhimer, D.; Carilli, C.; Datta, A.; Aguirre, J.

2007-12-01

The Precision Array to Probe the Epoch of Reionization (PAPER) is an experiment that is being designed to detect the faint HI signal from the epoch of reionization. Our instrumentation goals include: the design and building of dipole elements that are optimized for operation from 120-190 MHz with a clean beam response; amplifiers and receivers with good impedance match and overall flat gain response over a large bandpass; and an FPGA correlator capable of producing full Stokes products for the array. The array is being built and evaluated in stages at the Green Bank Observatory in West Virginia with deployment of the full instrument in Western Australia. We present results from an eight-station deployment in Green Bank and four-station deployment in Western Australia, including phase and amplitude calibration, RFI mitigation and removal, full sky maps, and wide-field snapshot imaging. We have discovered new ways to improve our system's stability and sensitivity from these early experiments, and are applying these concepts to a 16-element array in Green Bank in early 2008 and a 32-element array in Western Australia later in 2008.

Rapid Production of Mixed-Base Hydrogen Peroxide by Direct-Contact Liquefied Nitrogen Evaporation; Process Design, Scale-Up, and Validation

DTIC Science & Technology

2004-01-01

phase in November 1996. 1-2. BASIC HYDROGEN PEROXIDE In the early COIL work, either potassium hydroxide (KOH) or sodium hydroxide (NaOH) was the base of...the candidate refrigerants include: R22, R404a, R134a, carbon dioxide, and ammonia. 2-3-3. Surface Evaporator To improve the heat transfer efficiency...monohydrate (LiOH.H20), sodium hydroxide (NaOH), and potassium hydroxide (KOH). The use of solids allows numerous variations of blending sequence and heat

Effects of Simulated Pathophysiology on the Performance of a Decision Support Medical Monitoring System for Early Detection of Hemodynamic Decompensation in Humans

DTIC Science & Technology

2017-02-01

only during the LBNP trial (P=0.001). There were no 230 differences in MAP between the LBNP and blood loss trials at any level (P≥0.42). At...and blood loss 256 conditions (P≥0.23). Similarly, there was no effect of condition or level for MAP-MCAv LF 257 coherence, gain, or phase (P≥0.10...designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No . 0704-0188 Public reporting burden for this collection of

Development and marketing of a prosthetic urinary control valve system

NASA Technical Reports Server (NTRS)

Tenney, J. B., Jr.; Rabinowitz, R.; Rogers, D. W.; Harrison, H. N.

1983-01-01

An implantable prosthetic for the control of urinary incontinence was developed and marketed. Three phases are presented: bench development studies, animal trials, and human clinical trials. This work was performed under the direction of a Research Team at Rochester General Hospital (RGH). Bench trials were completed on prototype hardware and provided early verification of the device's ability to withstand repeated cyclic testing. Configurational variants were evaluated and a preferred design concept was established. Silicone rubber (medical grade) was selected as the preferred material for the prosthesis.

Performance and safety testing of lithium batteries for the Expendable, Mobile, ASW Training Target (EMATT)

NASA Astrophysics Data System (ADS)

Hallal, P. B.; Bis, R. F.

1986-08-01

The developmental EMATT (expendable, mobile, ASW training target) may use a high-energy (lithium/sulfuryl chloride) battery system. Safety problems with the original battery cell design were experienced during early performance and safety testing. After redesign of the battery cell, performance and safety tests were made under specified abuse conditions, as well as under simulated launch conditions. The test results showed that the power system now meets all safety requirements, and that the EMATT vehicle is safe to deploy for its engineering development phase.

Commutated automatic gain control system

NASA Technical Reports Server (NTRS)

Yost, S. R.

1982-01-01

The commutated automatic gain control (AGC) system was designed and built for the prototype Loran-C receiver is discussed. The current version of the prototype receiver, the Mini L-80, was tested initially in 1980. The receiver uses a super jolt microcomputer to control a memory aided phase loop (MAPLL). The microcomputer also controls the input/output, latitude/longitude conversion, and the recently added AGC system. The AGC control adjusts the level of each station signal, such that the early portion of each envelope rise is about at the same amplitude in the receiver envelope detector.

Neutrophils dominate the immune cell composition in non-small cell lung cancer. | Office of Cancer Genomics

Cancer.gov

The response rate to immune checkpoint inhibitor therapy for non-small-cell lung cancer (NSCLC) is just 20%. To improve this figure, several early phase clinical trials combining novel immunotherapeutics with immune checkpoint blockade have been initiated. Unfortunately, these trials have been designed without a strong foundational knowledge of the immune landscape present in NSCLC. Here, we use a flow cytometry panel capable of measuring 51 immune cell populations to comprehensively identify the immune cell composition and function in NSCLC.

Phase Boundary Propagation in Li-Alloying Battery Electrodes Revealed by Liquid-Cell Transmission Electron Microscopy

DOE PAGES

Leenheer, Andrew J.; Jungjohann, Katherine L.; Zavadil, Kevin R.; ...

2016-05-31

Battery cycle life is directly influenced by the microstructural changes occurring in the electrodes during charge and discharge cycles. In this study, we image in situ the nanoscale phase evolution in negative electrode materials for Li-ion batteries using a fully enclosed liquid cell in a transmission electron microscope (TEM) to reveal early degradation that is not evident in the charge–discharge curves. To compare the electrochemical phase transformation behavior between three model materials, thin films of amorphous Si, crystalline Al, and crystalline Au were lithiated and delithiated at controlled rates while immersed in a commercial liquid electrolyte. This method allowed formore » the direct observation of lithiation mechanisms in nanoscale negative electrodes, revealing that a simplistic model of a surface-to-interior lithiation front is insufficient. For the crystalline films, a lithiation front spread laterally from a few initial nucleation points, with continued grain nucleation along the growing interface. The intermediate lithiated phases were identified using electron diffraction, and high-resolution postmortem imaging revealed the details of the final microstructure. Lastly, our results show that electrochemically induced solid–solid phase transformations can lead to highly concentrated stresses at the laterally propagating phase boundary which should be considered for future designs of nanostructured electrodes for Li-ion batteries.« less

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

PubMed

Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Longitudinal 1H MR spectroscopy of rat forebrain from infancy to adulthood reveals adolescence as a distinctive phase of neurometabolite development

PubMed Central

Morgan, Jonathan J.; Kleven, Gale A.; Tulbert, Christina D.; Olson, John; Horita, David A.; Ronca, April E.

2013-01-01

The present study represents the first longitudinal, within-subject 1H MRS investigation of the developing rat brain spanning infancy, adolescence, and early adulthood. We obtained neurometabolite profiles from a voxel located in a central location of the forebrain, centered on the striatum, with smaller contributions for cortex, thalamus, and hypothalamus, on postnatal days 7, 35, and 60. Water-scaled metabolite signals were corrected for T1 effects and quantified using the automated processing software LCModel, yielding molal concentrations. Our findings indicate age-related concentration changes in N-acetylaspartate + N-acetylaspartylglutamate, myo-inositol, glutamate + glutamine, taurine, creatine + phosphocreatine, and glycerophosphocholine + phosphocholine. Using a repeated measures design and analysis, we identified significant neurodevelopment change across all three developmental ages and identified adolescence as a distinctive phase in normative neurometabolic brain development. Between postnatal days 35 and 60, changes were observed in concentrations of N-acetylaspartate + N-acetylaspartylglutamate, glutamate + glutamine, and glycerophosphocholine + phosphocholine observed between postnatal days 35 and 60. Our data replicate past studies of early neurometabolite development and, for the first time, link maturational profiles in the same subjects across infancy, adolescence, and adulthood. PMID:23322706

Unified approach for extrapolation and bridging of adult information in early-phase dose-finding paediatric studies.

PubMed

Petit, Caroline; Samson, Adeline; Morita, Satoshi; Ursino, Moreno; Guedj, Jérémie; Jullien, Vincent; Comets, Emmanuelle; Zohar, Sarah

2018-06-01

The number of trials conducted and the number of patients per trial are typically small in paediatric clinical studies. This is due to ethical constraints and the complexity of the medical process for treating children. While incorporating prior knowledge from adults may be extremely valuable, this must be done carefully. In this paper, we propose a unified method for designing and analysing dose-finding trials in paediatrics, while bridging information from adults. The dose-range is calculated under three extrapolation options, linear, allometry and maturation adjustment, using adult pharmacokinetic data. To do this, it is assumed that target exposures are the same in both populations. The working model and prior distribution parameters of the dose-toxicity and dose-efficacy relationships are obtained using early-phase adult toxicity and efficacy data at several dose levels. Priors are integrated into the dose-finding process through Bayesian model selection or adaptive priors. This calibrates the model to adjust for misspecification, if the adult and pediatric data are very different. We performed a simulation study which indicates that incorporating prior adult information in this way may improve dose selection in children.

Uses of infrared thermography in the low-cost solar array program

NASA Technical Reports Server (NTRS)

Glazer, S. D.

1982-01-01

The Jet Propulsion Laboratory has used infrared thermography extensively in the Low-Cost Solar Array (LSA) photovoltaics program. A two-dimensional scanning infrared radiometer has been used to make field inspections of large free-standing photovoltaic arrays and smaller demonstration sites consisting of integrally mounted rooftop systems. These field inspections have proven especially valuable in the research and early development phases of the program, since certain types of module design flaws and environmental degradation manifest themselves in unique thermal patterns. The infrared camera was also used extensively in a series of laboratory tests on photovoltaic cells to obtain peak cell temperatures and thermal patterns during off-design operating conditions. The infrared field inspections and the laboratory experiments are discussed, and sample results are presented.

Legacy of the Space Shuttle from an Aerodynamic and Aerothermodynamic Perspective

NASA Technical Reports Server (NTRS)

Martin, Fred W.

2011-01-01

The development of the Space Shuttle Orbiter thermal protection system heating environment is described from a design stand point that began in the early 1970s. The desire for a light weight, reusable heat shield required the development of new technology, relative to previous manned spacecraft, and a systems approach to the design of the vehicle, entry guidance, and thermal protection system. Several unanticipated issues had to be resolved in both the entry and ascent phases of flight, which are discussed at a high level. During the life of the Program, significant improvements in computing power and numerical methods have been applied to Space Shuttle aerodynamic and aerothermodynamic issues, with the Shuttle Program often being the motivation, and or sponsor of the analysis development.

End of Mission Considerations

NASA Technical Reports Server (NTRS)

Hull, Scott M.

2013-01-01

While a great deal of effort goes into planning and executing successful mission operations, it is also important to consider the End of the Mission during the planning, design, and operations phases of any mission. Spacecraft and launch vehicles must be disposed of properly in order to limit the generation of orbital debris, and better preserve the orbital environment for all future missions. Figure 30-1 shows a 1990's projected growth of debris with and without the use of responsible disposal techniques. This requires early selection of a responsible disposal scenario, so that the necessary capabilities can be incorporated into the hardware designs. The mission operations must then be conducted in such a way as to preserve, and then actually perform, the planned, appropriate end of mission disposal.

Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns.

PubMed

Soules, M R; Clifton, D K; Cohen, N L; Bremner, W J; Steiner, R A

1989-10-01

Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P secretion in LPD is decreased P pulse amplitude; 3) the finding of similar serum FSH levels in the two groups in both the early and late follicular phases did not support compromised folliculogenesis as an etiological factor for LPD.

Mechanisms underlying hemodynamic and neuroendocrine stress reactivity at different phases of the menstrual cycle

PubMed Central

Gordon, Jennifer L.; Girdler, Susan S.

2014-01-01

This study examined the association of menstrual cycle phase with stress reactivity as well as the hormonal and neuroendocrine mechanisms contributing to cycle effects. Fifty-seven women underwent a modified Trier Social Stress Test (TSST) during the early follicular, late follicular and luteal phases of the menstrual cycle. Greater increases in cardiac index (CI) and greater decreases in vascular resistance index (VRI) during speech were observed in the luteal phase relative to other phases, while greater increases in epinephrine (EPI) was observed during the late follicular and luteal phases compared to the early follicular phase. Luteal phase estradiol predicted luteal EPI reactivity but not CI or VRI reactivity while luteal phase EPI reactivity predicted luteal phase CI and VRI reactivity. Thus, cycle-related changes in EPI reactivity may be a stronger determinant of cycle effects on hemodynamic reactivity than sex hormones per se. PMID:24397365

Ionic liquid stationary phases for gas chromatography.

PubMed

Poole, Colin F; Poole, Salwa K

2011-04-01

This article provides a summary of the development of ionic liquids as stationary phases for gas chromatography beginning with early work on packed columns that established details of the retention mechanism and established working methods to characterize selectivity differences compared with molecular stationary phases through the modern development of multi-centered cation and cross-linked ionic liquids for high-temperature applications in capillary gas chromatography. Since there are many reviews on ionic liquids dealing with all aspects of their chemical and physical properties, the emphasis in this article is placed on the role of gas chromatography played in the design of ionic liquids of low melting point, high thermal stability, high viscosity, and variable selectivity for separations. Ionic liquids provide unprecedented opportunities for extending the selectivity range and temperature-operating range of columns for gas chromatography, an area of separation science that has otherwise been almost stagnant for over a decade. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A dual frequency microstrip antenna for Ka band

NASA Technical Reports Server (NTRS)

Lee, R. Q.; Baddour, M. F.

1985-01-01

For fixed satellite communication systems at Ka band with downlink at 17.7 to 20.2 GHz and uplink at 27.5 to 30.0 GHz, the focused optics and the unfocused optics configurations with monolithic phased array feeds have often been used to provide multiple fixed and multiple scanning spot beam coverages. It appears that a dual frequency microstrip antenna capable of transmitting and receiving simultaneously is highly desirable as an array feed element. This paper describes some early efforts on the development and experimental testing of a dual frequency annular microstrip antenna. The antenna has potential application for use in conjunction with a monolithic microwave integrated circuit device as an active radiating element in a phased array of phased array feeds. The antenna is designed to resonate at TM sub 12 and TM sub 13 modes and tuned with a circumferential microstrip ring to vary the frequency ratio. Radiation characteristics at both the high and low frequencies are examined. Experimental results including radiating patterns and swept frequency measurements are presented.

Research on the use of space resources

NASA Technical Reports Server (NTRS)

Carroll, W. F. (Editor)

1983-01-01

The second year of a multiyear research program on the processing and use of extraterrestrial resources is covered. The research tasks included: (1) silicate processing, (2) magma electrolysis, (3) vapor phase reduction, and (4) metals separation. Concomitant studies included: (1) energy systems, (2) transportation systems, (3) utilization analysis, and (4) resource exploration missions. Emphasis in fiscal year 1982 was placed on the magma electrolysis and vapor phase reduction processes (both analytical and experimental) for separation of oxygen and metals from lunar regolith. The early experimental work on magma electrolysis resulted in gram quantities of iron (mixed metals) and the identification of significant anode, cathode, and container problems. In the vapor phase reduction tasks a detailed analysis of various process concepts led to the selection of two specific processes designated as ""Vapor Separation'' and ""Selective Ionization.'' Experimental work was deferred to fiscal year 1983. In the Silicate Processing task a thermophysical model of the casting process was developed and used to study the effect of variations in material properties on the cooling behavior of lunar basalt.